PRECIS:Artificial intelligence-derived macular thinning patterns were associated with central visual field progression in glaucoma and outperformed global thickness metrics in predicting progression across disease severities. PURPOSE:To provide spatial patterns of ganglion cell complex thickness and assess their associations with central visual field progression in glaucoma. METHODS:Macular patterns from the ganglion cell complex were determined using an artificial intelligence algorithm termed archetypal analysis (AA). The diagnostic accuracy of spatial patterns for detecting 10-2 central visual field progression in eyes with at least five 10-2 visual field tests was calculated and compared with the mean global ganglion cell complex thickness. Eyes with progression on either of 2 trend-based methods (significant MD slope less than -0.5 dB/y or clustered pointwise linear regression) were classified as "progressors." RESULTS:A total of 4031 macular scans of 1093 eyes (611 patients) were included, with a mean (SD) age of 67.8 (12.7) years. Eleven distinct spatial patterns were identified. While the macular vulnerable zone was preferentially affected in 4 patterns, most of the less vulnerable zones were preserved. The AA models at baseline achieved AUROC [0.73 (95% CI, 0.62-0.84)] and outperformed global ganglion cell complex thickness [0.55 (95% CI, 0.46-0.61), P =0.01] for predicting central VF progression in eyes with early disease at baseline. The AA models AUROC [0.70 (95% CI, 0.59-0.80)] also outperformed ganglion cell complex thickness [0.55 (95% CI, 0.48-0.60), P =0.02] for predicting central VF progression across all severities. CONCLUSIONS:Using unsupervised artificial intelligence, characteristic patterns of macular thinning were identified and associated with progression in the central visual field. Spatial macular pattern analysis may enhance individualized care and improve risk stratification for those at risk of central VF damage.

PURPOSE:To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes. DESIGN:Retrospective, propensity score-matched cohort study. PARTICIPANTS:Adults with diabetes who initiated a GLP-1RA or another noninsulin antidiabetic agent. In Epic Cosmos, 2 797 686 GLP-1RA users were matched 1:1 to 2 797 686 active comparators. METHODS:We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-VEGF treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models. MAIN OUTCOME MEASURES:Incidence of any AMD and nAMD. RESULTS:In the matched Epic Cosmos cohort (total N = 5 595 372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% confidence interval {CI}, 0.182%-0.192%] vs. 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs. 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs. 6.540% [95% CI, 6.017%-7.108%]); all P < 0.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs. 0.065%), 5 years (0.280% vs. 0.340%), and 10 years (1.874% vs. 2.393%); all P < 0.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P < 0.001) and was not associated with an increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P = 0.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups. CONCLUSIONS:Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To evaluate outcomes of phacoemulsification plus Tanito microhook (TMH) trabeculotomy and assess differences by incision extent, glaucoma severity, and baseline medications classes. Retrospective cohort of 880 open-angle glaucoma eyes (119 exfoliation glaucoma, 761 primary open-angle glaucoma) undergoing phaco-TMH. Success was defined using the American Academy of Ophthalmology (AAO) minimally invasive glaucoma surgery (MIGS) endpoint for cataract-combined procedures ( ≥ 1 medication reduction without intraocular pressure [IOP] increase, or ≥20

PURPOSE:To evaluate associations between parapapillary choriocapillaris microvascular dropout (MvD) and optical coherence tomography (OCT)-detected deep optic nerve head (ONH) structures in glaucomatous eyes with and without myopia. DESIGN:Cross-sectional study from clinical trial data. METHODS:394 eyes from 262 patients with primary open-angle glaucoma (POAG) and glaucoma suspects were stratified into three groups of no myopia (axial length (AL)<24 mm; n = 144), mild myopia (24 mm ≤ AL < 26 mm; n = 174), and high myopia (AL ≥ 26 mm; n = 76). Spectralis ONH OCT radial B-scans were acquired relative to the Foveal-Bruch's Membrane Opening (FoBMO) axis. Bruch's Membrane Opening (BMO) and anterior scleral canal opening (ASCO) were manually segmented, and their size and shape were calculated. BMO/ASCO offset magnitude, neural canal obliqueness, and neural canal minimum cross-sectional area (NCMCA) were measured. The presence, area, and angular circumference of juxtapapillary MvD were evaluated using OCT-angiography en face choroidal images and B-scans. RESULTS:The MvD area (95% CI) was significantly greater in highly myopic eyes (0.38 [0.30, 0.47] mm²), compared with mild myopia (0.33 [0.27, 0.39] mm²) and no myopia (0.21 [0.14, 0.27] mm²) (P = .002). The MvD angular circumference was also significantly larger in mild myopia (75.4 [64.0, 86.9]°), followed by high myopia (74.5 [58.0, 90.9]°) and no myopia (52.6[39.9, 65.3]°) (P = .017). The highly myopic group showed a significantly larger BMO area, NCMCA ovality index, BMO/ASCO offset magnitude, and neural canal obliqueness, along with smaller NCMCA, compared to the other groups (all P < .01). In multivariable analysis, NCMCA, NCMCA ovality index, BMO/ASCO offset magnitude, and neural canal obliqueness were significantly associated with both MvD presence (all P < .05) and MvD area (all P < .05). Additionally, NCMCA ovality index and neural canal obliqueness were associated with MvD angular circumference (P = .01 and P = .004, respectively). CONCLUSIONS:In myopic POAG eyes, the presence and area of MvD were associated with NCMCA, NCMCA ovality index, BMO/ASCO offset magnitude, and neural canal obliqueness, whereas MvD angular circumference was associated only with NCMCA ovality index and neural canal obliqueness. Evaluating choriocapillaris MvD alongside deep ONH structural alterations may provide clinical insights into the pathogenesis of glaucoma in myopia.

PURPOSE:To investigate whether baseline microvasculature dropout (MvD) is associated with subsequent structural and functional changes in preperimetric glaucoma. DESIGN:Subgroup analysis of prospective cohort study data. METHODS:This study included 93 eyes from 70 participants with a glaucomatous optic disk appearance but no repeatable visual field defects, who were followed with optical coherence tomography, optical coherence tomography angiography, and visual field (VF) over a mean of 4.9 years. Circumpapillary retinal nerve fiber layer thickness and circumpapillary capillary density (cpCD) were assessed. Eyes were grouped based on the presence or absence of MvD at baseline. Mixed-effects models were used to identify factors associated with structural and functional progression. RESULTS:Mean age was 67.7 (95% CI, 65.4-70.0) years. Among the 93 eyes, those with baseline MvD (32 eyes) showed faster loss of cpCD (-0.88 [95% CI, -1.08 to -0.67] %/year) compared to eyes without MvD (-0.23 [95% CI, -0.42 to -0.04] %/year). In multivariable models, the presence of MvD was independently associated with faster cpCD loss (-0.63 [95% CI, -0.95 to -0.32] %/year, P < .001). In contrast, it was not associated with circumpapillary retinal nerve fiber layer loss (0.03 [95% CI, -0.33 to 0.38] µm/year, P = .886). Moreover, PPG eyes that had MvD at baseline developed VF loss more frequently than those without MvD. (62.5% vs 26.2%, P < .001). CONCLUSIONS:Baseline MvD in PPG is associated with both faster vessel density loss and subsequent VF loss, and higher rates of developing glaucomatous visual field damage. Assessment of MvD can be used to estimate risk and guide the frequency of follow-up in patients with PPG.

PURPOSE:To evaluate the predictive ability of baseline widefield OCT-based risk scores for the development of perimetric glaucoma in glaucoma suspect eyes. DESIGN:A prospective cohort study. PARTICIPANTS:Two hundred fifty-seven glaucoma suspect eyes with normal visual fields (VFs) at baseline from 180 patients. METHODS:Baseline macular and peripapillary inner retinal layer thickness measurements were obtained using swept-source OCT widefield scans (12 mm × 9 mm) that included both the optic disc and macula. Three OCT-based risk scores were calculated for each eye using measurement segments and grids from the OCT reports. Glaucoma progression was defined as the development of repeatable abnormal VF results. Marginal Cox proportional hazards model was applied to evaluate baseline predictors, including risk scores and individual OCT thickness metrics, with adjustment for confounding factors. MAIN OUTCOME MEASURES:Time-dependent receiver operating characteristic (ROC) curves and decision curve analysis evaluated model performance and clinical utility. RESULTS:The mean follow-up time for glaucoma suspects was 2.8 years. During this period, 80 suspect eyes progressed to perimetric glaucoma. Circumpapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell complex thickness, ganglion cell-inner plexiform layer thickness, mean deviation, and the 3 OCT-based risk scores were predictors of progression in univariable models, showing significant hazard ratios, whereas only the OCT-based risk scores remained statistically significant in multivariable models. Each 10-point increase in OCT-based risk scores across the 3 models corresponded to a 1.15-fold to 1.21-fold increase in risk. The risk scores demonstrated higher area under ROCs, compared to individual OCT parameters, across all time points. Decision curve analysis showed that individual OCT parameters offered no greater net benefit than treating all patients regardless of risk, whereas the Fukai risk scores consistently yielded higher net benefit. CONCLUSIONS:Baseline OCT-based risk scores from a single wide scan, incorporating both peripapillary RNFL and macular thickness measurements, are associated with the subsequent development of perimetric glaucoma development in glaucoma suspect eyes, offering valuable insights for risk stratification in a single integrated metric and may aid in early intervention and clinical management in glaucoma suspects. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Importance:Early detection of glaucoma progression is essential. Optical coherence tomography angiography (OCTA) vascular metrics may identify progression before structural OCT or visual field changes. Objective:To evaluate timing and agreement of event-based progression detection among OCT, OCTA, and visual field testing in glaucoma. Design, Setting, and Participants:This was a retrospective cohort study designed in August 2024. Included were patients from the Diagnostic Innovations in Glaucoma Study (DIGS) who underwent OCT and OCTA imaging and visual field testing from January 2015 to April 2023. Inclusion required 2 or more years of follow-up and 4 or more visits with each modality. Exposures:OCT, OCTA, and visual field testing. Main Outcomes and Measures:OCT and OCTA progression were defined as change exceeding test-retest variability thresholds at 2 consecutive visits; visual field progression was assessed with guided progression analysis. Progression rates and lead times were compared. Results:A total of 180 eyes (111 perimetric, 69 preperimetric) from 116 patients (mean [SD] age, 67.6 [13.7] years; 61 female [52.6%]) were included in this analysis. During mean (SD) follow-up of 5.1 (1.4) years, 107 eyes (59.4%) had progression detected by at least 1 modality as follows: 58 eyes (32.2%) by OCTA vessel density, 45 eyes (25.0%) by OCT circumpapillary retinal nerve fiber layer (CPRNFL) thickness, and 59 eyes (32.8%) by visual field testing. Among eyes with progression, the earliest detection occurred with OCTA vessel density in 40 eyes (37.4%), OCT CPRNFL thickness in 32 eyes (29.9%), and visual field testing in 26 eyes (24.3%). Among 45 stable eyes, specificity was 75.6% for OCT CPRNFL thickness and 68.9% for OCTA vessel density. Mean lead times were 2.3 years for OCTA vessel density before visual field progression (95% CI, 1.3-3.2 years), 1.5 years for OCT CPRNFL thickness before visual field progression (95% CI, 0.6-2.4 years), and 0.2 years for OCT CPRNFL thickness vs OCTA vessel density (95% CI, -0.6 to 0.9 years). Conclusions and Relevance:Results of this cohort study suggest that OCTA vessel density may detect event-based glaucoma progression earlier than OCT or visual field testing at the cost of a slight decrease in specificity compared with OCT. These findings support a potential complementary role for OCTA in glaucoma monitoring, although the cost-benefit of additional testing requires further evaluation.

BACKGROUND/AIMS:To apply retinal nerve fibre layer (RNFL) optical texture analysis (ROTA) to investigate (1) the patterns of RNFL bundle defects, and (2) the frequency of papillomacular and papillofoveal bundle involvement across early, moderate and advanced glaucoma. METHODS:All eyes underwent 24-2 visual field (VF) testing and optical coherence tomography (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. 24-2 VF stimulus projections were mapped onto the corresponding topographic areas of ROTA images. Multilevel logistic regression analysis was applied to evaluate the structure-function association. RESULTS:Papillomacular bundle defects were highly prevalent in glaucoma, increasing from 87.7% in early to 95.35% in moderate and 100% in advanced glaucoma. Papillofoveal bundle defects were also common, increasing from 29.7% in early to 36.05% in moderate and 60.98% in advanced glaucoma. Central four 24-2 test locations that projected onto the trajectories of papillomacular or papillofoveal RNFL bundle defects demonstrated significantly increased likelihood of VF sensitivity abnormality (ORs of 22.42 at PDP<5% and 20.26 at TDP<5%, respectively, p<0.001 for both). CONCLUSION:ROTA uncovers a wide spectrum of RNFL bundle defects spanning the entire glaucoma continuum. It also provides visualisation of the preserved RNFL bundles in advanced glaucoma. Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with early, moderate and advanced glaucoma, and, when detected, they significantly increase the likelihood of abnormality in the corresponding central 24-2 test locations.

PRCIS:This matched-cohort study compares the original and Shoji editions of the Tanito microhook trabeculotomy (TMH), a reusable, FDA-cleared MIGS device, when combined with cataract surgery. Both designs demonstrated similar 2-year surgical success and safety profiles. While the Shoji edition incorporates ergonomic refinements, no significant differences in clinical outcomes were observed, supporting the continued use of either version in routine glaucoma care. PURPOSE:To compare the clinical efficacy and safety of the Shoji edition of the Tanito microhook trabeculotomy (TMH Shoji edition) with the original version, both performed in combination with phacoemulsification and intraocular lens implantation, in patients with open angle glaucoma. METHODS:A retrospective matched-cohort study including 518 eyes (original: 259, Shoji: 259) was conducted. Groups were matched on age, sex, glaucoma type, baseline IOP, visual field mean deviation, and number of medications. The primary outcome was surgical success over 2 years, followed by the American Academy of Ophthalmology's recommended criteria for MIGS combined with cataract surgery: ≥1 medication reduction without IOP increase, or ≥20% IOP reduction to ≤21 mm Hg without additional surgery, loss of light perception vision, or hypotony. IOP, number of medications, and postoperative complications were also recorded. Statistical analyses included Fisher exact tests and Kaplan-Meier survival with log-rank testing. RESULTS:At 12 months, surgical success was achieved in 46.4% of the original group and 50.1% of the Shoji group; at 24 months, the rates were 32.0% and 44.2%, respectively. Kaplan-Meier estimates showed no significant difference between groups (log-rank P = 1.000). Both groups achieved reductions from baseline in mean IOP and number of glaucoma medications at all time points. Postoperative complications were infrequent and comparable between groups. CONCLUSIONS:Both versions of TMH trabeculotomy combined with cataract surgery demonstrated acceptable mid-term surgical success and safety profiles. The Shoji edition, designed to improve access and usability, may offer advantages in certain surgical settings.

PURPOSE:To investigate the relationship of structural progression, β-zone parapapillary atrophy (PPA) progression, and microvascular dropout (MvD) in glaucoma suspect eyes. DESIGN:Retrospective cohort study. METHODS:Eyes were included if optic disc photographs were available at least 5 years before optical coherence tomography angiography imaging. During follow-up, structural progression and β-zone PPA progression were recorded. Structural progression was graded using stereophotographs; eyes were classified as progressing if new or enlarged retinal nerve fiber layer defects or neuroretinal rim thinning were detected. β-zone PPA was quantified (area, radial width, angular extent), with progression defined as a ≥20% increase in any parameter. The presence of MvD at the last visit was evaluated using en-face choroidal vessel density maps. Multivariable logistic regression was used to assess the association between MvD and structural progression, adjusting for covariates and β-zone PPA progression. Margins analysis was performed to estimate predicted probabilities of structural progression by MvD status and β-zone PPA progression. RESULTS:A total of 180 eyes from 134 glaucoma suspect patients were included, of which 58 eyes (32.2%) had MvD. The mean follow-up duration for fundus photographs was 19.0 (95% CI, 17.9-20.1) years. The presence of MvD and also β-zone PPA progression were significantly associated with structural progression (15.8 [95% CI, 5.6-44.6], P < .001; 3.8 [95% CI, 1.2-11.7], P = .022, respectively). Margin plots indicated that eyes exhibiting both MvD and β-zone PPA progression had the highest estimated probability of structural progression (0.75). CONCLUSIONS:In glaucoma suspect eyes, the presence of both MvD and β-zone PPA progression were independently associated with structural optic disc progression. These structural changes were observed in glaucoma suspect eyes that remained clinically stable and did not convert to perimetric glaucoma during the period of observation in this study. Recognition of these changes may enhance more timely management to prevent glaucomatous vision loss.

Purpose To evaluate the association between menopausal hormone therapy (MHT) and strabismus outcomes in menopausal women. Design Retrospective clinical cohort study. Participants Female patients in Epic Cosmos with a first menopause diagnosis between ages 44 and 60 years from January 1, 2010, to October 31, 2025 were included. MHT exposure was defined as estrogen or combined estrogen-progestin use for ≥90 days after menopause diagnosis; patients with prior MHT use were excluded. Methods Demographic, clinical, and MHT data were extracted. Associations between MHT and strabismus diagnosis, surgery, and reoperation were assessed using time-varying Cox proportional hazards models adjusted for age and year of menopause diagnosis, race, and ethnicity. Main Outcome Measures Strabismus diagnosis, strabismus surgery, and reoperation, excluding congenital, mechanical, neurological, paralytic, and traumatic causes. Results Among 2,154,255 menopausal patients, 197,576 (9.2%) received MHT and 1,956,679 (90.8%) did not. Mean age at menopause diagnosis was 54.9 (4.1) years, and 67.3% identified as White. MHT use was associated with higher hazards of strabismus diagnosis (HR 1.11, 95% CI 1.02-1.22; P = 0.015) and strabismus surgery (HR 1.76, 95% CI 1.38-2.25; P < 0.001), but not reoperation. Conclusion MHT was associated with increased risk of strabismus diagnosis and surgery in menopausal women, suggesting a potential relationship between MHT and ocular alignment outcomes.

PURPOSE:To evaluate the association between obstructive sleep apnea (OSA), recorded positive airway pressure (PAP) device use, and incident glaucoma in a large multicenter electronic health record (EHR) cohort. DESIGN:A retrospective cohort study. PARTICIPANTS:Adults in Epic Cosmos were included if they had an index encounter for OSA evaluation between January 1, 2010, and October 31, 2025, no prior glaucoma diagnosis, and at least 180 days of follow-up. Patients were categorized as sleep-tested controls without OSA, OSA without a PAP device record, or OSA with a PAP device record within 180 days. METHODS:Follow-up began at a 180-day landmark after the index OSA evaluation and continued until incident glaucoma, death, or last encounter. Positive airway pressure exposure was defined using a code-based EHR proxy for PAP therapy within 180 days. Cox proportional hazards models adjusted for baseline covariates were used to estimate associations with incident glaucoma. Incidence rates were calculated per 1000 person-years from the landmark to censoring. MAIN OUTCOME MEASURES:Incident glaucoma defined as at least 2 glaucoma diagnosis codes within 365 days, with the first qualifying diagnosis occurring after the 180-day landmark. RESULTS:The cohort included 12 516 607 patients with a mean (standard deviation) age of 60.4 (11.6) years; 43.7% were women. Over a mean (standard deviation) follow-up of 5.2 (3.7) years, 153 083 incident glaucoma events occurred. Crude incidence rates per 1000 person-years were 1.74 in controls, 2.38 in OSA without a PAP device record, and 3.39 in OSA with a PAP device record. Compared with sleep-tested controls, adjusted hazards of incident glaucoma were higher in OSA without a PAP device record (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.22-1.32) and OSA with a PAP device record (HR, 2.10; 95% CI, 1.80-2.45). At 10 years, cumulative incidence was 1.58%, 2.30%, and 3.86%, respectively. CONCLUSIONS:Obstructive sleep apnea was associated with a higher risk of incident glaucoma compared with sleep-tested controls. The observed risk gradient does not establish whether PAP itself increases or decreases glaucoma risk relative to untreated OSA because residual confounding by OSA severity and treatment indication is likely. Ophthalmic monitoring may be warranted in patients undergoing clinical evaluation or treatment for OSA. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PURPOSE:To determine the impact of progression of central visual field (VF) and global VF on vision-related quality of life (VRQOL). DESIGN:Retrospective cohort study. METHODS:This study included 364 eyes of 235 primary open-angle glaucoma participants who had at least five 24-2 VF tests over a minimum of 2-year follow-up. The slopes of global mean deviation (MD) and central mean total deviation (MTD10) (12 test points within the central 10° of 24-2) were calculated. Analyses were conducted using different slope thresholds to define VF-based progression, and mean composite National Eye Institute Visual Function Questionnaire Rasch-calibrated scores associated with these progression thresholds were quantified using linear mixed-effects models. RESULTS:The baseline 24-2 VF MD of all participants was -5.6 (95% CI -6.4, -4.9) decibels (dB). At baseline, eyes with MTD10 progression had significantly worse 24-2 VF MD compared to those without MTD10 progression. When fast progression was defined as MTD10 slope <-0.50 dB/y, fast progressors had a mean baseline 24-2 MD of -9.71 dB (95% CI -11.89, -7.53) compared to -5.24 dB (95% CI -6.02, -4.46) in slow progressors (P < .001). Eyes exhibiting MTD10 progression consistently displayed worse mean composite VRQOL scores across various thresholds compared to global MD. Notably, a similar level of VRQOL impairment was observed at a lower threshold for MTD10 compared to MD, consistent across all glaucoma severity groups. In the overall cohort, eyes progressing at a rate of -0.5 dB/y or faster for MTD10 had a mean composite VRQOL score comparable to those progressing at -1.0 dB/y or faster for global MD. CONCLUSIONS:Central VF change had a greater impact on VRQOL compared to global VF change. Conventional assessments based on global MD may underestimate the effect of central VF changes. Refining progression detection strategies to include central VF is necessary to better reflect changes in patient-centered outcomes like VRQOL.

Mentor: Robert N. Weinreb Program: Ophthalmology Type: Original Research Background: Preserving central retinal ganglion cells is crucial in glaucoma management, as macular damage in the 10-2 visual field (VF) impacts quality of life. The purpose of this study is to characterize spatial patterns of macular ganglion cell complex (GCC) thickness and assess their associations with central VF progression in glaucoma. Methods: A total of 4219 macula scans of 1116 eyes (613 participants) were included in this retrospective cohort study (NCT00221897, NCT00221923). Macular patterns from GCC were determined by an artificial intelligence (AI) unsupervised algorithm (archetypal analysis (AA)). Diagnostic accuracy of spatial patterns to detect 10-2 central VF progression in 262 eyes (175 patients) with a minimum of five 10-2 VF tests was calculated and compared with mean naive GCC thickness. VF progression was defined based on pointwise linear regression and trend-based methods. Results: AA identified 11 distinct spatial patterns across different glaucoma stages ( Figure 1). The AA model at baseline achieved Area Under the Receiver Operating Characteristic curve (AUROC) of 0.73 (95% CI [0.60 – 0.84]) and outperformed mean GCC thickness (0.55, 95% CI [0.46 – 0.61], P = 0.006) for predicting central VF progression tin eyes with early stages of glaucoma. The AA model (AUROC: 0.70 95% CI [0.59 – 0.80]) outperformed mean GCC (0.55 [95% CI 0.48 – 0.60], P = 0.012) thickness for predicting central VF progression across all severities. Figure 1 Eleven macula ocular coherence tomography (OCT) patterns for varying glaucoma severity, as determined by unsupervised archetypal analysis. The percentage above each archetype indicates the respective average decomposition weight in our dataset for each pattern. Conclusion: AI-driven spatial GCC patterns exhibit distinct characteristics associated with central VF progression in glaucoma. Macular patterns may enhance patient care and risk stratification.

PURPOSE:To compare the prevalence of fast central visual field (VF) progression with global VF progression in individuals with glaucoma receiving routine clinical care across different stages of glaucoma severity at baseline. DESIGN:Retrospective cohort study. METHODS:This study included 1117 eyes of 759 participants with primary open-angle glaucoma (POAG) with at least five 24-2 VF tests over a minimum of 2-year follow-up. Eyes were classified as early (>-6 dB), moderate (-6 dB to -12 dB), and advanced (-12 dB to -20 dB) based on baseline VF mean deviation (MD). The slopes of global MD and central mean total deviation (MTD10) (12 test points within the central 10° region of 24-2 VF test) were calculated. Proportions of fast progressors (≤-1.0 dB/y for MD and ≤-0.5 dB/y for MTD10) in each glaucoma severity group were determined. RESULTS:Overall, 7.5% of eyes demonstrated fast rates of progression based on MD, while 12.8% of eyes showed fast rates of progression based on MTD10. When eyes were stratified by baseline glaucoma severity, 6.9% (early), 11.1% (moderate), and 5.8% (advanced) of eyes exhibited fast rates of progression based on MD. Although fast MTD10 progressors were most prevalent in the advanced glaucoma group (20.9%), a notable proportion of eyes with early (10.8%) and moderate glaucoma (15.2%) also exhibited fast rates of change centrally. A considerable proportion of eyes showed fast rates of progression based on MTD10 without concurrent fast MD progression consistent across all glaucoma severity groups (5.5% [early glaucoma], 6.6% [moderate glaucoma], and 15.1% [advanced glaucoma]). In contrast, fast progression based on MD was detected in isolation in a much smaller proportions of patients (1.7% in early glaucoma, 2.5% in moderate glaucoma, and none in advanced glaucoma). CONCLUSIONS:Selective analysis of the MTD10 detected a greater proportion of eyes that exhibited fast progression across all disease severity groups compared to measurements from the entire VF, underscoring the importance of close monitoring for progressive central VF changes in all stages of glaucoma.

Purpose To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. Design Retrospective cohort study. Methods Setting: Multi-center.Study Population: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations.Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates.Main Outcome Measure: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. Results We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). Conclusions Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

PURPOSE:To investigate the association between baseline optic nerve head prelaminar schisis and the rates of visual field mean deviation (VF MD) slopes in glaucoma. DESIGN:Retrospective clinical cohort study. METHODS:This study included 563 eyes (446 with primary open-angle glaucoma and 117 glaucoma suspect eyes) from 332 patients. Two independent graders evaluated the baseline presence and severity of prelaminar schisis using optical coherence tomography radial scans. The severity was graded on a four-point ordinal scale: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The interrater reliability was assessed using weighted kappa. Two linear mixed-effect models were employed to assess the association between the presence of schisis (model 1) and schisis severity (model 2) with VF MD slopes, while adjusting for relevant demographic and ocular characteristics. RESULTS:Prelaminar optic nerve head schisis was observed in 258 eyes (45.8%). Among these, grade 1 was identified in 36 eyes (14.0%), grade 2 in 181 eyes (70.2%), and grade 3 in 41 eyes (15.9%). The weighted kappa was 0.66. In multivariable models, the presence of schisis was associated with a faster VF MD slope (-0.22 dB/y; 95% confidence interval [CI]: -0.30, -0.13 P ≤ .001). Compared to eyes without prelaminar schisis (grade 0), those with schisis were associated with faster VF MD slopes. This was more significant with grade 3 (-0.40 dB/y; 95% CI: -0.63, -0.18; P < .001) than with grade 1 (-0.18 dB/y; 95% CI: -0.34, -0.03; P = .023), or grade 2 (-0.18 dB/y; 95% CI: -0.26, -0.09; P < .001). Age and baseline VF MD were also independently associated with VF progression in both models. CONCLUSIONS:The presence and severity of severe prelaminar schisis were associated with faster VF progression, suggesting its potential as a biomarker to identify patients at higher risk of progression and to guide clinical management in glaucoma.

Purpose:This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography. Methods:In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders. Visual field tests were performed with the imo perimeter (CREWT Medical Systems, Inc., Tokyo, Japan) at central gaze, 6° abduction, and 6° adduction positions as fixation points. A mixed-effects model was used to compare MS under all conditions. Results:The analysis included a total of 82 eyes, with 41 POAG and 41 healthy after matching. The mean (standard deviation) age was 68.0 (11.0) years, with a mean deviation of -9.9 (6.6) dB for POAG and -1.0 (1.9) dB for healthy eyes using Humphrey field analysis 24-2. MS did not significantly differ among central gaze (27.0 [1.8] dB), abduction (27.1 [1.9] dB), and adduction (26.9 [2.2] dB) in healthy eyes (P = 0.650). However, MS was significantly lower for adduction (17.2 [5.9] dB) compared to central gaze (18.1 [5.9] dB) and abduction (17.9 [5.9] dB) in glaucoma eyes (P = 0.001 and P = 0.022, respectively). Conclusions:Horizontal gaze, especially in adduction, significantly reduces visual sensitivity in glaucoma, suggesting a specific vulnerability associated with eye movement. This finding highlights the importance of eye positioning in glaucoma, warranting further investigation of its clinical significance.

PURPOSE:To explore the prognostic significance of short-term rates of visual field (VF) mean deviation (MD) change in predicting progression across various levels of glaucoma severity. DESIGN:Observational cohort. PARTICIPANTS:A total of 349 eyes from 254 patients followed up to 5 years. METHODS:Primary open-angle glaucoma eyes were included with ≥ 5 24-2 VFs tests during the initial 2 years over a period of up to 5 years. Two assessment methods, Guided Progression Analysis (GPA) and a United States Food and Drug Administration (FDA)-consistent end point, were utilized to identify progression events. Rates of change in VF MD during the initial 2 years were calculated, and survival models were employed to evaluate the risk of faster initial VF MD loss on the development of GPA and FDA-consistent end points. MAIN OUTCOME MEASURES:Risk of progression based on initial MD change rates. RESULTS:Over a mean follow-up of 4.3 years, progression was observed in 17.2% (GPA end point) and 24.9% (FDA-consistent end point) of eyes. Faster initial rates of VF MD loss significantly increased the progression risk (hazard ratio [HR] per 0.1 dB/year faster for GPA: 1.16, 95% confidence interval [CI]: 1.12-1.20; HR for FDA: 1.16, 95% confidence interval: 1.12-1.21; both P < 0.001) with survival-adjusted R2 values of 0.67 for GPA and 0.75 for FDA-consistent end points. Global initial 2-year slopes showed the highest predictive accuracy for FDA progression events, with adjusted R2 values of 0.75 overall, 0.71 for early glaucoma, and 0.42 for moderate-to-advanced glaucoma. Superior and inferior sectoral slopes demonstrated lower abilities to explain the variability across all severity groups. The model's predictive accuracy was higher in early glaucoma (R2, 0.71) compared to moderate-advanced stages (R2, 0.42) for both criteria. CONCLUSIONS:The initial 2-year rate of VF MD change predicts subsequent progression events based on FDA-consistent criteria in both early and moderate-to-advanced glaucoma eyes. These findings suggest initial VF MD change rates identify patients at higher risk of future progression, enabling timely management decisions and, also, potentially serving as a progression end point in clinical trials. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.