OCTA在全身性疾病中的应用

Background: This study aimed to evaluate the location of retinal fractal dimension (FD) abnormalities in individuals with diabetes mellitus (DM) and hypertension (HTN) without retinopathy. Methods: The annular zone of 6 mm × 6 mm OCTA images centered on the fovea was partitioned into thin annuli and analyzed using fractal analysis to measure FDs. Results: The cohort (n = 114) had an average age of 55.7 years, with 87% self-identifying as male; 29% (n = 33) had HTN, 8% (n = 9) had DM, and 11% (n = 12) had both. Individuals with DM showed significantly lower FDs in the C5 partition of the deep vascular plexus (DVP), located 1.77 mm to 2.14 mm from the foveal center compared to controls without DM (1.57 ± 0.003 vs. 1.58 ± 0.006; p = 0.014). Those with both DM and HTN exhibited significantly lower FDs in the entire superficial vascular plexus (SVP) annulus (1.84 ± 0.01 vs. 1.85 ± 0.007; p = 0.006), as well as the C3 (1.58 ± 0.02 vs. 1.60 ± 0.02; p = 0.008), C4 (1.57 ± 0.002 vs. 1.57 ± 0.01; p = 0.036), C5 (1.56 ± 0.01 vs. 1.57 ± 0.008; p < 0.001), and C6 (1.58 ± 0.01 vs. 1.59 ± 0.008; p < 0.001) partitions of the SVP (1.03 mm to 2.50 mm from the foveal center) and the C4 (1.57 ± 0.008 vs. 1.58 ± 0.008; p = 0.015) and C5 (1.57 ± 0.01 vs. 1.58 ± 0.006; p = 0.012) partitions of the DVP (1.40 mm to 1.77 mm from the foveal center) compared to the controls with neither DM nor HTN. Conclusions: While our study examined FDs in a predominantly male veteran population, our findings align with prior studies that reported lower FDs in DM and HTN cohorts. Our study further localizes these microvascular changes, with the most prominent differences occurring at C5 and C6 of the SVP, representing an area between 1.77 and 2.50 mm from the center of the fovea. These data lay the groundwork for developing screening protocols to identify individuals at risk of developing vasculopathies.

Objective To investigate the potential of quantitative ophthalmic posterior segment optical coherence tomography angiography (OCTA) imaging metrics to serve as biomarkers for systemic involvement in three rheumatologic diseases, systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Behçet disease (BD), by reviewing the reported correlations between such OCTA metrics and clinically relevant features of systemic involvement in these diseases. Methods This review is a correlational study conducted through a systematic review of the PubMed database for articles reporting OCTA metrics in any of SSc, SLE, and BD. Articles correlating ophthalmic posterior segment OCTA metrics to clinically relevant features of systemic involvement, specifically serum, cerebrospinal fluid (CSF), or other established biomarkers; systemic symptom and severity scores; stage; non-ocular organ involvement; non-ocular imaging findings; and medication use were included. Results OCTA parameters have been significantly correlated to autoantibody presence, digit and pulmonary involvement, disease stage, and medication use in SSc with significance values ranging from p = 0.008 to p = 0.048. OCTA parameters have been significantly correlated to serum markers, renal and cardiac involvement, damage indices, and medication use in SLE with significance values ranging from p < 0.0001 to p = 0.028. OCTA parameters have been correlated to systemic vascular involvement in BD with significance value p = 0.006. Conclusion Ophthalmic posterior segment OCTA metrics may provide value in prognosis, stratification, and treatment monitoring of the examined rheumatologic conditions. These results warrant further study.

Purpose To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design Prospective, cross-sectional, observational study. Participants and controls Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

No abstract available

Purpose To correlate retinal imaging findings with systemic disease activity in children with sickle cell disease (SCD). Design A retrospective consecutive series. Subjects Children with SCD aged ≤18 years who had an ophthalmic examination at Boston Children's Hospital between January 1998 and August 2022 were included. Main Outcome Measures Systemic findings included the number of hospitalizations, number of strokes, treatment with hydroxyurea, hemoglobin (Hgb), and fetal Hgb levels, and time-averaged mean velocity (TAMV) in the right middle cerebral artery (RMCA) and left middle cerebral artery (LMCA) on transcranial Doppler (TCD). Methods Total retinal thickness was measured on macular OCT (Spectralis OCT2, Heidelberg Engineering). Vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and superficial foveal avascular zone area were measured on 6 × 6-mm OCT angiography (OCTA) scans. Results Six hundred six eyes from 303 pediatric SCD patients (53% males) were included. OCT and OCTA images were acquired on 104 (17.2%) and 60 (9.9%) eyes at presentation and on 159 (26.2%) and 100 (16.5%) eyes at the final visit, respectively. When adjusting for race and age, retinal thinning on OCT was associated with a higher frequency of hospitalizations, a higher frequency of strokes, and treatment with hydroxyurea. Retinal thickness in the inferior and temporal macula was positively correlated with TAMV in RMCA and in LMCA. Foveal retinal thickness was positively correlated with Hgb level. Similarly, reduced VD in the SCP and DCP in the inferior temporal macula correlated with a higher number of hospitalizations and strokes. A higher VD of the DCP in the inferior-temporal macula positively correlated with TAMV in RMCA (ρ = 0.328, P = 0.3) and in LMCA (ρ = 0.342, P = 0.029). A higher Hgb level correlated with a higher prevalence (ρ = 0.237, P = 0.037) and severity (ρ = 0.299, P = 0.008) of peripheral retinopathy in HbSC, while it correlated with lower prevalence (ρ = −0.183, P = 0.004) and severity (ρ = −0.185, P = 0.004) of peripheral retinopathy in HbSS genotypes. Visual acuity did not correlate with TCD velocity, Hgb level, or number of hospitalizations in HbSS or HbSC genotypes. Conclusions OCT and OCTA findings are correlated with the severity of systemic disease in children with SCD. Imaging parameters were better correlated with key outcomes such as stroke and hospitalizations than visual acuity. The results suggest that quantitative measures on retinal imaging could be used as biomarkers to predict systemic disease risk and activity. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical coherence tomography (OCT) is an integral component of present-day ophthalmologic practice. As use of OCT has increased in popularity and frequency of use, a growing number of systemic diseases are now known to have associated findings on both OCT and OCT angiography (OCTA). This review was written to discuss how a multitude of cardiovascular, neurodegenerative, neoplastic, infectious, and autoimmune diseases manifest on OCT and OCTA. The findings thus far highlight the potential utility of OCT and OCTA for diagnosing and monitoring progression of these disease processes. Many current studies are limited by small sample sizes, varying image processing algorithms, image artifact, and differing machines used to acquire images, underscoring the need for further research with increased patient numbers and standardized image acquisition and image processing protocols. Despite these current limitations, the steadily increasing volume of data suggests that there will ultimately be a role for both OCT and OCTA to noninvasively monitor the progression of systemic disease over time.

This study aimed to characterize conjunctival and retinal microvascular alterations in Systemic lupus erythematosus (SLE) using swept-source optical coherence tomography angiography (SS-OCTA), and to evaluate their correlation with systemic clinical manifestations. This cross-sectional study enrolled 32 SLE patients and 32 age, sex, and spherical equivalent matched controls. Participants underwent swept-source OCTA imaging of nasal and temporal conjunctiva (16 × 12 mm scans) and macula (6 × 6 mm scans). Vessel density of conjunctival vessel, superficial vascular plexus (SVP), and deep vascular plexus (DVP) were quantified using automated segmentation. Correlation analyses were conducted to evaluate the association between conjunctival and retinal vascular densities, as well as their relationships with clinical parameters of systemic involvement and disease activity. SLE patients showed significant reductions in nasal (45.0% vs. 60.1%, p < 0.001) and temporal (51.8% vs. 60.5%, p = 0.009) conjunctival vascular density, alongside pan-retinal DVP attenuation (p < 0.05). Combined nasal conjunctival and retinal nasal DVP analysis yielded high diagnostic accuracy (AUC 0.897). Microvascular loss was independent of organ involvement or disease activity (p > 0.05). SLE is associated with significant reductions in conjunctival and retinal DVP vascular density. Combined multimodal SS-OCTA analysis achieved superior diagnostic accuracy, with microvascular loss independent of disease activity or organ-specific involvement, suggesting systemic microvascular injury as a unifying SLE feature. Conjunctival-retinal vascular metrics may serve as potential new biomarkers for SLE.

Metabolic liver disease, historically characterized as nonalcoholic fatty liver disease (NAFLD) and recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged as a global public health crisis. It is increasingly recognized not merely as a liver-specific pathology, but as a complex multisystemic disorder strongly associated with widespread systemic microvascular dysfunction. The retina, sharing similar anatomical and physiological features with the systemic microcirculation, provides a unique, * in vivo * window for non-invasive vascular assessment. A systematic review with semi-quantitative synthesis was conducted in strict adherence to the PRISMA guidelines. We comprehensively searched the PubMed, Embase, and Cochrane Library databases for relevant studies published from inception to March 2026. Studies employing optical coherence tomography angiography (OCTA) to evaluate the macular microvasculature in patients with metabolic liver disease were included. Study quality was rigorously appraised using the Newcastle–Ottawa Scale (NOS). A total of 7 cross-sectional and retrospective studies encompassing approximately 520 participants met the stringent inclusion criteria. Across the included cohorts, a consistent and statistically significant reduction in retinal vessel density (VD) was observed. Notably, this vascular rarefaction was predominantly localized within the deep capillary plexus (DCP). Furthermore, an abnormal enlargement of the foveal avascular zone (FAZ) was consistently reported in patients with metabolic liver disease compared to matched healthy controls, indicating subclinical macular ischemia. Metabolic liver disease is significantly associated with early retinal microvascular alterations detectable by OCTA, preceding visually significant ocular symptoms. These subclinical findings highlight a profound pathological link between hepatic steatosis and systemic microvascular dysfunction. OCTA metrics, particularly DCP vessel density and FAZ area, may serve as novel, non-invasive biomarkers for identifying patients at high risk for systemic vascular complications.

No abstract available

Coronary artery disease (CAD) is a leading cause of cardiovascular mortality worldwide, and its early diagnosis is essential for prevention and treatment. Emerging evidence from ocular imaging suggests that structural and functional alterations in the retinal vasculature may mirror systemic vascular changes, offering a promising avenue for the early identification of cardiovascular conditions such as CAD. Among these techniques, OCTA stands out as a non-invasive, high-resolution modality capable of capturing detailed microvascular architecture and quantifying retinal blood flow dynamics. In this study, we analyzed OCTA images from 747 participants including 332 patients with CAD and 415 controls to extract retinal microvascular parameters and evaluate their associations with disease status. The results revealed that patients with CAD exhibited significantly lower retinal vessel density, vessel length density, tortuosity, and vascular bifurcation complexity on OCTA compared to controls, particularly in the left eye. This suggests possible lateral asymmetry in microvascular responses associated with CAD. Overall, we highlight the potential of OCTA-derived retinal biomarkers in supporting the early diagnosis of CAD, providing a standard tool for future clinical services and research. Biomarkers in retinal OCTA images can provide useful information for clinical decision making and diagnosis of CAD.

Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by inflammatory arthritis and extraarticular manifestations. It is a chronic inflammatory disease of unknown etiology which affects synovial joints. Its typical presentation starts with inflammation of small peripheral joints which is often symmetric then involves proximal joints if it is not treated. RA may affect the vascular tissue in the body including eye as it affects superficial and deep capillary plexus in foveal avascular zone (FAZ) area, superficial foveal vessel density and choroid. The Disease Activity Score (DAS)ESR is a major scoring system that evaluate activity of RA. The DAS score provides a score between 0 and 10, a larger number indicating more active disease. DAS28 score is calculated according to a formula that is composed of the number of tender joints and swollen joints and ESR. To investigate the correlation between retinal vasculature by OCTA and retinal thickness in RA patients with different disease activity scores 60 participants divided into three groups (mild, moderate, and severe) according to disease activity score (DAS), were included in this comparative cross-sectional study. Participants underwent a complete ophthalmologic assessment, measurement of RNFL thickness and retinal thickness using SD-OCT, vessel density using OCTA. There were significant difference in perifoveal nasal retinal thickness, parafoveal (inferior and superior quadrants) (superior hemisphere) (average parafoveal retinal thickness), peripapillary vessel density with increased disease activity score. There was no significant difference in RNFL thickness and retinal vessel density with increased disease activity score. There was significant relation between perifoveal retinal thickness in all quadrants and duration of treatment. There was significant relation between parafoveal retinal thickness in superior quadrants and duration of treatment. There was significant relation between DCP whole image and duration of treatment. There was no significant difference in RNFL thickness, OCTA of optic disc with increased duration of treatment. There was significant difference between 3 groups in RNFL thickness (temporal and inferior quadrants). There were significant differences in parafoveal retinal thickness (inferior quadrant. There were no significant differences between 3 groups regarding OCTA results. retinal thickness in perifoveal and parafoveal superior quadrant and DCP vessel density showed decremental pattern with increased duration of treatment. RNFL thickness in temporal and inferior quadrants showed thinning with increased DAS28 score. Perifoveal retinal thickness in superior and inferior hemispheres, nasal and inferior quadrants showed thinning with increased DAS28 score. There was no correlation between DAS28 score, duration of treatment and CFT and FAZ.

The retina is our only non-invasive access to microworld of the body's capillaries and cellular activities. Leveraging the multimodal synergy of combining dynamic methods of OCT/OCTA, with Adaptive Optics SLO, clinicians have new opportunities to better appreciate some of the complexities of human disease. Serial OCTA imaging can reveal inconsistencies in retinal perfusion not appreciated on single images and can be used to measure activity status of sickle cell microvasculopathy. This approach facilitates earlier detection and immediate assessment of disease burden. AOSLO imaging provides cellular level resolution for confirmation of these OCTA events. En face OCT reflectance images which accompany OCTA studies offer a glimpse of the macrophage-like cellular activity above the retinal surface which responds to systemically instigated vascular events below. The complementary use of AOSLO to characterize morphology of these cells provides clues to their activation status and potential role in tissue maintenance and repair. Features of clinical OCT/OCTA interpreted by AOSLO imaging have the potential to become useful clinical biomarkers of disease activity and response to treatment.

Ophthalmology has progressively evolved into a multidisciplinary field with significant potential for systemic disease detection through non-invasive ocular biomarkers. This review aims to analyze current scientific evidence on the relationship between retinal findings and systemic conditions, including cardiovascular, neurodegenerative, metabolic, and renal diseases. A structured narrative review was conducted using high-impact literature published from 2020 onward, focusing on studies indexed in major biomedical databases. The selected evidence was categorized into key domains, including vascular, neurological, metabolic, imaging, and artificial intelligence applications. The findings demonstrate that ocular biomarkers, particularly those derived from retinal imaging modalities such as fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA), are consistently associated with systemic pathophysiological processes. Strong correlations were identified in neurodegenerative and cardiovascular diseases, where retinal structural and microvascular alterations reflect broader systemic involvement. Additionally, advances in artificial intelligence have enhanced the predictive capacity of ocular imaging, enabling the identification of systemic risk factors through data-driven approaches. Ocular biomarkers also show potential in early detection, risk stratification, and disease monitoring, supporting their integration into preventive medicine frameworks. Despite these advances, challenges related to standardization, reproducibility, and longitudinal validation remain. Overall, the evidence supports the expanding role of ophthalmology as a diagnostic interface for systemic health, with promising applications in both clinical practice and public health, particularly in diverse healthcare settings.

No abstract available

Vessel tortuosity (VT) is a parameter used to assess retinal involvement in patients affected by systemic diseases such as Fabry disease (FD). In this study, we assessed a retinal VT index (VTI) using optical coherence tomography angiography (OCTA) in a group of patients with FD (FD cohort) compared to a healthy control group (HC cohort). This is a single-center, retrospective study analysis of all consecutive patients with genetically tested and confirmed FD who underwent regular ophthalmological visits from December 2017 to January 2020 at the Department of Ophthalmology at the University Hospital of Zurich, Switzerland. VTI was calculated for each OCTA image and the results were compared between FD and HC cohort. A total of 56 participants, 32 (male:female ratio 12:20) in the FD cohort and 24 (male:female ratio 13:11) in the HC cohort. Classic onset was determined in 18 patients. Overall, mean VTI (±SD) was 0.21 (±0.07). Male patients with classic-onset FD had a significantly higher mean VTI (0.33, SD ± 0.35) compared to all other subgroups (p-value < 0.05). Further investigations of retinal VTI in patients with FD could be helpful to use OCTA as a noninvasive screening and follow-up modality to assess disease progression in affected patients.

Introdução: Chronic kidney disease (CKD) and retinal microvascular disease share common pathophysiological pathways, as the retinal and renal microcirculations exhibit analogous structural and autoregulatory properties. This parallel positions the eye as a non-invasive window into systemic microangiopathy via optical coherence tomography (OCT) and OCT angiography (OCTA). However, existing reviews are dominated by end-stage and dialysis populations, in which acute fluid shifts and hemodynamic instability confound ocular imaging and obscure the underlying chronic microvascular pathology of early disease. Objetivo: To quantify differences in retinal neurovascular biomarkers measured by OCT/OCTA between patients with pre-dialysis CKD (stages G1–G3) and controls, and to assess correlations between these metrics and renal markers (eGFR, UACR). Método: This PROSPERO-registered, PRISMA-guided systematic review searched CENTRAL, Embase, MEDLINE, and PubMed using combined OCT/OCTA, retinal microvasculature, and CKD term blocks. Observational studies of adults with KDIGO stage G1–G3 CKD versus controls reporting quantitative OCT/OCTA metrics were eligible; dialysis, transplant, and confounding ocular pathologies were excluded. Continuous outcomes were pooled with a random-effects model using mean difference (MD) or standardized mean difference (SMD) as appropriate; correlations were synthesized narratively. Heterogeneity was assessed with I². Resultados: Eight studies were included. Superficial capillary plexus vessel density was significantly lower in CKD (pooled SMD −0.44, 95% CI −0.74 to −0.14; p = 0.004; I² = 0.0%), confirmed in a sensitivity analysis incorporating a different OCTA platform (SMD −0.34, 95% CI −0.64 to −0.04; p = 0.027). GC-IPL thickness was significantly reduced (pooled MD −3.67 µm, 95% CI −5.60 to −1.75; p = 0.0002; I² = 0.0%), concordant when re-expressed as SMD (−0.53). Narrative synthesis showed OCTA vessel density correlating positively with eGFR (r ≈ 0.28–0.38) and inversely with urinary albumin, including after multivariable adjustment. Pooled analyses were based on a small number of studies, limiting precision. Conclusão: Retinal neurovascular alterations—reduced macular vessel density and thinner GC-IPL—are detectable in early, pre-dialysis CKD and correlate with renal function, supporting the eye–kidney axis concept. Given the small, heterogeneous evidence base, these preliminary findings require confirmation in larger, standardized longitudinal studies.

Purpose To examine the associations of optical coherence tomography angiography (OCTA)–derived retinal capillary flux with systemic determinants of health. Methods This is a cross-sectional study of subjects recruited from the African American Eye Disease Study. A commercially available swept-source (SS)-OCTA device was used to image the central 3 × 3 mm macular region. Retinal capillary perfusion was assessed using vessel skeleton density (VSD) and flux. Flux approximates the number of red blood cells moving through vessel segments and is a novel metric, whereas VSD is a previously validated measure commonly used to quantify capillary density. The associations of OCTA derived measures with systemic determinants of health were evaluated using multivariate generalized linear mixed-effects models. Results A total of 154 eyes from 83 participants were enrolled. Mean VSD and flux were 0.148 ± 0.009 and 0.156 ± 0.016, respectively. In a model containing age, systolic blood pressure, diabetes status, hematocrit, and presence of retinopathy as covariates, there was a negative correlation between VSD and age (P < 0.001) and retinopathy (P = 0.02), but not with hematocrit (P = 0.85) or other factors. There was a positive correlation between flux and hematocrit (P = 0.02), as well as a negative correlation for flux with age (P < 0.001), systolic blood pressure (P = 0.04), and diabetes status (P = 0.02). A 1% decrease in hematocrit was associated with the same magnitude change in flux as ∼1.24 years of aging. Signal strength was associated with flux (P < 0.001), but not VSD (P = 0.51). Conclusions SS-OCTA derived flux provides additional information about retinal perfusion distinct from that obtained with skeleton density-based measures. Flux is appropriate for detecting subclinical changes in perfusion in the absence of clinical retinopathy.

Early detection of subclinical retinopathy in systemic lupus erythematosus patients and correlation between OCTA findings and lupus disease activity. 13 systemic lupus erythematosus (SLE) patients (26 eyes) with no clinical ophthalmic manifestations, diagnosed according to the European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus and 13 healthy subjects (26 eyes) were enrolled. Patients and controls were matched regarding age and sex. Optical coherence tomography equipped with Angiovue (OCTA) was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary plexuses around the macula. SLE disease activity was assessed by the SLEDAI-2 K scoring system and patients were classified into two subgroups: low disease activity (LDA) (SLEDAI≤6) and high disease activity (HDA) (SLEDAI>6). Patients with SLE, even in the absence of ophthalmic manifestations, presented with a significant reduction in retinal thickness of all the macular sectors (P < 0.05) with a highly significant reduction in the parafoveal and perifoveal temporal and superior regions and parafoveal inferior region (P < 0.01). A statistically significant reduction in superficial capillary plexus (SCP) and DCP vessel density (VD) between patients and controls was found in the whole image area, fovea and temporal parafoveal region (P < 0.05). No statistically significant difference (p > 0.05) in foveal avascular zone (FAZ) parameters was found except for foveal density (FD) was found to be significantly lower (P < 0.05) in SLE patients than in healthy controls. There was no statistically significant difference between SLE groups with LDA and HDA in FAZ or any of the other areas, including SCP and DCP. However, there was a statistically significant difference between HDA and control groups concerning SCP VD of the whole image region and DCP VD in the parafoveal temporal region (P < 0.05). Correlation between OCTA findings and SLEDAI-2 k revealed a negative correlation with retinal thickness in the inferior region of the perifovea (P = 0.05), while no significant correlation was found between SLEDAI-2 k and the retinal vessel density in either layer. Additional statistically significant negative correlations between SCP and DCP VD and age, disease duration, CRP, Serum creatinine and liver enzymes were found. Patients with SLE had diminished retinal thickness and reduced superficial and deep capillary plexus densities compared to healthy controls. OCTA findings (SCP VD and DCP VD) in SLE patients significantly correlated with disease duration and laboratory data (acute phase reactants), while retinal thickness only, correlated with disease activity (SLEDAI-2K score). Retinal involvement in systemic lupus erythematosus may remain asymptomatic for many years and may finally be associated with severe visual deterioration, therefore it is essential for patients with SLE to be screened by OCTA even when asymptomatic and any OCTA vascular changes should prompt a closer follow up. Better control of disease activity is vital in prevention and treatment of ophthalmic manifestations in SLE patients.

PURPOSE To identify genetic, systemic and biological factors associated with the occurrence of sickle cell maculopathy (SCM). To evaluate microvascular macular alterations using optical coherence tomography angiography (OCTA) in sickle cell disease (SCD). DESIGN Cross-sectional study. METHODS One hundred fifty-one eyes of 78 adult SCD patients (43 HbSS, 30 HbSC, 4 S/β+ and 1 HbSLepore) and 40 eyes of 20 healthy controls underwent spectral domain optical coherence tomography (SD-OCT) and OCTA using Spectralis. We analyzed the occurrence of SCM, the foveal avascular zone (FAZ) area and the severity of macular ischemia and studied their relationships with genetic, systemic and biological parameters using multivariate logistic regression analysis. RESULTS Maculopathy occurred in 66 eyes (44%), and more frequently in HbSS patients (71%, p = 0.004). Multivariate analysis identified HbSS genotype and lower prothrombin ratio (PR) as independently associated with SCM (p = 0.01). Proliferative sickle cell retinopathy was also associated with SCM (p = 0.02). FAZ enlargement was associated with higher lactate dehydrogenase level (p = 0.02). Macular ischemia was more severe in patients with lower hemoglobin level (p = 0.004) and lower PR (p = 0.01). No flow areas were identified with OCTA even in eyes with no macular thinning (36 eyes, 42%) and appeared more frequently in the temporal superior subfield (36%). CONCLUSIONS HbSS genotype, abnormal coagulation and hemolysis increase the risk of SCM. OCTA provides valuable criteria to identify potential risk factors of SCM. OCTA also improves detection of early microvascular changes before the onset of macular thinning.

Background Assessment and maintenance of end-organ perfusion are key to resuscitation in critical illness, although there are limited direct methods or proxy measures to assess cerebral perfusion. Novel non-invasive methods of monitoring microcirculation in critically ill patients offer the potential for real-time updates to improve patient outcomes. Main body Parallel mechanisms autoregulate retinal and cerebral microcirculation to maintain blood flow to meet metabolic demands across a range of perfusion pressures. Cerebral blood flow (CBF) is reduced and autoregulation impaired in sepsis, but current methods to image CBF do not reproducibly assess the microcirculation. Peripheral microcirculatory blood flow may be imaged in sublingual and conjunctival mucosa and is impaired in sepsis. Retinal microcirculation can be directly imaged by optical coherence tomography angiography (OCTA) during perfusion-deficit states such as sepsis, and other systemic haemodynamic disturbances such as acute coronary syndrome, and systemic inflammatory conditions such as inflammatory bowel disease. Conclusion Monitoring microcirculatory flow offers the potential to enhance monitoring in the care of critically ill patients, and imaging retinal blood flow during critical illness offers a potential biomarker for cerebral microcirculatory perfusion.

It is evident that the physiopathological pathways of ocular and renal microvascular tissues in patients with systemic lupus are similar. Previously, this was confirmed by employing traditional fundus examination, optical coherence tomography, and high-resolution color electroretinography. Recent years have seen the development of Optical Coherence Tomography Angiography (OCTA) as a non-intrusive procedure that can be employed to image the microvasculature of the retina and choroid. The aim of this study is to assess the correlation between renal functional and histologic features with the retinal microvasculature alterations in systemic lupus patients through OCTA analysis. This case-control study enrolled thirty-six eyes from 18 lupus nephritis (LN) patients, thirty-six eyes from 18 systemic lupus erythematosus (SLE) patients, and thirty eyes from 15 healthy controls. An ophthalmological evaluation, including history, examination, and investigations, was conducted using OCTA for all participants. Prior to ocular examination and investigation, all SLE patients underwent a rheumatological evaluation, encompassing disease-related clinical and laboratory assessments. Specimen retrieval and renal biopsy examinations were also performed, categorizing them into lupus and lupus nephritis patients. Regarding central foveal thickness (CFT) and parafoveal thickness (PFT), there were no significant differences compared to healthy subjects. A comparison of the foveal avascular zone area (FAZ-A) among the three groups revealed a significant increase in both patient groups compared to healthy controls. Whole superficial capillary plexus (SCP) vascular density (VD) in the parafoveal and foveal regions showed a significant reduction in both SLE patient groups compared to healthy controls (HC). Specifically, SCP values were 42.65 ± 2.23% in the SLE with nephritis group, 44.88 ± 2.09% in the SLE without nephritis group, and 49.10 ± 3.12% in the healthy control group. SCP parafoveal VD values were 40.77 ± 3.27% in SLE with nephritis, 47.19 ± 2.63% in SLE without nephritis, and 50.98 ± 4.80% in healthy controls. SCP foveal VD was 18.96 ± 3.43% in SLE with nephritis, 21.61 ± 4.00% in SLE without nephritis, and 24.16 ± 2.69% in healthy controls. The whole deep capillary plexus (DCP), parafoveal, and foveal VD were significantly reduced in the SLE with nephritis group but showed only marginal differences in the SLE without nephritis group compared to healthy controls, as DCP values were 48.04 ± 3.93% in SLE with nephritis, 53.63 ± 2.19% in SLE without nephritis, and 54.88 ± 3.57% in healthy controls. DCP parafoveal VD was 54.56 ± 2.37% in SLE with nephritis, 56.93 ± 1.90% in SLE without nephritis, and 57.39 ± 5.99% in healthy controls. DCP foveal VD was 34.42 ± 3.12% in SLE with nephritis, 41.96 ± 3.19% in SLE without nephritis, and 42.55 ± 7.74% in healthy controls. OCT angiography has a considerable role in the detection of the early changes of the retinal vascular plexus in patients with SLE, especially those with lupus nephritis, even before the development of retinopathy.

Background Systemic lupus erythematosus (SLE) and lupus nephritis (LN) are associated with retinal microvascular changes that may reflect disease severity. This study aimed to evaluate differences in retinal vascular density (VD) between SLE patients with and without LN and assess the impact of rheumatological treatments on VD. Methods A cross-sectional study was conducted with 54 SLE patients (21 with LN, 33 without LN). Retinal VD was measured using optical coherence tomography angiography (OCTA), focusing on superficial and deep capillary plexus VD (SCP-VD and DCP-VD). The impact of Belimumab and other treatments was analyzed. Linear regression assessed the effects of LN status and treatments on DCP parafoveal VD. Lymphocyte subsets and cytokines were compared before and after Belimumab treatment. Result LN patients showed significantly reduced macular vascular density compared with non-LN patients. Belimumab treatment (≥8 times) and hydroxychloroquine use (>5 years) were independently associated with lower DCP-VD, particularly in parafoveal areas. Cumulative doses of HCQ and glucocorticoids negatively correlated with VD. Linear regression showed a significant negative association between Belimumab treatment and parafoveal DCP-VD. Notably, Belimumab treatment led to reductions in serum CD19+ B cells and IL-10 levels. Conclusions LN patients demonstrated distinct retinal microvascular alterations. Long-term Belimumab and HCQ treatments were associated with decreased retinal VD. Regular retinal health monitoring was recommended to prevent microvascular complications in SLE patients undergoing prolonged treatment.

Objective We aimed to detect the correlation between retinal microvascular changes by optical coherence tomography angiography (OCTA) and nailfold capillaroscopic findings in patients with systemic sclerosis (SSc). Methods Forty SSc patients and thirty healthy controls were included. A complete history was taken, general and rheumatological examination and laboratory investigations were performed. In addition, all the participants were examined using nail fold capillaroscopy (NFC) and OCTA. Results Our patients have decreased nailfold capillary density, central macular thickness, superficial full vessel density (VD), superior, inferior, and medial superficial peri-foveal VD, superior, inferior, and temporal superficial parafoveal VD, and temporal para-foveal full VD compared to the controls. The modified Rodnan skin score was negatively correlated with the nail fold capillary density, central macular thickness, superficial full VD, superior, temporal, and medial superficial perifoveal VD, superior superficial parafoveal VD, and temporal perifoveal full VD. The nailfold capillary density was positively correlated with the central macular thickness, the superficial full VD, the superior, temporal, and medial superficial perifoveal VD, the superior superficial parafoveal VD, and temporal perifoveal full VD. Conclusion The nailfold capillary density measured by NFC positively correlates with the retinal VD measured by OCTA, suggesting that NFC could be a valuable marker for retinal vessel involvement in SSc patients. In addition, our results highlight the importance of combining OCTA with NFC for diagnosing and monitoring microvascular changes in SSc patients.

Optical coherence tomography angiography (OCTA) non-invasively and quantitatively images the microvasculature of the eye's posterior segment in 3 dimensions. OCTA has known utility in the diagnosis and management of certain ocular conditions and is now being used to assess systemic conditions, including respiratory, cardiovascular, renal, obstetric, neurologic, rheumatologic, and genetic conditions, among others. OCTA may improve our understanding of the pathophysiology of systemic conditions and identify biomarkers useful in their diagnosis, prognosis, and management. We detail known associations between quantitative retinal, optic nerve head, and choriocapillaris OCTA findings and clinically relevant features of systemic conditions, including laboratory markers and disease severity and prognosis. We find that the breadth and depth of such correlations solidify OCTA's role in the emerging field of oculomics, which seeks to identify ocular imaging biomarkers for use in the study and management of non-ocular conditions.

AIM To evaluate the choroidopathy in patients with systemic lupus erythematosus (SLE) using enhanced depth imaging spectral domain optical coherence tomography (EDI SD-OCT) and optical coherence tomography angiography (OCTA). METHODS A total of 74 patients with SLE and 40 healthy volunteers were included in this cross-sectional study. SLE patients were further divided into three subgroups based on clinical and blood biochemistry findings. Ocular parameters obtained on ophthalmologic examination and optical imaging (EDI SD-OCT and OCTA) included the best corrected distance visual acuity (logMAR CDVA), subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI) and vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS SLE patients had significantly lower values for CVI and VD of DCP (DVD) than control subjects. Amongst SLE patients, gender and chloroquine dose were found to be independent determinants of CVI while age predicted SCT. Steroid dose was a significant predictor for foveal VD of SCP (SVD), chloroquine dose for parafoveal SVD, gender for total DVD, and gender and steroid dose for perifoveal DVD. No correlation of logMAR CDVA and SCT was noted between SLE patients and control subjects. No correlation of SCT was noted with disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, hydroxychloroquine (HCQ) dose or steroid dose. No correlation of CVI was noted with patient age, disease duration, SLEDAI score, HCQ dose or steroid dose. No significant difference was noted between SLE subgroups in terms of any of the ocular parameters studied. CONCLUSION The findings reveal the presence of ocular findings suggestive of early onset choroidopathy on EDI SD-OCT and OCTA in SLE patients, in the absence of ocular manifestations or active disease.

Systemic sclerosis (SSc) is an autoimmune disease with ocular affection. This study aimed to evaluate the retinal microvascular changes in SCSs patients using optical coherence tomography angiography (OCTA). This prospective observational case–control study comprised 20 eyes of 20 SSc patients as group I and another 20 eyes of 20 normal patients as group II. All the study members were examined with OCTA in addition to a complete ophthalmic examination. Both groups had more females sex than males without significant differences between them. Also, the mean age difference was statistically insignificant, with nearly the same range, which was 30–59 years in group I and 32–58 years in group II. Analysis of OCTA parameters revealed significantly lower differences in group I in the superficial vessel density (VD) at parafoveal, temporal, superior, and nasal quadrants. Lower values were recorded in group I at all zones of the deep capillary plexus with statistically significant differences except at the foveal zone. VD measurements of the choriocapillaris revealed no statistically significant differences between groups in all zones. The OCTA has demonstrated the impairment of retinal microcirculation, confirming the presence of vascular damage. The duration of the disease correlated with the deep capillary plexus-VD and choriocapillaris VD. So, once SSc has been diagnosed, microvascular retinal and choroidal evaluations should be considered to identify any subclinical alterations using OCTA.

Researchers have explored choroidal features in the eyes of diabetic patients without clinically visible diabetic retinopathy (DM-NoDR) employing optical coherence tomography angiography (OCTA); however, the results are controversial. We systematically searched PubMed, Embase, and Ovid databases for OCTA studies comparing choroidal parameters between DM-NoDR eyes and healthy controls or non-proliferative diabetic retinopathy (NPDR) eyes. Outcomes included choriocapillaris (CC) perfusion density (PD), flow area (FA), and flow deficits (FD). 36 studies were finally included in the quantitative meta-analysis, involving 1,908 DM-NoDR eyes, 792 NPDR eyes, and 1,391 healthy control eyes. DM-NoDR eyes had significantly lower CC PD in the foveal region (P=0.0005) and superior parafoveal region (P=0.003) than healthy control eyes, but no significant difference was found in other parafoveal subregions (P>0.05). DM-NoDR eyes were also associated with increased CC FD (P<0.00001) and decreased CC FA (P<0.0001) in whole OCTA images with a 3×3 mm2 field of view (FOV). Compared with all-stage NPDR eyes, DM-NoDR eyes had higher CC PD in the foveal region (P<0.0001), parafoveal region (P<0.00001), and the whole OCTA images with a 6×6 mm2 FOV (P<0.00001). Early choroidal microvascular changes may precede clinically visible DR and can be detected early using OCTA in DM-NoDR eyes.

Background/Objectives: This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Methods: Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t0) and 2 years later (t1). Results: At t1, VD in the whole en face SCP and in the CC was notably reduced compared to t0 (SCP: p = 0.001, CC: p = 0.013). VD in the DCP, CRT and FAZ area showed no difference at t1 compared to t0 (DCP: p = 0.128, FAZ: p = 0.332, CRT fovea: p = 0.296). Correlation analysis between the increase in cumulative doses of HCQ between t0 and t1 and the VD of the whole en face SCP did not show any correlation (Spearman r = 0.062 (95% CI −0.367; 0.477). Conclusions: SLE patients demonstrated a decrease in the retinal VD of the SCP and CC over a 2-year period. There was no correlation with the change in cumulative doses of HCQ. These results suggest an ongoing effect of the disease on the retinal and choriocapillary microcirculation.

Abstract Introduction: Optical coherence tomography angiography (OCTA) is an emerging technique to investigate retinal and choroidal microvascular alterations in patients with systemic sclerosis (SSc). This systematic review and meta-analysis aimed to evaluate the features of retinal and choroidal microvasculature using OCTA among SSc patients. Methods: The methodology of the study was based on PRISMA guidelines. PubMed, Scopus, Web of Science, and Embase were searched systematically on November 25, 2023, for relevant studies utilizing OCTA as the main diagnostic tool to assess the retinal and choroidal microvasculature in SSc patients versus healthy controls. Random-effect or fixed model meta-analysis was used based on the heterogeneity of studies. Results: Eleven observational comparative studies, including 366 patients with SSc and 350 healthy controls, conducted between 2020 and 2023, were included in this review. Meta-analysis findings revealed a significant decrease in vessel densities in both the superficial and deep capillary plexuses among SSc patients compared to controls. However, there were no significant differences observed in the foveal avascular zone area and choriocapillaris flow area between SSc patients and controls. Moreover, central macular thickness (CMT) consistently exhibited a decrease in SSc patients, while retinal nerve fiber layer thickness showed no significant differences. Although radial peripapillary capillary vessel density, subfoveal choroidal thickness, and cup/disk ratio yielded mixed results, with some studies indicating significant changes in the SSc group, meta-analysis could not be performed due to variations in the OCTA machines used across the included studies. Conclusion: This systematic review demonstrates retinal and choroidal microvascular abnormalities in SSc using OCTA. Longitudinal studies are needed to understand how these abnormalities evolve over time in patients with SSc and whether these abnormalities correlate with the clinical features of SSc.

To assess the retinal microvasculature of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography Angiography (OCTA). Twenty adult SLE patients without disease activity and no ocular manifestations were recruited and cross-sectionally assessed. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is vascular density (VD). As secondary outcomes, foveal avascular zone (FAZ) parameters, total vessel length (TVL), vessel length density (VLD), vessel diameter and tortuosity, branchpoint density (BD) and fractal dimension (FD) were evaluated. Forty eyes of 40 women (20 SLE patients and 20 healthy subjects) were enrolled with a mean ± SD age of 36.7 ± 9.9 years. In both the superficial and deep capillary plexuses, SLE patients presented significantly lower VD and TVL values, mean vessel diameter and FD (all p < 0.005). No significant differences were found in FAZ values. A negative correlation was found between age and FAZ parameters and between age and TVL, VLD and FD in the superficial capillary plexus (all p < 0.05). This study supports the evidence of subclinical retinal microvascular changes in adult SLE patients, providing a more comprehensive characterization of vascular changes. We found vessel diameter and length and FD are decreased in SLE. NCT05863689, 2023-10-19. SLE patients present reduced macular VD without overt ocular involvement when compared to healthy subjects. OCTA is able to detect subclinical microvascular changes that can be characterized beyond the quantification of vascular density. The retinal microvascular system of SLE patients is reduced in density, length, and diameter, and the fractal dimension is also lower compared to healthy subjects.

No abstract available

To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p  < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p  < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion ( p  = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients ( p  < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration ( r  = 0.67, p  = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.

No abstract available

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune connective tissue disease that affects several vascular territories. This systematic review sought to assess the role of optical coherence tomography angiography (OCTA) in detecting subclinical microvascular alterations in SLE patients. PubMed, Scopus, and Web of Science databases were systematically searched until January 21st, 2023. Studies using OCTA as a primary diagnostic method to evaluate the macular microvasculature of SLE patients versus healthy controls were included. Primary outcomes were macular vessel density (VD) and foveal zone parameters. A meta-analysis was performed using a random-effects model. Of 301 screened abstracts, 15 were found eligible, enrolling 1246 eyes from 1013 patients. SLE patients presented a reduction of macular VD at both plexuses in all zones (whole scan, fovea, parafovea, and perifovea), and of foveal density compared with healthy controls. No differences were found at foveal avascular zone parameters. SLE patients presented a reduction of macular vessel density without signs or symptoms of SLE ocular involvement. OCTA application for the assessment of subclinical microvascular changes needs to be elucidated with longitudinal studies.

Aims To investigate the correlation between the retinal microvasculature using optical coherence tomography angiography (OCTA) and systemic factors in type 2 diabetes mellitus (T2DM) patients. Methods This cross-sectional study obtained OCTA data from patients with T2DM administered at hospital and referred to ophthalmic services. Patient data about demographics, comorbid conditions, and blood biomarkers were extracted from electronic medical records. Data from OCTA scans obtained by CIRRUS HD-OCT Model 5,000 were obtained. Vessel density (VD) and perfusion density (PD) within the superficial capillary plexus, and foveal avascular zone (FAZ) area were automatically segmented. These parameters were tested for their correlations with systemic factors by univariate and multivariable linear regression analyses. Results A total of 144 T2DM patients (236 eyes) were available for analysis, with mean age of 53.6 (SD = 10.34) and 56.9% were male. Chronic kidney disease, cardiovascular disease, increased serum creatinine (Scr), red blood cell count (RBC), platelets (PLT), apolipoprotein B (APOB), and decreased urine albumin to creatinine ratio (UACR) were significantly associated with lower VD and PD (all p < 0.013). UACR and triglyceride (TRIG) were significantly correlated with FAZ area (all p < 0.017). In multivariate analyses, PLT, eGFR, and APOB were independent risk factors for retinal rarefaction, and UACR was a significant predictor of FAZ area. Conclusion We found several systemic risk factors, such as PLT, renal function and lipid profiles were associated with PD, VD, and FAZ area among Chinese T2DM patients.

Background: Lupus retinopathy, an ocular manifestation of systemic lupus erythematosus (SLE), is the major pathology attributed to retinal vasculopathy. Our study is to analyze the changes in retinal vessels in patients with SLE by optical coherence tomography angiography. Methods: A total of 61 SLE patients without obvious retinal manifestation and 71 healthy people were included. The SLE patients were further divided into a lupus nephritis (LN) group and a non-LN group. The changes in central macular thickness (CMT) and the retinal vessel densities were compared between the two groups, and the correlation between retinal vascular changes and disease activity was analyzed. Results: Compared with healthy control, the CMT and the retinal vascular densities in both superficial and deep retina were decreased significantly in SLE patients. There was no significant difference in retinal vascular densities between LN groups and non-LN groups. Conclusion: The CMT and retinal vessel densities were decreased in SLE patients without clinical manifestations, which might serve as a sensitive biomarker for early changes of lupus retinopathy in SLE patients.

Background: Hypertension (HTN) affects cardiovascular, renal and neurological systems. The poorly controlled blood pressure may also cause structural and functional retinal damage. Objective: To assess changes in foveal avascular zone (FAZ) and macular vessel density using Optical Coherence Tomography Angiography (OCTA) in hypertensive patients. Patients and Methods: This case control observational study was performed on 120 eyes, divided into 3 groups. Group A: 40 eyes of 26 patients with HTN for more than 10 years, group B: 40 eyes of 22 patients with HTN less than 10 years, and group C: 40 eyes of 20 normal subjects with completely normal ophthalmological examination. All participants underwent OCTA. Results: There was no significant variation in age, gender or FAZ between the three studied groups. Superficial capillary plexuses in parafovea, parafovea superior hemi, parafovea inferior hemi, perifovea, perifovea superior hemi, and perifovea inferior hemi were considerably higher in group C than in group A (p =0.002, 0.001, 0.011, 0.014, 0.041, and 0.002, respectively) and group B (p <0.001). Deep capillary plexuses in parafovea, parafovea superior hemi, parafovea inferior hemi, perifovea, perifovea superior hemi, and perifovea inferior hemi were considerably higher in group C than in group A (p <0.001), and group B (p =0.004, 0.004, 0.003, 0.002, 0.001, and 0.003, respectively). No significant difference were observed in the studied parameters between group A and B. Conclusion: Eyes of HTN patients have lower macular vessel densities (superficial and deep ) compared to those of healthy controls. The duration and control of hypertension didn’t account any substantial differences between the two groups of hypertensive patients.

Objective The aim was to investigate the changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus (SLE) using optical coherence tomography angiography (OCTA). Methods Twenty-nine patients with SLE (29 eyes) and 25 control subjects (25 eyes) were enrolled. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Retinal thickness (RT), inner retinal thickness (IRT), outer retinal thickness (ORT), choroidal thickness (ChT), retinal superficial vascular density (SVD), retinal deep vascular density (DVD), choriocapillary vascular density (CCVD), foveal avascular zone (FAZ), superficial FAZ (sFAZ), and deep FAZ (dFAZ) were measured using OCTA. The retinal and choroidal thickness and vascular density between the control group and SLE group were compared. The relationships between SLEDAI scores and the retinal and choroidal thickness and vascular density in SLE group were analyzed. Results The SVD was significantly increased, and the DVD and CCVD were significantly decreased in the SLE group compared to the control group (p < .05). The results of receiver operating characteristic (ROC) showed that the area under the curve (AUC) values of SVD, DVD, and CCVD were 0.873, 0.729, and 0.727, indicating a high accuracy in discriminating patients with SLE from controls. Correlation analysis showed that the SLEDAI scores were positively correlated with dFAZ (r = 0.589, p = .001) and FAZ (r = 0.451, p = .018), and negatively correlated with DVD (r = −0.491, p = .009) and CCVD (r = −0.521, p = .005). Conclusions DVD and CCVD were decreased in the SLE and might be related to the disease activity. SVD, DVD, and CCVD may hold promise in the discovery of biomarkers for diagnosing SLE.

Abstract Introduction: The aim of the study was to investigate the correlation between systemic inflammation biomarkers and morphological changes of retinal neurovascular unit (RNVU) under optical coherence tomography (OCT) and OCT angiography (OCTA) in type 2 diabetic patients with early signs of diabetic retinopathy (DR). Methods: This cross-sectional study was carried out among 93 type 2 diabetic patients with early signs of DR (170 eyes), ranging from level 10 to level 35 based on ETDRS DR severity scale score. Age-, sex-, and axial length-matched normal subjects were enrolled as controls. Systemic inflammation biomarkers including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammatory index (SII) were calculated based on peripheral blood results. Retinal neuronal changes of RNVU were identified by accessing the thickness of macular retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) using OCT. Retinal microvascular alterations of RNVU were evaluated by measuring macular vessel density (VD) and size of foveal avascular zone (FAZ) using OCTA. Results: GCL thickness was significantly correlated with NLR (r = −0.183, p = 0.017) and MLR (r = −0.235, p = 0.002), RNFL thickness was significantly associated with MLR (r = −0.210, p = 0.008), FAZp was positively correlated with NLR (r = 0.153, p = 0.046) and MLR (r = 0.187, p = 0.014), FAZa was positively correlated with MLR (r = 0.189, p = 0.014), and VD was significantly correlated with NLR (r = −0.188, p = 0.014) on spearman correlation analysis. Additionally, VD was independently associated with SII in both univariable and multivariable GLM analysis (p < 0.05). This difference still remained statistically significant during subgroup analysis after controlling DM duration. Conclusion: Systemic inflammation biomarkers including NLR, MLR, and SII are significantly associated with not only retinal microvascular alterations but also retinal neuronal changes, providing evidence that systemic inflammation may play a crucial role on the early morphological changes of RNVU and early DR pathogenesis. SII is independently associated with VD, which supports SII may serve as a potential biomarker for monitoring early microvascular changes of DR. Plain Language Summary This study investigated the correlation between systemic inflammation biomarkers and retinal neurovascular unit (RNVU) changes in early signs of diabetic retinopathy (DR). Early DR can be identified by monitoring early RNVU changes. However, the results of RNVU changes are not widely applied by clinicians. Therefore, we explored whether simple blood white cell tests, which linked to inflammation, could predict these early retinal changes. We measured retinal neuronal parameters (e.g., retinal nerve fiber layer [RNFL] and ganglion cell layer [GCL] thickness) and retinal microvascular parameters (e.g., macular vessel density [VD] and foveal avascular zone [FAZ] size) using OCT and OCT angiography (OCTA). Systemic inflammation biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammatory index (SII), were calculated from peripheral blood tests. Results showed significant associations between NLR, MLR, SII, and retinal microvascular and neuronal changes. Notably, SII was independently correlated with VD in both univariable and multivariable generalized linear models. These findings highlight systemic inflammation’s role in early diabetic RNVU changes and suggest that easily accessible biomarkers like SII could serve as convenient and cost-effective tools for monitoring early retinal microvascular alteration. This study bridges a critical gap by linking systemic inflammation biomarkers to early diabetic RNVU changes, offering a practical method to identify potential retinal microvascular damage in early DR.

Purpose To compare and evaluate the diagnostic performance of OCT-angiography (OCT-A) parameters in diabetic retinopathy (DR) detection compared to fluorescein angiography (FA). Methods This is a cross-sectional, prospective study including 118 diabetic patients (214 eyes). All patients had a complete clinical examination with FA as well as macular OCT-A imaging (3 × 3 mm, 6 × 6 mm). We compared the detection of fundamental DR lesions using both imaging modalities and assessed the diagnostic value of different OCT-A parameters. Results Microaneurysms were more frequently detected by FA than with OCT-A. Intraretinal microvascular anomalies were equally visualized by OCT-A (0.27 ± 0.777) and FA (0.27 ± 0.71). Average of foveal avascular zone (FAZ) surface was less significant at superficial capillary plexus (SCP) (0.353 ± 0.107 mm²) compared to deep capillary plexus (DCP) (0.537 ± 0,135 mm²), (p < 0.001). FAZ remodeling was observed even in DR free eyes and was better identified in DCP (61.1%) than SCP (47.2%). Loss of FAZ circularity was estimated at 0.792 ± 0.081 and 0.741 ± 0.107 respectively in SCP and DCP, (p < 0.001). Average surface area of capillary non-perfusion zones (CNPZ) was 0.487 ± 0.514 mm² in SCP and 0.145 ± 0.223 mm² in DCP, (p < 0.001). The Most reliable OCT-A quantitative parameters for DR screening were: CNPZ surface in DCP (p = 0.0046), total vascular density (VDt) in the DCP (p = 0.003) and CNPZ surface in the SCP (p = 0.0027). Conclusion OCT-A enables diabetic microvascular abnormalities detection even at a preclinical stage. Certain OCT-A parameters may provide a valuable quantitative approach for diagnosis and grading of DR severity.

Purpose: To analyze the retinal and choriocapillaris changes in diabetic patients with no or with early signs of diabetic retinopathy using high-definition (HD) angio optical coherence tomography angiography (OCTA) software and spectral-domain (SD) OCT. Methods: A total of 112 eyes (54 eyes from 27 diabetic patients and 58 eyes from 29 control subjects) were included in this retrospective cross-sectional study of healthy and diabetic adults. Retinal microvascular changes were assessed by using HD-OCTA software to calculate vascular density (VD) and foveal avascular zone (FAZ). SD-OCT was used to assess retinal thickness and volume in parafovea as well as ganglion cell complex (GCC) parameters. Results: The VD-whole image was significantly higher in the healthy control group (MW z = 1109.5, p = 0.012; t = 2.611, p = 0.010). Also, VD-parafovea was significantly higher in the healthy subjects (MW z = 1053.5, p = 0.004; t = 3.207, p = 0.002). GCC focal loss volume (FLV) was significantly decreased in diabetic patients (p = 0.051). Non-flow FAZ did not show a statistically significant difference between groups, although the FAZ was larger in the diabetic patients. Conclusions: Diabetic patients with no or early signs of diabetic retinopathy have decreased VD compared to healthy individuals. They also present retinal changes at the GCC that are correlated with initial neurodegeneration. HD-OCTA and SD-OCT can detect vascular changes and structural signs of retinal neurodegeneration before clinically apparent diabetic retinopathy. Potentially, these methods may offer new biomarkers for monitoring disease progression and visual prognosis.

Purpose To quantify choriocapillaris (CC) flow deficits using projection-resolved optical coherence tomographic angiography (PR-OCTA) and to evaluate whether they are correlated with diabetic retinopathy (DR). Methods In this retrospective study, OCTA scans covering a range of DR severities were acquired. Shadowing artifacts caused by hard exudates, large inner retinal vessels, and vitreous floaters were detected, along with the retinal fluid area. The CC deficit ratio (percentage of deficit area) was measured and compared with shadowing artifacts and area beneath retinal fluid excluded to assess the effect of these confounding features. The Spearman correlation between the CC deficit ratio and disease severity was calculated, as well as the diagnostic performance (area under the receiver operating characteristic curve). Results One hundred eighty-three participants were enrolled in this study. We found a significant positive correlation between age and CC deficit ratio in normal controls (Pearson correlation, P = 0.02). There was no significant difference in deficit ratio between measurements excluding only shadows and those excluding both shadows and the area beneath the fluid (Mann-Whitney U-test, P = 0.81). The CC deficit ratio was positively correlated with DR severity (Spearman correlation, P < 0.01). It was significantly higher in nonproliferative DR and PDR patients compared to normal controls (Tukey HSD, P < 0.01) but not in those with diabetes without DR. The proposed CC deficit segmentation method achieved high repeatability with an intraclass correlation coefficient of 0.92. Conclusions The CC deficit ratio measured by the proposed method correlates with the presence and severity of DR.

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

Purpose To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. Methods A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. Results Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: β coefficient = -0.351, p = 0.023; perifovea: β coefficient = -0.338, p = 0.036). Perifoveal VLD (β coefficient = -0.343, p = 0.031) and FD (β coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (β coefficient = -0.396, p = 0.008), perifoveal VLD (β coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (β coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (β coefficient = -0.373, p = 0.023) and number of flow voids (β coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. Conclusions Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

Purpose To explore the relationship between peripapillary atrophy (PPA) and diabetic retinopathy (DR), and to uncover potential mechanisms using swept-source optical coherence tomography (SS-OCT) angiography. Methods This cross-sectional study included 845 patients with type 2 diabetes (T2DM), who underwent detailed systemic and ophthalmic evaluations. A state-of-the-art deep learning method was employed to precisely identify the parapapillary beta and gamma zones. Based on PPA characteristics, eyes were categorized into four groups: without beta or gamma zone (Group A), isolated beta zone (Group B), isolated gamma zone (Group C), and with both beta and gamma zone (Group D). Digital fundus photography was utilized to diagnose and stage DR severity, while SS-OCT angiography quantified retinal and choroidal vasculature. Results Participants had a mean age of 66 ± 8.8 years, with 437 (51.7%) male. Beta and gamma PPA zones were observed in 574 (67.9%) and 256 (30.3%) eyes, respectively. Beta zone PPA was associated with older age, whereas gamma zone PPA was correlated with longer axial length (AL), lower vessel density, and reduced choroidal thickness. Adjusted analyses revealed that eyes with isolated (Group C) or concurrent (Group D) gamma zone PPA conferred significantly lower DR grade, independent of known risk factors including systemic diabetes risk factors and AL. Conclusion This study finds that gamma zone PPA is linked to a reduced risk of developing DR. These results imply that the gamma zone may reflect progressive myopia-associated thinning and microvascular depletion in posterior ocular tissues, potentially contributing to structural resilience against DR. This novel insight offers a promising avenue for understanding the interplay between PPA and DR.

No abstract available

PURPOSE To evaluate the utility of extended field swept-source Optical Coherence Tomography Angiography (SS-OCTA) imaging biomarkers in predicting the occurrence of clinically significant outcomes in eyes with Non-Proliferative Diabetic Retinopathy (NPDR). DESIGN Retrospective clinical case-control study. METHODS Single-center clinical study. 88 eyes with NPDR from 57 participants (median age: 64.0 years; mean duration of diabetes: 15.8 years) with at least two consecutive SS-OCTA scans over a follow-up period of at least six months were included. The presence of intraretinal microvascular abnormalities (IRMAs) at baseline and the stability of IRMAs during follow-up period on 12 × 12-mm angiograms were evaluated. Baseline nonperfusion ischemia index (ISI) and other SS-OCTA metrics were calculated on FIJI and ARI Network. Significant clinical outcomes were defined as occurrence of one or more of the following events at the last available clinical visit:1. significant DR progression (2-step DR progression or progression to proliferative DR (PDR)); 2) development of new center-involving diabetic macular edema (CI-DME); and 3) initiation of treatment with PRP or anti-VEGF injections during the follow-up period. Mixed-effects Cox regression models was used to explore these outcomes. RESULTS Following a clinical follow-up period lasting 25.1 ± 10.8 months, we observed significant clinical outcomes in 17 eyes (19.3%). Among these, 7 eyes (8.0%) experienced significant progression and 4 eyes (4.5%) developed CI-DME. Anti-VEGF injections were initiated in 15 eyes (17.0%), while PRP was initiated in 2 eyes (2.3%). Upon adjusting for age, the duration of DM, and prior Anti-VEGF treatments, our analysis revealed that non-stable IRMAs during the follow-up periods and a higher ischemia index at baseline were significantly associated with the occurrence of significant clinical outcomes with HRs of 3.88 (95% CI: 1.56-9.64; p=0.004) and 1.05 (95% CI: 1.02-1.09; p=0.004), respectively. CONCLUSIONS In conclusion, NPDR eyes with non-stable IRMAs over time and more ischemia at baseline are in higher risk of developing significant clinical outcomes. Our findings suggest that expanded field SS-OCTA may offer additional prognostic benefits for clinical DR staging and predicting high-risk patients.

Similar to ultrasound adapting soundwaves to depict the inner structures and tissues, optical coherence tomography (OCT) utilizes low coherence light waves to assess characteristics in the eye. Compared to the previous gold standard diagnostic imaging fluorescein angiography, OCT is a noninvasive imaging modality that generates images of ocular tissues at a rapid speed. Two commonly used iterations of OCT include spectral-domain (SD) and swept-source (SS). Each comes with different wavelengths and tissue penetration capacities. OCT angiography (OCTA) is a functional extension of the OCT. It generates a large number of pixels to capture the tissue and underlying blood flow. This allows OCTA to measure ischemia and demarcation of the vasculature in a wide range of conditions. This review focused on the study of four commonly encountered diseases involving the retina including age-related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), and macular telangiectasia (MacTel). Modern imaging techniques including SD-OCT, TD-OCT, SS-OCT, and OCTA assist with understanding the disease pathogenesis and natural history of disease progression, in addition to routine diagnosis and management in the clinical setting. Finally, this review compares each imaging technique’s limitations and potential refinements.

Purpose To investigate structure–function associations between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics across stages of non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR), without diabetic macular oedema. Methods Prospective cross-sectional study in 140 eyes of 99 patients: 33 mild NPDR, 24 moderate/severe NPDR, 15 PDR, 33 diabetic without DR (DMnoDR) and 46 control eyes. Mixed-effects multivariable regression models to evaluate associations between quantitative contrast sensitivity function (Adaptive Sensory Technology) and vessel density (VD) and vessel skeletonised density (VSD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) on same-day imaging with WF SS-OCTA (Plex Elite 9000, Carl Zeiss Meditec). Results Standardised β coefficients for area under the logarithm of contrast sensitivity function curve (AULCSF) versus visual acuity (VA) at 3×3 mm scans: SCP VSD (β=0.32, p<0.001 vs −0.18, p=0.044), DCP VSD (β=0.30, p<0.001 vs −0.21, p=0.02), SCP VD (β=0.25, p=0.004 vs −0.13, p=0.129), DCP VD (β=0.26, p=0.003 vs −0.19, p=0.034). AULCSF was significantly reduced in mild NPDR (β=−0.28, p<0.001) and DMnoDR (β=−0.19, p=0.005) versus controls, while VA was not significantly different. AULCSF performed better than VA in differentiating between controls and DMnoDR (0.69 vs 0.50), controls and mild NPDR (0.76 vs 0.61) and controls and moderate/severe NPDR (0.89 vs 0.73). Conclusions DR-induced microvascular changes on OCTA are associated with larger changes on CS than in VA. CS is affected earlier than VA in the course of DR and performed better in discriminating between controls, DMnoDR and across DR stages.

Purpose To determine whether baseline retinal and choriocapillaris (CC) vascular features measured by OCT angiography (OCTA) can predict diabetic retinopathy (DR) progression or visual acuity (VA) decline in a multiethnic longitudinal cohort. Design Prospective longitudinal cohort study. Subjects A total of 309 eyes from 192 patients with type 2 diabetes mellitus were recruited from a tertiary eye center in Singapore. Methods All participants underwent 3 × 3 mm swept-source OCTA imaging at baseline. Quantitative vascular parameters—including vessel density (VD), perfusion density (PD), and CC flow deficit percentage—were obtained from the superficial and deep retinal layers and from the CC. Larger retinal arterioles and venules were analyzed separately from capillary networks. Diabetic retinopathy progression was defined as a ≥2-step increase on the ETDRS severity scale over 2 years, while VA decline was defined as >1-line reduction in best-corrected VA. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were used to evaluate predictive performance. Main Outcome Measures Progression of DR and VA decline over 2 years, as predicted by baseline OCTA metrics. Results Over 2 years, 49 eyes (15.9%) demonstrated DR progression. Significant predictors in the superficial layer included larger foveal avascular zone (FAZ) area (odds ratio [OR] = 6.612; P = 0.034), longer perimeter (OR = 1.583; P = 0.002), poorer circularity (OR = 3.23; P = 0.019), higher large-vessel PD (OR = 1.561; P < 0.001) and VD (OR = 2.878; P < 0.001), and lower whole-vessel VD (OR = 0.798; P = 0.010). Adding FAZ perimeter and large-vessel VD improved prediction accuracy (AUC increased from 0.709–0.822). For VA loss, higher superficial large-vessel PD (OR = 1.609; P = 0.002) and lower capillary PD (OR 0.8; P = 0.010) were significant predictors, improving AUC from 0.602 to 0.702. Conclusions Enlargement and irregularity of the FAZ, along with increased superficial large VD, independently predict DR progression. Incorporating FAZ and large-vessel OCTA parameters enhances prediction models for both DR worsening and vision decline in patients with diabetes. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE To prospectively determine the relationship of OCT angiography (OCTA) metrics to diabetic retinopathy (DR) progression and development of diabetic macular edema (DME). DESIGN Prospective, observational study. PARTICIPANTS A total of 205 eyes from 129 patients with diabetes mellitus followed up for at least 2 years. METHODS All participants underwent OCTA with a swept-source OCT device (DRI-OCT Triton, Topcon, Inc, Tokyo, Japan). Individual OCTA images of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were generated by IMAGEnet6 (Basic License 10). After a quality check, automated measurements of foveal avascular zone (FAZ) area, FAZ circularity, vessel density (VD), and fractal dimension (FD) of both SCP and DCP were then obtained. MAIN OUTCOME MEASURES Progression of DR and development of DME. RESULTS Over a median follow-up of 27.14 months (interquartile range, 24.16-30.41 months), 28 of the 205 eyes (13.66%) developed DR progression. Of the 194 eyes without DME at baseline, 17 (8.76%) developed DME. Larger FAZ area (hazard ratio [HR], 1.829 per SD increase; 95% confidence interval [CI], 1.332-2.512), lower VD (HR, 1.908 per SD decrease; 95% CI, 1.303-2.793), and lower FD (HR, 4.464 per SD decrease; 95% CI, 1.337-14.903) of DCP were significantly associated with DR progression after adjusting for established risk factors (DR severity, glycated hemoglobin, duration of diabetes, age, and mean arterial blood pressure at baseline). Lower VD of SCP (HR, 1.789 per SD decrease; 95% CI, 1.027-4.512) was associated with DME development. Compared with the model with established risk factors alone, the addition of OCTA metrics improved the predictive discrimination of DR progression (FAZ area of DCP, C-statistics 0.723 vs. 0.677, P < 0.001; VD of DCP, C-statistics 0.727 vs. 0.677, P = 0.001; FD of DCP, C-statistics 0.738 vs. 0.677, P < 0.001) and DME development (VD of SCP, C-statistics 0.904 vs. 0.875, P = 0.036). CONCLUSIONS The FAZ area, VD, and FD of DCP predict DR progression, whereas VD of SCP predicts DME development. Our findings provide evidence to support that OCTA metrics improve the evaluation of risk of DR progression and DME development beyond traditional risk factors.

To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI’s extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10–15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05). Perfusion macular metrics on OCT-A correlated with UWF-FA’s non-perfusion (NP), particularly in the retina’s mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.

There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR). We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas. On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group. Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization.

PURPOSE To assess the real-world clinical utility of wide-field OCT angiography (WF-OCTA) for detecting retinal neovascularization (RNV) in eyes with proliferative diabetic retinopathy (PDR). DESIGN A retrospective cross-sectional study. PARTICIPANTS Consecutive eyes clinically suspected of PDR by physicians at a tertiary eye center between March 2021 and November 2022. METHOD All eyes underwent ultra-widefield fluorescein angiography (UWF-FA) (California, Optos) and WF-OCTA (S1, Canon) with a 23×20 mm scan area. Two independent graders detected individual RNV lesions using UWF-FA and used them as the ground truth. WF-OCTA images were first evaluated to determine whether the images successfully illustrated retinal vasculature, regardless of the image quality index or the presence of vitreous hemorrhage. The graders then identified the RNV lesions with WF-OCTA. We detected RNV by utilizing both the whole retinal slab, including flow signals in the retina, and the custom vitreoretinal interface slab, defined as flow signals from 20 microns below the internal limiting membrane (ILM) to 2000 microns above the ILM. We evaluated the applicability to real-world clinical practice by not correcting segmentation errors. MAIN OUTCOME MEASURES The success rate of imaging and the detection rate of RNV using WF-OCTA. RESULTS Initially, 69 consecutive patients who underwent UWF-FA were identified. Of these, 114 eyes from 57 (83%) patients underwent both UWF-FA and WF-OCTA. Of the 114 eyes, 108 (95%) produced gradable WF-OCTA images. Using UWF-FA, the graders identified 175 RNV lesions in 40 eyes. WF-OCTA achieved a sensitivity of 95% and specificity of 88% for detecting eyes with RNV. At the level of individual RNV lesions, graders detected 156 RNV lesions with WF-OCTA, with 118 of these confirmed by UWF-FA (true positive). Among the 57 false negative lesions, the primary causes were being out of the scan range (26 lesions) and segmentation errors (21 lesions). CONCLUSION WF-OCTA imaging had a high success rate, achieving a sensitivity of 95% and a specificity of 88% for detecting eyes with RNV in a real-world clinical setting. Despite a 67% detection rate for individual RNV lesions, WF-OCTA may serve as a valuable non-invasive method for RNV detection in eyes with DR.

No abstract available

Purpose To evaluate the performance of a customized deep learning algorithm for automated segmentation of nonperfusion area (NPA) on ultra-widefield swept-source OCTA (UWF SS-OCTA) and its utility in diabetic retinopathy (DR) severity assessment. Design Cross-sectional study. Subjects A total of 180 eyes from 122 participants representing all grades of DR severity. Methods We developed a convolutional neural network based on a multiscale U-Net backbone with squeeze-and-excitation attention for segmentation of NPAs on en face SS-OCTA all-retinal-layer images from 3 scan patterns: 6 × 6 mm, 12 × 12 mm, and 29 × 24 mm. Ground-truth annotations of NPAs and nongradable area (NGA) on en face OCTA images were generated by 2 independent graders and adjudicated by a vitreoretinal specialist. A corresponding en face structural OCT image was incorporated to distinguish true NPAs from shadow artifacts. Segmentation outputs included NPA, NGA, and shadow artifacts. Pixel-level accuracy was assessed with the F1 score. Nonperfusion index (NPI) was defined as NPA/gradable area. The level of agreement between human-labeled and algorithm-predicted NPI was analyzed using Bland–Altman analysis. Main Outcome Measures Algorithm F1 score and NPI. Results The algorithm for NPA segmentation achieved a mean F1 score of 0.82 ± 0.01 in 6 × 6 mm, 0.84 ± 0.03 in 12 × 12 mm, and 0.83 ± 0.02 in 29 × 24 mm, with no significant difference across fields of view (P = 0.12). Algorithm-derived NPI strongly agreed with expert grading (intraclass correlation coefficient >0.979). Both human- and algorithm-derived NPI increased progressively with increased DR severity in all scan patterns demonstrated by the Kruskal–Wallis test (6 × 6 mm: human: P = 0.02; algorithm: P = 0.03; 12 × 12 mm: algorithm P < 0.001; human P < 0.001; 29 × 24 mm: algorithm: P < 0.001; human: P < 0.001) with the largest magnitude of increase in 29 × 24 mm scans. The algorithm for foveal avascular zone segmentation also achieved a mean F1 score of 0.88 ± 0.05 for 6 × 6 mm images and 0.85 ± 0.05 for 12 × 12 mm images. Conclusions This deep learning algorithm was validated on single-scan UWF SS-OCTA for automated NPA segmentation and quantification. It demonstrates high accuracy and scalability across multiple scan sizes, supporting its potential integration into objective DR OCTA biomarker analysis. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose of Review The present article serves as a comprehensive review of the published research literature surrounding the retinal microvasculature, characterized through the optical coherence tomography angiography (OCTA) and its potential clinical value for understanding and detecting cerebrovascular diseases. Recent Findings Studies from the past 3 years (2020–2023) have identified a degeneration of the retinal microvasculature, commonly defined through the loss of vascular density, in ischemic stroke, dementia, carotid artery stenosis, cerebral small vessel disease, and a series of rare, potentially inherited cerebrovascular disorders. These retinal microvascular changes often correlate with structure and functional changes in the brain and sometimes occur prior to debilitating neurodegeneration. Summary While further investigations with longitudinal data and larger sample sizes are necessary, OCTA shows promising results for characterizing the retinal microvasculature as a potential imaging biomarker in reflecting the changes in the cerebral microvasculature for early detection, prevention, and treatment of cerebrovascular diseases.

No abstract available

Optical coherence tomography angiography (OCTA) is a quick, noninvasive modality that visualizes retinal microvasculature. The retina is known to be the mirror of the brain, thus it is pertinent to employ OCTA to study covert cerebral small vessel disease (CSVD). This is an observational case–control study of 40 patients with CSVD and 20 healthy controls. Mini-mental state examination (MMSE) was performed for all subjects, to exclude dementia. Fazekas grading and SVD score were determined by MRI. OCTA was performed for both groups and included various parameters of superficial and deep retinal capillary plexus density, macular, foveal and ganglion cell complex thickness, in addition to optic nerve head scans. Seventy percent of the patients had a low SVD score (1). Case group had significantly lower scores on most parameters of retinal capillary plexus density and macular thickness p < 0.05. Impairment of OCTA parameters was associated with higher Fazekas and SVD scores. OCTA is a handy, noninvasive tool that enables the visualization of diminished retinal microvascular density in cases of early CSVD. It can serve as a screening tool for identifying vulnerable populations, facilitating early management for CSVD.

Biomarker tests of Alzheimer’s disease (AD) are invasive and expensive. Recent developments in optical coherence tomography (OCT) and OCT angiography (OCTA) have enabled noninvasive, cost-effective characterization of retinal layer vasculature and thickness. Using OCTA and OCT, we characterized retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD and assessed their correlation with structural changes in each retinal neuronal layer. We also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Retinal layer thickness did not differ between MCI patients (40 eyes) and controls (37 eyes, all p > 0.05). MCI patients had lower vessel density (VD) (p = 0.003) of the superficial capillary plexus (SCP) and larger foveal avascular zone area (p = 0.01) of the deep capillary plexus (DCP) than those of controls. VD of the SCP correlated with the ganglion cell layer (r = 0.358, p = 0.03) and inner plexiform layer thickness (r = 0.437, p = 0.007) in MCI patients. APOE-ε4-carrying MCI patients had a lower VD of the DCP than non-carriers (p = 0.03). In conclusion, retinal microvasculature was reduced in patients with AD-associated MCI, but retinal thickness was not changed; these changes might be affected by the APOE genotype. OCTA of the retinal microvasculature may be useful to detect vascular changes in AD.

ABSTRACT Purpose To analyze structural and vascular changes of the retina and choroid in pediatric patients with coronavirus disease 2019 (COVID-19) using optical coherence tomography (OCT)/OCT angiography (OCTA). Methods This comparative cross-sectional study consists of the COVID-19 group including pediatric COVID-19 patients and the control group including healthy children. Vessel density (VD), central macular thickness,, and choroidal thickness (ChT) measurements were performed using swept-source OCT/OCTA 12 weeks after the recovery from COVID-19. Results The mean VD measurements in the central fovea and nasal quadrants of all three retinal layers and choriocapillaris showed insignificantly lower values in the COVID-19 group when compared to the control group (0:002 < p < 0:05 for all). Similar to VD measurements, insignificant lower ChT measurements were obtained in the central fovea and nasal points in the COVID-19 group. Conclusion OCTA can be used as a non-invasive and valid biomarker in the assessment of early microvascular dysfunction associated with COVID-19.

No abstract available

The authors report the optical coherence tomography angiography (OCTA)-based comparative assessment of the retinal microvasculature in a rare pair of 96-year-old female monozygotic twins discordant for Alzheimer's disease (AD). Using automated mapping of the superficial capillary plexus, the authors observed that the twin with advanced AD had a significantly reduced vessel density and a larger foveal avascular zone in the superficial capillary plexus as well as a thinner choroid compared to the twin who was cognitively normal. This unique twin discordance report adds to the evidence supporting the use of retinal microvasculature changes in the superficial capillary plexus on OCTA as a possible noninvasive biomarker for AD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:440-444.].

Rising morbidity and mortality from cardiovascular disease (CVD) have increased interest in precision and preventive management to reduce long-term sequelae. While retinal imaging has traditionally been recognized for identifying vascular changes in systemic conditions such as hypertension and type 2 diabetes mellitus, a new ophthalmologic field, cardiac-oculomics, has associated retinal biomarker changes with other cardiovascular diseases with retinal manifestations. Several imaging modalities visualize the retina, including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA), which visualize the retinal surface, the individual retinal layers, and the microvasculature within those layers, respectively. In these modalities, imaging-derived biomarkers can present due to CVD and have been linked to the presence, progression, or risk of developing a range of CVD, including hypertension, carotid artery disease, valvular heart disease, cerebral infarction, atrial fibrillation, and heart failure. Promising artificial intelligence (AI) models have been developed to complement existing risk-prediction tools, but standardization and clinical trials are needed for clinical adoption. Beyond risk estimation, there is growing interest in assessing real-time cardiovascular status to track vascular changes following pharmacotherapy, surgery, or acute decompensation. This review offers an up-to-date assessment of the cardiac-oculomics literature and aims to raise awareness among cardiologists and encourage interdepartmental collaboration.

Abstract Background Vessel skeletal density (VSD), derived from Optical Coherence Tomography Angiography (OCTA), reflects capillary density and has been linked to cognitive performance and cerebrovascular health. VSD is considered a potential early biomarker for small vessel disease (SVD), detecting microvascular changes before traditional imaging. Blood‐based biomarkers, such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (pTau181), are markers of neuronal injury, tau pathology, and neuroinflammation, and have been shown to be elevated in neurodegenerative diseases, including Alzheimer's disease and SVD. However, it is unclear whether neurodegeneration, neuroinflammation, and AD pathology contribute to changes in the retinal microvasculature. This study investigated the association between NfL, pTau181, and GFAP with OCTA‐derived VSD in older adults from the Framingham Heart Study (FHS). Methods Participants from the FHS Offspring cohort exam cycle 10 (n = 718, mean age: 65.7 ± 6.7 years) underwent OCTA imaging to assess VSD. Blood samples were collected at exam cycle 9 and analyzed for NfL, pTau181, and GFAP levels using Quanterix Simoa assays. To assess the association between VSD and blood‐based biomarkers, we performed a series of multivariate linear regression models. Model 1 was adjusted for age, sex, time between OCTA and exam 9, and eGFR (for NfL only), while Model 2 additionally adjusted for smoking, hypertension, and diabetes mellitus. Statistical significance was set at a 5% level. Results NfL was not significantly associated with VSD (Model 1: (β ± standard error: ‐0.001 ± 0.001, p = 0.170; Model 2: ‐0.001 ± 0.001, p = 0.186). We observed a significant interaction between NfL and age (p = 0.045). In participants younger than 66 years only, those in the highest as compared to the lowest NfL quartile had significantly lower VSD (‐0.0036 ± 0.0014, p = 0.010). In contrast, no significant association was observed in participants aged 66 years and older. Our study found no significant association between either GFAP or pTau181 and VSD. Conclusion These findings suggest that higher NfL levels may be associated with reduced retinal capillary density in younger individuals and may indicate a link between neurodegeneration and microvascular health.

BackgroundEarly detection of diabetic retinopathy (DR) is crucial for preventing blindness. Optical coherence tomography angiography (OCTA) offers a non-invasive method for visualizing retinal microvasculature and may facilitate earlier detection of DR. This systematic review evaluates the current evidence regarding OCTA-derived biomarkers for the identification of early DR.MethodsA systematic review of the literature was performed. Due to substantial heterogeneity in study designs, OCTA protocols, and outcome measures, a meta-analysis was not feasible.ResultsTwenty-one studies were included. OCTA scan sizes ranged from 3 × 3 mm to 6 × 6 mm and evaluated both the superficial and deep capillary plexuses. Vessel density (VD) was the most consistently reported biomarker, with reduced VD observed in early DR in 13 of 15 studies. Enlargement of the foveal avascular zone (FAZ) was reported in 9 of 17 studies. Microaneurysms were more frequently identified in diabetic eyes in 3 of 5 studies, while increased vessel tortuosity was reported in 2 of 5 studies.DiscussionCurrent evidence suggests that OCTA can detect retinal microvascular abnormalities associated with early DR before advanced clinical manifestations become evident. Reduced VD emerged as the most consistent indicator of early disease, while an increased microaneurysm burden may serve as a complementary marker. In contrast, the diagnostic value of FAZ alterations remains uncertain.ConclusionBy identifying the OCTA parameters most strongly associated with early DR, this review suggests the potential role of OCTA in earlier diagnosis, risk stratification, and monitoring of diabetic patients.

Purpose Remnant cholesterol (RC) is a well-recognized risk factor for cardiovascular diseases (CVDs) and an important biomarker of cardiovascular risk. However, studies on the effects of RC on the early retinal microvasculature are still scarce. Therefore, this study aimed to investigate the association between RC and the retinal capillary plexus (RCP) using optical coherence tomography angiography (OCTA). Methods This cross-sectional study evaluated data from participants of the Jidong Eye Cohort Study. All participants underwent comprehensive ophthalmic examinations and laboratory tests. The RC values were calculated using a recognized formula. OCTA was used to measure vessel density in the RCP. Results This study included a total of 3903 participants, with a mean age of 43.42 ± 9.88 years; 1946 were female (49.86%). After adjusting for confounding factors, higher RC levels were significantly associated with lower deep RCP vessel density in the parafovea (β = −0.578 per 1-mmol/L increase; 95% confidence interval, −0.875 to −0.282; P < 0.001). Moreover, a significant interaction was observed between sex and RC for deep RCP vessel density in the parafovea (P for interaction = 0.029), with a stronger negative association in male participants. Conclusions Higher RC levels were significantly associated with lower deep RCP vessel density. Our findings provide evidence supporting the adverse effects of high RC levels on the retinal microvasculature. Translational Relevance These findings highlight that RC regulation may help prevent microvascular complications, with implications for clinical strategies targeting microvascular health.

Background/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer’s disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer’s disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (β42), amyloid-β42/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer’s disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer’s disease family history, and APOE ε4 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer’s disease.

Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8–48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = − 0.6; p < 0.0001). This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.

Importance Noninvasive retinal imaging may detect structural changes associated with Parkinson disease (PD) and may represent a novel biomarker for disease detection. Objective To characterize alterations in the structure and microvasculature of the retina and choroid in eyes of individuals with PD and compare them with eyes of age- and sex-matched cognitively healthy control individuals using optical coherence tomography (OCT) and OCT angiography (OCTA). Design, Setting, and Participants This cross-sectional study was conducted at the Duke Neurological Disorders Clinic in Durham, North Carolina. Individuals aged 50 years or older with a diagnosis of PD were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 50 years or older and without subjective cognitive dysfunction, a history of tremor, or evidence of motor dysfunction consistent with parkinsonism were solicited from the clinic or the Duke Alzheimer's Disease Prevention Registry. Individuals with diabetes, glaucoma, retinal pathology, other dementias, and corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity worse than 20/40 Snellen were excluded. Data were analyzed between January 1, 2020, and March 30, 2020. Exposures All participants underwent OCT and OCTA imaging. Main Outcomes and Measures Generalized estimating equation analysis was used to characterize the association between imaging parameters and PD diagnosis. Superficial capillary plexus vessel density (VD) and perfusion density (PFD) were assessed within the ETDRS 6 × 6-mm circle, 6 × 6-mm inner ring, and 6 × 6-mm outer ring, as was the foveal avascular zone area. Peripapillary retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness, subfoveal choroidal thickness, total choroidal area, luminal area, and choroidal vascularity index (CVI) were measured. Results A total of 124 eyes of 69 participants with PD (39 men [56.5%]; mean [SD] age, 71.7 [7.0] years) and 248 eyes of 137 control participants (77 men [56.2%]; mean [SD] age, 70.9 [6.7] years) were analyzed. In the 6 × 6-mm ETDRS circle, VD (β coefficient = 0.37; 95% CI, 0.04-0.71; P = .03) and PFD (β coefficient = 0.009; 95% CI, 0.0003-0.018; P = .04) were lower in eyes of participants with PD. In the inner ring of the 6 × 6-mm ETDRS circle, VD (β coefficient = 0.61; 95% CI, 0.20-1.02; P = .003) and PFD (β coefficient = 0.015; 95% CI, 0.005-0.026; P = .004) were lower in eyes of participants with PD. Total choroidal area (β coefficient = -1.74 pixels2; 95% CI, -3.12 to -0.37 pixels2; P = .01) and luminal area (β coefficient = -1.02 pixels2; 95% CI, -1.86 to -0.18 pixels2; P = .02) were greater, but CVI was lower (β coefficient = 0.5%; 95% CI, 0.2%-0.8%; P < .001) in eyes of individuals with PD. Conclusions and Relevance This study found that individuals with PD had decreased retinal VD and PFD as well as choroidal structural changes compared with age- and sex-matched control participants. Given the observed population differences in these noninvasive retinal biomarkers, further research into their clinical utility in PD is needed.

Abstract: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Early diagnosis remains a major challenge due to the invasive, expensive, and limited accessibility of conventional diagnostic methods such as PET scans and cerebrospinal fluid analysis. Recent research highlights the retina as a promising non-invasive biomarker for detecting neurodegeneration, owing to its direct connection with the brain. Advanced imaging techniques such as Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) enable detailed visualization of retinal layers and microvasculature. This survey reviews current approaches that use retinal imaging combined with Artificial Intelligence (AI), particularly deep learning models, to detect Alzheimer’s Disease. Key indicators such as Retinal Nerve Fiber Layer (RNFL) thinning, Ganglion Cell Layer (GCL) degeneration, and amyloid-beta plaque accumulation are analyzed. This survey demonstrates that AI-integrated retinal imaging frameworks, such as DeepRetina, offer a scalable paradigm for early Alzheimer’s Disease detection. Deep learning models, particularly CNNs, enable precise quantification of retinal structural and microvascular biomarkers from OCT/OCTA data. These approaches demonstrate high sensitivity and specificity while remaining non-invasive and cost-effective. Further advances in model generalization and large-scale clinical validation are essential for real-world deployment. Keywords: Alzheimer’s Disease, Retinal Imaging, Optical Coherence Tomography (OCT), Deep Learning, Convolutional Neural Networks (CNN), Retinal Nerve Fiber Layer (RNFL), Early Detection.

Retinal imaging has been proposed as a biomarker for neurological diseases such as multiple sclerosis (MS). Recently, a technique for non-invasive assessment of the retinal microvasculature called optical coherence tomography angiography (OCTA) was introduced. We investigated retinal microvasculature alterations in participants with relapsing–remitting MS (RRMS) without history of optic neuritis (ON) and compared them to a healthy control group. The study was performed in a prospective, case–control design, including 58 participants (n = 100 eyes) with RRMS without ON and 78 age- and sex-matched control participants (n = 136 eyes). OCTA images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 Spectral-Domain OCT with AngioPlex OCTA, Carl Zeiss Meditec, Dublin, CA). The outcome variables were perfusion density (PD) and foveal avascular zone (FAZ) features (area and circularity) in both the SCP and DCP, and flow deficit in the CC. MS group had on average higher intraocular pressure (IOP) than controls (P < 0.001). After adjusting for confounders, MS participants showed significantly increased PD in SCP (P = 0.003) and decreased PD in DCP (P < 0.001) as compared to controls. A significant difference was still noted when large vessels (LV) in the SCP were removed from the PD calculation (P = 0.004). Deep FAZ was significantly larger (P = 0.005) and less circular (P < 0.001) in the eyes of MS participants compared to the control ones. Neither LV, PD or FAZ features in the SCP, nor flow deficits in the CC showed any statistically significant differences between the MS group and control group (P > 0.186). Our study indicates that there are microvascular changes in the macular parafoveal retina of RRMS patients without ON, showing increased PD in SCP and decreased PD in DCP. Further studies with a larger cohort of MS patients and MRI correlations are necessary to validate retinal microvascular changes as imaging biomarkers for diagnosis and screening of MS.

No abstract available

Background The retina serves as a non-invasive window to visualize systemic health, with optical coherence tomography angiography (OCTA) enabling simultaneous assessment of retinal structural thickness and vascular density. Suboptimal cardiovascular-kidney-metabolic (CKM) health status, defined by the early stage of CKM syndrome, may impact retinal neurovascular integrity, yet comprehensive OCTA-based evaluations remain limited and controversial. This study aimed to investigate retinal structural and vascular alterations in the early-stage CKM using OCTA and explore its potential as a biomarker tool. Methods A cross-sectional study included 2,153 participants undergoing OCTA during health checks (2023–2024). Early-stage CKM (stages 1–2) is characterized by abnormal levels of glucose, lipid profile, uric acid, or blood pressure. Retinal thickness and vessel density in nine ETDRS grid regions were measured. Univariate and multivariate logistic regression analyses identified associations between early-stage CKM and OCTA parameters, adjusting for age and gender. Results Early-stage CKM subjects (n = 1,843, 94.5%) exhibited significantly reduced retinal thickness and vessel density across multiple regions compared to healthy controls (all p < 0.05). Multivariate analysis revealed outer temporal thickness (OR = 0.986, p < 0.001), outer superficial vessel density (OR = 1.04, p = 0.020), and inner superior vessel density (OR = 0.962, p = 0.010) as independent predictors of early-stage CKM, alongside age and gender. Specific abnormalities, such as hypertension and diabetes, were associated with distinct regional decreases in thickness and density, suggesting a dose-dependent impact of glycemic dysregulation on retinal health. Conclusion Early-stage CKM syndrome is associated with subtle retinal structural and vascular alterations detectable by OCTA, particularly within the macular layers. OCTA-derived biomarkers, including outer temporal thickness and macular vessel density, may serve as non-invasive tools for evaluating systemic health status, offering promise for the early detection of metabolic and cardiovascular risks.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

Background. Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. Early diagnosis and risk stratification in individuals without clinically manifest pathology is of particular importance. Retinal microcirculation parameters ob tained using optical coherence tomography angiography (OCTA) are regarded as promising noninvasive biomarkers of subclinical vascular dysfunction. Purpose: To assess the diagnostic value of retinal microcirculation parameters for detecting microvascular alterations in individuals without established cardiovascular disease and to determine their association with cardiovascular risk level. Materials and methods. The study included 220 patients aged 35–65 years with no clinical signs of CVD. All subjects underwent comprehensive clinical and laboratory evaluation, cardiovascular risk assessment using the SCORE2 algorithm, and retinal OCTA with quantitative analysis of vascular parameters. Results. Participants with moderate and high cardiovascular risk demonstrated a decrease in vessel density and vessel length in the macular region, enlargement of the foveal avascular zone (FAZ) area, an increased FAZ acircularity index, and expansion of flow voids within the choriocapillaris layer. Statistically significant correlations were identified between OCTA parameters and blood pressure, lipid profile, and SCORE2-derived cardiovascular risk. Conclusion. OCTA-derived metrics have high prognostic value for evaluating subclinical vascular dysfunction. Their application may facilitate the early detection of microvascular impairment and enable more accurate cardiovascular risk stratification in individuals without overt clinical manifestations of disease.

Key Points Question Can evaluation of retinal microvasculature by optical coherence tomography angiography (OCTA) serve as a diagnostic tool for detecting subclinical coronary atherosclerosis? Findings In this clinic-based cross-sectional cohort study that included 1286 patients who underwent both coronary computed tomography angiography (CTA) and OCTA, coronary artery calcium score, presence of plaque, obstructive coronary artery disease (CAD), severe CAD, segment stenosis score, and segment involvement score were significantly associated with parafoveal vascular density (PFVD). Meaning Reduced retinal PFVD was associated with subclinical coronary atherosclerosis and, alongside cardiovascular risk factors, may help identify patients needing comprehensive coronary screening.

Cardiovascular (CV) disease (CVD) is the main cause of death around the world, and assessing a patient's CV risk factors (CVRF) can play a major role in its prevention. Since it has been shown that retinal vascular alterations may reflect several systemic processes such as CVRF, we conducted a systematic review in order to summarize which ocular microvasculature changes can be found using Optical Coherence Tomography Angiography (OCTA) in patients without ocular diseases and with systemic pathologies/conditions that affect the CV system when compared to healthy subjects. We searched on online databases, namely PubMed, Scopus, Cochrane and Web of Science, and obtained additional studies through citation tracking. Case reports and review articles were excluded. A total of 47 articles were included in our review. We describe that patients with hypertension, diabetes mellitus, kidney disease, preeclampsia, coronary artery disease, carotid artery stenosis and obstructive sleep apnoea syndrome have, in general, lower retinal and choroidal Vessel Density (VD) and Length (VL), as well as an increased foveal avascular zone area and perimeter. Additionally, several characteristics and/or conditions in healthy subjects, such as smoking status, hyper or hypoxia conditions, race, among others, are also related to ocular vascular changes and should be accounted for. We concluded that OCTA could be a useful tool to assess a patient's CV risk profile in a non-invasive way, possibly integrating the diagnostic and prognostic algorithms of the most prevalent CV diseases in the future.

Background: Our study evaluated the correlation between internal carotid artery stenosis (ICAS) and retinal microvascular changes in patients with hypertensive retinopathy, dyslipidemia and ICAS. We analyzed vascular measurements provided by optical coherence tomography angiography (OCTA) and carotid Doppler ultrasonography (US) and linked OCTA parameters with carotid artery US measurements on the same side. Statistical differences in OCTA analysis among three groups (no stenosis, mild stenosis and moderate stenosis) were evaluated and correlated with carotid Doppler parameters. Our study aimed to evaluate whether OCTA can be proposed as a screening method in patients diagnosed with mild and moderate ICAS in order to improve the early detection of carotid changes, thus potentially reducing the rate of cardiovascular and cerebral complications of ICAS. Methods: We conducted a study on hypertensive patients with ICAS using six OCTA parameters in the analysis of the retinal vasculature and carotid Doppler US velocities of three carotid arteries and the vertebral artery (VA). Kruskal–Wallis and Dunn’s post hoc tests were used to determine whether there were statistically significant differences between the normal, mild and moderate stenosis groups. Spearman and Pearson correlation were used to obtain correlations among OCTA parameters such as the foveal avascular zone (FAZ), non-flow area (NFA), vascular flow area (VFA) and blood flow velocity on carotid Doppler US. Results: In the final analysis, 49 patients were included and 3 groups of stenosis were obtained, comprising 21 subjects with no stenosis, 19 with mild stenosis and 9 with moderate stenosis. Right eye and left eye groups were formed. In the right eye group with right ICAS, we found statistically significant results for FAZ circularity when comparing the normal stenosis group to the mild stenosis group (p = 0.025) and the mild stenosis group to the moderate stenosis group (p = 0.006). Statistically significant results were also observed for NFA when comparing the normal stenosis group to the moderate stenosis group (p = 0.004) and the mild stenosis group to the moderate stenosis group (p = 0.011). When comparing the FAZ area (p = 0.016) and VFA (p = 0.037) for the normal and moderate groups, statistically significant values were obtained. When comparing the normal and moderate stenosis groups with regard to the left eye, we found statistically significant results for VFA (p = 0.041), NFA (p = 0.045) and VFA (p = 0.029). When comparing the mild and moderate carotid artery stenosis groups, we obtained statistically significant results for NFA (p = 0.001), FAZ area (p = 0.007) and VFA (p = 0.013). In the right eye group, correlations between internal carotid artery (ICA) peak systolic velocity (PSV) and VFA (rho = −0.286), ICA end-diastolic velocity (EDV) and NFA (r = 0.365), external carotid artery (ECA) PSV and VFA (r = −0.288; rho = −0.317), common carotid artery (CCA) PSV and NFA (rho = −0.345), CCA EDV and NFA (rho = −0.292) and VA PSV and VFA (r = −0.327; rho = −0.379) were found. When analyzing OCTA parameters, we found statistically significant results for NFA and VFA (r = −0.374; rho = −0.288). Correlations were also found in the left eye group between ICA PSV and NFA (r = −0.351; rho = −0.313), ICA EDV and VFA (r = −0.421; rho = −0.314), ECA PSV and NFA (r = −0.412; rho = −0.457), CCA PSV and NFA (p = −0.288; rho = −0.339), and CCA EDV and NFA (r = −0.404; rho = −0.417). Conclusions: Our study found correlations between carotid Doppler velocities and OCTA vascular flow parameters; thus, OCTA may be used as a tool for monitoring the microvascular changes associated with carotid stenosis. OCTA can provide insights concerning the overall vascular condition of the patient, since it provides subjective data on vessel density and flow; therefore, by monitoring hypertensive patients with both OCTA and carotid Doppler US, we may be able to increase efficiency in screening and diagnosing patients with IACS.

Supplemental Digital Content is Available in the Text. This study demonstrates optical coherence tomography angiography's utility in assessing retinal microvascular changes in ischemic stroke patients, revealing significant alterations associated with stroke etiology, particularly in micro-/macroangiopathy cases. Purpose: To investigate retinal microvascular changes in ischemic stroke patients using optical coherence tomography angiography (OCT-A) and assess these alterations based on stroke etiology. Methods: Case–control study conducted at Montpellier University Hospital from May 2021 to March 2022 (Institutional Review Board: 202000607). Retinal vascular features were compared between strokes patients and age-matched and sex-matched controls. Optical coherence tomography angiography was performed using RTVue-XR-Avanti with AngioVue (Optovue). Multivariate mixed-effects analysis of covariance models adjusted for age, sex, intraocular pressure, and cardiovascular risk factors were used. Results: Ninety-two eyes were included: 21 with micro-/macroangiopathy stroke, 12 with etiologically ambiguous stroke, 13 with cardioembolic stroke, and 46 eyes from control subjects. After adjusting for age, sex, and intraocular pressure, stroke patients had significantly lower parafoveal superficial capillary plexus vessel density (P = 0.013) and superficial capillary plexus flow index (P = 0.023) compared with control subjects, especially in the macro-/microangiopathy subgroup. When cardiovascular risk factors were included, only the superficial capillary plexus flow index difference remained significant (P = 0.023). Optical coherence tomography angiography's diagnostic accuracy was validated with an area under the receiver operating characteristic curve of 0.83. Conclusion: Optical coherence tomography angiography effectively detects retinal microvascular alterations in stroke patients, with persistent alterations in macro-/microangiopathy strokes after adjusting for cardiovascular risk factors. These findings support OCT-A's role in stroke subtype classification.

No abstract available

The microvascular network of the retina is unique in that it can be noninvasively and directly visualized and quantified. With the advent of optical coherence tomography- angiography (OCT-A), a new innovative research method, the interest of many scientists in studying biomarkers has increased significantly. This method allows to more accurately and effectively identify various changes in the body. The purpose of this review is to analyze current research’s on the use of OCT-A biomarkers in the context of heart failure. In this review, we described some modern studies using this method and identified the main biomarkers of cardiovascular pathology, such as: decrease in standard vascular diameter (SVD), decrease in venule diameter (DVD), foveolar avascular zone (FAZ) in the superficial capillary plexus (SCP), namely their decrease, increase and correlations between each other observed in the macular and peripheral zones, which can serve as predictors of systemic disorders such as chronic heart failure.

We evaluated the association between macular perfusion assessed via optical coherence tomography angiography (OCTA) and the cardiovascular risk profiles of patients with acute myocardial infarction (AMI). Patients with AMI who underwent comprehensive ophthalmological examinations and retinal OCTA were evaluated retrospectively. Retinal OCTA was performed for each patient within 3 days of admission. Quantitative analyses of the vessel density (VD) of the superficial capillary plexus (SCP) layers, deep capillary plexus layers (DCP), and choriocapillaris were performed after image processing. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD), Global Registry of Acute Coronary Events (GRACE) score, reduction of atherothrombosis for continued health (REACH) score, and thrombolysis in myocardial infarction (TIMI) risk score were assessed. Sixty patients were included. VD in SCP and DCP was not associated with a 10-year ASCVD risk; however, choriocapillaris flow void features were significantly correlated with the 10-year ASCVD risk: decreased count, increased average size, and increased signal void area were correlated with increased 10-year ASCVD risk, GRACE score, REACH score, and TIMI risk score. In the multivariate analysis, a 10-year ASCVD risk (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.08) and brain natriuretic peptide (adjusted OR, 1.00; 95% CI, 1.00–1.01) were significantly associated with the highest tertile of the average size of the choriocapillaris. Choriocapillaris flow void features measured using OCTA were associated with cardiovascular risk profiles in patients with AMI. OCTA may be used as an indicator of cardiovascular risk profiles and could improve cardiovascular risk assessments.

Systemic Lupus Erythematosus (SLE) patients have a 3- fold risk of CV events compared to the general population, mainly due to accelerated atherosclerosis that is not completely explained by the presence of traditional CV risk factors. Individuals with increased Intimal medial thickness (IMT) carry a higher risk to develop carotid atherosclerosis. Accordingly, IMT acts as a marker of subclinical atherosclerosis. In recent studies, SLE patients showed a significant higher IMT compared to healthy subjects. On the other side, SLE retinal involvement can be detected in 7-29% of cases, it is characterized mainly by retinal vasculopathy and it can be a marker of systemic vascular involvement. Optical Coherence Tomography Angiography (OCTA), a new diagnostic technique that can visualize retinal blood flow and evaluate the Fovea Avascular Zone (FAZ), has been investigated as an instrument for early detection of subclinical retinal vascular impairment in SLE.Aim of this study is to examine a possible correlation between IMT and retinal vascular impairment assessed through OCTA in SLE.We recruited SLE patients fulfilling 2019 EULAR/ACR classification criteria. Patients with other rheumatic, ophthalmological diseases, diabetes or history of CV diseases were excluded. We also collected patients’ demographic and clinical data, including sex, age, smoking habit, BMI, systolic and diastolic blood pressure (BP), C-Reactive Protein (CRP), total cholesterol, LDL, HDL, triglycerides. All patients underwent an ophthalmological evaluation, including OCTA estimation of superficial and deep retinal vessel density (VD), considering both the whole image and the foveal region, and FAZ area. Carotid ultrasound (US) comprising IMT assessment was also performed. Statistical analysis was accomplished using unpaired t-test or Mann Whitney U test, Pearson or Spearman rank correlation when appropriate.We enrolled 37 SLE patients; demographic, clinical and US data are displayed in Table 1. Nine patients (24.3%) had uncontrolled arterial hypertension. According to US evaluation, carotid plaques were detected in six patients (16.2%). OCTA data were correlated with IMT values showing a negative correlation between IMT and both superficial and deep fovea VD (p=0.003, r=-0.4 and p=0.004, r=-0.4), while a positive correlation was found with FAZ area (p=0.02, r=0.4).Table 1.Demographic, clinical and US data of the study populationFemale sex n(%)28 (75.6)Age, yrs49.2±14.7Smokers n(%)12 (32.4)BMI25.1±5.2SBP, mmHg118.5±15.7DBP, mmHg73.3±11.6IMT, μM549.6±124IMT positively correlated with traditional CV risk factors, particularly age (p<0.0001, r=0.7), BMI (p=0.007, r=0.3) and systolic BP (p=0.001, r=0.4). Patients with high BP levels showed not only a significant higher IMT compared to the group with normal BP values (p=0.04), but also a significant increased FAZ area (p=0.02). FAZ area correlated positively with CRP levels (p=0.0001, r=0.5). Triglycerides showed a positive correlation with IMT values (p=0.001, r=0.4) and FAZ area (p=0.04, r=0.3) while correlated negatively with deep fovea VD (p=0.04, R=-0.4). A reduction in deep whole retinal VD was detected among patients with carotid plaques compared to the group without (p=0.02), together with higher IMT values (p=0.04).Retinal vascular impairment in SLE has been associated with IMT, atherosclerotic plaques and some CV risk factors as hypertension, hypertriglyceridemia and CRP levels. Search for new markers of preclinical CV damage in SLE is currently ongoing and OCTA might be an additional instrument to assess preclinical cardiovascular involvement in SLE.None declared

The recent rise of artificial intelligence represents a revolutionary way of improving current medical practices, including cardiovascular (CV) assessment scores. Retinal vascular alterations may reflect systemic processes such as the presence of CV risk factors. The value of swept-source retinal optical coherence tomography–angiography (SS OCT-A) imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features. We report on the interest of using machine-learning (ML) and deep-learning (DL) models for CV assessment from SS OCT-A microvasculature imaging. We assessed the accuracy of ML and DL algorithms in predicting the CHA2DS2-VASc neurocardiovascular score based on SS OCT-A retinal images of patients from the open-source RASTA dataset. The ML and DL models were trained on data from 491 patients. The ML models tested here achieved good performance with area under the curve (AUC) values ranging from 0.71 to 0.96. According to a classification into two neurocardiovascular risk groups, the EfficientNetV2-B3, a well suited DL model for retinal OCT-A images, predicted risk correctly in 68% of cases, with a mean absolute error (MAE) of approximately 0.697. Our models enable a confident prediction of the CHA2DS2-VASc score from SS OCT-A imaging, which could be a useful tool contributing to the assessment of neurocardiovascular profiles in the future.

No abstract available

BACKGROUND Cardiovascular diseases (CVD) are the leading cause of death worldwide. The observability of retinal vessel changes in the context of CVD by funduscopy has been known for a long time. Optical coherence tomography angiography (OCTA) is a novel technique for noninvasive detailed imaging and quantification of the retinal microcirculation. The OCTA enables the visualization of vascular changes in a simple and well-reproducible way. Its applications are not limited to the field of ophthalmology. In recent years, several experimental and clinical studies have been published on vascular changes detectable with OCTA in CVD. This review summarizes the most important findings of these studies. METHODS This work is based on a comprehensive review of the literature and on the presentation of own data. RESULTS Nowadays, OCTA studies are available for many diseases of the cardiovascular spectrum. This indicates that systemic vascular diseases are associated with changes in the retinal microcirculation. These changes can be visualized and reproducibly quantified with OCTA. In many diseases subclinical changes, which are detectable by OCTA, occur before the underlying disease causes otherwise measurable changes or noticeable symptoms for the patient. CONCLUSION The OCTA is a promising imaging method in the context of CVD in both scientific and clinical applications. It can be used for the diagnostics and quantification of retinal vascular changes. Further studies will show whether OCTA can be of assistance in the estimation of individual systemic cardiovascular risk profiles.

Purpose To identify retinal and systemic factors linked to macular microaneurysms (MAs) in referable diabetic retinopathy (refDR). Methods Eighty-three eyes from 65 patients with refDR without diabetic macular edema underwent multiple 3 × 3-mm optical coherence tomography angiography (OCTA) scans. The scans were averaged, and OCTA metrics were calculated, including vessel length density in the deep capillary plexus (VLD-DCP). Ultra-widefield fluorescein angiography was used to extract macular MA count within a 3-mm circle centered on the fovea and the nonperfusion index (NPI) across the entire visible retina. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m² for at least 3 months. Linear mixed models were used to assess the relationships with MA count, and receiver operating characteristic curve analysis evaluated MA diagnostic performance for detecting CKD. Results The median MA count was 6 (interquartile range, 2–12). In univariate analysis, macular MA count was significantly associated with CKD, NPI, and several OCTA parameters. In multivariable models adjusting for age, sex, CKD, NPI, and one OCTA parameter per model, CKD (P = 0.007–0.013) and VLD-DCP (P = 0.003) remained independently associated with MA count. A threshold of 14 macular MAs yielded the highest Youden index for CKD, with a sensitivity of 58.8%, a specificity of 86.4%, and an area under the curve of 0.755. Conclusions CKD and reduced VLD-DCP were independently associated with higher macular MA count in refDR, suggesting that MA count may serve as a marker for systemic microvascular disease.

Cardiovascular diseases (CVD) and chronic kidney disease (CKD) are associated with microcirculation disorders that can be diagnosed by examination of eye vessels. The review deals with capabilities of ophthalmological methods (i.e., laser Doppler flowmetry [LDF] and optical coherence tomography angiography [OCTA]) to detect microvascular abnormalities associated with ischemic heart disease (including myocardial ischemia/angina with non-obstructive coronary artery disease [INOCA/ANOCA] and myocardial infarction with non-obstructive coronary artery disease [MINOCA]), arterial hypertension and CKD). These techniques provide evaluation of vascular density, blood flow velocity, and other parameters at a preclinical stage. Patients with CVD and CKD show typical ophthalmological signs correlating with systemic vascular pathology. The analysis demonstrates that eye microcirculation monitoring can be an important addition to conventional methods of diagnosis and monitoring of a cardiovascular risk. Integration of ophthalmological approaches into cardiological and nephrological practice opens up fresh opportunities for personalized medicine. Further studies should be conducted to standardize these methods and to confirm their clinical relevance. KEYWORDS: conjunctiva, retina, microcirculation, endothelial dysfunction, ischemic heart disease, chronic kidney disease. FOR CITATION: Enkhtaivan B., Yusupova A.O., Slepova O.A., Pakhtusov N.N., Belenkov Yu.N., Siplivyi V.I., Safonova T.N., Kintyukhina N.P., Sandulyak V.I. Microcirculation disorders in conjunctival and retinal vessels in patients with cardiovascular diseases and chronic kidney disease, as well as their prognostic significance. Russian Journal of Clinical Ophthalmology. 2025;25(3):195–202 (in Russ.). DOI: 10.32364/2311-7729-2025-25-3-6

This study evaluated retinal microvasculature changes in children with chronic kidney disease (CKD) using optical coherence tomography angiography (OCTA). It aimed to identify associations between OCTA parameters and serum levels of vitamin D, asymmetric dimethyl arginine (ADMA), vascular endothelial growth factor-A (VEGF-A), and angiopoietin-2 (Ang-2), and to examine their relationship with CKD progression as measured by estimated glomerular filtration rate (eGFR). A single-center, cross–sectional, prospective correlation study used OCTA to compare retinal vessel density (VD) and foveal avascular zone area in 105 children: 35 on dialysis, 35 with nondialysis CKD, and 35 controls. Blood tests assessed kidney function and microvascular markers including ADMA, VEGF-A, and Ang-2. Compared with controls, both CKD groups showed significantly lower VD in the macula. Additionally, both CKD groups had a larger foveal avascular zone area. In the dialysis group, vitamin D levels positively correlated with VD, while ADMA and Ang-2 levels negatively correlated. In the nondialysis group, albumin and vitamin D levels positively correlated with VD, while ADMA, VEGF, and Ang-2 levels were negatively correlated. Our findings suggest that OCTA is a valuable tool for monitoring microvascular health in children with CKD and highlights the potential roles of vitamin D, ADMA, Ang-2, and VEGF in CKD progression and microvascular damage.

PURPOSE To investigate the association of retinal and choroidal vessel density with renal function using optical coherence tomographic angiography (OCTA). METHOD The present study prospectively recruited consecutive diabetes patients admitted to Beijing Liangxiang Hospital from October 2023 to March 2024. All participants underwent comprehensive ophthalmologic examinations and laboratory analysis at the first visit. Quantitative parameters of OCTA scans included retinal superficial vascular complex (SVC) and deep vascular complex (DVC) vessel densities, and choriocapillaris flow deficits (CCFD%). RESULTS A total of 85 patients were included in the present study. After adjusting for severity of diabetic retinopathy and other confounding factors, every 1% increased SVC within in ETDRS grid was associated with reduced incidence of CKD (OR=0.86 95%CI:[0.73-1.01]), decreased urine albumin-to-creatinine ratio (ACR, coefficient=-0.65, 95%CI:[-1.22, -0.08]), and increased eGFR (coefficient=1.55, 95%CI:[0.14, 2.96]). Every 1% increased CCFD% was significantly associated with increased incidence of CKD (OR=1.72, 95%CI:[1.14-2.58]) and decrease eGFR (coefficient=-6.47, 95%CI:[-9.68, -3.26]). Non-linear regression revealed that SVC vessel density was associated with eGFR among patients with advanced retinal microvasculature damage. CONCLUSIONS Retina and choroid blood flow were associated with the onset and severity of CKD. Decreased SVC and decreased CCFD% can be used for non-invasively screening CKD in diabetes patients.

To compare retinal microvascular perfusion between the eyes of hypertensive patients with and without chronic kidney disease (CKD), the vessel density (VD) and fractal dimension (FD) of the superficial (SVP) and deep retinal vascular plexus (DVP) were analyzed on 6 × 6 mm fovea-centered optical coherence tomography angiography (OCTA) images of patients with hypertension. The retina was divided into an inner ring (IR) and outer ring (OR) according to the Early Treatment of Diabetic Retinopathy Study grid. The glomerular filtration rate (GFR) was determined and CKD was diagnosed (GFR < 60 mL/min/1.73 m2). Ninety-six eyes from 52 patients with hypertension were included in this analysis. Twenty patients (n = 37 eyes) were diagnosed with CKD. The mean age was 69 ± 11.7 years and 60.4 ± 9.2 years in the CKD group and in the control group, respectively. The univariate model revealed a significant difference in VD between patients without and with CKD in the superficial IR (0.36 ± 0.03 vs. 0.34 ± 0.04, p = 0.03), the superficial OR (0.35 ± 0.02 vs. 0.33 ± 0.04, p = 0.02), the deep OR (0.24 ± 0.01 vs. 0.23 ± 0.02, p = 0.003), and the FD in the SVP (1.87 ± 0.01 vs. 1.86 ± 0.02, p = 0.02) and DVP (1.83 ± 0.01 vs. 1.82 ± 0.01, p = 0.006). After adjusting for age and sex, these differences did not remain statistically significant. Similar results were observed for the FD in the SVP and DVP. In our cohort, patients with hypertension and CKD did not differ from patients without CKD in regard to microvascular perfusion status in the macular area as assessed using OCTA.

Objective: This study aimed to assess microvascular changes in the retina over time in patients with chronic kidney disease (CKD) following kidney transplantation. Methods: A total sample of 54 CKD patients (108 eyes) was prospectively observed for 2 years to evaluate the dynamics of microvascular parameters. Two study groups were formed: Group 1 comprised 36 patients (72 eyes) who underwent kidney transplantation, and Group 2 comprised 18 patients (36 eyes) receiving hemodialysis and conservative treatment. Patients were examined before the operation, within 2 months post-operation (early postoperative period), and at 12 months post-operation (late postoperative period). Results: Optical coherence tomography angiography (OCTA) results demonstrated that retinal parameters, including area, perimeter, and circularity index of the foveal avascular zone (FAZ), showed recovery over the 12-month observation period after kidney transplantation, indicating a positive trend in the macular region. Similar trends were observed for overall vessel density, perfusion, and choroidal vascularity index (CVI) parameters. Statistical analysis revealed significant differences (p<0.05) between the groups in terms of FAZ area and CVI. Conclusion: The primary microvascular changes in the retinas of patients with end-stage CKD involve reduced vessel density and perfusion volume in the superficial capillary layer. KEYWORDS: chronic kidney disease; kidney transplantation; microvascular changes; optical coherence tomography angiography (OCT-A).

Background Chronic kidney disease (CKD) is a major public health issue because of the rising number of patients with the risk of progression to end-stage renal disease. The retinal micro-vasculatures provide a unique window to assess systemic microcirculation. Optical Coherence Tomography Angiography (OCTA) parameters may provide a non-invasive method for systemic correlation. This research aims to compare the association of OCTA parameters in different causes of CKD. Methods This is a single-center cross-sectional study on patients with CKD at the Universiti Kebangsaan Malaysia Medical Centre over 2 years. Patients with CKD were divided into three groups: DM group (diabetic CKD), HPT group (hypertensive CKD), and AG group (autoimmune-related glomerulonephritis CKD). The OCTA parameters, namely, the foveal avascular zone (FAZ), vascular density (VD), perfusion density (PD), and macular volume (MV), were measured and recorded using OCTA. Blood and urine analyses were taken as the patient’s CKD profile. The demographic data, the OCTA parameters and the CKD profiles, were analyzed using SPSS version 23. Results The right eyes of 232 patients were included. The median age of the control and CKD subjects were 36 and 61 years old respectively. The proportion of the subjects under the control, diabetes mellitus (DM), HPT, and AG group were 30.6, 53.4, 5.6, and 10.4% respectively. There was no significant difference in FAZ, but there is a significant difference in the VD, PD, and MV between the control and CKD groups. There was a statistically significant difference between the three different causes of CKD in VD and PD (p < 0.001, p = 0.001, respectively). When compared with the control group for VD and PD, there were significant differences between the DM-control group (p < 0.001, p < 0.001) even when the age variable was considered, but no significant difference when comparing the HPT-control and the AG-control. There was a significant correlation between age, FBS, and HbA1c with VD and PD. There was no significant association between CKD profile and FAZ. Conclusion Our study showed the meaningful reduction of VD and PD in patients with diabetes and CKD. However, the use of OCTA to screen or predict CKD in patients living with diabetes mellitus, hypertension, or autoimmune nephritis was not shown to be useful.

One distinctive pathological sign of chronic kidney disease (CKD) is microcirculatory disorders, which mark it as a microvascular disease. Similarity in the blood supply of the retina and kidneys, in the anatomy of their vascularization lead to identical complications in these organs. The retinal-choroidal microvascular system is easily accessible for clinical and morphological assessment and can be examined by the reproducible and non-invasive method - optical coherence tomography (OCT) and OCT angiography (OCTA). The study of significant diagnostic tomographic retinal biomarkers in CKD and monitoring of their changes are of great clinical importance. The article presents clinical cases of changes in the retina and choroid depending of the stage of CKD. Retinal microvascular changes precede functional impairment. A significant decrease in retinal and choroidal thickness correlates with a decrease in the glomerular filtration rate (GFR) and the degree of albumin excretion in the urine. All clinical cases were observed to exhibit retinal microcirculation disorders, capillary rarefaction in both capillary plexuses accompanied by a decrease in vessel density and a decrease in the circularity index of the foveal avascular zone as a result of regression of the parafoveal capillary networks. OCTA allowed visualization of morphological changes at the microcirculatory level in the form of blunt ends of capillaries, their increased tortuosity and the presence of local areas of decreased perfusion. The severity of retinal microvascular changes varied depending on the stage of CKD and was not associated with either age or the presence of diabetes mellitus. Assessment of the retinal microvasculature can help with monitoring of microvascular lesions, early prediction of the risk of development and progression of decreased renal function, as well as allow avoiding aggressive diagnostic biopsy.

Background: Widespread neural and microvascular injuries are common in chronic kidney disease (CKD), increasing risks of neurovascular complications and mortality. Early detection of such changes helps assess the risks of neurovascular complications for CKD patients. As an extension of central nervous system, the retina provides a characteristic window to observe neurovascular alterations in CKD. This study aimed to determine the presence of retinal neurovascular impairment in different stages of CKD. Methods: One hundred fifteen non-diabetic and non-dialytic CKD patients of all stages and a control group of 35 healthy subjects were included. Retinal neural and microvascular parameters were obtained by optical coherence tomography angiography (OCTA) examination. Results: CKD 1–2 group (versus control group) had greater odds of having decreased retinal ganglion cell-inner plexiform layer thickness (GC-IPLt) (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.86–0.98), increased ganglion cell complex-focal loss volume (GCC-FLV) (OR: 3.51; 95% CI: 1.27–9.67), and GCC-global loss volume (GCC-GLV) (OR: 2.48; 95% CI: 1.27–4.82). The presence of advanced stages of CKD (CKD 3–5 group versus CKD 1–2 group) had greater odds of having decreased retinal vessel density in superficial vascular plexus (SVP)-WholeImage (OR: 0.77, 95% CI: 0.63–0.92), SVP-ParaFovea (OR: 0.83, 95% CI: 0.71–0.97), SVP-ParaFovea (OR: 0.76, 95% CI: 0.63–0.91), deep vascular plexus (DVP)-WholeImage (OR: 0.89, 95% CI: 0.81–0.98), DVP-ParaFovea (OR: 0.88, 95% CI: 0.78–0.99), and DVP-PeriFovea (OR: 0.90, 95% CI: 0.83–0.98). Besides, stepwise multivariate linear regression among CKD patients showed that β2-microglobulin was negatively associated with GC-IPLt (β: –0.294; 95% CI: –0.469 ∼ –0.118), and parathyroid hormone was positively associated with increased GCC-FLV (β: 0.004; 95% CI: 0.002∼0.006) and GCC-GLV (β: 0.007; 95% CI: 0.004∼0.01). Urine protein to creatinine ratio was positively associated with increased GCC-FLV (β: 0.003; 95% CI: 0.001∼0.004) and GCC-GLV (β: 0.003; 95% CI: 0.001∼0.006). Conclusion: Retinal neuronal impairment is present in early stages of CKD (stages 1–2), and it is associated with accumulation of uremic toxins and higher UACR, while retinal microvascular hypoperfusion, which is associated with worse eGFR, was only observed in relatively advanced stages of CKD (stages 3–5). The results highlight the importance of monitoring retinal neurovascular impairment in different stages of CKD.

PURPOSE To study the main structural and microvascular changes in the retina and choroid in patients with diabetic retinopathy (DR) and chronic kidney disease (CKD), and their relationship with impaired renal function. MATERIAL AND METHODS The study included 158 patients (304 eyes). The 1st group consisted of 50 patients with CKD (97 eyes); group 2 - 65 patients with DR (119 eyes), group 3 - 43 patients with CKD and DR (86 eyes). All study patients underwent complete ophthalmological examination, including optical coherence tomography (OCT) and OCT angiography (OCTA) of the macular region. RESULTS The analysis of structural parameters in groups of patients showed a decrease in the thickness of the ganglion cell layer and the inner plexiform layer of the retina in patients with DR (70.85±14.49 μm), with the lowest value in the CKD+DR group (65.84±15.34 μm) in comparison with the CKD group (75.64±10.32 μm). In the groups of patients with CKD, the thickness of the choroid (207.3±40.36 μm) was significantly reduced in comparison with the group of patients with DR (258.8±26.63 μm) and correlated with the stage of the disease. Patients in the CKD+DR group had the lowest perfusion and vascular density in the macular region (31.23±10.91% and 13.15±2.73 mm), an increase in the area and perimeter of the foveal avascular zone (0.55±0.26 mm2, 3.30±0.84 mm). Pronounced correlations of decrease in choroidal thickness, vascular density, and perfusion volume with low glomerular filtration rate and CKD stage, as well as urea and creatinine levels were determined. An increase in the area of the foveal avascular zone correlated with lower retinal capillary density, decreased perfusion volume, and the stage of both DR and CKD. CONCLUSION Structural and hemodynamic disorders of the retina and choroid can be recognized as significant biomarkers for non-invasive diagnosis of microvascular complications of diabetes mellitus and impaired renal function.

AIMS To explore the associations between the microvascular/microstructural changes in the retina measured by optical coherence tomography angiography (OCTA) and renal function in type 2 diabetes patients with early chronic kidney disease (CKD). METHODS This cross-sectional study, including 150 type 2 diabetes patients, was conducted from July 2017 to January 2019. We obtained retinal vessel density (VD) and retinal thickness using OCTA. The correlations between OCTA-derived parameters and CKD-related systemic data were assessed by multiple regression analyses. RESULTS We found a significant decrease of VD in patients with CKD. Multiple regression analyses showed that: a) decreased eGFR (estimated glomerular filtration rate) was significantly correlated with decreased VD of superficial vascular complex (SVC) in macular area; b) increased UACR (urine albumin to creatinine ratio) was significantly associated with increased macular thickness; c) decreased HGB/HCT (Hemoglobin or Hematocrit) was significantly correlated with both decreased VD of SVC and increased retinal thickness in macular area. CONCLUSIONS Decrease in the microcirculation of the retina and thickening of the macula associated with impaired renal function in type 2 diabetes. Our finding encourages the application of OCTA-derived metrics in diabetic eyes to monitor the progression of CKD.

No abstract available

Background: Chronic kidney disease (CKD) is associated with systemic microvascular dysfunction, yet the relationship between retinal changes and mineral metabolism disturbances across CKD treatment modalities remains incompletely characterized. Methods: We performed a baseline cross-sectional analysis of 77 participants (29 hemodialysis [HD] patients, and 48 kidney transplant recipients [KTR]) who underwent 7 × 7 mm structural optical coherence tomography (OCT) and 6 × 6 mm OCT angiography (OCTA) imaging. Structural parameters included central macular thickness (CMT), ganglion cell layer plus inner plexiform layer (GCL+), ganglion cell complex (GCL++), and subfoveal choroidal thickness (SCT). Microvascular parameters included superficial and deep capillary plexus vessel density (SVPD, DVPD), choriocapillaris density (CCD), and foveal avascular zone (FAZ) area. Serum mineral metabolism markers were correlated with retinal findings. Eyes were analyzed separately as the primary approach, while generalized estimating equation (GEE) models adjusted for age, sex, body mass index, diabetes, and hypertension (HTN) were used for confirmation. Results: FAZ area, SVPD, DVPD, CCD, GCL+, GCL++, and CMT did not differ significantly between cohorts in either per-eye analyses or adjusted GEE models. SCT was lower in HD patients than in KTR in the right eye (p = 0.019) and remained significantly higher in KTR in the adjusted GEE models (p = 0.016), a difference that persisted after excluding participants with diabetes and after adjustment for HTN grade. HTN grade was associated with FAZ area in HD and SCT in KTR. Serum magnesium was inversely associated with FAZ area in HD (B = −95.27, p = 0.034) and positively associated with GCL+ in KTR (B = 10.55, p = 0.048). Conclusions: Retinal microvascular and inner-retinal structural parameters were largely comparable between HD patients and KTR, with SCT the only parameter showing a consistent between-cohort difference (higher in KTR). Serum magnesium and HTN grade were the metabolic and clinical variables most consistently associated with retinal measures.

SuMMAry – Introduction. Ocular microvascular changes can be related to kidney deterioration in chronic kidney disease (CKd). We aimed to identify the association between retino-choroidal parameters and kidney deterioration in diabetics and non-diabetics. Methods. The study group consisted of CKd patients (cross-sectional study) with arterial hypertension with different stages of CKd. Complete eye examination was completed with optical coherence tomography angiography (OCtA) scans of the macular region. According to the value of glomerular filtration rate (gfr) and albuminuria, patients were divided into groups: low gfr (<60ml/min) and high gfr (>60ml/min) and CKd patients without albuminuria and CKd with micro or macroalbuminuria. Results. One hundred and six eyes of 106 chronic kidney disease patients were evaluated. The mean retinal thickness in gfr <60 ml/min group was 275,73±9,65 micron (µ), whereas in a gfr >60 ml/min group was 274,36±10,77 µ. OCtA showed lower deep vascular density (dvd) in CKd with albuminuria versus CKd without albuminuria group (p < 0.001). Albuminuria was inversely related to choroidal and retinal thickness measures of superficial (Svd) and dvd. Conclusions. CKd is associated with retinal diluting and decreasing kidney function with reduction of retinal and choroidal vascular density.

Purpose The aim of this study was to describe the distribution and ocular and systemic associations of the foveal avascular zone (FAZ) area in Caucasians in a population-based setting. Methods We included 1004 participants (aged 59.91 ± 9.39 years; 49.3% female) of the 10-year follow-up of the Gutenberg Health Study, a population-based, prospective cohort Study in Mainz, Germany, with gradable optical coherence tomography angiography of the macula. The FAZ area of the total retina was measured manually. Linear regression analysis was conducted to evaluate the associations of the FAZ area with ocular and systemic factors. Results The mean FAZ area was 0.27 ± 0.12 mm2. It was associated with female sex (B-estimate 0.04; 95% confidence interval [CI], 0.03–0.06; P < 0.001) and inversely with axial length (B-estimate −0.02; 95% CI, −0.03 to −0.01; P < 0.001). Multivariable analysis of the FAZ area confirmed the associations with sex and axial length. No association was found with age, body mass index, blood pressure, diabetes, smoking, chronic kidney disease, socioeconomic status, or best-corrected visual acuity. Conclusions The FAZ area was larger in females and in participants with a shorter axial length indicating that both ocular and anthropometric factors may influence FAZ size. Translational Relevance This study provides normative data of the foveal avascular zone area in an adult Caucasian population and describes the ocular and systemic associations that have to be taken into account when interpreting optical coherence tomography angiography data in Caucasians.

Imaging the retina is a powerful non-invasive probe of systemic vascular, neurological, metabolic, and renal disease, making it a cornerstone of the new field of systemic oculomics. Advanced retinal imaging techniques like optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) provide detailed imaging of structural and microvascular changes potentially associated with systemic disease. Derived from fundus photography, structural imaging, vascular imaging, and artificial intelligence-based image analysis, retinal biomarkers have been associated with cardiovascular and cerebrovascular disease, neurodegenerative disorders, diabetes, chronic kidney disease, and related clinical outcomes. However, the translational maturity of these biomarkers is variable depending on imaging modality, target disease, intended clinical use, and level of validation. Longitudinally, retinal vascular characteristics have been associated with cardiovascular as well as cerebrovascular outcomes. In addition, optical coherence tomography has provided reproducible measures of neuroaxonal injury in selected neurological conditions. This is especially true for multiple sclerosis. The majority of retinal biomarkers in Alzheimer disease, Parkinson disease, chronic kidney disease, and systemic risk prediction remain experimental because of heterogeneous methodologies, insufficient external validation, and insufficient evidence for incremental clinical utility. Diabetes is the most developed translational model with established retinal screening pathways and validated ocular applications of imaging and artificial intelligence, although these cannot be directly extrapolated to systemic diagnosis or treatment guidance. This narrative review assesses retinal biomarkers for cardiovascular, neurological, metabolic, and renal disease with a focus on analytical validity, clinical validity, incremental value, clinical utility, and implementation. The retina is increasingly accepted as a site for discovery of systemic biomarkers and adjunctive risk assessment, although most applications to systemic disease remain to be standardized, validated independently, and studied prospectively before being suitable for routine clinical use.

No abstract available

PURPOSE This study evaluates swept-source OCT Angiography (SS-OCTA) quantitative metrics as non-invasive biomarkers of diabetic nephropathy (DN) in patients with diabetes mellitus. DESIGN This is a cross-sectional study of patients with Diabetes Mellitus. SUBJECTS This study included 375 eyes of 234 patients imaged using 12 × 12-mm angiograms centered on the fovea. METHODS OCTA metrics that were analyzed included non-perfusion area (NPA), foveal avascular zone area (FAZ), vessel density (VD), and vessel skeletonized density (VSD). These metrics were compared with the presence and severity of DN. MAIN OUTCOME MEASURES Primary outcomes were albuminuria (albumin-to-creatinine ratio ≥30 mg/g) and chronic kidney disease (CKD, estimated glomerular filtration rate ≤60 or >60 ml/min/1.73 m2 with albuminuria). Secondary outcomes included albuminuria severity (A1: <30, A2: 30-300, A3: >300 mg/g), CKD severity (normal GFR: ≥90, mild CKD: 60-89, moderate-severe CKD: ≤59 ml/min/1.73 m2) and Kidney Disease Improving Global Outcomes (KDIGO) risk categories for CKD progression and/or mortality. Subgroup analysis assessed early microvascular changes in patients with no or mild diabetic retinopathy (DR) and DN association. Multivariate regression adjusted for age, smoking status, glycosylated hemoglobin, and mean arterial blood pressure. RESULTS Of 234 patients, 145 (62%) had CKD and 111 (47%) had albuminuria. Increasing NPA was associated with albuminuria (Odd's ratio (OR): 1.17, p=0.038), CKD (OR: 1.06, p<0.001), CKD severity (p<0.05), and KDIGO risk categories on pairwise analysis (p<0.05). VD and VSD were significantly different between extremes of KDIGO risk categories (very high versus low and moderate risk, p<0.05) and albuminuria severity (A3 versus A1, p<0.05). In the no/mild DR subgroup, more circular FAZ and higher VD were associated with absent albuminuria (p<0.05). CONCLUSIONS NPA is a potential biomarker for predicting DN and is associated with DN severity. This study is the first to link OCTA metrics with KDIGO risk categories for CKD severity and mortality.

No abstract available

BACKGROUND Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder characterized by cholesterol and cholestanol accumulation, leading to neurological and ocular complications. While cataracts and optic neuropathy are common, retinal structural and vascular alterations remain poorly understood. OBJECTIVE To comprehensively evaluate ophthalmologic findings and retinal imaging characteristics in CTX patients. METHODS This prospective, cross-sectional study included detailed ophthalmologic examinations of CTX patients, including best corrected visual acuity (BCVA), intraocular pressure (IOP), biomicroscopy, and fundus examination. Retinal imaging was performed using optical coherence tomography (OCT) and OCT-angiography (OCTA). Central foveal thickness (CFT), parafoveal retinal thickness (RT), ganglion cell layer thickness (GCLT), and vessel densities (VDs) of the superficial (SCP) and deep capillary plexus (DCP) were analyzed and compared with age-matched healthy controls. RESULTS A total of 18 eyes from 9 CTX patients and 18 eyes from 9 controls were included. Five patients (55.5%) had prior cataract surgery. All eyes that underwent cataract surgery exhibited myopic/astigmatic refractive errors, and 3 (30%) had elevated IOP. Fundoscopy revealed optic disc hypoplasia, pallor, blurred disc margins, and increased vascular tortuosity in some cases (44.4%). BCVA, parafoveal RTs, and parafoveal SCP-VDs were significantly lower in CTX patients (P < .05). CFT, foveal SCP-VD, and GCLT were lower but not statistically significant (P > .05). CONCLUSION Cataracts and optic nerve abnormalities are the most common ocular findings in CTX. Eyes undergoing cataract surgery should be closely monitored for refractive errors and IOP. Retinal neurovascular pathologies can be detected noninvasively using OCT and OCTA imaging.

Abstract Background The logopenic variant of Primary Progressive Aphasia (lvPPA) is a neurodegenerative disorder affecting primarily language functions. In 86% of lvPPA cases, the underlying pathology is amyloidopathy, as seen in Alzheimer's disease (AD). Since the retina is considered an extension of the brain, recent research has explored optical coherence tomography (OCT) and OCT‐angiography (OCT‐A) as non‐invasive biomarkers in AD. However, their potential in lvPPA remains unexplored. The aim of this study was to compare retinal findings in lvPPA patients and healthy controls using OCT and OCT‐A. Methods We conducted a cross‐sectional study recruiting participants with lvPPA (diagnostic criteria by Gorno‐Tempini, 2011) and healthy controls matched for sex and age. Participants were excluded if they had preexisting neurological or eye conditions. An extensive ophthalmological assessment was conducted to rule out eye diseases. OCT/OCTA imaging was then performed for all participants. For lvPPA patients, the Clinical Dementia Rating scale and a lumbar puncture were performed to assess disease stage and underlying pathology. Results Ten lvPPA patients and eleven controls were enrolled. All lvPPA patients had amyloidopathy confirmed by lumbar puncture. Mean CDR global score was 0.55 ± 0.16 (indicating mild dementia). Retinal nerve fiber layer (RNFL) in the temporal region was significantly thinner in the lvPPA group compared to controls (63.1 ± 3.3 μm vs 75.6 ± 3.2 μm, p = 0.013). Foveal avascular zone (FAZ) circularity was also significantly lower in the lvPPA group (0.69 ± 0.02 vs 0.77 ± 0.02, p = 0.002). Conclusions Our findings suggest decreased RNFL thickness and reduced FAZ circularity in lvPPA. Decreased RNFL thickness reflects neuronal degeneration and its underlying mechanisms include retinal amyloid accumulation or retrograde degeneration. This suggests that amyloid‐induced brain atrophy leads to a lack of trophic factors, resulting in thinning of the RNFL while reduced FAZ circularity could signal early vascular alterations induced by amyloid. Altogether, these findings suggest that OCT and OCT‐A could serve as valuable biomarkers for lvPPA, thus enhancing early diagnosis.

Subacute sclerosing panencephalitis (SSPE) is an irreversible and progressive neurological disorder. A 20-year-old woman with SSPE presented with a decline in visual acuity. Anterior segment was evaluated with slit lamp and in vivo confocal microscopy, revealing the presence of dendritiform keratic precipitates and +2 cells in the anterior chamber. In fundus examination, white-yellowish lesions involving the macula and periphery were observed, which gradually progressed into atrophy over time. Optical coherence tomography (OCT) imaging showed progression to atrophy of moth-eaten shaped cavities including all retinal layers due to necrotizing retinitis. OCT angiography (OCTA) further revealed reduced vessel densities and flow void areas. Notably, to the best of our knowledge, this is the first case documenting anterior segment findings in SSPE in detail. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Multiple Sclerosis (MS) is thought to be an autoimmune demyelinating disorder in which neuroaxonal degeneration is the principal driver of disability. Microvascular abnormalities in the central nervous system (CNS) may contribute to or be a biomarker of the disease process. Global reduction in cerebral perfusion has been repeatedly illustrated in imaging studies of MS, which could simply be a sequela of neurodegeneration or could be mediated by concomitant inflammatory vasculopathy. Endothelial cell dysfunction, excessive platelet activation, evidence of oxidative stress, altered blood- brain barrier permeability, vascular occlusions within demyelinating lesions, and hypoxia-like tissue injury have all been reported in people with MS (PwMS). Optical Coherence Tomography Angiography (OCTA) enables visualization of the ocular microvasculature through non-invasive, high-resolution enface and depth-resolved imaging. Using OCTA, non-invasive in vivo studies of neurological disorders through the human eye have emerged for MS, Alzheimer’s disease (AD), and various optic neuropathies. To document changes in the peripapillary vascular network and retinal vascular plexuses in patients with optic neuritis due to MS and compare it to healthy individuals. 26 eyes of 26 patients with Optic Neuritis (ON) caused by MS and 26 eyes of 26 sex and age- matched healthy controls. We used OCT AngioVue Enhanced Microvascular Imaging System aiming to quantify and compare microvasculature changes in the macula and peripapillary region between these two groups. this Cross-Sectional Study which has been conducted on patients from Ain Shams university hospitals, after the approval of the research ethics committee in the Faculty of Medicine, Ain Shams University between March to October. All cases underwent a Complete ophthalmological examination. the examination included Visual acuity assessment and Best corrected visual acuity. Slit Lamp Biomicroscopy examination with fundus examination, with OCT angiography (RTVue XR OCT Avanti System: Optovue, Fremont, USA) was done on the patients with MS during the attack of ON and to the healthy group. In our study, we found a statistically significant decrease in the superficial and deep vessel density in the macular area in the patients with ON compared to the healthy controls. Superficial vessel density in the macular area in the healthy ones was 49.90±3.4 (range: 42.4-54.6) while in those with MS was 44.09±4.9 (range 34.0-55.2). Deep vessel density in the macular area in patients without MS was 51.71±6.8 (range 35.3-61.4) while in patients with MS was 45.51±5.7 (range 37.0-57.8). There were statistically significant differences between groups (P = 0.001). There is a decrease in superficial and deep vessel density and Radial peripapillary vessel density in patients with ON caused by MS in comparison to healthy controls.

Vascular changes are increasingly recognized as important factors in the pathophysiology of neuroinflammatory disease, especially in multiple sclerosis (MS). The relatively novel technology of optical coherence tomography angiography (OCTA) images the retinal and choroidal vasculature non-invasively and in a depth-resolved manner. OCTA provides an alternative quantitative measure of retinal damage, by measuring vascular density instead of structural atrophy. Preliminary results suggest OCTA is sensitive to retinal damage in early disease stages, while also having less of a “floor-effect” compared with commonly used OCT metrics, meaning it can pick up further damage in a severely atrophied retina in later stages of disease. Furthermore, it may serve as a surrogate marker for vascular pathology in the central nervous system. Data to date consistently reveal lower densities of the retinal microvasculature in both MS and neuromyelitis optica spectrum disorder (NMOSD) compared with healthy controls, even in the absence of prior optic neuritis. Exploring the timing of vascular changes relative to structural atrophy may help answer important questions about the role of hypoperfusion in the pathophysiology of neuroinflammatory disease. Finally, qualitative characteristics of retinal microvasculature may help discriminate between different neuroinflammatory disorders. There are however still issues regarding image quality and development of standardized analysis methods before OCTA can be fully incorporated into clinical practice.

PurposeTo review the clinical and research value of optical coherence tomography angiography (OCTA) in the field of neurology.MethodsCurrent literature involving OCTA were reviewed through PubMed using the search terms “optical coherence tomography angiography”, with “multiple sclerosis”, “Alzheimer’s disease”, “optic neuropathy”, or other closely-related terms.ResultsOCTA has been applied in research to advance our understanding of the pathobiology of neurological disorders. OCTA-derived blood flow and vessel density measures are altered in multiple sclerosis (MS), Alzheimer’s disease (AD), and various optic neuropathies (ON) in varying regions of the posterior segment vasculature of the eye. These emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological disorders.ConclusionOCTA may be beneficial for neurological research. Additional investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders.

Moyamoya disease (MMD) is a structural abnormality of the cerebral vasculature characterized by cerebral ischemia, and is rare but its incidence is increasing. Digital subtraction angiography (DSA) of the brain is the primary means of diagnosing and evaluating this disease. But its high price and invasiveness limit its use as a monitoring tool for disease progression. As a non-invasive test for ophthalmic disorders, the optical coherence tomography angiography (OCTA) is widely used. In addition to ophthalmic diseases, OCTA has also been used in some neurological diseases. The aim of this study was to assess fundus changes in patients with MMD by OCTA and to investigate whether these changes could be a diagnostic and assessment marker for MMD. This study evaluated cerebral vessels, superficial macular capillary vessel density (SMC-VD) and macular retinal thickness (MRT) in subjects in the non-operated group (nGO), operated group (OG) and healthy controls (HC) using DSA, OCTA and other techniques. Analyses of variance (ANOVA) and Bonferroni post hoc analysis were used to calculate statistical differences between the three groups. Correlations between SMC-VD and MRT were assessed using Pearson correlation analysis. In addition, the ability of the SMC-VD and the MRT to distinguish MMD from HC was analyzed using receiver operating characteristic (ROC) curves. We found that the SMC-VD and MRT in the nOG group were significantly lower than those in the HC group and had not returned to normal levels at one month postoperatively. In the nOG, the SMC-VD and MRT were positively correlated in the Full region (6*6 mm) and in the Inner region (3*3 mm), and in many subregions they showed high ability to distinguish MMD from HC. The above findings indicate significant reduction in the SMC-VD and the MRT in patients with MMD even in the absence of ocular clinical manifestation. Most importantly, SMC-VD and MRT have a strong ability to distinguish between MMD patients and HC, suggesting that OCTA, a relatively inexpensive and non-invasive method, is useful in assessing cerebrovascular changes in MMD patients.

Purpose: This article identifies subclinical microvascular changes in systemic lupus erythematosus (SLE) patients using vascular perfusion densities derived from optical coherence tomography angiography (OCTA). Methods: A retrospective review was performed on individuals with SLE (10 eyes of 5 patients) and age-matched controls imaged with a spectral-domain OCT system (XR Avanti, Optovue, Inc). A split-spectrum amplitude-decorrelation algorithm (SSADA) generated OCTA of the superficial retinal capillaries, deep retinal capillaries, and foveal avascular zone (FAZ). Skeletonized OCTAs were used to create capillary vessel density (VD) values for each image. VD values were compared with clinical staging, and groups were compared using Kruskal–Wallis and Mann–Whitney tests. Results: Both the superficial (SCP) and deep capillary plexus (DCP) had a statistically significant decrease in VD in the SLE group when compared with the control group (P < .05). The average VD ± SD for normal individuals in the 3 mm × 3 mm scans was 26.11 ± 1.2 and 37.45 ± 1.8 for the SCP and DCP, respectively. For SLE patients the mean ± SD was 18.46 ± 0.84 and 30.22 ± 1.5 for SCP and DCP, respectively. The mean FAZ was found to be 0.207 mm ± 0.02 for healthy controls and 0.350 mm ± 0.02 for SLE patients (P < .001). Conclusions: In this paper we demonstrate a significantly enlarged FAZ and decreased VD in a small sample of patients with lupus. The SCP VD demonstrated a dose-response–type negative relationship with increased systemic lupus severity. Larger-sample, prospective studies may allow us to further characterize subclinical SLE pathology with OCTA, and OCTA may further provide a means for monitoring the severity or progression of other microvascular diseases.

No abstract available

Retinopathy in systemic lupus erythematosus (SLE) has an incidence of 7%–29% and is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival.1 Recently, we demonstrated a subclinical retinal involvement in patients with SLE that seems to be related to kidney involvement where hydroxychloroquine had a protective role.2 The pathogenesis of lupus retinopathy is attributed to a vasculopathy most commonly immune complex-mediated microangiopathy.1 Optical coherence tomography angiography (OCTA) is a non-invasive technique for imaging the microvasculature of the retina and choroid that may quantify foveal avascular zone, non-perfused or low-perfused areas. Quantitative measurements based on OCTA may have value in managing retinopathy but also correlate with visual outcome and mirror vascular involvement in systemic diseases.3 The aim of this study was to evaluate retinal microvasculature using OCTA in patients with SLE without signs of retinopathy according to standard lupus retinopathy classification4 and correlate abnormal vascular density with disease activity, damage …

Systemic lupus erythematosus, Hydroxychloroquine, retinal structure and microcirculation, SS-OCTA. The application of swept-source optical coherence tomography angiography (SS-OCTA) technique is used to detect the effects of long-term use of hydroxychloroquine (HCQ) on retinal structure and microcirculation in patients with systemic lupus erythematosus (SLE) before visual dysfunction occurs. Retrospective case-control study. A total of 73 SLE patients (73 eyes) who had taken HCQ regularly for a long period of time were included as the SLE patient group, while 21 healthy individuals (21 eyes) were included as the control group. Based on the duration of HCQ use (HCQ course), the SLE patient group was divided into baseline group (6 months ≤ medication time < 1 year), low-risk group ( 1 year ≤ medication time < 5 years), and high-risk group (medication time ≥ 5 years). All participants underwent bilateral SS-OCTA macular imaging (6 mm*6 mm), slit-lamp examination, non-contact tonometry, computerized visual field (30 − 2) test, and fundus autofluorescence imaging (FAF). Compared among the groups, the full-layer retinal thickness and superficial blood vessel density of the fovea, below the inner circle, temporal side of the outer circle and above the outer circle decreased in the macular area (6 mm*6 mm) in high-risk group of SLE patients, while the area and circumference of FAZ increased (P < 0.0125). Correlation analysis suggested that the duration of SLE disease and HCQ cumulative dose were negatively correlated with superficial retinal capillary plexus vessel density (SCP-VD) in the three regions of inner retina, full-layer retinal thickness in the fovea, fovea, temporal side of the inner circle, and above the inner circle (r < 0,P < 0.05), and positively correlated with the area and circumference of FAZ (r > 0,P < 0.05). Analysis by SS-OCTA examination showed that long-term HCQ treatment had adverse effects on the inner retina, SCP-VD and FAZ parameters in subclinical SLE patients without visual impairment.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three‐prime repair exonuclease‐1) gene mutations, often proned to misdiagnosed.

No abstract available

Optical coherence tomography angiography (OCTA) enables non-invasive visualization of retinal microvasculature, and accurate 3D vessel segmentation is essential for quantifying biomarkers critical for early diagnosis and monitoring of diabetic retinopathy. However, reliable 3D OCTA segmentation is hindered by capillary invisibility, complex vascular topology, and motion artifacts, which compromise biomarker accuracy. Furthermore, the scarcity of manually annotated 3D OCTA microvascular data constrains methodological development. To address this challenge, we introduce our publicly accessible 3D microvascular dataset and propose MT-Net, a multi-view, topology-aware 3D retinal microvascular segmentation network. First, a novel dimension transformation strategy is employed to enhance topological accuracy by effectively encoding spatial dependencies across multiple planes. Second, to mitigate the impact of motion artifacts, we introduce a unidirectional Artifact Suppression Module (ASM) that selectively suppresses noise along the B-scan direction. Third, a Twin-Cross Attention Module (TCAM), guided by vessel centerlines, is designed to enhance the continuity and completeness of segmented vessels by reinforcing cross-view contextual information. Experiments on two 3D OCTA datasets show that MT-Net achieves state-of-the-art accuracy and topological consistency, with strong generalizability validated by cross-dataset analysis. We plan to release our manual annotations to facilitate future research in retinal OCTA segmentation.

PURPOSE: To compare peripapillary and parafoveal microvasculature between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) at different disease stages using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: This retrospective study classified eyes into early, moderate, or severe visual field defect based on Hodapp-Parrish-Anderson criteria. OCTA was used to assess radial peripapillary capillaries (RPCs), retinal nerve fiber layer (RNFL), parafoveal vessel density, and ganglion cell complex thickness. Global and sectoral parameters were compared between POAG and NTG, with subgroup analysis by disease severity. RESULTS: In early-stage glaucoma, global RNFL thickness was significantly lower in NTG eyes (87.5 ± 11.3 µm) compared to POAG eyes (92.4 ± 10.5 µm, P = 0.034), especially in the superior-nasal sector (111.7 ± 28.4 µm vs. 122.7 ± 26.8 µm, P = 0.030). In severe-stage glaucoma, POAG eyes showed lower nasal-superior RPCs (32.1% ± 9.8% vs. 39.2% ± 8.8%, P = 0.044), nasal-inferior RPCs (32.9% ± 10.6% vs. 40.0 ± 6.9%, P = 0.012), and temporal-superior RNFL thickness (53.0 ± 15.0 µm vs. 69.9 ± 21.7 µm, P = 0.019). CONCLUSION: The microvasculature in the sectoral peripapillary and parafoveal regions shows significant differences between POAG and NTG across various stages. This suggests that the mechanisms underlying these glaucoma subtypes may differ at different stage.

BACKGROUND AND OBJECTIVE Optical coherence tomography angiography (OCTA) is a non-invasive technique to visualize changes in retinal microvasculature. The relationship between the retinal blood flow and systemic diseases can be studied using biomarkers extracted from the OCTA en-face images. However, these images are prone to various artifacts that can hinder the image quality. Thus, image quality assessment is essential to improve the retinal biomarker analysis pipeline. METHODS In this paper, we propose a novel method called Relative-distance-based Patch Distribution Modeling (R-PaDiM) that compares the probabilistic representation of good and bad quality images in a relative manner using patch features extracted from pre-trained encoders. With our method, it is possible to both classify OCTA en-face images into good and bad quality, and obtain patch-wise quality score maps to highlight the bad quality regions within the image for better interpretability. Five different backbones are thoroughly investigated for image quality assessment on two public and one private datasets: DRAC Challenge, OCTA-25K-IQA-SEG, and MeyeHeart. RESULTS We achieve state-of-the-art results on all backbones and datasets. Our best results are observed on the DRAC Challenge dataset with a WideResNet-50 backbone that has an accuracy of 98.0 ± 1.1, an AUC of 99.3 ± 0.5, and a Kappa score of 86.4 ± 7.6. We also report a higher correlation between the patch-wise quality scores and the artifact affected regions compared to other methods. CONCLUSIONS The proposed method is highly robust and efficient in obtaining quality scores that correspond to the specific regions within the image related to the classification decision. Due to its versatile nature, it can be applied to many other tasks with various imaging modalities for better explainability of the deep learning models.

Artificial intelligence (AI)-based vessel segmentation converts color fundus photographs, scanning laser ophthalmoscopy (SLO), optical coherence tomography angiography (OCTA), structural OCT, and anterior-segment images into quantitative vascular biomarkers. Strong performance within individual datasets has not consistently yielded reliable clinical measurements because errors can arise during acquisition, anatomical preprocessing, vessel extraction, biomarker calculation, and deployment. This structured narrative review compares segmentation tasks involving retinal vascular trees, OCTA capillary plexuses, the structural choroid and choriocapillaris, macular neovascularization, corneal neovascularization, and conjunctival microvasculature. We assess modern architectures in relation to vessel geometry, severe foreground-background imbalance, scale variation, crossings, and susceptibility to artifacts. The methods considered include multiscale feature pyramids, deformable and directional operators, Transformers, state-space models, diffusion approaches, and foundation models. We organize the synthesis around five evaluation levels: pixel overlap, centerline recovery, vascular topology, biomarker agreement, and clinical actionability. Public fundus and OCTA datasets are catalogued with their acquisition and annotation characteristics, and gaps in public anterior-segment vessel benchmarks are discussed. Because devices, data splits, labels, and post-processing differ substantially, reported metrics are summarized without ranking studies against one another. The review distinguishes structural OCT choroidal vascularity index from OCTA choriocapillaris flow-deficit mapping, as well as true vessel segmentation from global hyperemia grading. Clinical translation will require ocular-magnification correction, quality control of retinal layers and projection artifacts, external testing across devices and populations, out-of-distribution rejection, DICOM/PACS interoperability, prospective impact studies, and regulation as software as a medical device. We conclude that clinical utility depends on an auditable pipeline that measures structural error, biomarker uncertainty, and failure states throughout the workflow.

[This corrects the article DOI: 10.1016/j.jscai.2024.102520.].

Purpose: To assess the role of multimodal Optical Coherence Tomography Angiography (OCTA) analysis in glaucoma diagnosis. Methods: This Institutional Review Board (IRB) approved, retrospective, single academic center study consisted of 357 patients (635 eyes), including 193 healthy, 99 Ocular Hypertension (OHT), 128 open angle Glaucoma Suspect (GS) and 215 POAG eyes. The following clinical data was collected for all patients: Retinal Nerve Fiber Layer Thickness (RNFL), Cup/Disc Ratio (CDR), Central Corneal Thickness (CCT) and history of myopia, hyperopia, Hypertension (HTN), Diabetes (DM) and Cardiovascular Disease (CVD). OCTA scans of the optic nerve head and macula were analyzed using Open-Source Software (OpenCV), calculating Vessel Density (VD), Vessel Length Density (VLD) and fractal dimension (FD). The data was divided into a training and testing set. Using the training data, we created five diagnostic models (demographic, VD-FD, VLD-FD, clinical and multimodal). We calculated Receiver Operating Curves (ROC) using the testing data and compared the models using Area Under the Curve (AUC) analysis. Results: VD, VLD and FD were significantly reduced in the POAG group (p < 0.0001). The multimodal model performed the best (AUC = 0.898), followed by the clinical model (AUC = 0.888), the VD-FD model (AUC = 0.780), the VLD-FD model (AUC = 0.774) and the demographic model (AUC = 0.741). The multimodal model performed significantly better than all other models (p = 0.035). Conclusion: Our analysis indicates that diagnosing glaucoma with a multimodal approach utilizing OCTA is superior to using clinical and structural data alone.

Purpose: To design dual inhibitors against Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) via pharmacoinformatics approach. Methods: Dual Drug Candidates (DDC) were designed and explored for their molecular interaction with several AD and T2DM targets. Pterostilbene, a natural anti-T2DM compound was coupled with different cholinesterase inhibitors to design DDC. Orisis Datawarrior online property calculator tools, Autock 4.2 and Hex 5.1 were used to investigate the potency of all DDC relative to positive controls. Results: The study found that DDC2 (pterostilbene methylene linker -octa hydro amino phenothiazine), DDC3 (pterostilbene ethylene linker N-phthalimide) and DDC5 (pterostilbene carbonyl linker 2-methyl-4-aminoquinoline) were the most promising out of all the DDCs. DDC2 showed strong molecular interaction with most of the AD and T2DM targets, including acetylcholinesterase, butrylcholinesterase, β-secretase, receptor for advanced glycation end products and ATP sensitive potassium channel, dipeptidyl peptidase IV and sodium glucose transport protien 2. The findings also revealed the amyloid anti-aggregation potential of DDC. Conclusion: The results show that DDC3 and DDC5 significantly interfer with the primary nucleation process of β amyloid. Thus, DDC2, DDC3 and DDC5 have strong anti-T2DM and anti-AD potential.

Functional neurological disorders (FND) are conditions marked by disruptions in brain network function without structural abnormalities. Sleep disturbances, though under-researched, are commonly observed in FND patients and may worsen symptoms and overall health. This systematic review had been registered prospectively in PROSPERO with the registration number: CRD42023446306. Search of PubMed, MEDLINE, Embase, and Cochrane databases identified 218 articles. After removing duplicates and applying exclusion criteria, 9 studies were included in the final analysis. The analysis showed a significant prevalence of sleep disorders among FND patients, with 58% reporting sleep disturbances, similar to other neuropsychiatric conditions. Studies on psychogenic non-epileptic seizures (PNES) indicated poorer subjective sleep quality and higher insomnia rates compared to epilepsy controls. Limited data on specific measures such as wake after sleep onset (WASO) and Epworth Sleepiness Scale (ESS) scores prevented definitive conclusions. This review is the first systematic examination of sleep disorders in FND. The findings reveal a high prevalence of sleep disturbances, especially among PNES patients, correlating with lower quality of life and increased symptom severity. However, the heterogeneity of studies and limited reporting of specific sleep metrics weaken these conclusions. Further research is needed to investigate the direct impact of sleep quality on FND pathogenesis and management. Sleep disturbances are prevalent in FND patients and can significantly affect their quality of life. Increased awareness and routine evaluation of sleep in FND patients are recommended. Future studies should explore the relationship between sleep deprivation and FND to develop targeted therapeutic interventions.

INTRODUCTION In a cohort of adults with Functional Neurological Disorder (FND), we aim to: METHODS: 91 patients participating in a FND 5-week outpatient program completed baseline self-report questionnaires for total phobia, somatic symptom severity, attention deficit hyperactivity disorder (ADHD) and dyslexia. Patients were grouped by Autism Spectrum Quotient (AQ-10) score of <6 or ≥ 6 and compared for significant differences in tested variables. This analysis was repeated with patients grouped by alexithymia status. Simple effects were tested using pairwise comparisons. Multistep regression models tested direct relationships between autistic traits and psychiatric comorbidity scores, and mediation by alexithymia. RESULTS 36 patients (40%) were AQ-10 positive (scoring ≥6 on AQ-10). A further 36 patients (across AQ-10 positive and AQ-10 negative groups) (40%) screened positive for alexithymia. AQ-10 positive patients scored significantly higher for alexithymia, depression, generalised anxiety, social phobia, ADHD, and dyslexia. Alexithymia positive patients scored significantly higher for generalised anxiety, depression, somatic symptoms severity, social phobia, and dyslexia. Alexithymia score was found to mediate the relationship between autistic trait and depression scores. CONCLUSION We demonstrate a high proportion of autistic and alexithymic traits, in adults with FND. A higher prevalence of autistic traits may highlight a need for specialised communication approaches in FND management. Mechanistic conclusions are limited. Future research could explore links with interoceptive data.

The occurrence of Functional Neurological Disorder (FND) and Somatic Symptom Disorder (SSD) in PD was not commonly accepted until recently, despite some evidence that emerged in the pre and early L-Dopa era. More recently, the recognition of FND and SSD were noted to be relevant for the management of PD. FND and SSD appear early in the course of PD, often preceding motor symptoms, may interfere with treatment outcomes, often acquire psychotic features during progression, and are mixed with and often concealed by the progressive cognitive decline. We review the related features from the range of the available reports and discuss theoretical models conceived to explain the potential pathophysiological background of these disorders. Finally, we suggest that FND and SSD should be included among the non-motor symptoms of PD and be considered a prodromal feature in a subset of patients. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

The extant literature confirms that an array of polymorphic genes related to- neurotransmitters and second messengers govern the net release of dopamine in the Nucleus Accumbens (NAc) in the mesolimbic region of the brain. They are linked predominantly to motivation, anti-stress, incentive salience (wanting), and wellbeing. Notably, in 2000 the Nobel Prize was awarded to Carlsson, Greengard, and Kandel for their work on the molecular and cellular function of dopaminergic activity at neurons. This historical psychopharmacological work involved neurotransmission of serotonin, endorphins, glutamate, and dopamine, and the seminal work of Blum, Gold, Volkow, Nestler, and others related to neurotransmitter function and related behaviors. Currently, Americans are facing their second and worst opioid epidemic, prescribed opioids, and easy access drive this epidemic of overdoses, and opioid use disorders (OUDs). Presently the clinical consensus is to treat OUD, as if it were an opioid deficiency syndrome, with long-term to life-long opioid substitution therapy. Opioid agonist administration is seen as necessary to replace missing opioids, treat OUD, and prevent overdoses, like insulin is used to treat diabetes. Treatment of OUD and addiction, in general, is similar to the endocrinopathy conceptualization in that it views opioid agonist MATs as an essential core to therapy. Is this approach logical? Other than as harm reduction, is using opioids to treat OUD therapeutic or harmful in the long term? This historical Trieste provides a molecular framework to understand the current underpinnings of endorphinergic/dopaminergic mechanisms related to opioid deficiency syndrome and generalized reward processing depletion. WC 249.

Summary Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding Bill & Melinda Gates Foundation.

BACKGROUND Systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) exhibits marked clinical heterogeneity. While pathogenic variants in bone morphogenetic protein receptor type Ⅱ (BMPR2) gene and other PAH-related genes drive pulmonary vascular remodeling in idiopathic/ familial PAH, their role in SLE-associated PAH remains unclear. RESEARCH QUESTION What is the prevalence of rare variants in PAH-related gene in patients with SLE-associated PAH and how do these variants associate with clinical phenotypes and outcomes? STUDY DESIGN AND METHODS Based on the Chinese SLE Treatment and Research Group (CSTAR)-PAH cohort, 241 patients with SLE-associated PAH were recruited and screened for rare deleterious variants in 12 definitive and 9 candidate PAH-related genes by whole exome sequencing. Clinical features, hemodynamic characteristics and outcomes were compared between variant carriers and noncarriers. Another 87 patients with SLE-associated PAH were included as genetic replication cohort. RESULTS In the discovery cohort, 7.2% patients carried rare variants in PAH-related genes, which trended higher than control subjects (4.5%, P value = 0.085). This trend remained consistent in the independent validation cohort (8.5% vs. 4.8%; P value = 0.148) and reached statistical significance in the combined cohort analysis (7.4% vs. 4.7%; P value = 0.036). Variant carriers had a significantly higher proportion of PAH as the onset symptom of SLE and significantly lower SLE disease activity. Carrying rare variants in PAH-related genes was identified as an independent prognostic factor of mortality (hazard ratio [HR]=5.89, 95% confidence intervals [CI] 1.56-22.27, P value = 0.009). INTERPRETATION We showed that rare variants in PAH-related genes associated with a distinct vasculopathy phenotype and worse outcomes in patients with SLE-associated PAH, demonstrating the clinical implications of better risk stratification and personalized treatment strategies for patients with SLE-associated PAH.