The Impact of the Coronavirus Disease 2019 Pandemic on Adherence to Ocular Hypotensive Medication in Patients with Primary Open-Angle Glaucoma.

PURPOSE: Emerging evidence suggests that the coronavirus disease 2019 (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 National Institutes of Health-funded study initiated before 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 before and after the segmentation. We compared the 2 slopes using the Davies test. MAIN OUTCOME MEASURES: 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 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 [standard deviation, 8 years]). Segmented regression identified a breakpoint at day 28 after the declaration of the pandemic. The slope in the period after the breakpoint (-0.04%/day) was significantly different from zero (P < 0.001) and from the slope in the period before the breakpoint (0.006%/day; P < 0.001). Mean adherence in the period before the segmentation breakpoint was significantly worse in Black patients (median, IQR: 80.6%, 36.2%) compared with White patients (median, IQR: 97.2%, 8.7%; chi-square, 15.4; P = 0.0004). A significant positive association was observed between the Connor-Davidson resilience score and the change in slope between the periods before and after the breakpoint (P = 0.002). CONCLUSIONS: Adherence to ocular hypotensive medication worsened during the COVID-19 pandemic and seems to be related to patient resilience. This collateral consequence of the pandemic may translate into vision loss that may manifest beyond its containment.

Revisiting disease genes based on whole-exome sequencing in consanguineous populations.

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.

Whitecoat Adherence in Patients With Primary Open-Angle Glaucoma.

Purpose: Whitecoat adherence refers to improved medication adherence in the days surrounding clinic visits. This may lead to clinical measures that are not representative of those outside of clinical encounters. In glaucoma, whitecoat adherence to prescribed hypotensive therapy may lead to intraocular pressure readings within the target range, which may impact clinical decision-making. We aimed to quantify and identify factors associated with whitecoat adherence. Methods: In this cohort study, patients with primary open-angle glaucoma were selected from an ongoing longitudinal NIH-funded study if they used hypotensive eyedrops, had a clinic visit during the parent study, and had adherence data during the 28 days evenly bracketing the clinic visit. Adherence within the implementation phase was measured using Medication Event Monitoring System (MEMS) caps. Wilcoxon tests were used to compare mean adherence between the following periods: Pre14-4 (days 14 to 4 preceding the clinic visit) and Pre3-1 (days 3 to 1 preceding the visit); Post1-3 (days 1 to 3 following the clinic visit) and Post4-14 (days 4 to 14 following the visit). Analyses were performed in the full sample and in patients with optimal (≥80%, n = 49) and suboptimal adherence (<80%, n = 17). Results: Sixty-six patients were included, of which 51.5% were female. Mean age was 70.8 ± 8.1 years. In the 6 months evenly bracketing the clinic visit, mean and median adherence were 86.3% (standard deviation = 17.7) and 95.6% (interquartile range = 21.2), respectively. Overall, mean adherence increased from Pre14-4 to Pre3-1 (85.5% ± 21.2 to 88.5% ± 23.2, p = 0.01) and decreased from Post1-3 to Post4-14 (87.0 ± 23.9 to 84.9 ± 23.3, p = 0.02). In patients with optimal adherence, adherence increased from Pre14-4 to Pre3-1 (94.0 ± 11.7 to 97.7 ± 7.4, p = 0.001) and from Post1-3 to Post4-14 (95.2 ± 12.0 to 95.4 ± 5.7, p = 0.007). Whitecoat adherence was not observed in patients with suboptimal adherence. Conclusion: We documented the presence of whitecoat adherence in this cohort. Due to its potential impact on clinical outcomes and decisions, providers should remain vigilant for this phenomenon and prioritize it during patient-provider discussions.

Rate of Corneal Grafting Post-Glaucoma Drainage Device Use in Pediatric and Adult Patients.

PRCIS: Kaplan-Meier analysis was used to compare the rate of corneal grafting after glaucoma drainage device (GDD) placement in pediatric and adult patients. Adults were at an increased risk of receiving a corneal graft after device placement. PURPOSE: The goal of this study was to compare the rate of corneal graft implantation after GDD placement in pediatric and adult patients. PATIENTS: Patients receiving a GDD between January 1, 1985 and December 31, 2017 were selected from the medical records. Patients receiving their first device while <18 years of age were considered children for the extent of the study. METHODS: We compared the rate of receiving a corneal graft after GDD implantation using Kaplan-Meier analysis. Baseline patient characteristics and surgical characteristics were compared using a generalized estimating equation. RESULTS: Corneal grafting occurred in 8.6% of adults and 4.7% of children from the original cohort. The rate of receiving a corneal graft at 5, 10, and 15 years was 9.4%, 16.8%, 39.4% and 1.6%, 1.6%, 12.5% for adults and children, respectively. However, certain characteristics were different between the 2 groups. CONCLUSION: Adult patients were more likely to receive a corneal graft after GDD placement. However, pediatric and adult patients differed in the prevalence of preexisting corneal disease, glaucoma type, GDD type used, and types of previous surgeries. Elucidation of the impact of these factors on corneal graft rate requires a larger cohort size.

Need for Additional Glaucoma Surgery and Complications Following Glaucoma Drainage Device Surgery.

PRCIS: 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.

Rates of Diplopia in Ahmed FP7, Baerveldt 250, and 350 Glaucoma Patients Compared With Medical Controls.

PRECIS: Diplopia was present in ~20% of patients with Ahmed FP7 (FP7) or Baerveldt 350 (B350), compared with 5% to 6% in those with Baerveldt 250 (B250) or controls, suggesting risk of diplopia should be included in preoperative counseling. PURPOSE: The purpose of this study was to examine the prevalence of diplopia and strabismus in patients with B250, B350, or FP7 glaucoma drainage devices (GDD). MATERIALS AND METHODS: In this cohort study, glaucoma patients 18 years and above who had received, or would be receiving, a B250, B350, or FP7 GDD, and medically treated controls were consecutively enrolled from August 8, 2017, through July 31, 2019. The Diplopia Questionnaire was administered ≥30 days postoperatively, and upon enrollment to the controls. All diplopic patients underwent orthoptic measurements, which were reviewed by a strabismus specialist. Patients with GDDs in quadrants other than superotemporal, multiple GDDs, or scleral buckles were excluded. Bonferroni correction was applied for pairwise comparisons. RESULTS: Diplopia was reported in 23/129 (17.8%) GDD patients and 5/99 (5.1%) control patients (P=0.003): 8/35 (22.9%) FP7, 2/32 (6.3%) B250, and 13/62 (21.0%) B350, with significant differences between FP7 versus controls (P=0.014) and B350 versus controls (P=0.011). Diplopia was attributable to GDD in 2 FP7 (5.9%, 95% confidence interval: 0.7-19.2), 0 B250, and 4 B350 (6.5%, 95% confidence interval: 1.7-15.2) patients, without significant differences between the GDDs. CONCLUSIONS: Patients with the larger (B350) or the higher profile plate (FP7) GDDs were more likely to experience diplopia than controls, and diplopia was attributable to the GDD in ~6% of patients with either a FP7 or a B350 GDD. Since diplopia can affect patients' quality of life, preoperative counseling for GDD surgery, particularly B350 and FP7, should include a discussion of the risk of diplopia.

Discordance Rate Among Bilateral Simultaneous and Sequential Temporal Artery Biopsies in Giant Cell Arteritis: Role of Frozen Sectioning Based on the Mayo Clinic Experience.

IMPORTANCE: Frozen 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 PARTICIPANTS: In 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 MEASURES: Sensitivity and specificity of frozen section TAB for detecting GCA, and discordance rates of bilateral permanent section TAB. RESULTS: Of 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], 1.04; 95% CI, 1.01-1.07; P = .008), vision loss (OR, 2.72; 95% CI, 1.25-5.75; P = .01), diplopia (OR, 3.33; 95% CI, 1.00-10.29; P = .04), headache (OR, 2.32; 95% CI, 1.25-4.53; P = .01), weight loss (OR, 2.37; 95% CI, 1.26-4.43; P = .007), and anorexia (OR, 5.65; 95% CI, 2.70-11.89; P < .001). CONCLUSIONS AND RELEVANCE: These results support the hypothesis that negative findings from frozen sections should not be solely relied on to refute the diagnosis of GCA, whereas positive findings from frozen sections can be reliably used to defer a contralateral biopsy pending the permanent section results.