Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema.

Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a multi-ancestry GWAS to assess DME risk in a total of 1,502 DME patients and 5,603 non-DME controls in discovery and replication datasets. Two loci reached GWAS significance (p<5x10-8). The strongest association was rs2239785, (K150E) in APOL1. The second finding was rs10402468, which co-localized to PLVAP and ANKLE1 in vascular / endothelium tissues. We conducted multiple sensitivity analyses to establish that the associations were specific to DME status and did not reflect diabetes status or other diabetic complications. Here we report two novel loci for risk of DME which replicated in multiple clinical trial and biobank derived datasets. One of these loci, containing the gene APOL1, is a risk factor in African American DME and DKD patients, indicating that this locus plays a broader role in diabetic complications for multiple ancestries. Trial Registration: NCT00473330, NCT00473382, NCT03622580, NCT03622593, NCT04108156.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

ASSOCIATION OF DIABETIC MACULAR EDEMA WITH QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES: The Fushun Diabetic Retinopathy Cohort Study.

PURPOSE: To report the vision-related quality of life in patients with diabetic macular edema (DME) in a population-based study. METHODS: In this cross-sectional study, we analyzed 1,659 subjects with type 2 diabetes. Questionnaires were administered to assess the patient's vision-related quality of life. Diabetic macular edema severity was graded according to the established protocols. A subject's DME score ranged from 1 (no DME in either eye) to 7 (severe bilateral DME) using predefined criteria. RESULTS: Composite 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores for participants with DME were 88.9 (interquartile range [IQR]: 76.2-94.9) compared with 92.0 (IQR: 82.7-96.0) for those without DME ( P < 0.001). Locally weighted scatterplot smoothing plots depicted a consistent decline in composite NEI-VFQ-25 scores corresponding to the escalation of bilateral DME severity: starting from 88.59 for no DME in either eye, progressing through 86.65, 85.83, 85.31, 84.91, 83.85, and culminating at 82.71 for bilateral severe DME. Notably, the locally weighted scatterplot smoothing plots highlighted significant NEI-VFQ-25 composite score reduction at unilateral mild DME (slope m = -1.94). CONCLUSION: Significant changes in vision-related quality of life manifest in the early stage of DME. Therefore, early identification and intervention for these patients are crucial clinical objectives.

Tablet-based tests of everyday visual function in a diabetic macular oedema (DME) clinic waiting area: A feasibility study.

PURPOSE: (1) To assess the feasibility of conducting tablet-based vision tests in hospital clinic waiting areas; (2) To test the hypothesis that increasing severity of diabetic macular oedema (DME) is associated with the performance of tablet-based surrogates of everyday tasks and self-reported visual function. METHODS: Sixty-one people with mild (n = 28), moderate (n = 24) or severe (n = 9) DME performed two tablet-based tests of 'real-world' visual function (visual search and face recognition) while waiting for appointments in a hospital outpatient clinic. Participants also completed a tablet-based version of a seven-item, visual-functioning (VF-7) patient-reported outcome measure. Test performance was compared to previously published 99% normative limits for normally sighted individuals. RESULTS: Thirty-four participants (56%; 95% confidence interval [CI] 43%-68%) exceeded normative limits for visual search, while eight (13%; 95% CI 65%-24%) exceeded normative limits for face discrimination. Search duration was significantly longer for people with severe DME than those with mild and moderate DME (p = 0.01). Face discrimination performance was not significantly associated with DME severity. VF-7 scores were statistically similar across DME severity groups. Median time to complete all elements (eligibility screening, both tablet-based tasks and the VF-7) was 22 (quartiles 19, 25) min. Further, 98% and 87% of participants, respectively, reported the search task and face discrimination task to be enjoyable, while 25% and 97%, respectively, reported finding the two tasks to be difficult. CONCLUSIONS: Portable tablet-based tests are quick, acceptable to patients and feasible to be performed in a clinic waiting area with minimal supervision. They have the potential to be piloted in patients' homes for self-monitoring.

Atopic Dermatitis Associated Retinal Detachment and Retinal Vasculitis: A Case Report.

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

The effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy in type II diabetes mellitus patients: A clinical trial.

INTRODUCTION: Diabetic retinopathy (DR) is one of the most threatening complications of diabetes and a leading cause of visual loss in working-age population. Although exercise is beneficial in diabetes, previous studies have showed contradictory and inconclusive results on how it effects DR. In this study, we aimed to investigate the effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy. MATERIALS & METHODS: In this before-after clinical trial, 40 patients with diabetic retinopathy were enrolled by convenient sampling method in Shahid Labbafinejad Hospital in Tehran during 2021-2022. Before the intervention, central macular thickness (CMT, microns) measured by optical coherence tomography (OCT) and fasting blood sugar (FBS, mg/dl) were obtained. Then, patients took part in a 12-week moderate-intensity aerobic exercise (3 sessions per week, each session 45 min). Data were analyzed using SPSS version 26.0. RESULTS: Out of 40 examined patients, 21 (52.5 %) were male and 19 (47.5 %) were female. The mean age of the patients was 50.8 years. The mean rank of FBS (mg/dl) significantly decreased from 21.12 before the exercise to 8.75 after the exercise (p < 0.001). Also, the mean rank of CMT (microns) showed a significant decrease from 21.11 before the intervention to 16.20 after the exercise (p < 0.001). There was a significant positive correlation between patients' age and FBS (mg/dl) before (rho = 0.457, p = 0.003) and after (rho = 0.365, p = 0.021) the intervention. Also, a significant positive correlation was found between patients' age and CMT (microns) before (rho = 0.525, p = 0.001) and after (rho = 0.461, p = 0.003) moderate exercise. CONCLUSION: Moderate-intensity aerobic exercise leads to lower FBS (mg/dl) and CMT (microns) in patients with diabetic retinopathy, so it may be beneficial for diabetic patients to avoid sedentary lifestyle.

Factors affecting central macular thickness of diabetic macular oedema patients after an induction treatment of intravitreal ranibizumab.

OBJECTIVE: Intravitreal ranibizumab is one of the anti-vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions. METHODS: Cross-sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post-treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness. RESULTS: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 µm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029]. CONCLUSION: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab.

Immunity status and expression of molecular markers (ICAM-1, CD5, CD25, CD95) on lymphocytes of patients with recurrent anterior uveitis complicated by macular edema.

BACKGROUND: Treatment of macular edema in uveitis is a key goal of treatment, because this complication remains a potential therapeutic problem for specialists. MATERIAL AND METHODS: Examination was carried out in 1-2 groups - 50 persons with uncomplicated recurrent anterior uveitis (AU) in the stage of relapse or remission - and 3-4 groups - 26 persons with recurrent AU complicated by uveitic macular edema (UME) in the stage of relapse or remission of AU. Control group - 27 healthy volunteers. All patients underwent an ophthalmologic examination, using OCT (Spectralis HRA + OCT (Heidelberg Engineering)). The state of cellular and humoral immunity and the expression of activation markers on blood lymphocytes in all patients were assessed. An immunohistocytochemical analysis using monoclonal antibodies (the peroxidase-anti-peroxidase method) was employed to assess the expression of lymphocyte activation markers. The monoclonal antibody panel (MCAP) for immunophenotyping included antibodies reacting with CD5, CD54 (ICAM-1), CD25, and CD95 (FAS) antigens. Immunophenotyping was performed using immunohistochemistry. RESULTS: In the patients with AU + UME, the parameters of the T-cell link of the immune response were increased and the parameters of humoral immunity (CD19, IgA, IgG) were decreased in comparison with the uncomplicated AU patients. The absolute and relative numbers of natural killer cells in the peripheral blood were higher, and the relative numbers of phagocytic neutrophils were lower in the group of anterior uveitis with UME than in uncomplicated AU. The absolute and relative expression levels of ICAM-1 (CD54) and the absolute expression level of CD5 on peripheral blood lymphocytes were increased in relapse at patients with AU + UME compared with uncomplicated AU. The expression levels of CD25 and CD95 were not different in these groups. CONCLUSION: Activation of cellular immunity markers ICAM-1 and CD5 seems to play a role in uveitic macular edema. The expression levels of CD25 and CD95 were not significantly different in these groups.

BETTER BASELINE VISION LEADS TO BETTER OUTCOMES AFTER THE 0.19-mg FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT IN DIABETIC MACULAR EDEMA.

PURPOSE: Analysis of a 3-year, Phase 4, open-label, observational study evaluating the association of baseline best-corrected visual acuity (BCVA) with visual, treatment burden, and retinal thickness variability (RTV) outcomes and intraocular pressure (IOP)-related events after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant. METHODS: Data from patients with diabetic macular edema (DME) who did not have a clinically significant rise in IOP after previous corticosteroid treatment (N = 202 eyes from 159 patients) were segregated by baseline BCVA of ≥20/40 or <20/40 and analyzed for BCVA, number of yearly supplemental DME treatments, RTV, and incidence of IOP-related events. RESULTS: At 36 months post-FAc, eyes with better baseline BCVA (≥20/40) maintained baseline BCVA, whereas vision in eyes with worse baseline BCVA (<20/40) increased by approximately 7 letters to 61.34 letters (Snellen equivalent approximately 20/60; P < 0.05). Treatment burden and RTV decreased post-FAc regardless of baseline BCVA. Eyes with better baseline BCVA (≥20/40) had numerically fewer IOP-related events post-FAc versus eyes with worse baseline BCVA (<20/40), including a lower incidence of incisional IOP-lowering surgery. CONCLUSION: The 0.19-mg FAc implant improved RTV and treatment burden regardless of baseline BCVA. Better baseline BCVA (≥20/40) was associated with long-term BCVA maintenance. Although eyes with worse baseline BCVA (<20/40) experienced significantly improved BCVA, it never rose to the level of those with better baseline BCVA. These data indicate that early, effective intervention in DME, before significant vision loss occurs, is key to maintaining visual outcomes.

Central retinal artery occlusion without cherry-red spots.

BACKGROUND: Cherry-red spots are a very important sign for the clinical diagnosis of central retinal artery occlusion (CRAO). We retrospectively summarized the clinical manifestations of CRAO and analysed the causes and characteristics of CRAO without cherry-red spots. In this study, we explored a diagnostic method for CRAO without cherry red spots. METHODS: Seventy patients (70 eyes) with CRAO were examined retrospectively. Corrected distance visual acuity, fundus photos, FA and OCT images were collected at the first outpatient visit. The causes of CRAO without cherry-red spots were analysed through fundus photos. The incidence of increased hyperreflectivity of the inner retina, central macular thickness (CMT) and arteriovenous transit time in patients with and without cherry-red spots were compared. RESULTS: Fundus examination showed posterior retinal whitening in 57 cases (81.43%) and cherry-red spots in 39 cases (55.71%). Thirty-one patients presented at the first outpatient visit without cherry-red spots. The reasons for the absence of cherry-red spots included leopard fundus (32.26%), retinal vein occlusion (25.81%), no obvious inner retinal coagulative necrosis (19.35%), ciliary retinal artery sparing (12.90%), high macular oedema (9.68%) and cherry-red spot enlargement (3.23%). OCT revealed increased hyperreflectivity of the inner retina in 67 CRAO patients (95.71%). All 3 patients without increased hyperreflectivity of the inner retina did not present with cherry-red spots at the first visit. The median CMT in patients without cherry-red spots was 166.00 µm, while the median MCT in patients with cherry-red spots was 180.00 µm; there was no significant difference between these two groups (P = 0.467). FA showed delayed arteriovenous transit time > 23 s in 20 patients (28.57%), > 15 s in 43 patients (61.43%) and no delay in 27 patients (30.77%). The median arteriovenous transit time in patients without cherry-red spots was 19.00 s, while it was 18.00 s in patients with cherry-red spots; there was no significant difference between these two groups (P = 0.727). CONCLUSIONS: There are multiple factors that could cause the absence of cherry-red spots in CRAO. The use of OCT to observe increased hyperreflectivity of the inner retina is the most effective imaging method for the early diagnosis of CRAO without cherry-red spots.

Triple retinal arterial macroaneurysms in a hypertensive patient with hypothyroidism.

PURPOSE: To present the unique case of numerous, recurring retinal arterial macroaneurysms (RAMs) in a hypothyroid patient with hypertension. METHODS: 67-year-old woman's clinical findings, laboratory results, fundus fluorescein angiography, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) are given. Over a two-year period, the patient was monitored. RESULTS: A 67-year-old woman presented to the outpatient clinic with vitreous and dense subretinal hemorrhages in her right eye. RAM rupture was discovered along the suprotemporal retinal arteriole. A diagnosis of systemic arterial hypertension was made. Two months later, the vitreous hemorrhage spontaneously resolved and the patient's vision improved. After nine months of initial presentation, the patient developed another RAM. Meanwhile the patient developed ichthyosis caused by hypothyroidism. Because fundus fluorescein angiography revealed that the first RAM was still active, an intravitreal injection of anti-VEGF was administered six months afterwards. More proximal RAM with macular edema developed after another six months necessitating laser photocoagulation. However macular edema didn't resolve and a second injection of intravitreal anti-VEGF was given. CONCLUSIONS: Patients with RAMs, particularly if multiple or recurring, should be thoroughly investigated and assessed, particularly for secondary causes of hypertension. OCT and OCTA are useful tools for RAM confirmation and follow-up. It is important to look into how RAM behavior interacts with coexisting macular edema, and other variables affecting hemodynamic status.

Change in Sub-aspects of Vision-Related Quality of Life after Three Months of Using an App to Categorize Metamorphopsia. / Veränderung von Teilaspekten der sehbezogenen Lebensqualität nach 3-monatiger Verwendung einer App zur Kategorisierung von Metamorphopsien.

AIM: Distorted vision (metamorphopsia) is a leading symptom in retinal disease and can be categorized with the app MacuFix. This prospective controlled pilot study examined the influence of the app MacuFix as a method to assess metamorphopsia on vision-related quality of life. METHODS: Forty-five patients suffering from metamorphopsia in at least one eye were recruited for the study. Vision-related quality of life before and after 3 months of optional home monitoring using the app MacuFix were compared with the questionnaire National Eye Institute Visual Function Questionnaire-25. RESULTS: The 45 participants (18 women, 27 men) were, on average, 68 years old (SD ± 9.7) and had a mean best-corrected visual acuity of 0.6 (SD ± 0.25). Of 90 eyes, 18 revealed no maculopathy. Age-related macular degeneration existed in 52 eyes, epiretinal gliosis in 6, and macular hole in 1 eye. Macular edema was present in two eyes due to diabetes, four eyes due to uveitis, one eye after retinal venous thrombosis, four eyes because of an Irvine Gass syndrome, and two eyes caused by central serous thrombosis. After 3 months, 35 persons used the app for home monitoring, 8 persons applied the Amsler Grid, and 2 did not use any test. App users showed a highly significant improvement in vision-related quality of life in questions on mental health and concern about vision, and a significant improvement in performance, dejection, control, and embarrassing situations. CONCLUSION: The results suggest that MacuFix can possibly ameliorate partial aspects of vision-related quality of life.

Combined Treatment of Persistent Diabetic Macular Edema with Aflibercept and Triamcinolone Acetonide in Pseudophakic Eyes.

Background and Objectives: The main cause of the vision loss in diabetics is the development of diabetic macular edema, regardless of the stage of diabetic retinopathy. The paper aimed to examine whether the additional intravitreal application of triamcinolone acetonide to continuous anti-vascular endothelial growth factor therapy could improve therapeutic outcomes for pseudophakic eyes with persistent diabetic macular edema. Materials and Methods: twenty-four pseudophakic eyes with refractory diabetic macular edema, that had appeared despite three previously administered intravitreal injections of aflibercept, were divided into two groups (twelve eyes in each group). The first group continued to have aflibercept administered according to a fixed dosing regimen (once in two months). Triamcinolone acetonide 10 mg/0.1 mL (administered once per four months) was included for the second group, i.e., their treatment continued with a combination of aflibercept + triamcinolone acetonide. Results: The reduction in central macular thickness was higher in the eyes treated with combined therapy (aflibercept + triamcinolone acetonide) compared with the use of aflibercept alone during the entire 12-month follow-up period (3rd month p = 0.019; 6th month p = 0.023; 9th month p = 0.027; 12th month p = 0.031). As was evident from the p-values, the differences were statistically significant. No statistically significant difference was recorded for visual acuity: 3rd month p = 0.423; 6th month p = 0.392; 9th month p = 0.413; 12th month p = 0.418. Conclusions: Combined anti-vascular endothelial growth factor and steroid therapy leads to a better anatomical outcome of persistent diabetic macular edema in pseudophakic eyes, but does not lead to a more significant improvement in visual acuity than continuous anti-VEGF therapy alone.

Analysis of ganglion cell-inner plexiform layer thickness in retinal vein occlusion with resolved macular edema.

PURPOSE: To analyze the retinal ganglion cell-inner plexiform layer (GCIPL) changes in retinal vein occlusion (RVO) eyes with resolved macular edema using optical coherence tomography. METHODS: We compared the average and minimum GCIPL thickness in RVO eyes with fellow eyes and healthy controls including 40 unilateral RVO patients and 48 healthy subjects. The average GCIPL thickness in BRVO eyes was segmented into the affected and opposite area according to the site of lesion, comparing them with corresponding areas in fellow eyes. Furthermore, maximum central macular thickness (CMT), visual acuity (VA), and intravitreal injection times were recorded to investigate their relationship with the GCIPL thickness. RESULTS: Despite no significant difference in CMT (P = 0.96), the average (P = 0.02 and P < 0.001, respectively) and minimum (both P < 0.001) GCIPL thicknesses were decreased in RVO eyes with resolved macular edema after treatment in comparison to fellow eyes and healthy eyes. Maximum CMT thickness was negatively correlated with the minimum GCIPL thickness (r = - 0.47, P = 0.003). VA and average GCIPL thickness were associated (rs = - 0.49, P = 0.002). In a subgroup analysis that only included BRVO patients, the opposite area revealed no significant difference between two eyes (P = 0.91) although the affected area in BRVO eyes was decreased (P < 0.001). CONCLUSIONS: A decrease of GCIPL thickness in RVO was observed even after anatomic restoration and associated with VA prognosis. These GCIPL defects could be attributable to systemic risks and RVO itself, not anti-VEGF effects.

Statin use and the risk of progression to vision threatening diabetic retinopathy.

PURPOSE: This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). METHODS: Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. RESULTS: Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR = 1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR = 1.03, 95% CI: 0.99-1.07, p = 0.13), PDR (HR = 0.89, 95% CI: 0.79-1.02, p = 0.09), DME (HR = 0.94, 95% CI: 0.86-1.03, p = 0.21), VH (HR = 1.00, 95% CI: 0.86-1.16, p = 0.99), and TRD (HR = 1.11, 95% CI: 0.89-1.38, p = 0.36). CONCLUSION: Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

Screening of telangiectatic capillaries in chronic macular edema based on multimodal imaging: a study of 101 eyes. LyoMAC1 study.

PURPOSE: To estimate the prevalence of telangiectatic capillaries (TCs) in patients followed for chronic macular edema (CME) (diabetic ME [DME] and ME associated with retinal vein occlusion [RVO]). METHODS: Real-life, prospective, bi-centric cohort study including all consecutive patients followed for a clinically significant CME secondary to diabetic retinopathy or RVO. Inclusion criteria were patients treated with intravitreal injection for their ME for at least 12 months who had to undergo follow-up angiography. Multimodal imaging with color retinophotography, spectral-domain optical coherence tomography (SD-OCT), OCT angiography, and en face OCT was performed in all patients. RESULTS: A total of 101 eyes of 71 patients were included between November 2019 and June 2020. Of the 101 eyes analyzed, indocyanine green angiography found at least one TC in 67 eyes (66.3%). No significant differences were found between the groups with and without TC except for the distribution of DME and RVO (p < 0.008). In 83.6% of eyes with TCs, TCs contributed to the formation of the ME. SD-OCT sensitivity for TC detection was 94%. CONCLUSION: In our study, the estimated prevalence of TCs in CME (DME and ME associated with RVO) was 66.3%, i.e., two-thirds of patients. SD-OCT was an excellent screening examination with a sensitivity of 94%.

MACULAR BLOOD FLOW CHANGES IN BRANCH RETINAL VEIN OCCLUSION EXAMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VARIABLE INTERSCAN TIME ANALYSIS.

PURPOSE: To examine the relationship between changes in retinal blood flow and the recurrence of macular edema in eyes with branch retinal vein occlusion. METHODS: This observational study included 32 eyes in 32 patients (18 men and 14 women) with branch retinal vein occlusion who visited the Department of Ophthalmology at Kyoto University Hospital (February 2021-November 2021). At the time of inclusion in the study, each patient underwent optical coherence tomography angiography on a macular area measuring 4 × 4 mm 2 . For variable interscan time analysis, different interscan times were set at 7.6 (IST 7.6 ) and 20.6 ms (IST 20.6 ) for the optical coherence tomography angiography. The parafoveal vessel densities were measured sectorally at IST 7.6 and IST 20.6 , and their relationship with the longitudinal changes evident in the retinal thicknesses during the variable interscan time analysis examination and 2 months later was evaluated. RESULTS: The parafoveal vessel densities in the affected sector was significantly greater at IST 20.6 than at IST 7.6 ( P = 0.011). At 2 months after the variable interscan time analysis examination, 6 patients (19%) showed recurrence of macular edema involving the fovea. The difference in the parafoveal vessel densities (IST 20.6 - IST 7.6 ) in the affected sector was significantly associated with longitudinal retinal thickening in the corresponding parafovea ( P = 0.020) and fovea ( P = 0.014). CONCLUSION: In eyes with branch retinal vein occlusion, optical coherence tomography angiography variable interscan time analysis facilitated the detection of retinal blood flow changes that might be predictive for the recurrence of macular edema.

ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

PURPOSE: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes. METHODS: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls. RESULTS: A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P < 0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (<2.46 mg/dL) and aqueous glucose (<6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME. CONCLUSION: Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

Aggravation of retinal hard exudates after intravitreal anti-vascular endothelial growth factor therapy for cystoid macular edema and the risk factors: a retrospective study.

BACKGROUND/AIMS: To evaluate retinal hard exudates (HEs) progression in patients with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) or branch retinal vascular occlusion (BRVO) after intravitreal injections of ranibizumab (IVR) treatment and identify the risk factors for the deterioration of HEs. METHODS: This retrospective study enrolled 288 eyes with center-involving CME secondary to DR or BRVO from 288 patients (one eye per patient). All patients were treated with three loading doses of ranibizumab intravitreally at a monthly interval. The morphologic features of HEs were observed, and the HEs areas were quantified using a semi-automatic method at baseline, 1 month after the first dose of IVR and 1 month after the third dose of IVR therapy. HEs progression was defined as having a > =2-grade increase in the HEs severity scale. The best-corrected vision acuity (BCVA) and alterations in HEs areas were compared between DR and BRVO groups. And logistic regression analyses were used to identify the risk factors for HEs exacerbation. RESULTS: Morphological changes of retinal HEs occurred in all eyes after IVR therapy, although HEs area was not significantly changed in some eyes. DR group has a higher percentage of eyes with progressed HEs area than the BRVO groups (34.9% vs. 21.8%, P = 0.019) 1 month after the first dose of IVR. Both DR and BRVO groups had a decreased percentage of enlarged HEs 1 month after the third injection, but the DR group is still higher than the BRVO group (17.1% vs. 8.4%, P = 0.027). At baseline, there was no correlation between VA and HEs areas. After the first and third doses of IVR, there still was no consistent correlation between HEs severity and change in VA over time. Furthermore, CME with subretinal fluid (SRF) is associated with a higher risk of HEs progression (P = 0.001). Long CME duration and high serum low-density lipoprotein cholesterol (LDL-C) level were identified as risk factors for HEs progression following IVR treatment in both univariable and multivariable regression analyses (Odds ratio (OR) = 1.88, P = 0.012 and OR = 1.14, P = 0.021, respectively). CONCLUSIONS: Alterations in the area of retinal HEs are widely observed after IVR treatment for CME. The eyes with CME secondary to DR have a higher percentage of progressed HEs than the BRVO eyes. DME with SRF, extended duration of CME, and high LDL-C level are potential risk factors of deteriorated HEs after IVR treatment.