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This study aims to evaluate the macular and the optic nerve head thickness and vascular profiles in KC patients and compare them with two groups of healthy emmetrope and subjects with myopic-astigmatism. This cross-sectional study was conducted at Khatam-Al-Anbia Eye Hospital between 2022 and 2023. Subjects aged 18 to 40 were prone to be included in the study. The participants in this study were grouped into three categories: emmetrope (E), myopic-astigmatic (MA), and keratoconus (KC). All participants underwent a comprehensive ocular examination, as well as macular and optic nerve head (ONH) optical coherence tomography angiography (OCTA). In this study, 143 subjects, 50 cases in the KCN group, 46 cases in the E group, and 47 cases in the MA group, enrolled. There was no difference between the three groups regarding age (p = 0.123) and gender (p = 0.632). The superficial and deep capillary densities at the fovea, parafovea, and perifovea were significantly lower in KC patients than in the control groups (p < 0.01). The radial peripapillary capillary (RPC)- all vessels' density is significantly lower in the KC group (p < 0.001). Besides, the choroidal vascularity index (CVI) and choroidal luminal area (CLA) were considerably higher in KC patients (p < 0.001). The macular and ONH vascular profile in KC patients significantly differs from the vascular profile of healthy controls. Further scientific evidence regarding the systemic implications of keratoconus on the vascular system would be desirable to understand the connections between KC and vascular disease., (© 2024. The Author(s).)

This study aimed to investigate clinical characteristics and glaucoma progression in eyes with disc hemorrhage (DH) in the region of peripapillary atrophy (PPA) or DH in temporal region among glaucoma patients with myopia. One hundred ninety-six eyes of 196 glaucoma patients with myopia who were observed at least 4 years and had more than six visual field (VF) tests were included. Eyes with DHs located in the optic disc region at the superotemporal or inferotemporal locations were defined as typical DH. PPA area, disc ovality ratio, and disc torsion were measured. Length of γ-zone PPA, distance from disc edge to fovea, angle of scleral bending were measured using optical coherence tomography. Comparison of baseline characteristics between eyes with and without DH in PPA/DH in temporal region showed similar axial length (26.95 ± 1.60 mm; 26.82 ± 1.07 mm). γ-zone PPA was longer and angle of scleral bending was larger in eyes with DH in PPA/DH in temporal region (both p ≤ 0.001). Longer γ-zone PPA (β = 1.001; p = 0.018) and larger angle of scleral bending (β = 1.033; p = 0.008) were associated with presence of DH in PPA/DH in temporal region using logistic regression analysis. Eyes with DH in PPA/DH in temporal region had a smaller mean deviation slope of VF, a larger disc ovality ratio, a longer γ-zone PPA, and a larger PPA area when compared to those of eyes typical DH. VF progression was associated with absence of DH in PPA/DH in temporal region (p = 0.030) and larger angle of scleral bending (p = 0.019) using Cox proportional hazards model. DH in PPA/DH in temporal region was associated with stretching and deformation of sclera that may be result from myopic changes. Associated factors with VF progression was the degree of scleral deformation, not the presence of DH in PPA/DH in temporal region, showing that DH related to scleral deformation may possess clinical significance in glaucoma with myopia., (© 2024. The Author(s).)

Purpose: The interplay between myopia and glaucoma has gained attention, with escalating myopia demonstrating a significant association with increased POAG rates, particularly in patients with severe myopia. This systematic review aimed to comprehensively analyze the relationship between myopia and glaucoma, focusing on the structural and functional implications, risk factors, and assessment modalities. Optical coherence tomography (OCT) played a crucial role in this study, particularly in highly myopic populations., Methods: This study's rigor is underscored by using the PRISMA guidelines, which ensured a meticulous search strategy was employed across multiple databases from 2012 to 2024. The inclusion criteria included individuals aged 18 years or older with high myopia, defined as a spherical equivalent of less than -6.0 diopters or an axial length > 26.0 mm, diagnosed with chronic glaucoma. Various study designs were incorporated, including randomized controlled trials, prospective cohort studies, and observational studies. Quality assessment was performed using the Jadad Scale, and statistical analyses were performed to summarize the study characteristics and outcomes., Results: Of the 350 initial articles, 15 met the inclusion criteria. OCT assessments revealed structural changes such as thinning of the retinal nerve fiber layer preceding functional losses. Meta-analyses demonstrated a heightened risk of POAG with increasing myopia severity, showing a significant nonlinear relationship. This meta-analysis of six studies involving 3040 patients revealed a relationship between myopia and glaucoma (OR = 12.0, 95% CI 10.1-4.7, P < 0.00001)., Conclusion: This comprehensive analysis consolidates the evidence of the relationship between myopia and glaucoma, emphasizing the pivotal role of OCT and other imaging modalities in early detection and monitoring., (© 2024. The Author(s).)

Purpose: To evaluate the peripapillary/parapapillary choroidal vascular parameters in the keratoconus (KC) and to determine the relationship between topography parameters and the peripapillary/parapapillary choroidal vascular parameters., Method: Ninety eyes of ninety patients with different stages of KC and 29 eyes of twenty-nine patients without KC were enrolled in the study. Patients with KC were divided into three groups according to the Amsler-Krumeich classification scale. The choroidal vasculature was assessed by choroidal vascular parameters [such as parapapillary choroidal microvascular density (pCMVd) and peripapillary choroidal vascularity index (pCVI)]. These parameters were also evaluated for correlation with other parameters., Result: The retinal nerve fibre layer thickness (RNFLT) of the superior-temporal area and the pCVI were decreased in group 3 compared to the control group (superiror-temporal RNFLT: 122.27 ± 21.43 vs 139.90 ± 21.7, p = 0.01 and pCVI: 67.04 ± 4.14 vs 69.99 ± 4.38, p = 0.04). The superior-temporal RNFLT was decreased in group 3 compared to group 2 (122.27 ± 21.43 vs 141.83 ± 25.58, p = 0.006). There was a negative correlation between pCVI and average simulated keratometry (mean sim K), but this association was weak (r = - 0.29 p = 0.001)., Conclusion: This study demonstrated that there may be changes in pCVI in patients with grade 3 KC and that there may be an association between pCVI and mean sim K. As KC grade increases, pCVI may decrease. Furthermore, pCVI may have a negative correlation with mean sim K., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The optic nerve head (ONH) is well known to be the initial site of glaucomatous damage; however, the molecular mechanisms initiating this pathology are not fully understood. To further understand the initiating factors in glaucomatous damage we utilized a novel mouse model of glaucoma, B6.EDA+/+ mice, which constitutively express fibronectin containing the extra domain A (FN+EDA). FN+EDA is a known damage-associated molecular pattern (DAMP) that activates Toll-like receptor 4 and elicits a fibro-inflammatory response., Methods: Eyes from B6.EDA+/+ and C57BL/6J mice were evaluated for retinal ganglion cell (RGC) death, retinal nerve fiber layer (RNFL) thickness, and optic nerve (ON) damage at 12 months and 22 months of age. ONH sections were isolated using laser capture microdissection for subsequent RNA-sequencing and Gene Set Enrichment Analysis (GSEA). GSEA results were confirmed using immunohistochemical (IHC) staining., Results: B6.EDA+/+ mice exhibit significantly higher intraocular pressure, loss of RGCs, thinning of the RNFL, and progressive levels of ON damage at 12 months and 22 months of age compared to C57BL/6J controls. Protein expression of DAMPs FN+EDA and biglycan was significantly increased in B6.EDA+/+ mice compared to C57BL/6J controls. GSEA analysis identified significantly up- and downregulated gene groupings at both 12 months and 22 months of age, and IHC staining at 12 and 18 months of age demonstrated significant increases of IFNα, IFNβ, and pSTAT1 expression in B6.EDA+/+ mice compared to C57BL/6J controls., Conclusions: Our study characterizes glaucomatous changes to the retina, ON, and ONH over the course of 2 years and identifies novel molecular pathways associated with these pathophysiological changes. These data illustrate the effects of FN+EDA on the fibro-inflammatory response in the aging ONH in a novel mouse model of glaucoma.

Purpose: To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis., Methods: For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations., Results: Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356)., Conclusions: Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.

Importance: Although optic disc hemorrhage (DH) is widely recognized as a glaucoma risk factor, its clinical relevance in relation to proximity has not been investigated., Objective: To determine the association of the proximal location of DH with glaucoma progression., Design, Setting, and Participants: In this longitudinal observational cohort study, 146 eyes of 146 patients at Seoul National University Hospital who had had 1 or more DH with at least 5 years of follow-up and had at least 5 reliable visual field examinations were included. These data were analyzed January 10, 2010, through June 27, 2017., Exposures: Laminar, marginal, rim, and parapapillary subtypes of DH were identified based on their respective proximal locations. The laminar and marginal subtypes were classified into the cup-type group, while the rim and parapapillary subtypes were classified into the peripapillary-type group. Kaplan-Meier survival analysis was used to compare survival experiences and multivariate analysis with the Cox proportional hazard model to identify risk factors for glaucoma progression. Regression analyses, both univariate and multivariate, were used to discover significant indicators of mean deviation (MD) loss., Main Outcome and Measure: The primary outcome was glaucoma progression. Glaucoma progression was defined either as structural or functional deterioration., Results: For all of the eyes, the mean follow-up period was 10.9 (3.7) years (range, 5.1-17.8 years), the mean age at which DH was first detected was 55.1 (11.3) years (range, 21-77 years), and 94 participants were female (64.1%). Over the mean follow-up period of 10.9 years, glaucoma progression was detected in 94 eyes (61.4%) with an MD change of -0.48 dB per year. The cup-type group showed a faster rate of MD change relative to the peripapillary-type group (-0.56 vs -0.32 dB per year; difference = -0.24; 95% CI, -0.37 to -0.11; P = .01). The cup group showed a higher cumulative probability of progression of glaucoma (80.4%) relative to the peripapillary group (54.4%; difference = 26.0%; 95% CI, 11.4%-40.6%; P < .001) in a life table analysis. The presence of cup hemorrhage was associated with an increased risk of glaucoma progression (hazard ratio, 3.28; 95% CI, 2.12-5.07; P < .001) in the multivariate Cox proportional hazard model. Cup-type DH was associated to MD loss rate in regression analysis., Conclusions and Relevance: This study showed glaucoma progression was higher in cases of DH classified as the cup type. These findings support the potential utility of assessing the proximal location of DH to predict how glaucoma might progress.

Objectives: To compare rates of change in peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) parameters among different race-ethnicities from a large electronic health record database of subjects with or suspected of glaucoma., Methods: In this retrospective cohort study, rates of change were obtained using joint longitudinal linear mixed models for eyes with ≥3 visits and ≥1 year of follow-up, adjusting for age, sex, intraocular pressure, central corneal thickness, and baseline pRNFL and mGCIPL thickness. Best linear unbiased predictor estimates of various parameters were stratified by baseline glaucoma severity and analysed by racial-ethnic group., Results: A total of 21,472 spectral domain optical coherence tomography (OCT) pRNFL scans and 14,431 mGCIPL scans from 2002 eyes were evaluated. A total of 200 (15.6%) and 601 (46.8%) subjects identified as non-Hispanic Black (NHB) and Hispanic, respectively. NHB eyes exhibited faster rates of change in pRNFL among glaucoma suspect (global pRNFL -0.57 ± 0.55 µm/year vs. -0.37 ± 0.62 µm/year among Hispanics, p < 0.001), mild glaucoma (superior pRNFL quadrant -1.20 ± 1.06 µm/year vs. -0.75 ± 1.51 µm/year among non-Hispanic Whites (NHW), p = 0.043), and moderate glaucoma eyes (superior pRNFL quadrant -1.31 ± 1.49 µm/year vs. -0.52 ± 1.26 µm/year among Hispanics, p = 0.003). NHB eyes exhibited faster rates of mGCIPL loss corresponding to pRNFL rates. Global pRNFL and mGCIPL rates were strongly correlated (R 2  = 0.70)., Conclusions: Adjusted rates of pRNFL and mGCIPL loss significantly differed between racial-ethnic groups when stratified by glaucoma severity, with faster rates among NHB patients. These differences highlight key racial-ethnic disparities in adjusted rates of glaucoma OCT parameters., (© 2024. The Author(s).)

Purpose: To identify damage to the inner retinal layer and microvasculature in the peripapillary area according to the severity of diabetic retinopathy (DR)., Methods: Patients were divided into four groups: control (group 1), type 2 diabetes (T2DM) without DR (group 2), mild to moderate nonproliferative DR (NPDR) (group 3), and severe NPDR (group 4). The peripapillary retinal nerve fiber layer (pRNFL) thickness and peripapillary vessel density (VD) were compared. Linear regression analysis was performed to identify factors associated with the DR severity., Results: The average pRNFL thicknesses were 96.2 ± 7.1, 94.1 ± 9.6, 92.0 ± 9.9, and 90.3 ± 12.4 μm in groups 1, 2, 3, and 4, respectively (P = 0.003) (post hoc analyses: group 1 vs. group 2, P = 0.529; group 2 vs. group 3, P = 0.627; group 2 vs. group 4, P = 0.172; group 3 vs. group 4, P = 0.823). The VDs of the outer ring were 18.9 ± 0.6, 18.4 ± 0.8, 17.9 ± 1.1, and 17.3 ± 1.6 mm -1 in groups 1, 2, 3 and 4, respectively (P < 0.001) (all pairwise comparisons, P < 0.050). In multivariate analysis, the VD of the outer ring (B = - 0.35, P < 0.001) was significantly associated with the DR severity., Conclusions: The peripapillary microvasculature reflects retinal damage following DR progression better than the structure of the pRNFL., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Objective: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients., Methods: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements., Results: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD., Conclusion: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The purpose of this study is to compare choroidal thickness in juvenile open angle glaucoma (JOAG) and healthy controls using spectral domain optical coherence tomography (SD-OCT) and study its correlations., Methods: In this case-control study, 56 eyes of 28 JOAG patients and an equal number of controls were recruited. SD-OCT was used to measure the choroidal thickness (ChT), in the macular region at 5 locations: subfoveal, 1500 µm and 3000 µm nasal and temporal to the foveal center, and in the peripapillary region at 6 locations: up to 1500 µm, nasal and temporal to the disc, respectively. The ChT and its correlations with age, intraocular pressure, cup-to-disc ratio, central corneal thickness, mean deviation, and axial length were studied., Results: The average macular ChT in JOAG was 306.30 ± 56.49 µm vs. 277.12 ± 64.68 µm in controls. The average peripapillary ChT in JOAG was 197.79 ± 44.05 µm vs. 187.24 ± 38.89 µm in controls. The average total ChT (p = 0.042), the average macular ChT (p = 0.022), the subfoveal ChT (p = 0.022), the ChT 1500 µm (p < 0.001), and 3000 µm temporal to the fovea (p = 0.002) were significantly thicker in the JOAG group. In the JOAG group, the average macular ChT had a significant negative correlation with age, whereas axial length was positively correlated with the average peripapillary ChT., Conclusions: In this South Asian cohort of JOAG, the average total ChT, average macular ChT, subfoveal ChT, and ChT at 1500 µm, and 3000 µm temporal to the fovea were significantly thicker when compared to healthy controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteogenesis imperfecta (OI), a rare genetic connective tissue disorder, primarily arises from pathogenic variants affecting the production or structure of collagen type I. In addition to skeletal fragility, individuals with OI may face an increased risk of developing ophthalmic diseases. This association is believed to stem from the widespread presence of collagen type I throughout various parts of the eye. However, the precise consequences of abnormal collagen type I on different ocular tissues remain unknown. Of particular significance is the sclera, where collagen type I is abundant and crucial for maintaining the structural integrity of the eye. Recent research on healthy individuals has uncovered a unique organizational pattern of collagen fibers within the sclera, characterized by fiber arrangement in both circular and radial layers around the optic nerve head. While the precise function of this organizational pattern remains unclear, it is hypothesized to play a role in providing mechanical support to the optic nerve. The objective of this study is to investigate the impact of abnormal collagen type I on the sclera by assessing the fiber organization near the optic nerve head in individuals with OI and comparing them to healthy individuals. Collagen fiber orientation of the sclera was measured using polarization-sensitive optical coherence tomography (PS-OCT), an extension of the conventional OCT that is sensitive to materials that exhibit birefringence (axial changes in light refraction). Birefringence was quantified and used as imaging contrast to extract collagen fiber orientation as well as the thickness of the radially oriented scleral layer. Three individuals with OI, exhibiting different degrees of disease severity, were assessed and analyzed, along with seventeen healthy individuals. Mean values obtained from individuals with OI were descriptively compared to those of the healthy participant group. PS-OCT revealed a similar orientation pattern of scleral collagen fibers around the optic nerve head between OI individuals and healthy individuals. However, two OI participants exhibited reduced mean birefringence of the radially oriented scleral layer compared to the healthy participant group (OI participant 1 oculus dexter et sinister (ODS): 0.34°/μm, OI participant 2: ODS 0.26°/μm, OI participant 3: OD: 0.29°/μm, OS: 0.28°/μm, healthy participants: ODS 0.38 ± 0.05°/μm). The radially oriented scleral layer was thinner in all OI participants although within ±2 standard deviations of the mean observed in healthy individuals (OI participant 1 OD: 101 μm, OS 104 μm, OI participant 2: OD 97 μm, OS 98 μm, OI participant 3: OD: 94 μm, OS 120 μm, healthy participants: OD 122.8 ± 13.6 μm, OS 120.8 ± 15.1 μm). These findings imply abnormalities in collagen organization or composition, underscoring the necessity for additional research to comprehend the ocular phenotype in OI., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To develop deep learning (DL) algorithm to detect glaucoma progression using optical coherence tomography (OCT) images, in the absence of a reference standard., Design: Retrospective cohort study., Methods: Glaucomatous and healthy eyes with ≥5 reliable peripapillary OCT (Spectralis, Heidelberg Engineering) circle scans were included. A weakly supervised time-series learning model, called noise positive-unlabeled (Noise-PU) DL was developed to classify whether sequences of OCT B-scans showed glaucoma progression. The model used 2 learning schemes, one to identify age-related changes by differentiating test sequences from glaucoma vs healthy eyes, and the other to identify test-retest variability based on scrambled OCTs of glaucoma eyes. Both models' bases were convolutional neural networks (CNN) and long short-term memory (LSTM) networks which were combined to form a CNN-LSTM model. Model features were combined and jointly trained to identify glaucoma progression, accounting for age-related loss. The DL model's outcomes were compared with ordinary least squares (OLS) regression of retinal nerve fiber layer (RNFL) thickness over time, matched for specificity. The hit ratio was used as a proxy for sensitivity., Results: Eight thousand seven hundred eighty-five follow-up sequences of 5 consecutive OCT tests from 3253 eyes (1859 subjects) were included in the study. The mean follow-up time was 3.5 ± 1.6 years. In the test sample, the hit ratios of the DL and OLS methods were 0.498 (95%CI: 0.470-0.526) and 0.284 (95%CI: 0.258-0.309) respectively (P < .001) when the specificities were equalized to 95%., Conclusion: A DL model was able to identify longitudinal glaucomatous structural changes in OCT B-scans using a surrogate reference standard for progression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To characterize structural differences and assess the diagnostic accuracy of optic nerve head (ONH) and macula optical coherence tomography (OCT) parameters to detect glaucoma in eyes with and without high axial myopia., Design: Cross-sectional study., Methods: Three hundred sixty-eight glaucoma and 411 healthy eyes with no axial myopia, 393 glaucoma and 271 healthy eyes with mild axial myopia and 124 glaucoma and 85 healthy eyes with high axial myopia were included. Global and sectoral peripapillary retinal nerve fiber layer thickness (pRNFLT), Bruch's membrane opening minimum rim width (BMO-MRW), ganglion cell inner plexiform layer thickness (GCIPLT), and macula RNFLT (mRNFLT) were compared and the diagnostic accuracy for glaucoma detection was evaluated using the adjusted area under the receiver operating characteristic curve (AUC)., Results: Diagnostic accuracy for ONH and macula parameters to detect glaucoma was generally high and differed by myopia group. For ONH parameters the diagnostic accuracy was highest for global (AUC = 0.95) and inferotemporal (AUC = 0.91) pRNFLT for high myopes and global BMO-MRW for nonmyopes (AUC = 1.0) and mild myopes (AUC = 0.97). For macula parameters, the diagnostic accuracy was higher in high myopes with 6 of the 11 GCIPLT global/sectors having adjusted AUCs > 0.90 compared to nonhigh myopes with no AUCs > 0.90. In all myopia groups, mRNFLT had lower AUCs than GCIPLT., Conclusions: The diagnostic accuracy for pRNFL and GCIPL was high for high axial myopic eyes and shows promise for glaucoma detection in high myopes. Further analysis is needed to determine whether the high diagnostic accuracy can be confirmed in other populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy., Methods: A 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)]., Results: Visual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction., Conclusions: This case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted., (© 2024. The Author(s).)

Purpose: To evaluate how often tests of structure and function detect glaucoma progression at the same study visit. Tests include current glaucoma clinical tests and a new 3-dimensional (3D) optical coherence tomography (OCT) rim measurement., Design: Prospective cohort study., Methods: For 124 open-angle glaucoma patients at a single institution, one eye was randomly selected for each patient. Patients were included if they had open-angle glaucoma and if they had at least 4 yearly study visits. Study visits included a full dilated eye exam, disc photography (DP), Humphrey visual field (HVF 24-2) testing, 2D OCT retinal nerve fibre layer (RNFL) thickness measurements, and 3D OCT neuroretinal rim measurements (i.e., minimum distance band or MDB). For each test at each study visit, eyes were classified as progressors or non-progressors using event-based analysis. Agreement occurred if tests progressed in the same eye at the same study visit. Agreements between all compared tests were calculated as percentages of agreement., Results: The study included 124 open-angle glaucoma eyes, which had an average follow-up period of 66.9 ± 16.4 months. Structural tests (i.e., DP, global RNFL thickness, and global MDB rim thickness) progressed at the same visit as the functional test (i.e., HVF testing) in only 5.0% (3/60) to 16.0% (13/81) of eyes. Global MDB thickness and global RNFL thickness showed similar agreement with functional HVF testing (i.e., 16.0% [13/81] and 8.3% [7/84], respectively), and global MDB thickness showed better structure-function agreement with HVF testing than between DP and HVF testing (i.e., 5.0% [3/60], P = 0.04). For all paired comparisons between testing methods, eyes with moderate glaucoma showed similar or better agreement than eyes with mild or severe glaucoma., Conclusions: Clinical tests of structure and function do not usually progress at the same clinic visit. Most of the time, glaucoma progression is only detected by one or two tests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the capability of ChatGPT for forecasting the conversion from ocular hypertension (OHT) to glaucoma based on the Ocular Hypertension Treatment Study (OHTS)., Design: Retrospective case-control study., Participants: A total of 3008 eyes of 1504 subjects from the OHTS were included in the study., Methods: We selected demographic, clinical, ocular, optic nerve head, and visual field (VF) parameters 1 year before glaucoma development from the OHTS participants. Subsequently, we developed queries by converting tabular parameters into textual format based on both eyes of all participants. We used the ChatGPT application program interface (API) to automatically perform ChatGPT prompting for all subjects. We then investigated whether ChatGPT can accurately forecast conversion from OHT to glaucoma based on various objective metrics., Main Outcome Measure: Accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and weighted F1 score., Results: ChatGPT4.0 demonstrated an accuracy of 75%, AUC of 0.67, sensitivity of 56%, specificity of 78%, and weighted F1 score of 0.77 in predicting conversion to glaucoma 1 year before onset. ChatGPT3.5 provided an accuracy of 61%, AUC of 0.62, sensitivity of 64%, specificity of 59%, and weighted F1 score of 0.63 in predicting conversion to glaucoma 1 year before onset., Conclusions: The performance of ChatGPT4.0 in forecasting development of glaucoma 1 year before onset was reasonable. The overall performance of ChatGPT4.0 was consistently higher than ChatGPT3.5. Large language models (LLMs) hold great promise for augmenting glaucoma research capabilities and enhancing clinical care. Future efforts in creating ophthalmology-specific LLMs that leverage multimodal data in combination with active learning may lead to more useful integration with clinical practice and deserve further investigations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To report a previously undescribed finding of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in Stickler syndrome., Design: Noncomparative case series., Subjects: Twenty-two eyes with anomalous optic disc from 11 Stickler syndrome patients were identified and imaged., Methods: Peripapillary hyperreflective ovoid mass-like structures were graded using enhanced-depth imaging OCT (EDI-OCT) according to the consensus recommendations of the Optic Disc Drusen Studies Consortium. All EDI-OCT scans were obtained using the Heidelberg Spectralis (Heidelberg Engineering) with a dense horizontal raster (15 × 10°, 97 sections) centered on the optic nerve head and graded by 2 independent assessors. In case of disagreement, the image was graded by a third assessor. The presence of any coexisting optic disc drusen was also assessed using EDI-OCT and autofluorescence., Main Outcome Measures: The presence of PHOMS, clinical characteristics and genetic mutations., Results: A pilot sample of 22 eyes with phenotypic optic disc abnormalities from 11 Stickler syndrome patients were identified and imaged. Eight patients were female and 3 were male. The mean age was 31 years (13-58 years). Peripapillary hyperreflective ovoid mass-like structures were present in 91% (n = 20) of imaged eyes. Seventy percent (n = 14) were type 1 Stickler syndrome and 30% (n = 6) were type 2 Stickler syndrome. All eyes were myopic and the degree of myopia did not seem to affect whether or not PHOMS was present in this cohort. One eye with PHOMS had retinal detachment, and 77.3% (n = 17) of eyes had undergone 360 o prophylactic retinopexy. Thirty-two percent (n = 7) of eyes with PHOMS were present in patients with coexisting hearing loss and 22.7% (n = 5) had orofacial manifestation of Stickler syndrome in the form of a cleft palate. Seventy-seven percent (n = 15) of eyes with PHOMS were present in patients who reported joint laxity or symptoms of arthritis. No coexisting optic disc drusen were identified and raised intracranial pressure was also excluded after neurological investigation., Conclusions: These data suggest that PHOMS are a novel finding in Stickler syndrome patients and should be considered when evaluating the optic nerves of these patients., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to 1) investigate the association between papillomacular and papillofoveal bundle defects with 10-2 visual field (VF) sensitivity abnormalities, and 2) integrate the information from RNFL bundle defect and 24-2 VF central test locations to determine the likelihood of 10-2 VF sensitivity abnormalities., Design: Cross-sectional., Methods: A total of 841 eyes (144 healthy, 317 glaucoma suspect, and 380 glaucoma) of 442 participants were included. Eyes underwent 24-2, and 10-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular, and papillofoveal bundles was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association., Results: Papillomacular (92.1%) and papillofoveal (37.9%) RNFL bundle defects were prevalent in eyes with glaucoma. A 10-2 VF location that was projected onto a papillomacular or a papillofoveal RNFL bundle defect had a significantly increased likelihood of reduced sensitivity (ORs of 18.61 at PDP < 5%, and 20.17 at TDP < 5%, respectively, P < .001 for both). When predicting the likelihood of VF abnormality in a 10-2 test location, noticeably higher odds ratios were observed when overlapping with an RNFL bundle defect, compared to when an abnormal corresponding 24-2 central point was present., Conclusions: Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with glaucoma. When detected, they significantly increase the likelihood of abnormality in the corresponding central VF test locations assessed by the 10-2 test., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the difference in ganglion cell layer (GCL) thickness on optical coherence tomography (OCT) and waveform on pattern electroretinography (PERG) among glaucoma suspects and healthy controls., Methods: An analytical, cross-sectional study was done on 100 eyes of 50 subjects, equally divided in the glaucoma suspect and control group. Subjects with an asymmetrically increased vertical cup-to-disc ratio and without any perimetric change were taken as suspects, and subjects with normal findings were taken as controls. GCL thickness was evaluated on spectral domain OCT at 3 mm, 3.45 mm, and 6 mm centering the foveola, and P50, N95 wave forms were recorded according to the standard PERG protocol., Results: In this study, we observed that the average GCL thickness is significantly less in glaucoma suspects at 3.45 mm (p = 0.045) and at 6 mm (p < 0.001) circle zone. On PERG, P50 amplitude was significantly low in glaucoma suspects in comparison to controls (p = 0.007). There was significantly increased implicit time for both P50 and N95 in glaucoma suspects (p < 0.001). For N95 amplitude, a non-significant (p = 0.127) difference was observed among the two groups. At 3.45 mm, average GCL thickness showed a weak negative correlation with N95 implicit time (r = - 0.286, p = 0.044), a weak positive correlation with P50 amplitude (r = 0.349, p = 0.013), and at 6 mm, a weak positive correlation with P50 amplitude (r = 0.311, p = 0.028) in glaucoma suspects., Conclusions: Analysing GCL thickness can help in the structural assessment of preperimetric glaucoma. PERG can be used as a valuable tool for the detection of ganglion cell dysfunction, even before cell loss., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To present a clinically based approach to the differentiation of optic disc edema (DE) cases, commonly seen in neuro-ophthalmology., Methods: Consecutive patients who were considered to have unilateral or bilateral DE during examinations in the outpatient clinic and were referred to the neuro-ophthalmology department were included in this prospective study. The examination findings and differential diagnosis based on clinical signs and symptoms, and neuro-ophthalmological approach were evaluated in cases of DE., Results: Of the 119 cases with DE, 69 (58%) were women and 50 (42%) were men, where 89 (75%) had true optic DE (ODE) and 30 (25%) had pseudo optic DE  (PODE). Non-arteritic anterior ischemic optic neuropathy (n = 40), increased intracranial pressure (n = 32), and anterior optic neuritis (n = 17) were determined as the causes of true ODE, whereas small and crowded optic disc (n = 12), tilted optic disc (n = 8), myelinated nerve fibers (n = 5) and optic disc drusen (n = 5) as the causes of PODE. Patients with optic neuritis were the youngest (28.41 years) group of ODE cases while those with non-arteritic anterior ischemic optic neuropathy were the oldest (59.98 years). The first symptoms were sudden and painless loss of vision and/or visual field in cases with non-arteritic anterior ischemic optic neuropathy, pain increasing with eye movements and loss of vision and/or visual field in cases with optic neuritis, headache, and from time to time blurred vision in cases with increased intracranial pressure. Patients having vision loss due to amblyopia constituted (30%) of PODE cases while 70% were determined incidentally and they had the best visual acuity. The accuracy of the preliminary diagnosis based on neuro-ophthalmologic examination findings was 79% in all cases., Conclusion: Detailed history taking and neuro-ophthalmological examination are essential in the differential diagnosis of ODE and PODE., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate retinal nerve fiber layer thickness (RNFLT) and radial peripapillary capillaries (RPC) density in adults with different degrees of myopia using optical coherence tomography angiography (OCTA) and explore their relationship with ocular factors, such as axial length (AL) and disc area., Methods: A total of 188 subjects were included in this cross-sectional study. The eyes were divided into four groups according to AL. OCTA was used for the assessment of RNFLT, RPC density, and other optic disc measurements, such as disc area. One-way analysis of variance was performed to compare differences between four groups, and P value < 0.01 was considered significant., Results: The RNFLT was significantly thinner in high myopia (HM) group at inferior nasal (IN) quadrant (P = 0.004) than low myopia (LM) group, but thicker at temporal inferior (TI) quadrant (P = 0.006). The RPC density of nasal superior (NS) quadrant, nasal inferior (NI) quadrant, and inferior nasal (IN) quadrant significantly decreased as AL increasing. By simple linear regression analysis, the inside disc RPC (iRPC) density tended to be correlated significantly with AL (0.3997%/mm, P < 0.0001). Peripapillary RPC (pRPC) density was in significant correlation with AL (-0.2791%/mm, P = 0.0045), and peripapillary RNFLT (pRNFLT) was in significant correlation with disc area (0.2774%/mm 2 , P = 0.0001)., Conclusion: RNFLT and RPC density were closely associated with AL and disc area. They might be new indexes in assessing and detecting myopia development via OCTA., (© 2024. The Author(s).)

Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have the potential application in evaluating pathological structural change of the optic nerve. We aimed to evaluate the value of the OCT and OCTA parameters of the optic disk and macular in differentiating early chronic primary angle-closure glaucoma (CPACG) and early pituitary adenoma (PA) in case of mild visual field defects (the mean defect (MD) > 6 dB). The results showed that regarding OCTA parameters, CPACG patients had lower retinal blood flow density of most layers of the optic disk and macular than PA patients. Regarding OCT parameters, CPACG patients had thinner circumpapillary retinal nerve fiber layer (CP-RNFL) in all quadrants and average CP-RNFL, ganglion cell layer (GCL) and macular ganglion cell complex (GCC) in each quadrant of macular inner and outer rings, and inner plexus layer (IPL) of macular inner ring, superior-outer ring and temporal-outer ring than PA patients. The Z test indicated that OCTA parameters and OCT parameters had similar value in the diagnosis of disease. In conclusion, in the case of similar visual field damage, early CPACG patients have smaller blood flow density and thinner optic disk and macular than early PA. OCTA has similar performance to OCT in diagnosing CPACG and PA., (© 2024. The Author(s).)

Purpose: To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT)., Methods: A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups., Results: In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05)., Conclusion: The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Train an automatic retinal image analysis (ARIA) method to screen glaucomatous optic neuropathy (GON) on non-mydriatic retinal images labelled with the additional results of optical coherence tomography (OCT) and assess different models for the GON classification., Methods: All the images were obtained from the hospital for training and 10-fold cross-validation. Two methods were used to improve the classification performance: (1) using images labelled with the additional results of OCT as the reference standard and (2) generating models using retinal features from the entire images, the region of interest (ROI) of the optic disc, and the ROI of the macula, and the combination of all the features., Results: Overall, we collected 1338 images with paired OCT scans. In 10-fold validation, ARIA achieved sensitivities of 92.2 %, 92.7% and 85.7%, specificities of 88.8%, 86.7% and 80.2% and accuracies of 90.6%, 89.9% and 83.1% using the retinal features from the entire images, the ROI of the optic disc and the ROI of the macula, respectively. We found the model combining all the features has the best classification performance and obtained a sensitivity of 92.5%, a specificity of 92.1% and an accuracy of 92.4%, which is significantly different from other models (p<0.001)., Conclusion: We used two methods to improve the classification performance and found the best model to detect glaucoma on colour fundus retinal images. It can become a cost-effective and relatively more accurate glaucoma screening tool than conventional methods., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of αVβ3 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating αVβ3 integrin expression using cilengitide (a known potent αVβ3 and αVβ5 inhibitor) and β3 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of αVβ3 integrin, ECM genes (Col1A1, α-SMA, fibronectin, vitronectin), and proliferation rates. The effects of αVβ3 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned αVβ3 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: αVβ3 integrin gene and protein expression were enhanced ( p < 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced αVβ3 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in αVβ3, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of αVβ3 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, αVβ3 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma.

Purpose: This study aims to assess the disparities in choroidal thickness and optic disc parameters between individuals diagnosed with chronic gout and an age- and gender-matched control cohort., Methods: This cross-sectional study involved 30 gout patients receiving treatment at the Rheumatology clinic, alongside 30 healthy control individuals matched for age and gender. A comprehensive ophthalmological assessment, encompassing visual acuity measurement, intraocular pressure evaluation, slit-lamp biomicroscopy, and dilated fundus examination, was conducted for all participants. Peripapillary retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and subfoveal choroidal thickness (SFCT) were quantified utilizing Spectral Domain Optical Coherence Tomography., Results: The mean age within the study group was 54.53 ± 9.43 years, while the control group's mean age was 53.20 ± 10.36 years. In both the gout and control cohorts, there were 28 men and 2 women. No significant differences were observed in age and gender between the groups. Gout patients manifested thinner RNFL and GCC across all quadrants; however, statistically significant thinning was only evident in the nasal and inferior quadrants for RNFL. Despite a thinner SFCT observed in gout patients compared to controls, this discrepancy did not attain statistical significance., Conclusion: Chronic phase gout patients may display alterations in optic disc and macular parameters, alongside potential variations in choroidal thickness. Nevertheless, more controlled studies encompassing a larger participant pool are imperative to substantiate our findings., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma., Methods: Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The RNFL-T was analyzed globally and in quadrants using a semi-automated segmentation software. From a set of 100 eyes, 18 eyes with the thinnest global RNFL-T were selected as the study group and 18 eyes with RNFL-T values around the 50th percentile were used as controls. A previously described automated segmentation algorithm was used for LC microstructure analysis. Parameters included beam thickness, pore diameter and their ratio (beam-to-pore ratio [BPR]), pore area and shape parameters, beam and pore volume, and connective tissue volume fraction (CTVF; beam volume/total volume). The LC microstructure was analyzed globally and in the following volumetric sectors: quadrants, central and peripheral lamina, and three depth slabs (anterior, middle, and posterior)., Results: Although no significant difference was detected between groups for age, weight, or disc size, the study group had significantly thinner RNFL than the control group (P < 0.01). The study group had significantly smaller global and sectoral pore diameter and larger BPR compared with the control group. Across eyes, the global RNFL-T was associated positively with pore diameter globally. BPR and CTVF were significantly and negatively associated with the corresponding RNFL-T in the superior quadrant., Conclusions: Global and sectoral microstructural differences were detected when comparing thin and normal RNFL-T eyes. Whether these LC differences are the cause of RNFL damage or the result of remodeling of the LC requires further investigation., Translational Relevance: Our findings indicate structural alterations in the LC of NHP exhibiting natural thinning of the RNFL, a common characteristic of glaucomatous damage.

Purpose: This study presents a novel, three-dimensional method for measuring the tilt angle of the tilted optic disc (TOD) using spectral-domain optical coherence tomography (SD-OCT) and investigates the correlation between ocular-related parameters and TOD., Methods: We included the right eyes of 243 healthy young individuals, categorized by axial length. We measured the ovality index (OI) and dihedral angle (DA) using SD-OCT infrared ray fundus photographs and high-resolution cross-sectional images of the optic disc, respectively. The relationships between OI, DA, and ocular-related parameters were analyzed., Results: Eyes in the longer axial length group exhibited a lower OI and a higher DA, along with thinner nasal and inferonasal circumpapillary retinal nerve fiber layer (cpRNFL) and thicker temporal and superotemporal cpRNFL. There was a significant relationship between DA and cpRNFL thickness. The new method utilizing DA to measure the tilt angle of TOD demonstrated high repeatability., Conclusions: We propose a novel, three-dimensional, and quantitative method for evaluating the tilt degree of TOD. A higher degree of myopia indicated a greater tilt angle of the TOD, and a greater TOD suggested additional changes in cpRNFL thickness. These findings should be considered when interpreting increased susceptibility and early assessment of glaucoma in myopia., Translational Relevance: DA could serve as a superior indicator for describing TOD morphology during eyeball elongation and evaluating its impact on related parameters of the optic disc and peripapillary structures in the myopic population.

Purpose: Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs)., Methods: In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter., Results: Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05)., Conclusions: Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter., Translational Relevance: The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG)., Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA)., Results: MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model., Conclusions: Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.

Purpose: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients., Methods: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression., Results: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648., Conclusions: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma., Translational Relevance: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.

Purpose: This study aimed to evaluate both short-term and long-term changes in the lamina cribrosa curvature index (LCCI) following trabeculectomy and investigate the factors influencing these changes., Methods: In this retrospective, observational study, 40 eyes of 40 patients with glaucoma who underwent trabeculectomy and had a follow-up of at least 2 years were included. Optic nerve head area was scanned by using spectral-domain optical coherence tomography before surgery (Pre&#95;OP), within 6 months postoperatively (Post&#95;OP1), and at the last visit (Post&#95;OP2). LCCI values calculated from B-scan images at six different planes (0°, 30°, 60°, 90°, 120°, and 150°) and their mean values were compared. Univariate and multivariate linear regression analyses were used to identify the clinical factors associated with the amount of LCCI changes., Results: The mean follow-up time was 38.3 ± 16.8 months. At Post&#95;OP1, the mean LCCI decreased from 9.28 ± 2.58 to 7.91 ± 2.57 (P < 0.001), and the mean intraocular pressure decreased from 22.0 ± 7.6 mm Hg to 12.2 ± 3.8 mm Hg (P = 0.001). At Post&#95;OP2, the mean LCCI was maintained at 7.74 ± 2.49 (P = 0.56 when compared to Post&#95;OP1 and P < 0.001 when compared to Pre&#95;OP). The mean intraocular pressure was 12.6 ± 5.4 mm Hg (P = 0.67 when compared to Post&#95;OP1 and P < 0.001 when compared to Pre&#95;OP). Long-term LCCI changes were associated with baseline age (P = 0.04), spherical equivalent (P = 0.02), mean IOP during follow-ups (P = 0.02), and preoperative LCCI (P = 0.04)., Conclusions: Glaucomatous eyes undergoing trabeculectomy demonstrated reductions in the LCCI after a mean follow-up of over 3 years. Greater long-term LCCI reduction was associated with younger age, lower mean IOP during follow-up period, greater spherical equivalent refractive error, and preoperative LCCI.

Objective: We developed an optimized decision support system for retinal fundus image-based glaucoma screening., Methods: We combined computer vision algorithms with a convolutional network for fundus images and applied a faster region-based convolutional neural network (FRCNN) and artificial algae algorithm with support vector machine (AAASVM) classifiers. Optic boundary detection, optic cup, and optic disc segmentations were conducted using TernausNet. Glaucoma screening was performed using the optimized FRCNN. The Softmax layer was replaced with an SVM classifier layer and optimized with an AAA to attain enhanced accuracy., Results: Using three retinal fundus image datasets (G1020, digital retinal images vessel extraction, and high-resolution fundus), we obtained accuracy of 95.11%, 92.87%, and 93.7%, respectively. Framework accuracy was amplified with an adaptive gradient algorithm optimizer FRCNN (AFRCNN), which achieved average accuracy 94.06%, sensitivity 93.353%, and specificity 94.706%. AAASVM obtained average accuracy of 96.52%, which was 3% ahead of the FRCNN classifier. These classifiers had areas under the curve of 0.9, 0.85, and 0.87, respectively., Conclusion: Based on statistical Friedman evaluation, AAASVM was the best glaucoma screening model. Segmented and classified images can be directed to the health care system to assess patients' progress. This computer-aided decision support system will be useful for optometrists., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Competing Interests: The authors report no conflicts of interest.

Purpose: To analyse baseline imaging characteristics and factors affecting poor visual acuity in diabetic papillopathy., Methods: This was a retrospective, observational study conducted at a tertiary eye care centre in eyes with a diagnosis of diabetic papillopathy. Demographic data including age, gender, duration of diabetes, type of diabetes, HbA1c values and other systemic co-morbidities were recorded. Baseline best corrected visual acuity (BCVA), and various imaging characteristics were noted., Results: 37 eyes of 22 patients with diagnosis of diabetic papillopathy were included [mean age of 46.6 ± 13.5 years, five (22.7%) females and 17 (77.3%) males]. Bilateral involvement was seen in 15 (68.2%) patients. The mean baseline BCVA was 0.51 ± 0.49 logMAR (Snellen equivalent 20/60). Two eyes (5.4%) had features of concurrent mild NPDR, 9 eyes (24.3%) had moderate NPDR, 10 eyes (27.03%) had severe NPDR while 16 (43.2%) other had PDR. All eyes had optic disc edema while 4 had disc pallor at presentation. Telangiectatic vessels/ neovascularisation of disc was present in 17 eyes (45.9%) detected either clinically or on optical coherence tomography (OCT) angiography. 11 (29.7%) eyes had a peripapillary cuff of subretinal fluid accompanying the disc edema. Sixteen eyes (43.2%) had centre involving macular edema seen on OCT. In eyes with a macular edema, the mean central macular thickness was 407.4 ± 71.42 microns at baseline. On assessing the baseline factors that contribute to the final visual acuity, presenting visual acuity was the only variable found to be statistically significant., Conclusion: Although described to have good visual outcome, eyes presenting with poor visual acuity tend to have worse vision on follow up. This may aid in prognosticating and guiding management plan., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes., Methods: A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures)., Results: A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm 3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm 3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05)., Conclusion: There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health., (© 2024 The Author(s). Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Prcis: Initial presentation of glaucoma at a major eye clinic mostly features advanced disease with a high proportion of blindness. This is likely a microcosm of a nationwide issue requiring concerted strategies to detect glaucoma early., Purpose: To characterize the severity stage of new glaucoma patients in Congolese attending a university eye clinic., Methods: New glaucoma patients (n=118) were labeled as early or late presenters based on visual field sensitivity in the worse eye., Results: Mean age was 58.9±15.7 years, 51.7% were males. Overall, the worse eye had advanced, whereas the better eye had moderate glaucoma, with an asymmetry of -7.4 dB ( P <0.001). Blindness was present in 30.5% of worse and 5.1% of better eyes. Seventy-two patients (61.0%) were late presenters. Visual acuity was lower ( P <0.001), intraocular pressure (IOP) higher ( P =0.02), cup-to-disc ratio larger ( P =0.011), and retinal nerve fiber layer thinner ( P =0.001) in late presenters' worse than better eye. The worse and better eyes of late presenters had advanced glaucoma, with a -9.6 dB interocular asymmetry ( P <0.001); 40.3% and 8.3% were blind, respectively. In early presenters, the worse and better eyes had moderate and early disease, respectively; the asymmetry was -3.2 dB ( P <0.001), and 15.2% were blind. Overall, 58.5% and 65.3% presented with advanced disease in the worse eye based on visual field and cup-to-disc ratio criteria of the Canadian Ophthalmological Society staging scale, respectively., Conclusions: Most new glaucoma patients had bilateral advanced but asymmetric disease. These findings call for the establishment of community-based measures for early detection of glaucoma and a referral network system connecting community healthcare to tertiary eye clinics., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Purpose: To analyze radial peripapillary capillaris (RPC) and intra-papillary capillaris (IPC) using optical coherence tomography angiography (OCTA) in acute retinal necrosis (ARN) with good outcome., Methods: RPC and IPC were analyzed by OCTA in patients diagnosed with ARN and treated with pharmacotherapy alone without surgery at the Tokyo Medical University Hospital., Results: A total of 13 patients were studied. Ophthalmoscopic examination showed no abnormality in the optic disc in 12 of the 13 patients. However, OCTA findings of the affected eye compared with the unaffected fellow eye revealed morphological abnormalities in RPC in nine cases (69%) and decrease in capillary network in RPC or IPC in eight cases (62%)., Conclusion: In ARN, RPC and IPC were impaired even in eyes that were healed with medical treatment only without requiring surgical intervention and had no abnormal findings on ophthalmoscopic examination. This result suggests the presence of some degrees of optic neuropathy even in mild cases with good visual prognosis.

Purpose: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning., Design: Retrospective, longitudinal, observational study., Participants: Ninety-five patients with unilateral NTG and 61 healthy controls., Methods: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis., Main Outcome Measures: The rate of progressive RNFL thinning and the associated factors., Results: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007)., Conclusions: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to analyze the thicknesses of the retinal sublayer and peripapillary retinal nerve fiber layer (pRNFL) in patients with juvenile systemic lupus erythematosus (JSLE) without lupus retinopathy., Methods: Thirty-six patients with JSLE (36 eyes) and 30 control subjects (30 eyes) were included retrospectively. Demographic data, disease duration, and clinical manifestations were recorded. Optical coherence tomography was used to examine the macula and optic disc. The thicknesses of the retina, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), and pRNFL were measured. The correlation between the thickness of retina and disease duration, erythrocyte sedimentation rate (ESR) were investigated., Results: The retinal thicknesses of I3 and T3 were thinner in the JSLE group than in the control group (P = 0.019, P = 0.043, respectively). The thicknesses of the I3 and S6 sectors of the GCL decreased significantly (P = 0.013, and P = 0.022, respectively). The thickness of the S6 sector of the IPL was reduced in the JSLE group compared with the control group (P = 0.047). The JSLE group showed significant decrease in the thickness of the central sector of the ONL (P = 0.034). No statistically significant differences in INL, OPL, RPE, and pRNFL thicknesses were found. The retinal thicknesses of I3 (r = -0.386, P = 0.020) and T3 (r = -0.384, P = 0.021) presented negative associations with ESR, but had no significant correlations with disease duration., Conclusions: Retinal thinning was observed in patients with JSLE without lupus retinopathy, and this change was more pronounced in the inner layer. Key Points • Retinal thinning occurs in JSLE patients without lupus retinopathy. • Changes in retinal thicknesses are related to the ESR., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: To investigate the predictive capabilities of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thinning to detect visual field (VF) progression in normal-tension glaucoma patients with an initial parafoveal scotoma (IPFS) or nasal step (INS)., Design: Retrospective cohort study., Methods: A total of 185 early-stage glaucoma eyes, followed for 10 years, were retrospectively stratified into IPFS and INS groups. Progressive pRNFL and mGCIPL thinning were assessed using spectral-domain optical coherence tomography and VF progression using both event- or trend-based analysis. Kaplan-Meier survival analysis compared VF survival in each VF phenotype with or without progressive pRNFL and mGCIPL thinning. Cox proportional regression analysis identified VF progression factors., Results: VF progression was detected in 42 IPFS (n = 86) and 47 INS (n = 99) eyes. Among VF progressors, pRNFL thinning was significantly faster in INS group compared to IPFS group (P < .01), while mGCIPL thinning was similar (P = .16). At 5 years, eyes with progressive mGCIPL thinning showed significantly lower VF survival in both VF phenotypes (all P < .05). Progressive pRNFL thinning showed significantly lower VF survival only in INS eyes (P = .015). Cox multivariate regression revealed that mGCIPL thinning predicted subsequent VF progression in IPFS eyes, while mGCIPL and pRNFL thinning had significant associations with VF progression in INS eyes., Conclusions: mGCIPL outperforms pRNFL at early follow-up in detecting VF progression in IPFS eyes but not INS eyes. Appropriate selection of structural parameters (mGCIPL vs. pRNFL) maximizes early VF progression detection according to initial VF defect location., (Copyright © 2024 Elsevier Inc. All rights reserved.)