Rates of Choriocapillaris Microvascular Dropout and Macular Structural Changes in Glaucomatous Optic Neuropathy With and Without Myopia.

PURPOSE: To evaluate the association between rates of juxtapapillary choriocapillaris microvasculature dropout (MvD) change and rates of ganglion cell inner plexiform layer (GCIPL) loss in primary open-angle glaucoma (POAG) and glaucoma suspect eyes with and without myopia. DESIGN: Cohort study from clinical trial data METHODS: 238 eyes from 155 POAG and glaucoma suspect patients were stratified into no-myopia (axial length (AL) ≤ 24 mm; n = 78 eyes), mild myopia (24 mm< AL ≤ 26 mm; n = 114 eyes), and high myopia (AL > 26 mm; n = 46 eyes). Eyes with a minimum of 3 visits and 1.5 years of follow-up with both optical coherence tomography angiography (OCT-A) and OCT macula scans were included. Presence, area, and angular circumference of juxtapapillary MvD were evaluated on en face choroidal images and horizontal B-scans obtained from OCT-A imaging. RESULTS: Over the mean follow-up of 4.4 years, the mean MvD area rates of change (95% CI) were largest in high and mild myopia group (0.04 (0.03, 0.05) mm2/year in both groups), followed by the no-myopia group (0.03 (0.02, 0.04) mm2/year). The mean MvD angular circumference rates of change (95% CI) were highest in mild myopia group (8.7o (6.9o, 10.5o)/year) followed by the high myopia and no-myopia groups (8.1o (5.3o, 10.9o)/year, and 7.4o (5.3o, 9.6o)/year, respectively). While the mean global GCIPL thinning rates between eyes with MvD at baseline compared to eyes without were similar in all myopia groups, the rates of MvD area change were significantly faster in all myopia groups with baseline MvD (all p≤0.004). Significant faster rates of MvD angular circumference change were found in the mild myopia group with baseline MvD (p<0.001) only. In multivariable models, the rates of GCIPL thinning over time were significantly associated with rates of MvD angular circumference change and MvD area change (R2=0.33, p<0.001 and R2=0.32, p=0.006, respectively). CONCLUSIONS: Rates of GCIPL thinning were associated with rates of MvD area and angular circumference change over time in myopic POAG eyes. Utilizing OCT-A to detect MvD may provide an additional tool for monitoring macular structural changes in glaucomatous eyes with myopia.

Diagnostic Accuracy of Optic Nerve Head and Macula OCT Parameters for Detecting Glaucoma in Eyes With and Without High Axial Myopia.

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.

Racial Differences in Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma.

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.

Association of Long-Term Intraocular Pressure Variability and Rate of Ganglion Complex Thinning in Patients With Glaucoma.

PURPOSE: To evaluate the association of mean intraocular pressure (IOP) and IOP variability (IOP fluctuation [SD of IOP] and the IOP range) with the rate of ganglion cell complex (GCC) layer thinning over time in patients with glaucoma. DESIGN: Prospective cohort study. METHODS: Participants with at least 4 visits and 2 years of follow-up of optical coherence tomography tests were included. A linear mixed-effect model was used to investigate the association of IOP parameters with the rates of GCC thinning. Subgroup analyses were conducted for eyes with early (MD ≥ -6 dB), and moderate to advanced stage (MD < -6 dB) at baseline. RESULTS: The cohort consisted of 369 eyes of 249 glaucoma patients (282 early glaucoma and 87 moderate to advanced glaucoma) with mean (standard deviation [SD]) age of 68.2 (10.7) years over 5.1 years of follow-up. The mean rate of GCC change was -0.59 (95% confidence interval [CI], -0.67 to -0.52) µm per year. In multivariable models, faster annual rate of GCC thinning was associated with a higher IOP fluctuation (-0.17 [95% CI, -0.23 to -0.11] µm per 1-mmHg higher, P < .001) or higher IOP range (-0.07 [95% CI, -0.09 to -0.05] µm per 1-mmHg higher, P < .001) after adjustment for mean IOP and other confounding factors. Similar results were found for early and moderate to advanced stages of glaucoma. CONCLUSIONS: IOP variability showed an independent association with macular change in patients with glaucoma regardless of severity at baseline, even after adjustment for mean IOP, supporting its potential value as a therapeutic target for clinical decision-making.

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention.

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents.

BACKGROUND: To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma. METHODS: This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races. RESULTS: There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (ß: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) µm vs ED: 1.34 (1.27, 1.40) µm; p=0.280). CONCLUSIONS: Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races.

Deep Learning Identifies High-Quality Fundus Photographs and Increases Accuracy in Automated Primary Open Angle Glaucoma Detection.

Purpose: To develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations. Methods: Image quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC). Results: The DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88). Conclusions: The DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model. Translational Relevance: Incorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents.

PURPOSE: To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED). DESIGN: Retrospective cohort study. METHODS: AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates). RESULTS: We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (-0.8 vs -0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%). CONCLUSIONS: Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races.

CAD/CAM-based 3D-printed and PVS indirect bonding jig system accuracy: a systematic review, meta-analysis, and comparative analysis of hard and soft CAD/CAM transfer trays.

BACKGROUND: The widespread use of CAD/CAM transfer trays warrants evaluation of their accuracy as compared to PVS transfer trays. OBJECTIVES: To quantify the accuracy of CAD/CAM and PVS transfer trays, investigating any differences between soft and hard trays CAD/CAM transfer trays. SEARCH METHODS: Eight different databases (Scopus, Web of Science, PubMed, Google Scholar, ProQuest, Embase, Cochrane Library, ClinicalTrials.gov) were searched, without restrictions, up to an end date of February 2023. SELECTION CRITERIA: Clinical trials (randomized and non-randomized) and in vitro studies reporting average imprecision values for bracket positioning obtained by digital superimpositions of digitally planned and real positions. DATA COLLECTION AND ANALYSIS: Data eligibility, data extraction, and risk of bias (RoB-2 and ROBINS-I) were conducted independently. The data, where possible, were synthesized and quantitatively analysed (meta-analysis of mean differences with 95% confidence intervals). The Grade of Recommendation, Assessment, Development and Evaluation (GRADE) analysis of the quality of evidence was performed. The t-test for independent samples was used to compare the transfer accuracy of hard and soft CAD/CAM transfer trays. RESULTS: Thirteen studies were synthesized in this systematic review, and then eight studies were included in the quantitative meta-analysis. As regards linear measurements, there was a mean transfer error of 0.0752 mm (95%CI: 0.0428, 0.1076) for mesiodistal measures, 0.0943 mm (95%CI: 0.0402, 0.1484) for vertical, and 0.0815 mm (95%CI: 0.0469, 0.1160) for buccolingual. As for angular measurements, there was an average transfer error of 1.2279° (95% CI: 0.6011, 1.8548) for inclination, 0.9397° (95%CI: 0.4672, 1.4123) for angulation, and 0.8721° (95%CI: 0.4257, 1.3185) for rotation. CAD/CAM transfer trays were less accurate than polyvinylsiloxane (PVS) transfer trays, with those made of soft material being more accurate than the hard ones, except for vertical dimension. The GRADE quality of evidence ranged from very low to moderate. CONCLUSIONS AND IMPLICATIONS: CAD/CAM transfer trays provide high bracket positioning accuracy, with soft transfer trays offering greater precision than rigid ones. Future randomized prospective trials are required to enhance the strength of the available evidence. REGISTRATION: Prospero (CRD42023401278 number).

Central visual field damage in glaucoma eyes with choroidal microvasculature dropout with and without high axial myopia.

PURPOSE: To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images. RESULTS: Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm2 vs 0.31 (0.19, 0.42) mm2, p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD. CONCLUSIONS: MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects.

Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT): Baseline Results.

PURPOSE: To describe baseline results of the Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT) for patients at federally qualified health centers (FQHCs). Candidates were persons at risk for glaucoma-associated diseases (GAD) based on age, race/ethnicity, current diagnosis of GAD, family history, and diabetes. DESIGN: Baseline screening visit followed by remote diagnosis and referral for follow-up examinations. METHODS: Patients presenting to FQHCs who were at least 18 years of age were enrolled and underwent screening for acuity, autorefraction, intraocular pressure, visual field testing, and fundus imaging. Results were transmitted to an ophthalmologist at University of Alabama at Birmingham for diagnosis who made referrals for follow-up; follow-up attendance was noted. Questionnaires assessed participants' perspectives on screening. Primary outcomes were rates of disease detection, referral for follow-up, follow-up attendance, and participant satisfaction. RESULTS: Of the 500 participants enrolled (mean age 58 years), 45.6% were African American and 51.6% White. Remote diagnostic evaluation of ocular screening by ophthalmologist revealed 30% GAD, 6.8% diabetic retinopathy, 37.6% cataract, 68.4% refractive error, 9.2% other eye conditions. In all, 47.2% of the participants were referred for follow-up examination and for acuity 20/40 or worse or IOP ≥23 mm Hg in one or both eyes. Follow-up examination attendance was 76.7% for those referred. Participants reported being very satisfied with screening (85.8%) and with the convenience of screening in their primary care clinic (92.2%). CONCLUSIONS: The high percentage of patients diagnosed with treatable eye conditions at telemedicine screening suggest these programs in FQHCs can be effective and scalable nationwide. Attendance when referred for follow-up examination was high. Participants welcomed screenings in their communities.

Displacement of the Lamina Cribrosa With Acute Intraocular Pressure Increase in Brain-Dead Organ Donors.

Purpose: To examine deformations of the optic nerve head (ONH) deep tissues in response to acute elevation of intraocular pressure (IOP). Methods: Research-consented brain-dead organ donors underwent imaging by spectral domain optical coherence tomography (OCT). OCT imaging was repeated while the eye was sequentially maintained at manometric pressures of 10, 30, and 50 mm Hg. Radial scans of the ONH were automatically segmented by deep learning and quantified in three dimensions by a custom algorithm. Change in lamina cribrosa (LC) depth and choroidal thickness was correlated with IOP and age by linear mixed-effect models. LC depth was computed against commonly utilized reference planes. Results: Twenty-six eyes from 20 brain-dead organ donors (age range, 22-62 years; median age, 43 years) were imaged and quantified. LC depth measured against a reference plane based on Bruch's membrane (BM), BM opening, and an anterior sclera canal opening plane showed both a reduction and an increase in LC depth with IOP elevation. LC depth universally increased in depth when measured against a sclera reference plane. Choroidal (-0.5222 µm/mm Hg, P < 0.001) and retinal nerve fiber layer thickness (-0.0717 µm/mm Hg, P < 0.001) significantly thinned with increasing IOP. The magnitude of LC depth change with IOP was significantly smaller with increasing age (P < 0.03 for all reference planes). Conclusions: LC depth changes with IOP reduce with age and are significantly affected by the reference plane of choice, which highlights a need for standardizing LC metrics to properly follow progressive remodeling of the loadbearing tissues of the ONH by OCT imaging and for the definition of a reference database.

Clinical Factors Associated With Long-Term OCT Variability in Glaucoma.

PURPOSE: To examine clinical factors associated with long-term optical coherence tomography (OCT)-measured retinal nerve fiber layer thickness (RNFLT) variability in glaucoma. STUDY DESIGN: Retrospective cohort study. METHODS: Glaucoma eyes from Diagnostic Innovations in Glaucoma Study (DIGS)/the African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2-years and 4-visit follow-up were included. RNFLT variability was calculated per visit as the absolute error of optic nerve head RNFLT residuals across longitudinal follow-up. Clinical factors examined included general demographics, baseline ocular measurements, prior and intervening cataract extraction (CE) or glaucoma surgery, scan quality, baseline RNFLT and RNFLT thinning rate, follow-up duration, and visit/testing frequency. Three multivariable linear mixed models (full model, baseline model, and parsimonious model) were fit to evaluate the effects of clinical factors on RNFLT variability, with 10-fold cross-validation to estimate real-world model performance. RESULTS: A total of 1140 eyes (634 patients) were included. The overall mean (95% CI) RNFLT variability was 1.51(1.45, 1.58) µm. Across different models, African American race (ß [standard error {SE} = 0.18 [0.06]), intervening CE (ß [SE] = 0.52 [0.07]), intervening glaucoma surgeries (ß [SE] = 0.15 [0.03]), and more positive RNFLT thinning rate (ß [SE] = 0.06 [0.02] per 1 µm/y more positive) showed consistent association with greater RNFLT variability, whereas more frequent visits/testing (ß [SE] = -0.11[0.05] per 1 visit/y higher) was associated with smaller RNFLT variability (P < .05 for all). CONCLUSIONS: Relevant clinical factors affecting long-term RNFLT variability in glaucoma were identified. These data enhance the evaluation of longitudinal structural change. Increasing the testing frequency, especially in eyes at risk for higher measurement variability, and resetting of baseline imaging after intervening procedures may help to more reliably detect OCT progression.

Multimodal Deep Learning Classifier for Primary Open Angle Glaucoma Diagnosis Using Wide-Field Optic Nerve Head Cube Scans in Eyes With and Without High Myopia.

PRCIS: An optical coherence tomography (OCT)-based multimodal deep learning (DL) classification model, including texture information, is introduced that outperforms single-modal models and multimodal models without texture information for glaucoma diagnosis in eyes with and without high myopia. BACKGROUND/AIMS: To evaluate the diagnostic accuracy of a multimodal DL classifier using wide OCT optic nerve head cube scans in eyes with and without axial high myopia. MATERIALS AND METHODS: Three hundred seventy-one primary open angle glaucoma (POAG) eyes and 86 healthy eyes, all without axial high myopia [axial length (AL) ≤ 26 mm] and 92 POAG eyes and 44 healthy eyes, all with axial high myopia (AL > 26 mm) were included. The multimodal DL classifier combined features of 3 individual VGG-16 models: (1) texture-based en face image, (2) retinal nerve fiber layer (RNFL) thickness map image, and (3) confocal scanning laser ophthalmoscope (cSLO) image. Age, AL, and disc area adjusted area under the receiver operating curves were used to compare model accuracy. RESULTS: Adjusted area under the receiver operating curve for the multimodal DL model was 0.91 (95% CI = 0.87, 0.95). This value was significantly higher than the values of individual models [0.83 (0.79, 0.86) for texture-based en face image; 0.84 (0.81, 0.87) for RNFL thickness map; and 0.68 (0.61, 0.74) for cSLO image; all P ≤ 0.05]. Using only highly myopic eyes, the multimodal DL model showed significantly higher diagnostic accuracy [0.89 (0.86, 0.92)] compared with texture en face image [0.83 (0.78, 0.85)], RNFL [0.85 (0.81, 0.86)] and cSLO image models [0.69 (0.63, 0.76)] (all P ≤ 0.05). CONCLUSIONS: Combining OCT-based RNFL thickness maps with texture-based en face images showed a better ability to discriminate between healthy and POAG than thickness maps alone, particularly in high axial myopic eyes.

Progressive Visual Field Loss and Subsequent Quality of Life Outcomes in Glaucoma.

PURPOSE: To evaluate the association between baseline severity of visual field (VF) damage and the initial rates of VF progression with quality of life (QOL) outcomes over an extended follow-up in glaucoma. DESIGN: Retrospective cohort study. METHODS: Both eyes of 167 glaucoma or suspected glaucoma patients were followed for 10.0±0.3 years. The National Eye Institute Visual Function Questionnaire (NEI-VFQ)-25 was performed at the end of the follow-up. Separate linear regression models included the VF parameters of the better eye, the worse eye, and the central and peripheral points of the integrated binocular VF to evaluate the association of baseline and initial rates of change of VF parameters (first half of the follow-up) with NEI-VFQ-25 Rasch-calibrated disability scores over an extended follow-up. RESULTS: All models demonstrated association of worse baseline severity of VF damage with worse subsequent NEI-VFQ-25 scores. Faster rates of decline in VF mean deviation of the better eye and the mean sensitivity of the central and peripheral test locations of the integrated binocular VF were significantly associated with worse subsequent NEI-VFQ-25 scores. VF parameters of the better eye performed better than those of the worse eye (R2 of 0.21, and 0.15, respectively), and the VF parameters of the central test locations performed better than those of the peripheral test locations (R2 of 0.25, and 0.20, respectively). CONCLUSIONS: Baseline severity and initial rates of change of VF damage are associated with QOL outcomes over an extended follow-up. Assessment of longitudinal VF changes, especially in better eye, provides prognostic utility to identify glaucoma patients at a higher risk for developing disease-related disability.

Association Between Longitudinal 10-2 Central Visual Field Change and the Risk of Visual Acuity Loss in Mild-to-Moderate Glaucoma.

PRCIS: Faster worsening of 10-2 visual field (VF) was associated with the development of visual acuity (VA) loss in mild-to-moderate glaucoma, suggesting longitudinal 10-2 VF change is associated with the risk of VA impairment. PURPOSE: To examine whether longitudinal 10-2 central VF change is associated with the risk of VA loss in glaucoma. PATIENTS AND METHODS: Primary open angle glaucoma and glaucoma suspect eyes with ≥3 years and 5 visits of 10-2 VF examinations were included. Cox proportional hazard modeling with shared frailty was used to evaluate the hazard ratio (HR) of 10-2 VF mean deviation (MD), superior hemifield mean sensitivity (hemi-MS), and inferior hemi-MS worsening rates for developing VA loss, defined as a change in logMAR VA ≥95% test-retest variability. RESULTS: Among the 252 eyes (148 participants, mean follow-up = 5.8 y), 30 eyes (21 participants, mean follow-up = 4.9 y) developed VA loss. There was no difference in baseline VF between eyes with and without VA loss ( P > 0.05). Eyes with VA loss showed faster 10-2 VF MD worsening [-0.39 (95% CI: -0.60, -0.18) dB/y] and hemi-MS decrease (range: -0.42~-0.38 dB/y), as compared with no-VA loss eyes [10-2 VF MD change = -0.11 (-0.16, -0.07) dB/y; hemi-MS change: -0.12~-0.07 dB/y; P < 0.05]. In the multivariable model, faster 10-2 VF MD worsening [HR (95% CI) = 4.05 (1.61, 10.22), per 1 dB/y faster], superior hemi-MS decrease [HR (95% CI) = 7.07 (2.48, 20.14), per 1 dB/y faster], and inferior hemi-MS decrease [HR (95% CI) = 8.32 (1.99, 34.91), per 1 dB/y faster] were all associated with increased risk of developing VA loss ( P < 0.05). CONCLUSIONS: Faster 10-2 VF MD and hemifield MS worsening are associated with the development of VA loss. Monitoring the longitudinal central 10-degree VF change may suggest that there is impending VA impairment in glaucoma.

Association of Rates of Ganglion Cell and Inner Plexiform Thinning With Development of Glaucoma in Eyes With Suspected Glaucoma.

Importance: In eyes with suspected glaucoma, it is clinically relevant to find diagnostic tests for the risk of development of perimetric glaucoma. Objective: To investigate the association between rates of ganglion cell/inner plexiform layer (GCIPL) and circumpapillary retinal nerve fiber layer (cpRNFL) thinning and the development of perimetric glaucoma in eyes with suspected glaucoma. Design, Setting, and Participants: This observational cohort study used data collected in December 2021 from a tertiary center study and a multicenter study. Participants with suspected glaucoma were followed up for 3.1 years. The study was designed in December 2021 and finalized in August 2022. Exposures: Development of perimetric glaucoma was defined as having 3 consecutive results showing abnormal visual fields. Using linear mixed-effect models, rates of GCIPL were compared between eyes with suspected glaucoma that did and did not develop perimetric glaucoma. A joint longitudinal multivariable survival model was used to investigate the performance of rates of GCIPL and cpRNFL thinning in predicting the risk of developing perimetric glaucoma. Main Outcomes and Measures: Rates of GCIPL thinning and hazard ratio (HR) of developing perimetric glaucoma. Results: Among a total of 462 participants, the mean (SD) age was 63.3 (11.1) years, and 275 patients (60%) were female. Of 658 eyes, 153 eyes (23%) developed perimetric glaucoma. The mean rates of GCIPL thinning were faster in eyes that developed perimetric glaucoma (-1.28 vs -0.66 µm/y for minimum GCIPL thinning; difference, -0.62; 95% CI, -1.07 to -0.16; P = .02). Based on the joint longitudinal survival model, every 1-µm/y faster rate of minimum GCIPL and rate of global cpRNFL thinning were associated with a 2.4 and 1.9 higher risk of developing perimetric glaucoma, respectively (HR, 2.4; 95% CI, 1.8 to 3.2, and HR, 1.99; 95% CI, 1.76 to 2.22, respectively; P < .001). Among the predictive factors, African American race (HR, 1.56; 95% CI, 1.05 to 2.34; P = .02), male sex (HR, 1.47; 95% CI, 1.02 to 2.15; P = .03), 1-dB higher baseline visual field pattern standard deviation (HR, 1.73; 95% CI, 1.56 to 1.91; P < .001), and 1-mm Hg higher mean intraocular pressure during follow-up (HR, 1.11; 95% CI, 1.05 to 1.17; P < .001) were associated with higher risk of developing perimetric glaucoma. Conclusions and Relevance: This study found that faster rates of GCIPL and cpRNFL thinning were associated with higher risks of developing perimetric glaucoma. Rates of cpRNFL thinning and specifically GCIPL thinning may be useful measures for monitoring eyes with suspected glaucoma.

Retinal electrophysiologic response to IOP elevation in living human eyes.

PURPOSE: The relationships between intraocular pressure (IOP), ocular perfusion pressure (OPP), retinal perfusion, and retinal electrophysiologic responses have been explored experimentally across several animal models. These studies have demonstrated that elevated IOP reduces OPP, and when this reduction in OPP exceeds the autoregulatory capacity of the retina vasculature, retinal perfusion and electrophysiologic responses are reduced. This study aimed to evaluate these interactions for the first time in the living human eye. METHODS: Five eyes from three research-consented brain-dead organ donors underwent optical coherence tomography with angiographic (OCT/A; Spectralis, Heidelberg Engineering) and electroretinographic (ERG, Diagnosys LLC) measurements while IOP was manometrically-elevated stepwise to pressures of 10, 30 and 50 mmHg. Systemic blood pressure (BP) was monitored continuously during testing. Correlation analysis was applied to assess association between ERG and OPP changes. In a single eye, prolonged IOP elevation was induced with viscoelastic injection and serial ERG measurements were obtained. RESULTS: Reductions in inner retinal function defined by photopic ERG were observed with elevation in IOP and concomitant reduction in OPP. Reductions, especially in b-wave, and photopic negative response (PhNR) amplitudes and implicit times were significantly correlated with elevation in IOP and reduction in OPP. There were more appreciable changes in perfusion and functional responses in eyes tested while systemic blood pressure was lower. With prolonged IOP elevation, selective loss of the PhNR response was observed. CONCLUSIONS: In the living human eye, retinal perfusion and inner retinal function are acutely impacted by elevation of IOP, and this impact is related to systemic BP and OPP. This novel approach provides a viable model to study the autoregulatory responses to IOP elevation in the living human eye.

Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

PURPOSE: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care. DESIGN: Observational study. PARTICIPANTS: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years. METHODS: This study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye. MAIN OUTCOME MEASURES: Prevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes). RESULTS: Based on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively. CONCLUSIONS: This study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Macula structural and vascular differences in glaucoma eyes with and without high axial myopia.

AIMS: To identify clinically relevant parameters for identifying glaucoma in highly myopic eyes, an investigation was conducted of the relationship between the thickness of various retinal layers and the superficial vessel density (sVD) of the macula with axial length (AL) and visual field mean deviation (VFMD). METHODS: 270 glaucoma patients (438 eyes) participating in the Diagnostic Innovations in Glaucoma cross-sectional study representing three axial myopia groups (non-myopia: n=163 eyes; mild myopia: n=218 eyes; high myopia (AL>26 mm): n=57 eyes) who completed macular optical coherence tomography (OCT) and OCT-angiography imaging were included. Associations of AL and VFMD with the thickness of the ganglion cell inner plexiform layer (GCIPL), macular retinal nerve fibre layer (mRNFL), ganglion cell complex (GCC), macular choroidal thickness (mCT) and sVD were evaluated. RESULTS: Thinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=34.5% and R2=32.9%; respectively p<0.001), but not with AL (all p>0.1). Thicker mRNFL showed a weak association with increasing AL (R2=2.4%; p=0.005) and a positive association with VFMD (global R2=19.2%; p<0.001). Lower sVD was weakly associated with increasing AL (R2=1.8%; p=0.028) and more strongly associated with more severe glaucoma VFMD (R2=29.6%; p<0.001). Thinner mCT was associated with increasing AL (R2=15.5% p<0.001) and not associated with VFMD (p=0.194). mRNFL was thickest while mCT was thinnest in all sectors of high myopic eyes. CONCLUSIONS: As thinner GCIPL and GCC were associated with increasing severity of glaucoma but were not significantly associated with AL, they may be useful for monitoring glaucoma in highly myopic eyes.