and for the BONSAI (Brain and Optic Nerve Study with Artificial Intelligence) Study Group Objective: To compare the diagnostic performance of an artificial intelligence deep learning system with that of expert neuro-ophthalmologists in classifying optic disc appearance. Methods: The deep learning system was previously trained and validated on 14,341 ocular fundus photographs from 19 international centers. The performance of the system was evaluated on 800 new fundus photographs (400 normal optic discs, 201 papilledema [disc edema from elevated intracranial pressure], 199 other optic disc abnormalities) and compared with that of 2 expert neuro-ophthalmologists who independently reviewed the same randomly presented images without clinical information. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were calculated. Results: The system correctly classified 678 of 800 (84.7%) photographs, compared with 675 of 800 (84.4%) for Expert 1 and 641 of 800 (80.1%) for Expert 2. The system yielded areas under the receiver operating characteristic curve of 0.97 (95% confidence interval [CI] = 0.96-0.98), 0.96 (95% CI = 0.94-0.97), and 0.89 (95% CI = 0.87-0.92) for the detection of normal discs, papilledema, and other disc abnormalities, respectively. The accuracy, sensitivity, and specificity of the system's classification of optic discs were similar to or better than the 2 experts. Intergrader agreement at the eye level was 0.71 (95% CI = 0.67-0.76) between Expert 1 and Expert 2, 0.72 (95% CI = 0.68-0.76) between the system and Expert 1, and 0.65 (95% CI = 0.61-0.70) between the system and Expert 2. Interpretation: The performance of this deep learning system at classifying optic disc abnormalities was at least as good as 2 expert neuro-ophthalmologists. Future prospective studies are needed to validate this system as a diagnostic aid in relevant clinical settings.

Objective Emerging evidence suggests that the COVID-19 pandemic is disrupting health behaviors such as medication adherence. The objective of this study was to determine whether adherence to ocular hypotensive medication was affected by the pandemic and to identify factors associated with this change. Design In this cohort study, we used a controlled interrupted time series design in which the interruption was the declaration of the COVID-19 pandemic in the United States on March 13, 2020. The 300-day monitoring period, which evenly bracketed this declaration, started on October 16, 2019, and ended on August 10, 2020. Participants Patients with primary open-angle glaucoma enrolled in an ongoing longitudinal NIH-funded study initiated prior to the onset of the pandemic were selected if they were prescribed ocular hypotensive medication and had adherence data spanning the 300-day period. Methods We applied segmented regression analysis using a “slope change following a lag” impact model to obtain the adherence slopes in the periods preceding and following the segmentation. We compared the two slopes using the Davies test. Main outcome and measure The main outcome measure was daily adherence to ocular hypotensive medication—defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Adherence was measured objectively using Medication Event Monitoring System (MEMS) caps. We assessed the associations between change in adherence and demographic, clinical, and psychosocial factors. Results The sample included 79 patients (mean age, 71 years [SD, 8 years]). Segmented regression identified a breakpoint at day 28 following the declaration of the pandemic. The slope in the post-breakpoint period (-0.04%/day) was significantly different from zero ( P < 0.001) and from the slope in the period preceding the breakpoint (0.006%/day) ( P < 0.001). A significant positive association was observed between the Connor-Davidson Resilience score and the change in slope between the pre- and post-breakpoint periods ( P = 0.002). Conclusions and Relevance Adherence to ocular hypotensive medication worsened during the COVID-19 pandemic and appears to be related to patient resilience. This collateral consequence of the pandemic may translate into vision loss that may manifest beyond its containment.

Assigning a causal role for genes in disease states is one of the most significant medical applications of human genetics research. The requirement for at least two different pathogenic alleles in the same gene in individuals with a similar phenotype to assign a causal link has not always been fully adhered to, and we now know that even two alleles may not necessarily constitute sufficient evidence. Autozygosity is a rich source of natural "knockout" events by virtue of rendering ancestral loss-of-function (LOF) variants homozygous. In this study, we exploit this phenomenon by examining 523 exomes enriched for autozygosity to call into question previously published disease links for several genes based on the identification of confirmed homozygous LOF variants in the absence of the purported diseases. This study highlights an additional advantage of consanguineous populations in the quest to improve the medical annotation of the human genome.

IMPORTANCEFrozen section temporal artery biopsy (TAB) may prevent a contralateral biopsy from being performed. OBJECTIVE To evaluate the sensitivity and specificity of TAB frozen vs permanent section pathology results for giant cell arteritis (GCA) and determine the discordance rate of bilateral TABs. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective cohort study, medical records were reviewed from 795 patients 40 years or older who underwent TAB from January 1, 2010, to December 1, 2018, treated at a single tertiary care center with the ability to perform both frozen and permanent histologic sections. Data were analyzed from January 2019 to December 2020. MAIN OUTCOMES AND MEASURESSensitivity and specificity of frozen section TAB for detecting GCA, and discordance rates of bilateral permanent section TAB. RESULTSOf the 795 included participants, 329 (41.4%) were male, and the mean (SD) age was 72 (10) years. From the 795 patients with 1162 TABs, 119 patients (15.0%) and 138 TABs had positive findings on permanent section. Of these 119 patients, 103 (86.6%) also had positive results on the frozen section, with 4 false-positives (0.6%) and 20 false-negatives (16.8%). Frozen section had a specificity of 99.4% (95% CI, 98.5-99.8), sensitivity of 83.2% (95% CI, 75.2-89.4), positive predictive value of 96.1% (95% CI, 90.4-98.9), negative predictive value of 96.6% (95% CI, 94.9-97.8), positive likelihood ratio of 140.6 (95% CI, 72.7-374.8), and a negative likelihood ratio of 0.17 (95% CI, 0.11-0.25). Simultaneous bilateral TABs were performed in 60 patients (7.5%) with a 5% discordance rate on permanent section. In comparison, bilateral frozen section-guided sequential TABs were performed in 307 patients (38.6%) with 5.5% discordance based on permanent section. In multivariate models, there was a greater odds of positive findings with age (odds ratio [OR],

Précis: In this longitudinal study of patients with open-angle (OAG), pseudoexfoliative (PXE), or neovascular glaucoma (NVG) receiving glaucoma drainage devices (GDD), posttube cumulative rates of reoperation, corneal graft, and visually threatening complications (VT-complications) increased beyond 5 years and were not significantly affected by glaucoma type.Purpose: To study the need for additional glaucoma surgery and development of complications after first GDD surgery in eyes with primary OAG, PXE, or NVG glaucoma.Patients and Methods: There were 306 eyes with OAG (n = 185), PXE (n = 60), or NVG (n = 61) glaucoma who received a first GDD between 1996 and 2017. Outcomes including glaucoma reoperation, corneal graft procedure, and VT-complications after GDD were measured. Kaplan-Meier analysis was used to compare cumulative rate of reaching outcomes over time after GDD placement among the 3 glaucoma groups.Results: When comparing the OAG, PXE, and NVG groups, there were no significant differences in post-GDD cumulative rates of reoperation (P = 0.33), corneal graft (P = 0.26), or VT-complications (P = 0.65) over time. For all eyes, the overall cumulative rates for each outcome measure increased beyond 5 years, and specific Kaplan-Meier rates (5-y, 10-y) included: reoperation (16%, 25%), corneal graft (6%, 12%), VT-complications (9%, 14%). When comparing specific GDDs, the Ahmed FP7 had a higher cumulative reoperation rate over time compared with the Baerveldt 350 (P = 0.019).Conclusion: Glaucoma type did not significantly affect post-GDD cumulative rates of reoperation, corneal graft, and VT-complication among the OAG, PXE, and NVG groups. For all eyes, cumulative rates of reoperation, corneal graft, and VT-complications increased beyond 5 years. The Ahmed FP7 had a significantly higher cumulative reoperation rate compared with the Baerveldt 350 over time.