Publications

2021

Freedman S, Beck A, Nizam A, VanderVeen D, Plager D, Morrison D, Drews-Botsch C, Lambert S, Infant Aphakia Treatment Study Group. Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2021;139(2):165–173.
Importance: Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. Objective: To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Design, Setting, and Participants: Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Interventions: Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcomes and Measures: Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. Results: In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus  glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Conclusions and Relevance: Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. Trial Registration: ClinicalTrials.gov Identifier: NCT00212134.
Keilty M, Houston K, Collins C, Trehan R, Chen YT, Merabet L, Watts A, Pundlik S, Luo G. Inpatient Virtual Vision Clinic Improves Access to Vision Rehabilitation Before and During the COVID-19 Pandemic. Arch Rehabil Res Clin Transl. 2021;3(1):100100.
Objective: To describe and evaluate a secure video call system combined with a suite of iPad vision testing apps to improve access to vision rehabilitation assessment for inpatients. Design: Retrospective. Setting: Two acute care inpatient rehabilitation hospitals and 1 long-term acute care (LTAC) hospital. Participants: Records of inpatients seen by the vision service. Interventions: Records from a 1-year telemedicine pilot performed at acute rehabilitation (AR) hospital 1 and then expanded to AR hospital 2 and LTAC hospital during coronavirus disease 2019 (COVID-19) were reviewed. In the virtual visits, an occupational therapist measured the patients' vision with the iPad applications and forwarded results to the off-site Doctor of Optometry (OD) for review prior to a video visit. The OD provided diagnosis and education, press-on prism application supervision, strategies and modifications, and follow-up recommendations. Providers completed the telehealth usability questionnaire (10-point scale). Main Outcome Measures: Vision examinations per month at AR hospital 1 before and with telemedicine. Results: With telemedicine at AR hospital 1, mean visits per month significantly increased from 10.7±5 to 14.9±5 (=.002). Prism was trialed in 40% of cases of which 83% were successful, similar to previously reported in-person success rates. COVID-19 caused only a marginal decrease in visits per month (=.08) at AR1, whereas the site without an established program (AR hospital 2) had a 3-4 week gap in care while the program was initiated. Cases at the LTAC hospital tended to be more complex and difficult to manage virtually. The telehealth usability questionnaire median category scores were 7 for , 8 for , 6 for , and 9 for . Conclusions: The virtual vision clinic process improved inpatient access to eye and visual neurorehabilitation assessment before and during the COVID-19 quarantine and was well accepted by providers and patients.
Dixit A, Yohannan J, Boland M. Assessing Glaucoma Progression Using Machine Learning Trained on Longitudinal Visual Field and Clinical Data. Ophthalmology. 2021;128(7):1016–1026.
PURPOSE: Rule-based approaches to determining glaucoma progression from visual fields (VFs) alone are discordant and have tradeoffs. To detect better when glaucoma progression is occurring, we used a longitudinal data set of merged VF and clinical data to assess the performance of a convolutional long short-term memory (LSTM) neural network. DESIGN: Retrospective analysis of longitudinal clinical and VF data. PARTICIPANTS: From 2 initial datasets of 672 123 VF results from 213 254 eyes and 350 437 samples of clinical data, persons at the intersection of both datasets with 4 or more VF results and corresponding baseline clinical data (cup-to-disc ratio, central corneal thickness, and intraocular pressure) were included. After exclusion criteria-specifically the removal of VFs with high false-positive and false-negative rates and entries with missing data-were applied to ensure reliable data, 11 242 eyes remained. METHODS: Three commonly used glaucoma progression algorithms (VF index slope, mean deviation slope, and pointwise linear regression) were used to define eyes as stable or progressing. Two machine learning models, one exclusively trained on VF data and another trained on both VF and clinical data, were tested. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPRC) calculated on a held-out test set and mean accuracies from threefold cross-validation were used to compare the performance of the machine learning models. RESULTS: The convolutional LSTM network demonstrated 91% to 93% accuracy with respect to the different conventional glaucoma progression algorithms given 4 consecutive VF results for each participant. The model that was trained on both VF and clinical data (AUC, 0.89-0.93) showed better diagnostic ability than a model exclusively trained on VF results (AUC, 0.79-0.82; P < 0.001). CONCLUSIONS: A convolutional LSTM architecture can capture local and global trends in VFs over time. It is well suited to assessing glaucoma progression because of its ability to extract spatiotemporal features that other algorithms cannot. Supplementing VF results with clinical data improves the model's ability to assess glaucoma progression and better reflects the way clinicians manage data when managing glaucoma.
Sokol J, Schechet S, Komati R, Eliott D, Vavvas D, Kaplan R, Ittiara S, Farooq A, Sheth V, MacCumber M, Ke R, Gentile R, Skondra D. Macular Hole Closure with Medical Treatment. Ophthalmol Retina. 2021;5(7):711–713.
Gonzalez-Buendia L, Delgado-Tirado S, An M, O’Hare M, Amarnani D, Whitmore H, Zhao G, Ruiz-Moreno J, Arboleda-Velasquez J, Kim L. Treatment of Experimental Choroidal Neovascularization via RUNX1 Inhibition. Am J Pathol. 2021;191(3):418–424.
Choroidal neovascularization (CNV) is a prevalent cause of vision loss in patients with age-related macular degeneration. Runt-related transcription factor 1 (RUNX1) has been identified as an important mediator of aberrant retinal angiogenesis in proliferative diabetic retinopathy and its modulation has proven to be effective in curbing pathologic angiogenesis in experimental oxygen-induced retinopathy. However, its role in CNV remains to be elucidated. This study demonstrates RUNX1 expression in critical cell types involved in a laser-induced model of CNV in mice. Furthermore, the preclinical efficacy of Ro5-3335, a small molecule inhibitor of RUNX1, in experimental CNV is reported. RUNX1 inhibitor Ro5-3335, aflibercept-an FDA-approved vascular endothelial growth factor (VEGF) inhibitor, or a combination of both, were administered by intravitreal injection immediately after laser injury. The CNV area of choroidal flatmounts was evaluated by immunostaining with isolectin B4, and vascular permeability was analyzed by fluorescein angiography. A single intravitreal injection of Ro5-3335 significantly decreased the CNV area 7 days after laser injury, and when combined with aflibercept, reduced vascular leakage more effectively than aflibercept alone. These data suggest that RUNX1 inhibition alone or in combination with anti-VEGF drugs may be a new therapy upon further clinical validation for patients with neovascular age-related macular degeneration.
Singh N, Singh R, Bowen RC, Abdel-Rahman M, Singh A. Uveal Melanoma in BAP1 Tumor Predisposition Syndrome: Estimation of Risk. Am J Ophthalmol. 2021;224:172–177.
PURPOSE: To estimate point prevalence of uveal melanoma in the patients with germline BAP1 pathogenic variant. DESIGN: Cohort study with risk assessment using Bayesian analysis. METHODS: The point prevalence estimate was obtained by Bayes's rule of reverse conditional probabilities. The probability of uveal melanoma given that BAP1 mutation exists was derived from the prevalence of uveal melanoma, prevalence of germline BAP1 pathogenic variants, and the probability of germline BAP1 pathogenic variant given that uveal melanoma is present. Confidence intervals (CIs) for each variable were calculated as the mean of Bernoulli random variables and for the risk estimate, by the delta method. The age at diagnosis and the gender of the uveal melanoma patients with BAP1 germline pathogenic variants obtained from previous publications or from authors' unpublished cohort was compared with those in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The point prevalence of uveal melanoma in patients with the germline BAP1 pathogenic variants in the US population was estimated to be 2.8% (95% CI, 0.88%-4.81%). In the SEER database, the median age at diagnosis of uveal melanomas was 63 (range 3-99 years) with a male-to-female ratio of 1.01:1. In comparison, uveal melanoma cases with BAP1 germline pathogenic variants from the US population (n = 27) had a median age at diagnosis of 50.5 years (range 16-71). CONCLUSIONS: Quantification of the risk of developing uveal melanoma can enhance counseling regarding surveillance in patients with germline BAP1 pathogenic variant.
Mori T, Kikuchi T, Koh M, Koda Y, Yamazaki R, Sakurai M, Tomita Y, Ozawa Y, Kohashi S, Abe R, Saburi M, Kato J. Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening. Bone Marrow Transplant. 2021;56(6):1266–1271.
Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.
Sharif F, Tayebi B, Buzsáki G, Royer S, Fernandez-Ruiz A. Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments. Neuron. 2021;109(2):363–376.e6.
The hippocampus is thought to guide navigation by forming a cognitive map of space. Different environments differ in geometry and the availability of cues that can be used for navigation. Although several spatial coding mechanisms are known to coexist in the hippocampus, how they are influenced by various environmental features is not well understood. To address this issue, we examined the spatial coding characteristics of hippocampal neurons in mice and rats navigating in different environments. We found that CA1 place cells located in the superficial sublayer were more active in cue-poor environments and preferentially used a firing rate code driven by intra-hippocampal inputs. In contrast, place cells located in the deep sublayer were more active in cue-rich environments and used a phase code driven by entorhinal inputs. Switching between these two spatial coding modes was supported by the interaction between excitatory gamma inputs and local inhibition.