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.

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.

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.

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.

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.

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.

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.

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.

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.

Literature- and Experience-Based Consensus for Acute Post-operative Endophthalmitis and Endogenous Endophthalmitis in Taiwan.

Clinical practices on acute post-operative and endogenous endophthalmitis (EnE) are highly variable among clinicians due to a lack of up-to-date, high-quality evidential support. An expert consensus is thus much needed. A panel consisting of ten retinal specialists in Taiwan was organized. They evaluated relevant literature and developed key questions regarding acute post-operative and EnE that are cardinal for practice but yet to have conclusive evidence. The panel then attempted to reach consensus on all the key questions accordingly. There were eight key questions proposed and their respective consensus statements were summarized as follows: Gram staining and culture are still the standard procedures for the diagnosis of endophthalmitis. Vitrectomy is recommended to be performed earlier than the timing proposed by the Endophthalmitis Vitrectomy Study (EVS). Routine intracameral antibiotic injection for post-cataract surgery endophthalmitis prophylaxis is not recommended because of potential compounding error hazards and a lack of support from high-quality studies. Routine fundus examination is recommended for all patients with pyogenic liver abscess. In EnE, vitrectomy is recommended if diffused and dense vitritis is present, or if the disease progresses. These consensus statements may work as handy guidance or reference for clinical practices of acute post-operative and EnE.

Association between non-steroidal anti-inflammatory drug use and development of age-related macular degeneration-A 10-year retrospective cohort study.

PURPOSE: To analyze the associations between development of age-related macular degeneration (AMD) and regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs). METHODS: We retrospectively recruited individuals who received ≥28-day prescriptions of aspirin or NA-NSAIDs exclusively between 2008 and 2017 in one tertiary center as regular users. Non-regular users were free from regular use of any anti-inflammatory drugs and were matched to regular users in terms of age, sex, and visit date at a ratio of 1-4:1. The aspirin cohort included 36,771 regular users and 110,808 matched non-regular users, while the NA-NSAID cohort included 59,569 regular users and 179,732 matched non-regular users. Stratified multivariate Cox regression analyses with adjustment for systemic confounding factors were performed for the development of AMD and neovascular AMD. RESULTS: In the aspirin cohort, the adjusted hazard ratios of aspirin use for AMD in the whole cohort, individuals without cardiovascular diseases (CVDs), and those with CVDs were 0.664, 0.618, and 0.702, respectively (P < 0.0001 for all), while those of aspirin use for neovascular AMD were 0.486, 0.313, and 0.584 (P < 0.05 for all), respectively. In the NA-NSAID cohort, regular use of NA-NSAIDs was associated with a decreased risk of AMD (hazard ratio = 0.823, P < 0.0001) and neovascular AMD (hazard ratio = 0.720, P = 0.040) only in people without arthritis. CONCLUSIONS: Regular use of aspirin or NA-NSAIDs had protective effects on AMD and neovascular AMD. The effect of aspirin was observed in all patients, while the effect of NA-NSAIDs was observed only in people without arthritis.

A Direct Current-Sensing VCO-Based 2nd-Order Continuous-Time Sigma-Delta Modulator for Biosensor Readout Applications.

A second-order voltage-controlled oscillator (VCO)-based continuous-time sigma-delta modulator (CTSDM) for current-sensing readout applications is proposed. Current signals from the sensor can directly be quantized by the proposed VCO-based CTSDM, which does not require any extra trans-impedance amplifiers. With the proportional-integral (PI) structure and a VCO phase integrator, the capability of second-order noise shaping is available to reduce the in-band quantization noise. The PI structure can be simply realized by a resistor in series with the integrating capacitor, which can reduce the architecture complexity and maintain the stability of the system. The current-steering digital-to-analog converter with tail and sink current sources is used on the feedback path for the subtraction of the current-type input signal. All the components of the circuit are scaling friendly and applicable to current-sensing readout applications in the Internet of Things (IoT). The proposed VCO-based CTSDM implemented in a 0.18-µm standard CMOS process has a measured signal-to-noise and distortion ratio (SNDR) of 74.6 dB at 10 kHz bandwidth and consumes 44.8 µw only under a supply voltage of 1.2 V, which can achieve a Figure-of-Merit (FoM) of 160.76 dB.

Guidelines and treatment patterns for primary rhegmatogenous retinal detachments: Expert consensus and survey in Taiwan Retina Society.

Rhegmatogenous retinal detachment (RRD) is a significant cause of vision loss and requires appropriate surgical intervention. There are several approaches available, including observation, laser demarcation, pneumatic retinopexy, scleral buckling, and pars plana vitrectomy, which are chosen based on patient condition, surgeon experience, and national health insurance policies. Despite the various options, there is still no consensus on the optimal intervention. To address this, the Taiwan Retina Society assembled an expert committee with 11 experienced retina specialists to review the current evidence and develop a guideline with seven recommendations for managing RRD patients. Additionally, a survey was conducted with six questions to assess treatment patterns in Taiwan, which included input from the expert committee and an open poll at the 2023 Congress of the Taiwan Retina Society. This report provides a comprehensive summary of the current knowledge and expert consensus on the treatment of RRD, discussing the characteristics of current approaches and providing an overview of current treatment patterns in Taiwan. These findings aim to provide ophthalmologists with the best possible treatment for RRD.

Vitreomacular traction in diabetic retinopathy.

PURPOSE: Vitreomacular traction (VMT) has unique presentations in eyes with diabetic retinopathy (DR). This study aimed to investigate the characteristics and clinical course of VMT in DR. STUDY DESIGN: A retrospective case series. METHODS: Thirty eyes from 30 patients with DR and concurrent VMT were retrospectively enrolled. Baseline and final best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) characteristics were reported. Linear regression models were used to analyze the correlating factors for visual outcome. RESULTS: Of the 30 eyes, a thickened posterior hyaloid membrane was noted in all cases and multi-layered traction from different directions in 14 eyes (46.7%). Twenty-one eyes (70%) had tractional macular retinoschisis, seven (23.3%) had foveal detachment, five (16.7%) had a lamellar macular hole, and three (10%) had a full-thickness macular hole, including two with macular hole retinal detachment. Three eyes had spontaneous release of the VMT within 3 months of observation. For the remaining 27 eyes receiving operations, the VMT, full-thickness macular hole, and serous foveal detachment all resolved postoperatively with residual macular schisis in 6 eyes (22.2%) only. None of the baseline OCT characteristics were associated with postoperative BCVA (P > .05). CONCLUSIONS: VMT in DR had a thickened posterior hyaloid, and many of them had multi-layered traction and/or concurrent macular retinoschisis. Lamellar macular hole, full-thickness macular hole, or concurrent retinal detachment may also occur. Spontaneous resolution of VMT rarely occurred, and those who underwent operation for VMT had improved vision and macular structures with resolution of the macular hole and retinal detachment.

Two-Year Real-World Results for Aflibercept Using the Treat-and-Extend Regimen in Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

INTRODUCTION: To evaluate the real-world efficacy of aflibercept using the treat-and-extend (TnE) regimen in treating neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), and to analyze biomarkers using optical coherence tomography (OCT) to predict treatment outcomes. METHODS: Patients diagnosed with nAMD or PCV who received an intravitreal injection of aflibercept following the TnE regimen for ≥ 2 years were retrospectively reviewed. Data on best-corrected visual acuity (BCVA), number of injections, treatment interval, and OCT biomarkers, including central macular thickness, presence of subretinal fluid (SRF), and serous pigmented epithelial detachment, were collected at baseline and at 3, 6, 12, 18, and 24 months after the first injection. RESULTS: A total of 43 patients were enrolled in this study, 24 of whom were diagnosed with nAMD and 19 with PCV. The BCVA in logMAR (mean ± standard deviation) improved from 0.75 ± 0.41 (baseline) to 0.60 ± 0.41 (P = 0.002) at 3 months after treatment initiation, and further improved to 0.66 ± 0.46 at 24 months (P = 0.137). The number of injections (mean ± standard deviation) within the 2-year treatment course was 10.95 ± 3.65. At month 24 of the TnE regimen, the treatment interval was extended to ≥ 16 weeks in 60.5% of all cases and to 78.9% of the PCV cases. After three loading injections, persistent subretinal fluid and intraretinal fluid were predictive of more frequent injections (P = 0.026) and poorer visual outcomes (P = 0.050), respectively. CONCLUSION: Aflibercept combined with a TnE regimen was effective in treating nAMD and PCV in a real-world setting. The treatment interval could be extended to ≥ 16 weeks in 60.5% of the cases after a 2-year treatment regimen. OCT can be used to predict the treatment course and visual outcomes.

BROAD VITREOMACULAR ATTACHMENT-INDUCED MACULAR HOLE: Structural Changes and Surgical Outcome.

PURPOSE: This study aims to describe the structural changes and surgical outcomes of full-thickness macular holes (FTMHs) induced by vitreomacular traction with broad vitreomacular attachment (VMA). METHODS: A retrospective analysis of idiopathic FTMHs from October 2010 to May 2022 was conducted. Patients with FTMHs and no retinal detachment (RD) induced by broad VMA (the study group) were compared with a control group consisting of typical FTMHs with focal VMA. RESULTS: Thirty-one eyes had broad VMA-associated FTMH, among which seven eyes (22%) were with concurrent RD. Among the total of 24 cases without RD, 8 (33%) exhibited schisis. The incidence of lamellar holes associated epithelial proliferation and multiple membrane traction was significantly higher in the study group. One hundred percent FTMH closure was observed postoperatively in both groups. Although the postoperative visual acuity was not significantly different, the study group showed a greater ellipsoid zone disruption length. CONCLUSION: Broad VMA-induced FTMHs are characterized by diverse macular structural changes, including schisis and macular detachment. These FTMHs are associated with a higher incidence of lamellar holes associated epithelial proliferation and multiple membrane traction. Surgical outcomes for FTMHs induced by broad VMA are similar to those induced by typical focal VMA, with both groups demonstrating a 100% hole-closure rate.

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.

Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study.

Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p < 0.001), and the medians [25th, 75th percentile] of bilateral-eye summed K-grading were 8 [7, 8] and 5 [4, 6] in ASD and TDC, respectively (p < 0.001). A significantly higher K-grading in the ASD participants' eyes was still observed after adjusting for the within-subject inter-eye correlation (p < 0.001). Youden Index showed the optimal cutoffs to differentiate ASD from TDC by bilateral-eye summed K-grading and single-eye K-grading was >6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.

Long-Term Change in Renal Function After Intravitreal Anti-VEGF Treatment for Diabetic Macular Edema: A 2-Year Retrospective Cohort Study.

INTRODUCTION: To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). METHODS: A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2 years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. RESULTS: After intravitreal anti-VEGF treatment, eGFR showed a mean decline of -10.4 ± 23.2% and -16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120 mL/min and 15-30 mL/min groups had the greatest decline (-32.0 ± 20.6% and -37.4 ± 30.9%, respectively) while those in the 61-90 mL/min group had the smallest decline (-4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). CONCLUSIONS: In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.