Progression or Aging? A Deep Learning Approach for Distinguishing Glaucoma Progression From Age-Related Changes in OCT Scans.

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.

Social history and glaucoma progression: the effect of body mass index, tobacco and alcohol consumption on the rates of structural change in patients with glaucoma.

BACKGROUND/AIMS: Although obesity, tobacco and alcohol consumption were linked to the progression of numerous chronic diseases, an association of these social history aspects with glaucoma progression is not yet determined. This study aims to investigate the effect of body mass index (BMI) and history of tobacco and alcohol use on the rates of retinal nerve fibre layer (RNFL) change over time in glaucoma patients. METHODS: 2839 eyes of 1584 patients with glaucoma from the Duke Ophthalmic Registry were included. Patients had at least two spectral-domain optical coherency tomography (SD-OCT) tests over a minimum 6-month follow-up. Self-reported history of alcohol and tobacco consumption was extracted from electronic health records and mean BMI was calculated. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on RNFL change over time. RESULTS: Mean follow-up time was 4.7±2.1 years, with 5.1±2.2 SD-OCT tests per eye. 43% and 54% of eyes had tobacco or alcohol consumption history, respectively, and 34% were classified as obese. Higher BMI had a protective effect on glaucoma progression (0.014 µm/year slower per each 1 kg/m2 higher; p=0.011). Tobacco and alcohol consumption were not significantly associated with RNFL change rates (p=0.473 and p=0.471, respectively). Underweight subjects presented significantly faster rates of structural loss (-0.768 µm/year; p=0.002) compared with normal weight. CONCLUSIONS: In a large clinical population with glaucoma, habits of tobacco and alcohol consumption showed no significant effect on the rates of RNFL change. Higher BMI was significantly associated with slower rates of RNFL loss.

Visual Field Outcomes in the Primary Tube Versus Trabeculectomy Study.

PURPOSE: To describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. DESIGN: Cohort analysis. PARTICIPANTS: A total of 155 eyes (155 subjects) randomly assigned to treatment with tube shunt surgery (n = 84) or trabeculectomy with mitomycin C (n = 71). METHODS: The PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without previous intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for 5 years. Standard automated perimetry tests were deemed reliable if the false-positive rate was ≤ 15%. Tests were excluded if visual acuity was ≤ 20/400 or loss of ≥ 2 Snellen lines from baseline because of a nonglaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the 2 groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP < 18 mmHg and mean IOP. MAIN OUTCOME MEASURES: Rate of change in SAP MD during follow-up. RESULTS: A total of 730 SAP tests were evaluated (average of 4.7 tests per eye). The average SAP MD at baseline was -12.8 ± 8.3 decibels (dB) in the tube group and -12.0 ± 8.4 dB in the trabeculectomy group (P = 0.57). The mean rate of change in SAP MD was -0.32 ± 0.39 dB/year in the trabeculectomy group and -0.47 ± 0.43 dB/year in the tube group (P = 0.23). Eyes with mean IOP 14 to 17.5 mmHg had significantly faster rates of SAP MD loss compared with eyes with mean IOP < 14 mmHg (-0.59 ± 0.13 vs. -0.27 ± 0.08 dB/year; P = 0.012), and eyes with only 50% to 75% of visits with IOP < 18 mmHg had faster rates than those with 100% of visits with IOP < 18 mmHg (-0.90 ± 0.16 vs. -0.29 ± 0.08 dB/year; P < 0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. CONCLUSIONS: No statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Improved Prediction of Perimetric Loss in Glaucomatous Eyes Using Latent Class Mixed Modeling.

PURPOSE: To evaluate whether the identification of distinct classes within a population of glaucoma patients improves estimates of future perimetric loss. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 6558 eyes of 3981 subjects from the Duke Ophthalmic Registry with ≥ 5 reliable standard automated perimetry (SAP) tests and ≥ 2 years of follow-up. METHODS: Standard automated perimetry mean deviation (MD) values were extracted with associated timepoints. Latent class mixed models (LCMMs) were used to identify distinct subgroups (classes) of eyes according to rates of perimetric change over time. Rates for individual eyes were then estimated by considering both individual eye data and the most probable class membership for that eye. Data were split into training (80%) and test sets (20%), and test set mean squared prediction errors (MSPEs) were estimated using LCMM and ordinary least squares (OLS) regression. MAIN OUTCOME MEASURES: Rates of change in SAP MD in each class and MSPE. RESULTS: The dataset contained 52 900 SAP tests with an average of 8.1 ± 3.7 tests per eye. The best-fitting LCMM contained 5 classes with rates of -0.06, -0.21, -0.87, -2.15, and +1.28dB/year (80.0%, 10.2%, 7.5%, 1.3%, and 1.0% of the population, respectively) labeled as slow, moderate, fast, catastrophic progressors, and "improvers" respectively. Fast and catastrophic progressors were older (64.1 ± 13.7 and 63.5 ± 16.9 vs. 57.8 ± 15.8, P < 0.001) and had generally mild-moderate disease at baseline (65.7% and 71% vs. 52%, P < 0.001) than slow progressors. The MSPE was significantly lower for LCMM compared to OLS, regardless of the number of tests used to obtain the rate of change (5.1 ± 0.6 vs. 60.2 ± 37.9, 4.9 ± 0.5 vs. 13.4 ± 3.2, 5.6 ± 0.8 vs. 8.1 ± 1.1, 3.4 ± 0.3 vs. 5.5 ± 1.1 when predicting the fourth, fifth, sixth, and seventh visual fields (VFs) respectively; P < 0.001 for all comparisons). MSPE of fast and catastrophic progressors was significantly lower with LCMM versus OLS (17.7 ± 6.9 vs. 48.1 ± 19.7, 27.1 ± 8.4 vs. 81.3 ± 27.1, 49.0 ± 14.7 vs. 183.9 ± 55.2, 46.6 ± 16.0 vs. 232.4 ± 78.0 when predicting the fourth, fifth, sixth, and seventh VFs respectively; P < 0.001 for all comparisons). CONCLUSIONS: Latent class mixed model successfully identified distinct classes of progressors within a large glaucoma population that seemed to reflect subgroups observed in clinical practice. Latent class mixed models were superior to OLS regression in predicting future VF observations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosuremay be found after the references.

Hazard Detection During Simulated Driving in Glaucoma Patients.

PRCIS: In this cross-sectional study, glaucoma patients showed slower reaction times (RTs) to hazardous situations when compared with control subjects during simulated driving. Worse RTs were associated with a greater magnitude of visual field loss. PURPOSE: The purpose of this study was to evaluate the impact of different hazardous traffic conditions on driving performance in glaucoma patients using a high-fidelity driving simulator. METHODS: The cross-sectional study was performed with 52 glaucoma patients and 15 control subjects. A series of hazard scenarios were presented, such as pedestrians crossing the street unexpectedly or vehicles suddenly pulling into the driver's lane. RTs in seconds (s) from first the evidence of a hazard to the time it took the driver to take the foot off the gas pedal ("Gas Off") and the time it took to depress the brake pedal ("Brake On") were compared between groups. RESULTS: Overall, mean RTs were statistically significantly slower in glaucoma patients (3.39±3.88 s) compared with controls (2.39±1.99 s; P =0.005) for the "Brake On" task but not for the "Gas Off" task (2.74±3.42 vs. 2.13±1.91 s, respectively; P =0.120). For subjects with glaucoma, multivariable models adjusted for age, gender, race, and visual acuity demonstrated significantly slower RTs for worse values of binocular mean sensitivity for both "Gas Off" and "Brake On" tasks (1.12 and 1.14 s slower per 10 dB worse; P =0.009 and P <0.001, respectively). Subjects with glaucoma took significantly longer times to brake for smaller (low saliency) hazards compared with larger (high saliency) hazards ( P =0.027). CONCLUSIONS: RTs in response to hazardous driving situations were slower for glaucoma patients compared with controls. Individualized assessment of driving fitness using hazardous scenarios in driving simulators could be helpful in providing an assessment of driving risk in glaucoma patients.

Increasing Rates of Herpes Zoster Ophthalmicus and the COVID-19 Pandemic.

Purpose: This epidemiologic study evaluates the variance in incidence of Herpes Zoster (HZ) and Herpes Zoster Ophthalmicus (HZO) within a single healthcare system with an aim to analyze their relationship to the COVID-19 pandemic. Methods: All patients attending the Duke University Health System (DUHS) from January 1, 2018, to December 31, 2021, were included. General and COVID-related trends of HZO and HZ were analyzed based on new ICD-9 or ICD-10 diagnosis codes, compared with the total number of patients seen at DUHS during this period, and the number of reported COVID-19 cases in North Carolina obtained using the CDC data tracker. Results: This study included 16,287 cases of HZ of whom 1,294 (7.94%) presented with HZO. The overall incidence of HZO showed an average yearly increase of 5.6%, however HZ incidence decreased by 5.3% per year. When comparing incidence rates of HZO in the 12-months before and after the COVID-19 pandemic onset in the United States (March 2020), the average incidence from March 2020 to February 2021 was 27.6 ± 11.6 compared to 18.0 ± 2.7 from March 2019 to February 2020 (p = 0.01). Moreover, 10/12 (83.3%) of the months had a higher incidence rate of HZO in the post-COVID onset year compared to their corresponding month in the pre-COVID year. Conclusion: The results show HZO incidence may be increasing, despite an overall lower HZ incidence. This could suggest a distinct mechanism for HZO appearance. The COVID pandemic, directly or indirectly, may have accelerated the already increasing HZO incidence.

Intraocular Pressure and Rates of Macular Thinning in Glaucoma.

PURPOSE: To evaluate the effect of intraocular pressure (IOP) on the rates of macular thickness (ganglion cell layer [GCL] and ganglion cell-inner plexiform layer [GCIPL]) change over time measured by spectral-domain (SD) OCT. DESIGN: Retrospective cohort study. PARTICIPANTS: Overall, 451 eyes of 256 patients with primary open-angle glaucoma. METHODS: Data were extracted from the Duke Ophthalmic Registry, a database of electronic medical records of patients observed under routine clinical care at the Duke Eye Center, and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality Spectralis SD-OCT macula scans were included. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of GCL and GCIPL thickness change over time. MAIN OUTCOME MEASURES: The effect of IOP on the rates of GCL and GCIPL thickness loss measured by SD-OCT. RESULTS: Eyes had a mean follow-up of 1.8 ± 1.3 years, ranging from 0.5 to 10.2 years. The average rate of change for GCL thickness was -0.220 µm/year (95% confidence interval [CI], -0.268 to -0.172 µm/year) and for GCIPL thickness was -0.231 µm/year (95% CI, -0.302 to -0.160 µm/year). Each 1-mmHg higher mean IOP during follow-up was associated with an additional loss of -0.021 µm/year of GCL thickness (P = 0.001) and -0.032 µm/year of GCIPL thickness (P = 0.001) after adjusting for potentially confounding factors, such as baseline age, disease severity, sex, race, central corneal thickness, and follow-up time. CONCLUSIONS: Higher IOP was significantly associated with faster rates of GCL and GCIPL loss over time measured by SD-OCT, even during relatively short follow-up times. These findings support the use of SD-OCT GCL and GCIPL thickness measurements as structural biomarkers for the evaluation of the efficacy of IOP-lowering therapies in slowing down the progression of glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spectral-Domain OCT Lens Meridian Position as a Metric to Estimate Postoperative Anatomical Lens Position.

PURPOSE: To evaluate the prediction of postoperative anatomical lens position (ALP) using intraoperative spectral-domain optical coherence tomography (SD-OCT) lens anatomy metrics in patients who underwent femtosecond laser-assisted cataract surgery. METHODS: Intraoperative SD-OCT (Catalys; Johnson & Johnson Vision) and postoperative optical biometry (IOLMaster 700; Carl Zeiss Meditec AG) were used to assess anterior segment landmarks, including lens thickness, lens volume, anterior chamber depth, lens meridian position (LMP), and measured ALP. LMP was defined as the distance from the corneal epithelium to the lens equator, and ALP was defined as the distance from the corneal epithelium to the IOL surface. Eyes were divided into groups according to axial length (> 22.5 mm, 22.5 to 24.5 mm, and > 24.5 mm) and IOL type (Tecnis ZCB00 [Johnson & Johnson Vision]; AcrySof SN-60WF [Alcon Laboratories, Inc], or enVista MX60E [Bausch & Lomb]) to further analyze the correlation between LMP and ALP. Theoretical effective lens position was back-calculated using a specific formula. Primary outcome was correlation between postoperative measured ALP and LMP. RESULTS: A total of 97 eyes were included in this study. Linear regression analysis displayed a statistically significant correlation between intraoperative LMP and postoperative ALP (R2 = 0.522; P < .01). No statistically significant correlation was observed between LMP and lens thickness (R2 = 0.039; P = .06) or between ALP and lens thickness (R2 = 0.02; P = .992). The greatest predictor for ALP was LMP (ß = 0.766, P < .001; R2 = 0.523). CONCLUSIONS: Intraoperative SD-OCT-measured LMP correlated better than anterior chamber depth and axial length to postoperative ALP. Further studies are necessary to analyze the impact of preoperative or intraoperative LMP measurements on postoperative refractive outcomes. [J Refract Surg. 2023;39(3):165-170.].

The Definition of Glaucomatous Optic Neuropathy in Artificial Intelligence Research and Clinical Applications.

OBJECTIVE: Although artificial intelligence (AI) models may offer innovative and powerful ways to use the wealth of data generated by diagnostic tools, there are important challenges related to their development and validation. Most notable is the lack of a perfect reference standard for glaucomatous optic neuropathy (GON). Because AI models are trained to predict presence of glaucoma or its progression, they generally rely on a reference standard that is used to train the model and assess its validity. If an improper reference standard is used, the model may be trained to detect or predict something that has little or no clinical value. This article summarizes the issues and discussions related to the definition of GON in AI applications as presented by the Glaucoma Workgroup from the Collaborative Community for Ophthalmic Imaging (CCOI) US Food and Drug Administration Virtual Workshop, on September 3 and 4, 2020, and on January 28, 2022. DESIGN: Review and conference proceedings. SUBJECTS: No human or animal subjects or data therefrom were used in the production of this article. METHODS: A summary of the Workshop was produced with input and approval from all participants. MAIN OUTCOME MEASURES: Consensus position of the CCOI Workgroup on the challenges in defining GON and possible solutions. RESULTS: The Workshop reviewed existing challenges that arise from the use of subjective definitions of GON and highlighted the need for a more objective approach to characterize GON that could facilitate replication and comparability of AI studies and allow for better clinical validation of proposed AI tools. Different tests and combination of parameters for defining a reference standard for GON have been proposed. Different reference standards may need to be considered depending on the scenario in which the AI models are going to be applied, such as community-based or opportunistic screening versus detection or monitoring of glaucoma in tertiary care. CONCLUSIONS: The development and validation of new AI-based diagnostic tests should be based on rigorous methodology with clear determination of how the reference standards for glaucomatous damage are constructed and the settings where the tests are going to be applied. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness for Diagnosing Early to Moderate Glaucoma.

PRCIS: In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes. PURPOSE: The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population. METHODS: A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >-12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter. RESULTS: Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91-0.96) and 0.93 (0.89-0.96), respectively; P =0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P =0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87-0.96) for RNFLT and 0.91 (0.86-0.95) for MRW ( P =0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P =0.230). CONCLUSIONS: MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.

Rates of Visual Field Change in Eyes With Optic Disc Drusen.

BACKGROUND: Optic disc drusen (ODD) are calcified deposits in the prelaminar portion of the optic nerve head. Although often asymptomatic, these deposits can cause progressive visual field defects and vision loss. The purpose of this study was to evaluate rates of functional loss in eyes with ODD and to investigate risk factors associated with rates of visual field progression. METHODS: This was a retrospective cohort study including 65 eyes of 43 patients with ODD from the Duke Ophthalmic Registry. All eyes had at least 12 months of follow-up and at least 3 reliable standard automated perimetry (SAP) tests. Linear mixed models were used to estimate rates of SAP mean deviation (MD) loss over time. Univariable and multivariable models were used to assess the effect of clinical variables and intraocular pressure (IOP) on rates of change. RESULTS: Subjects were followed for an average of 7.6 ± 5.3 years. The mean rate of SAP MD change was -0.23 ± 0.26 dB/year, ranging from -1.19 to 0.13 dB/year. Fifty-seven eyes (87.7%) had slow progression (slower than -0.5 dB/year), 6 eyes (9.2%) had moderate progression (between -0.5 dB/year and -1 dB/year), and 2 eyes (3.1%) had fast progression (faster than -1 dB/year). In multivariable models, older age and worse SAP MD at baseline were significantly associated with faster rates of change. Mean IOP was not associated with faster rates of MD change in both univariable and multivariable analyses. CONCLUSIONS: Most eyes with ODD had slow rates of visual field loss over time. Age and baseline severity were significantly associated with faster rates of visual field loss.

Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic.

PURPOSE: Glaucoma is the leading cause of irreversible blindness, a crippling disability resulting in higher risks of chronic health conditions. To better understand disparities in blindness risk, we identified risk factors of blindness on first presentation to a glaucoma clinic using a large clinical database. DESIGN: Retrospective cross-sectional study. METHODS: We used electronic health records of glaucoma patients from the Duke Ophthalmic Registry. International Classification of Diseases codes were used to identify glaucoma and exclude concurrent diseases. Blindness classification was based on the definition of legal blindness. Risk factors included gender, race, marital status, age, intraocular pressure, diabetes history, income level, and education. Odds ratios (ORs) and 95% CIs were calculated for risk factors using univariable and multivariable logistic regression. RESULTS: Our cohort consisted of 3753 patients, with 192 (5%) blind on first presentation. In univariable models, African American / Black race (OR 2.48, 95% CI 1.83-3.36), single marital status (1.74, 95% CI 1.25-2.44), prior diabetes diagnosis (2.23, 95% CI 1.52-3.27), and higher intraocular pressure (1.29 per 1 SD higher, 95% CI 1.13-1.46) were associated with increased risk of presenting blind, whereas higher annual income (0.75, 95% CI 0.65-0.86) and education (0.77, 95% CI 0.69-0.85) were associated with lower risk. These associations remained significant and in the same direction in a multivariable model apart from income, which became insignificant. CONCLUSIONS: Using a large real-world clinical database, we identified risk factors associated with presentation with blindness among glaucoma patients. Our results highlight disparities in health care outcomes and indicate the importance of targeted education to reduce disparities in blindness.

C-DU(KE) Calculator: A Clinical Tool for Risk Stratification in Infectious Keratitis.

PURPOSE: The aim of this study was to identify characteristics of infectious keratitis predictive of poor outcome to develop a web-based predictive calculator. METHOD: A retrospective chart review was performed at the Duke Eye Center. Two hundred fifteen adult patients with culture-proven infectious keratitis presenting between January 1, 2016, and December 31, 2020, were separated into a derivation set (136 patients, 53 positives; 83 controls) and a temporal validation set (79 patients, 26 positives; 53 controls). The poor outcome group consisted of patients requiring penetrating keratoplasty for visually significant scarring, penetrating keratoplasty for ulcer progression, or evisceration/enucleation for endophthalmitis. Univariable analysis was performed followed by stepwise multivariable logistic regression to obtain a predictive model in the derivation data set. Culture-naïve and postculture models were constructed. Discrimination and calibration were assessed using the area under the curve (AUC) and calibration plots, respectively. RESULTS: The culture-naïve model consisted of corticosteroid drop use postsymptom onset [Odds Ratio (OR) = 2.3, P = 0.054], decreased vision (OR = 2.4, P = 0.001), and increased ulcer area (OR = 1.017, P = 0.017). The postculture model additionally included fungal keratitis (OR = 5.4, P = 0.006) and elapsed time from symptoms to organism-sensitive therapy (OR = 1.027, P = 0.014). The models were summarized by the acronym C-DU(KE). The AUCs for the culture-naïve model were 0.794 in the derivation set and 0.850 in the validation set. The AUCs for the postculture model were 0.898 in the derivation set and 0.946 in the validation set. Calibration plots indicated goodness of fit in the data sets for both models. The calculator was deployed under the URL: https://duke-eye-calculator.shinyapps.io/Corneal_Ulcers/ . CONCLUSIONS: The C-DU(KE) calculator permits a data-driven prediction of outcome in infectious keratitis that can supplement clinical judgment.

24-2 SITA Standard versus 24-2 SITA Faster in Perimetry-Naive Normal Subjects.

PURPOSE: To compare the Swedish Interactive Thresholding Algorithm (SITA) Standard (SS) and SITA Faster (SFR) strategies in normal individuals undergoing standard automated perimetry (SAP) for the first time. DESIGN: Randomized, comparative, observational case series. PARTICIPANTS: Seventy-four perimetry-naive healthy individuals. METHODS: All individuals underwent SAP 24-2 testing with the Humphrey Field Analyzer III (model 850 Zeiss) using the SS and SFR strategies. One eye of each individual was tested. Test order between strategies was randomized, and an interval of 15 minutes was allowed between the tests. MAIN OUTCOME MEASURES: The following variables were compared: test time, foveal threshold, false-positive errors, number of unreliable tests, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and number of depressed points deviating at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total and pattern deviation probability maps. Specificity of the SS and SFR strategies were compared using Anderson's criteria for abnormal visual fields. RESULTS: The SFR tests were 60.4% shorter in time compared with SS (P < 0.001) and were associated with a significantly lower PSD (1.75 ± 0.80 decibel [dB] vs. 2.15 ± 1.25 dB; P = 0.016). There were no significant differences regarding the MD, VFI, foveal threshold, GHT, and number of points depressed at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total deviation and pattern deviation probability maps between SS and SFR. When all exams were analyzed and any of Anderson's criteria was applied, the specificity was 68% with SFR and 61% with SS (P = 0.250). The specificities observed with SFR and SS when only the first or second exams were analyzed were also similar (63% vs. 64% and 72% vs. 58%, respectively, P > 0.05). CONCLUSIONS: The SS and SFR were associated with similar specificities in perimetry-naive individuals. The SFR did not increase the number of depressed points in the total and pattern deviation probability maps. Ophthalmologists should be aware that both strategies are associated with disturbingly high false-positive rates in perimetry-naive individuals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Validation of Rates of Mean Deviation Change as Clinically Relevant End Points for Glaucoma Progression.

PURPOSE: To investigate whether rates of standard automated perimetry (SAP) mean deviation (MD) over an initial 2-year follow-up period were predictive of events of visual field progression over an extended follow-up. DESIGN: Longitudinal, prospective, observational study. PARTICIPANTS: Two hundred forty-six eyes of 168 patients with glaucoma followed up every 6 months for up to 5 years. METHODS: Patients were required to have a minimum of 5 reliable SAP tests during the first 2 years of follow-up. Events of progression were evaluated using 2 methods: Guided Progression Analysis (GPA; Carl Zeiss Meditec, Inc) and a United States Food and Drug Administration (FDA)-suggested end point. The date of the first test showing progression after the first 2 years was considered to be the event date. Rates of change in SAP MD were calculated for the first 2 years of follow-up, and joint longitudinal survival models were used to assess the risk of faster initial MD loss for subsequent progression based on each event analysis. MAIN OUTCOME MEASURE: Risk of having an event of progression based on initial rates of SAP MD change. RESULTS: Fifty-six eye (22.8%) showed an event of progression by the GPA and 51 eyes (20.7%) did so by the FDA end point. Each 0.1-dB/year faster rate of SAP MD loss in the first 2 years was associated with a 26% increase in risk of a GPA progression end point developing (R2 = 76%) and 32% risk of an FDA-based end point developing (R2 = 83%). A reduction of 30% in the rate of MD change in the first 2 years was associated with a 20% reduction in the cumulative probability of a progression event developing over 5 years of follow-up. CONCLUSIONS: Rates of SAP MD change for eyes with glaucoma calculated over the initial 2 years of follow-up were strongly predictive of events of progression over subsequent follow-up. Our findings give support for the use of slopes of MD change as suitable end points of progression in clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Deep Learning-Assisted Detection of Glaucoma Progression in Spectral-Domain OCT.

PURPOSE: To develop and validate a deep learning (DL) model for detection of glaucoma progression using spectral-domain (SD)-OCT measurements of retinal nerve fiber layer (RNFL) thickness. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 14 034 SD-OCT scans from 816 eyes from 462 individuals. METHODS: A DL convolutional neural network was trained to assess SD-OCT RNFL thickness measurements of 2 visits (a baseline and a follow-up visit) along with time between visits to predict the probability of glaucoma progression. The ground truth was defined by consensus from subjective grading by glaucoma specialists. Diagnostic performance was summarized by the area under the receiver operator characteristic curve (AUC), sensitivity, and specificity, and was compared with conventional trend-based analyses of change. Interval likelihood ratios were calculated to determine the impact of DL model results in changing the post-test probability of progression. MAIN OUTCOME MEASURES: The AUC, sensitivity, and specificity of the DL model. RESULTS: The DL model had an AUC of 0.938 (95% confidence interval [CI], 0.921-0.955), with sensitivity of 87.3% (95% CI, 83.6%-91.6%) and specificity of 86.4% (95% CI, 79.9%-89.6%). When matched for the same specificity, the DL model significantly outperformed trend-based analyses. Likelihood ratios for the DL model were associated with large changes in the probability of progression in the vast majority of SD-OCT tests. CONCLUSIONS: A DL model was able to assess the probability of glaucomatous structural progression from SD-OCT RNFL thickness measurements. The model agreed well with expert judgments and outperformed conventional trend-based analyses of change, while also providing indication of the likely locations of change. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Comparison of 10-2 and 24-2 Perimetry to Diagnose Glaucoma Using OCT as an Independent Reference Standard.

PURPOSE: To compare the performance of the 10-2 test versus 24-2 standard automated perimetry (SAP) test for the diagnosis of glaucoma using OCT as an independent standard for glaucomatous damage. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 1375 pairs of 10-2 and 24-2 SAP tests from 569 eyes of 339 subjects were used for the analysis. A total of 440 (77%) eyes had a diagnosis of glaucoma, and 129 (23%) eyes were normal. All participants underwent 10-2 and 24-2 SAP tests within 30 days. METHODS: Glaucomatous severity was quantified based on OCT macula ganglion cell layer (mGCL) and circumpapillary retinal nerve fiber layer. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare 10-2 and 24-2 metrics for discriminating healthy eyes from those of glaucoma, at different levels of disease severity. MAIN OUTCOME MEASURES: Areas under the ROC curves and sensitivities at fixed specificities of 80% and 95%. RESULTS: The overall AUC for mean deviation (MD) for the 24-2 test (0.808) was significantly higher than that of the 10-2 test (0.742; P < 0.001). When compared at different stages of the disease, the 24-2 test performed generally better than the 10-2 test, notably in the earlier stages of the disease. For early damage (first quartile), the 24-2 MD had an AUC of 0.658 versus 0.590 for 10-2 MD (P = 0.018). For advanced damage (fourth quartile), corresponding values were 0.954 vs. 0.903 (P = 0.013). Similar trends were observed when glaucoma severity was defined based on structural macular damage with mGCL thickness. CONCLUSIONS: The 24-2 SAP test had better diagnostic accuracy compared with that of the 10-2 test for detecting equivalent levels of glaucomatous damage, as measured by quantitative assessment of retinal nerve fiber layer and macula by OCT. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association of an Objective Structural and Functional Reference Standard for Glaucoma with Quality of Life Outcomes.

PURPOSE: To compare self-reported quality-of-life (QoL) outcomes of patients diagnosed as normal, glaucoma suspect, and glaucoma based on an objective reference standard for glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. PARTICIPANTS: 1884 eyes of 1019 patients were included in the study. METHODS: The data was sourced from the Duke Glaucoma Registry. Eyes were classified according to the presence and topographic correspondence of functional and structural damage, as assessed by parameters from standard automated perimetry (SAP) and spectral-domain OCT (SD-OCT). The objective diagnosis of the worse eye was used to define patient-level diagnosis. To assess QoL in the diagnostic groups, 14 unidimensional vision-related items of the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) were used to assess QoL in the diagnostic groups. Association between NEI VFQ-25 Rasch-calibrated scores and diagnostic groups was assessed through multivariable regression that controlled for confounding demographic and socioeconomic variables such as age, sex, race, income, marriage status, insurance status, and highest education level. MAIN OUTCOME MEASURES: NEI VFQ-25 Rasch scores compared with objective criteria diagnosis based on SAP mean deviation (MD) and SD-OCT retinal nerve fiber layer (RNFL) thickness. RESULTS: Overall, eyes classified as normal, glaucoma suspect, and glaucoma had decreasing mean scores in SAP MD (0.2 ± 1.0 dB, -0.9 ± 2.4 dB, -6.2 ± 7.0 dB, respectively; P < 0.001) and SD-OCT RNFL thickness (97.8 ± 9.5 µm, 89.0 ± 13.1 µm, 64.5 ± 12.8 µm, respectively; P < 0.001). The mean Rasch-calibrated NEI VFQ-25 score was significantly different among normal, suspect, and glaucoma groups (82.9 ± 13.0, 78.2 ± 14.8, and 72.6 ± 16.2, respectively; P < 0.001). When adjusted for confounding socioeconomic variables, glaucoma patients had significantly worse QoL than those classified as normal (ß = -6.8 Rasch score units; P < 0.001). CONCLUSION: A glaucoma diagnosis, based on an objective reference standard for GON, was significantly associated with worse Rasch-adjusted scores of QoL. Utilization of such objective criteria may provide clinically relevant metrics with potential to improve comparability of research findings and validation of newly proposed diagnostic tools. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Scheimpflug-Derived Corneal Lower and Higher Order Aberrations Post Intrastromal Corneal Ring Segments for Keratoconus.

Intrastromal corneal ring segments (ICRS) improve corneal topographic symmetry and reduce corneal aberrations through regularization of the corneal surface, thereby functioning as a viable surgical intervention for patients with keratoconus. This study aims to evaluate changes in lower- (LOAs) and higher-order aberrations (HOAs) amongst varying pupil sizes pre- and post- ICRS implantation in keratoconus patients. We specifically investigate the impact of pupil size on total corneal HOAs up to the 6th order. Twenty-one eyes that underwent ICRS implantation were included in this prospective interventional study. LOAs and HOAs measurements at the 6 mm, 4 mm, and 2 mm pupil diameters were collected preoperatively and at 6 months postoperatively using the Zernicke analysis function on a Scheimpflug device. ICRS implantation demonstrated a statistically significant effect in vertical coma with a −0.23 reduction (p = 0.015) for a 4 mm pupil size and a −1.384 reduction (p < 0.001) for 6 mm, with no significant effect at 2 mm. Horizontal coma, astigmatism 0°, astigmatism 45°, trefoil 5th order 30°, and RMS HOA demonstrated significant reductions at 4 mm or 6 mm pupil sizes but not at 2 mm. Our analysis demonstrates a favorable effect of ICRS implantation on larger pupil sizes, suggesting the importance of pupil size as it correlates with HOAs reduction.