Surgical outcomes and intraoperative parameters of 3D visualization system versus conventional microscopes for macular surgery in highly myopic eyes, a prospective randomized clinical trial.

PURPOSE: To investigate the surgical outcomes and intraoperative parameters of 3D visualization system for macular diseases in highly myopic eyes. METHODS: In this single-center, prospective, randomized, comparative interventional study, 40 highly myopic eyes (axial length > 26mm) were randomly assigned to either a 3D visualization system or a conventional microscope (CM) group. Surgical outcomes and intraoperative parameters, including the number of indocyanine green (ICG) injections, surgical time, and epiretinal membrane (ERM)/ internal limiting membrane (ILM) peeling time, were compared. RESULTS: The 3D group required significantly fewer ICG injections (1.3 ± 0.5 vs. 2.3 ± 0.7, p < 0.001), had shorter ERM/ILM peeling times (522.8 ± 258.0 vs. 751.8 ± 320.2 sec, p < 0.05), and experienced fewer intraoperative retinal hemorrhages (0 vs. 7 cases, p < 0.05) compared to the CM group. Anatomical and functional outcomes were comparable between the two groups. CONCLUSION: The 3D system exhibited a lower number of ICG injections, shorter ERM/ILM peeling times and a reduced incidence of intraoperative retinal hemorrhages, suggesting the 3D visualization system may offer advantages for macular surgery in highly myopic eyes.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Gender- and age-related differences in foveal pit morphology.

AIMS: To measure the foveal pit morphology parameters and evaluate their correlations with age and sex. SETTINGS AND DESIGN: A retrospective cross-sectional matched comparison study in a tertiary center. METHODS AND MATERIALS: Forty men and 40 age-matched women who had normal macular structures and foveal contours were enrolled. Foveal pit parameters including top width, base width, nasal width, temporal width, minimal thickness, nasal thickness, temporal thickness, nasal height, temporal height, nasal slope, and temporal slope were measured on horizontal B-scan macular optical coherence tomography and compared between men and women. STATISTICAL ANALYSIS USED: Paired t-tests and Pearson's correlation analysis. RESULTS: The average patient age was 51.4 ± 17.5 (21-84) years. Women had a wider base width (313.1 ± 68.0 µm vs 266.8 ± 70.9 µm, P = 0.006), wider temporal width (1043.1 ± 245.6 µm vs 968.9 ± 261.0 µm, P = 0.006), thinner nasal thickness (345.6 ± 36.2 µm vs 359.7 ± 35.8 µm, P = 0.048), and flatter temporal slope (11.60 ± 2.52° vs 12.98 ± 2.68°, P = 0.016) than men. With age, the base width (r = 0.35, P = 0.025) and temporal width (r = 0.54, P = 0.0003) tended to be wider and the temporal slope was flatter (r = -0.45, P = 0.003) in women but not men. The minimal thickness tended to be thinner in the elderly group (r = 0.038, P = 0.015). CONCLUSIONS: Women had a significantly wider base width, wider temporal width, thinner nasal thickness, and flatter temporal slope of the foveal pit than age-matched men. The base width and temporal width were wider and the temporal slope was flatter with age in women but not men.

Choroidal Changes in Patients with Diabetic Retinopathy: A Retrospective Study.

This study aimed to investigate the characteristic choroidal changes in patients with diabetic retinopathy and identify factors affecting choroidal thickness (CTh), choroidal vascular index (CVI), and choriocapillaris flow. We retrospectively analyzed 79 eyes of 48 patients with diabetes between August 2021 and February 2022. We collected laboratory data, including HbA1c, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels. Optical coherence tomography images of the foveal avascular zone, retinal vascular density, choroidal flow, retinal thickness, CTh, and CVI were analyzed. Possible determining factors affecting CTh, CVI, and choriocapillaris flow were analyzed using nonparametric multivariate analysis. LDL (p < 0.001) positively correlated with CTh, whereas CVI (p = 0.007) was negatively correlated with CTh in diabetic patients with diabetes. We also identified a negative correlation between choriocapillaris flow and deep parafoveal retinal vessel density in patients with low-grade diabetic retinopathy (DR), which diminished in those with more advanced DR. Our study provides further information on the changes in choroidal structure and blood flow in patients with diabetes.

Convolutional Neural Network-Based Prediction of Axial Length Using Color Fundus Photography.

Purpose: To develop convolutional neural network (CNN)-based models for predicting the axial length (AL) using color fundus photography (CFP) and explore associated clinical and structural characteristics. Methods: This study enrolled 1105 fundus images from 467 participants with ALs ranging from 19.91 to 32.59 mm, obtained at National Taiwan University Hospital between 2020 and 2021. The AL measurements obtained from a scanning laser interferometer served as the gold standard. The accuracy of prediction was compared among CNN-based models with different inputs, including CFP, age, and/or sex. Heatmaps were interpreted by integrated gradients. Results: Using age, sex, and CFP as input, the mean ± standard deviation absolute error (MAE) for AL prediction by the model was 0.771 ± 0.128 mm, outperforming models that used age and sex alone (1.263 ± 0.115 mm; P < 0.001) and CFP alone (0.831 ± 0.216 mm; P = 0.016) by 39.0% and 7.31%, respectively. The removal of relatively poor-quality CFPs resulted in a slight MAE reduction to 0.759 ± 0.120 mm without statistical significance (P = 0.24). The inclusion of age and CFP improved prediction accuracy by 5.59% (P = 0.043), while adding sex had no significant improvement (P = 0.41). The optic disc and temporal peripapillary area were highlighted as the focused areas on the heatmaps. Conclusions: Deep learning-based prediction of AL using CFP was fairly accurate and enhanced by age inclusion. The optic disc and temporal peripapillary area may contain crucial structural information for AL prediction in CFP. Translational Relevance: This study might aid AL assessments and the understanding of the morphologic characteristics of the fundus related to AL.

Fluid Biomarkers in Optical Coherence Tomography for Visual Outcome in Polypoidal Choroidal Vasculopathy.

Purpose: To investigate the associations between fluid accumulation at different levels in the retina and visual outcome in polypoidal choroidal vasculopathy (PCV). Design: A retrospective observational study. Institutional setting. Study Population: A total of 91 eyes from 91 patients of PCV were included, with 65 receiving intravitreal aflibercept monotherapy and 26 receiving combined intravitreal ranibizumab and photodynamic therapy (PDT). Observation Procedures: Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination results were recorded at baseline and 3, 6, and 12 months after treatment. Main Outcome Measures: The correlations between visual outcomes and fluid biomarkers including intraretinal fluid (IRF), subretinal fluid (SRF), serous pigment epithelium detachment (PED), and hemorrhage at fovea were analyzed. Results: No differences in treatment outcomes were noted between patients receiving aflibercept and those receiving combined ranibizumab and PDT. IRF and hemorrhage at baseline predicted poorer vision at 3, 6, and 12 months. The presence of IRF was associated with poorer vision at 6 months and 12 months (p < 0.05 for all). The presence of SRF or PED was not associated with better vision at any time point. No differences in the correlations between fluid markers and visual outcomes were noted between thin and thick subfoveal choroidal thickness groups. Conclusions: For PCV, IRF and hemorrhage at baseline served as surrogates for poor visual prognosis after treatment, and IRF was a biomarker for poor vision during the treatment course. No fluid markers predicted good visual prognosis or had a positive impact on vision at any time point.

Differential artery-vein analysis improves the OCTA classification of diabetic retinopathy.

This study investigates the impact of differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) on machine learning classification of diabetic retinopathy (DR). Leveraging deep learning for arterial-venous area (AVA) segmentation, six quantitative features, including perfusion intensity density (PID), blood vessel density (BVD), vessel area flux (VAF), blood vessel caliber (BVC), blood vessel tortuosity (BVT), and vessel perimeter index (VPI) features, were derived from OCTA images before and after AV differentiation. A support vector machine (SVM) classifier was utilized to assess both binary and multiclass classifications of control, diabetic patients without DR (NoDR), mild DR, moderate DR, and severe DR groups. Initially, one-region features, i.e., quantitative features extracted from the entire OCTA, were evaluated for DR classification. Differential AV analysis improved classification accuracies from 78.86% to 87.63% and from 79.62% to 85.66% for binary and multiclass classifications, respectively. Additionally, three-region features derived from the entire image, parafovea, and perifovea, were incorporated for DR classification. Differential AV analysis further enhanced classification accuracies from 84.43% to 93.33% and from 83.40% to 89.25% for binary and multiclass classifications, respectively. These findings highlight the potential of differential AV analysis in augmenting disease diagnosis and treatment assessment using OCTA.

Differential Capillary and Large Vessel Analysis Improves OCTA Classification of Diabetic Retinopathy.

Purpose: This study aimed to investigate the impact of distinctive capillary-large vessel (CLV) analysis in optical coherence tomography angiography (OCTA) on the classification performance of diabetic retinopathy (DR). Methods: This multicenter study analyzed 212 OCTA images from 146 patients, including 28 controls, 36 diabetic patients without DR (NoDR), 31 with mild non-proliferative DR (NPDR), 28 with moderate NPDR, and 23 with severe NPDR. Quantitative features were derived from the whole image as well as the parafovea and perifovea regions. A support vector machine classifier was employed for DR classification. The accuracy and area under the receiver operating characteristic curve were used to evaluate the classification performance, utilizing features derived from the whole image and specific regions, both before and after CLV analysis. Results: Differential CLV analysis significantly improved OCTA classification of DR. In binary classifications, accuracy improved by 11.81%, rising from 77.45% to 89.26%, when utilizing whole image features. For multiclass classifications, accuracy increased by 7.55%, from 78.68% to 86.23%. Incorporating features from the whole image, parafovea, and perifovea further improved binary classification accuracy from 83.07% to 93.80%, and multiclass accuracy from 82.64% to 87.92%. Conclusions: This study demonstrated that feature changes in capillaries are more sensitive during DR progression, and CLV analysis can significantly improve DR classification performance by extracting features that are specific to large vessels and capillaries in OCTA. Incorporating regional features further improves DR classification accuracy. Differential CLV analysis promises better disease screening, diagnosis, and treatment outcome assessment.

Vitreous substitutes and tamponades - A review of types, applications, and future directions.

Vitreous substitutes and tamponades occupy the vitreous cavity following vitrectomy in the management of various conditions such as retinal detachment, macular hole, and diabetic retinopathy. Such replacements can be for the short term (gases such as sulfur hexafluoride (SF6) and perfluoropropane (C3F8) or long term (such as silicone oils). Certain substitutes such as perfluorocarbon liquids are used only transiently during surgery as "a third hand" or rarely till a few days post surgery. Hydrogels and hyaluronan derivatives are among the newer vitreous substitutes that are showing promise for the future, albeit still under investigation. still being investigated for use as vitreous substitutes. These materials have properties similar to the natural vitreous and may offer advantages such as improved biocompatibility and biodegradability. Although vitreous substitutes are valuable tools in treating vitreoretinal conditions, they carry risks and potential complications such as cataract formation, glaucoma, and inflammation. The current communication extensively reviews the available literature on vitreous tamponades. It details the composition and properties of various vitreous substitutes and tamponades available for the clinician, highlighting the techniques of usage, indications, and limitations.

Clinical characteristics and optical coherence tomography of concomitant macular hole and rhgematogenous retinal detachment.

To study the clinical characteristics of macula off rhegmatogenous retinal detachment (RRD) with peripheral causative breaks and concomitant macular hole (RRD+MH). This is a bi-center study. Consecutive eyes of macula off RRD with or without macular hole (MH) were collected. Eyes in these two groups were compared with best corrected visual acuity in logarithm of minimal angle of resolution (logMAR BCVA), the presence of choroidal detachment (CD), proliferative vitreoretinopathy (PVR) and the extent of RRD. In the group of RRD+MH, regression analysis was used to evaluate the correlation of clinical factors and final logMar BCVA. In addition, optical coherence tomography was performed both pre-and post-operatively if possible. There were 40 eyes in the RRD+MH group and 80 eyes in the control group. Eyes with RRD+MH had worse initial and final logMar BCVA (p < 0.001), higher incidence of CD (p < 0.001), PVR and extensive RRD at baseline (p < 0.001). Among the eyes with RRD+MH, final BCVA was correlated with initial BCVA (p < 0.001, CI 0.637 to 0.837), recurrent RRD (p = 0.004, CI - 0.661 to - 0.126), duration of RRD (p = 0.021, CI - 0.576 to - 0.048) and presence of PVR (p = 0.001, CI - 0.131 to - 0.035). The hole closure rate at final follow up is 87.5%.11 of the 17 eyes had preoperative optical coherence tomography (OCT) obtained had ellipsoid zone lining the bottom of MH. CD, PVR and extensive RRD were more commonly observed in RRD+MH. The morphology of MH may suggest the pathogenesis of MH in RRD+MH include mechanism different from that of idiopathic MH.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. RESULTS: This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. CONCLUSION: Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Relationship between genotype, phenotype, and refractive status in patients of inherited retinal degeneration.

BACKGROUND: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients. SUBJECTS: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population. RESULTS: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations. CONCLUSIONS: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.