Faculty Bibliography

Purpose/UNASSIGNED:To report 2 cases with a novel finding of bullous epithelial keratopathy associated with netarsudil use. Observations/UNASSIGNED:A 72-year-old man with history of primary open angle glaucoma was started on netarsudil daily in both eyes for uncontrolled intraocular pressures despite treatment with latanoprost, brimonidine, and dorzolamide-timolol. One month later he presented with bilateral conjunctival hyperemia, predominantly inferior corneal epithelial bullae, and keratic precipitates without hypopyon. Netarsudil was discontinued, and the patient was started on topical steroids. One week later, the hyperemia and corneal edema had resolved while many small keratic precipitates persisted.A 29-year-old man with history of rubella-associated glaucoma and chronic postoperative inflammation on prednisolone was started on netarsudil in his left eye only for elevated intraocular pressures despite latanoprost, brimonidine, and dorzolamide-timolol. Two months later, he complained of eye pain and decreased vision since starting netarsudil. Examination revealed mild hyperemia and inferior corneal epithelial bullae without keratic precipitates. Netarsudil was discontinued, and two weeks later, conjunctival injection resolved and cornea cleared. Conclusions and importance/UNASSIGNED:Netarsudil ophthalmic solution 0.02% (Rhopressa) is a rho-kinase inhibitor recently approved for lowering intraocular pressure in open-angle glaucoma or ocular hypertension. As netarsudil continues to be increasingly used, physicians and patients need to be aware of this new possible adverse effect.

A 70-year-old woman with a history of Demodex blepharitis presented with a 1-year history of red-yellow nodules in the tarsus of her eyelids. Excisional biopsy revealed robust caseating granulomatous inflammation, consistent with the diagnosis of lupus miliaris disseminatus faciei. Lupus miliaris disseminatus faciei is a rare granulomatous dermatosis of unknown etiology. Estimated 200 cases have been reported to date, but none have been reported affecting the posterior lamellae of the eyelids. Lupus miliaris disseminatus faciei classically presents as symmetric yellow or brown papules on the central face and eyelid skin. Infectious etiologies and systemic granulomatous disease need to be ruled out with histologic staining and serologies.

Importance:Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. Objective:To quantify the association between patients' adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. Design, Setting, and Participants:This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. Exposures:Visit adherence was measured in 4 ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended). Average and max days were also categorized as on time (28-35 days), late (36-60 days), and very late (>60 days). Main Outcomes and Measures:Change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti-vascular endothelial growth factor drug, number of injections, and dosing regimen. Results:Of 1178 patients, the mean (SD) age was 79.1 (7.3) years, and 727 (61.7%) were women. The mean (SD) number of missed visits was 2.4 (3.1). Overall, 1091 patients (92.6%) had complete visit constancy during the entire study period. Average days were categorized with 1060 patients (90.0%) classified as on time, 108 (9.2%) were late, and 10 (0.8%) were very late. For max days between visits, 197 patients (16.7%) were on time, 773 (65.6%) were late, and 208 (17.7%) were very late. After controlling for covariates, the late (avg days = -6.1; max days = -2.0) and very late (avg days = -12.5; max days = -5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (P < .001). Conclusions and Relevance:These results provide evidence to support the concept that visit adherence contributes to VA outcomes in neovascular age-related macular degeneration. The magnitude of the association of visit adherence with VA outcomes in this clinical scenario suggests that substantial effort should be expended to strive for visit adherence or therapeutic strategies that reduce the visit burden without compromising VA outcomes. Trial Registration:ClinicalTrials.gov Identifier: NCT00593450.

Purpose/UNASSIGNED:To present a case of glioblastoma multiforme which initially presented with only ophthalmic manifestations. Observations/UNASSIGNED:A 48-year-old man presented with decreased vision and pain with eye movements of the right eye. MRI of the brain showed increased T2/FLAIR signal involving the right optic nerve with no other identified abnormalities. He was treated with intravenous steroids for presumed optic neuritis. His visual acuity then rapidly worsened to no light perception, with new orbital apex symptoms including central retinal artery and vein occlusions and inferior division third and fourth nerve palsies. Repeat MRI with contrast showed perineural enhancement surrounding the right optic nerve and markedly reduced diffusion along its entire course. After an unrevealing initial workup and then a 7 month period during which the patient refused follow up, he re-presented with left sided weakness, headache, and confusion. Repeat brain MRI revealed a large mass involving the right optic nerve, optic chiasm, basal ganglia, corpus callosum and brainstem. Biopsy led to a diagnosis of WHO grade IV glioblastoma multiforme. The disease was poorly responsive to temozolomide, bevacizumab and external beam radiation, and the patient passed away 5 months later. Conclusions and importance/UNASSIGNED:Malignant optic glioma of adulthood is a challenging diagnosis with a poor prognosis. This rare case highlights the importance of maintaining neoplasm in the differential for optic neuritis masqueraders.

Objective/UNASSIGNED:The purpose of this study is to evaluate the role mitochondrial inheritance plays in primary open-angle glaucoma (POAG) characteristics in African Americans. Methods/UNASSIGNED:= 0.97), sex (21 female and 5 male pairs), and family history of glaucoma (positive in 15/26 [58%] pairs) were included. Results/UNASSIGNED:= 0.99). Conclusion/UNASSIGNED:Results demonstrated worse glaucomatous cupping and more severe VF loss in the L1c2 compared to the L1b haplogroup despite comparable IOP. Findings implicate mitochondrial inheritance as a factor affecting POAG severity and may ultimately contribute to stratifying POAG patients into phenotypically and genotypically distinct subgroups.

Purpose:We investigate the function of the V83I polymorphism (m.6150G>A, rs879053914) in the mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) gene and its role in African American (AA) primary open-angle glaucoma (POAG). Methods:This study used Sanger sequencing (1339 cases, 850 controls), phenotypic characterization of Primary Open-Angle African American Glaucoma Genetics study (POAAGG) cases, a masked chart review of CO1 missense cases (V83I plus M117T, n = 29) versus wild type cases (n = 29), a yeast 2-hybrid (Y2H) cDNA library screen, and quantification of protein-protein interactions by Y2H and ELISA. Results:The association of V83I with POAG in AA was highly significant for men (odds ratio [OR] 6.5; 95% confidence interval [CI] 2.0-21.3, P = 0.0001), but not for women (OR 1.1; 95% CI, 0.62-2.00, P = 0.78). POAG cases having CO1 double missense mutation (V83I + M117T, L1c2 haplogroup) had a higher cup-to-disc ratio (0.77 vs. 0.71, P = 0.04) and significantly worse visual function (average pattern standard deviation, 6.5 vs. 4.3, P = 0.009; average mean deviation -10.4 vs. -4.5, P = 0.006) when compared to matched wild type cases (L1b haplogroup). Interaction of the V83I region of CO1 with amyloid beta peptide (Aβ) was confirmed by ELISA assay, and this interaction was abrogated by V83I. A Y2H screen of an adult human brain cDNA library with the V83 region of CO1 as bait retrieved the UBQLN1 gene. Conclusions:The V83I polymorphism was associated strongly with POAG in AA men and disrupts Aβ-binding to CO1. This region also interacts with a neuroprotective protein, UBQLN1.

OBJECTIVE:No method of grading visual field (VF) defects has been widely accepted throughout the glaucoma community. The SCHEIE (Systematic Classification of Humphrey visual fields-Easy Interpretation and Evaluation) grading system for glaucomatous visual fields was created to convey qualitative and quantitative information regarding visual field defects in an objective, reproducible, and easily applicable manner for research purposes. METHODS:The SCHEIE grading system is composed of a qualitative and quantitative score. The qualitative score consists of designation in one or more of the following categories: normal, central scotoma, paracentral scotoma, paracentral crescent, temporal quadrant, nasal quadrant, peripheral arcuate defect, expansive arcuate, or altitudinal defect. The quantitative component incorporates the Humphrey visual field index (VFI), location of visual defects for superior and inferior hemifields, and blind spot involvement. Accuracy and speed at grading using the qualitative and quantitative components was calculated for non-physician graders. RESULTS:Graders had a median accuracy of 96.67% for their qualitative scores and a median accuracy of 98.75% for their quantitative scores. Graders took a mean of 56 seconds per visual field to assign a qualitative score and 20 seconds per visual field to assign a quantitative score. CONCLUSION/CONCLUSIONS:The SCHEIE grading system is a reproducible tool that combines qualitative and quantitative measurements to grade glaucomatous visual field defects. The system aims to standardize clinical staging and to make specific visual field defects more easily identifiable. Specific patterns of visual field loss may also be associated with genetic variants in future genetic analysis.