Faculty Bibliography

PURPOSE/OBJECTIVE:To report a case of bilateral acute angle closure glaucoma associated with hyponatremia in the setting of chlorthalidone use and SARS-CoV-2 infection, and to demonstrate the challenges of managing this patient given her infectious status. METHODS:Case report. CASE/METHODS:A 65-year-old woman taking chlorthalidone for hypertension presented to the emergency room with headache, pain, and blurry vision in both eyes and was found to be in bilateral acute angle closure. On laboratory investigation, she was severely hyponatremic and also tested positive for SARS-CoV-2. B-scan ultrasound demonstrated an apparent supraciliary effusion in the right eye. Following stabilization of her intraocular pressures with medical management, she ultimately underwent cataract extraction with iridectomies and goniosynechiolysis in both eyes. CONCLUSIONS:We report a rare case of bilateral acute angle closure glaucoma associated with hyponatremia. Chlorthalidone use and perhaps SARS-CoV-2 infection may have contributed to this electrolyte abnormality and unique clinical presentation. Additionally, we discuss the challenges of managing this complex patient with active SARS-CoV-2 infection during the pandemic.

Importance/UNASSIGNED:Facial recognition is a critical activity of daily living that relies on macular function. Glaucomatous macular damage may result in impaired facial recognition that may negatively affect patient quality of life. Objective/UNASSIGNED:To evaluate the association of patterns of glaucomatous macular damage with contrast sensitivity and facial recognition among patients with glaucoma. Design, Setting, and Participants/UNASSIGNED:In this prospective cohort study at a single tertiary care center, 144 eyes of 72 consecutive patients with glaucoma with good visual acuity (20/40 or better in each eye) were studied. Data were collected from March to April 2019. Exposures/UNASSIGNED:Eyes with macular damage were categorized as having focal, diffuse, or mixed (focal and diffuse) damage based on optic disc and macular spectral-domain optical coherence tomography and 10-2 visual field (VF) damage. Only eyes with focal or diffuse damage were included. Higher-acuity and lower-acuity eyes were determined by 10-2 VF mean deviation (MD). Facial disability was defined as facial recognition scores at the 2% level of normal participants. Main Outcomes and Measures/UNASSIGNED:(1) Monocular contrast threshold as measured by the Freiburg Visual Acuity and Contrast Test and (2) binocular facial recognition as measured by the Cambridge Face Memory Test. Results/UNASSIGNED:Of the 72 included patients, 49 (68%) were White and 41 (57%) were female, and the mean (SD) age was 67.0 (11.6) years. Eyes with diffuse damage had greater contrast impairment compared with eyes with focal damage (β = -0.5; 95% CI, -0.6 to -0.4; P < .001) after adjusting for 10-2 VF MD, 24-2 VF MD, age, presence of an early cataract, and number of drops. Similarly, Cambridge Face Memory Test scores were significantly lower in patients with diffuse rather than focal macular damage, regardless of eye (better-seeing eye: β = 10.0; 95% CI, 2.0 to 18.2; P = .001; worse-seeing eye: β = 5.5; 95% CI, 0.8 to 10.0; P = .23). Relative risk of facial disability was greater for patients with diffuse but not focal macular damage in the better-seeing eye (relative risk, 86.2; 95% CI, 2.7 to 2783.3; P = .01). Conclusions and Relevance/UNASSIGNED:In this cohort study, diffuse rather than focal glaucomatous macular damage was associated with diminished facial recognition and contrast sensitivity. Evaluation of macular optical coherence tomography and 10-2 VF and resultant detection of diffuse macular damage may help minimize glaucoma-related visual disability.

Glaucoma is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness, worldwide. While the experimental research using animal models provides growing information about cellular and molecular processes, parallel analysis of the clinical presentation of glaucoma accelerates the translational progress towards improved understanding, treatment, and clinical testing of glaucoma. Optic nerve axon injury triggers early alterations of retinal ganglion cell (RGC) synapses with function deficits prior to manifest RGC loss in animal models of glaucoma. For testing the clinical relevance of experimental observations, this study analyzed the functional correlation of localized alterations in the inner plexiform layer (IPL), where RGCs establish synaptic connections with retinal bipolar and amacrine cells. Participants of the study included a retrospective cohort of 36 eyes with glaucoma and a control group of 18 non-glaucomatous subjects followed for two-years. The IPL was analyzed on consecutively collected macular SD-OCT scans, and functional correlations with corresponding 10-2 visual field scores were tested using generalized estimating equations (GEE) models. The GEE-estimated rate of decrease in IPL thickness (R = 0.36, P<0.001) and IPL density (R = 0.36, P<0.001), as opposed to unchanged or increased IPL thickness or density, was significantly associated with visual field worsening at corresponding analysis locations. Based on multivariate logistic regression analysis, this association was independent from the patients' age, the baseline visual field scores, or the baseline thickness or alterations of retinal nerve fiber or RGC layers (P>0.05). These findings support early localized IPL alterations in correlation with progressing visual field defects in glaucomatous eyes. Considering the experimental data, glaucoma-related increase in IPL thickness/density might reflect dendritic remodeling, mitochondrial redistribution, and glial responses for synapse maintenance, but decreased IPL thickness/density might correspond to dendrite atrophy. The bridging of experimental data with clinical findings encourages further research along the translational path.

PURPOSE/OBJECTIVE:The novel coronavirus, SARS-CoV-2 (COVID-19), has disrupted the practice of ophthalmology and threatens to forever alter how we care for our patients. Physicians across the country encounter unique clinical dilemmas daily. This manuscript presents a curated set of ethical dilemmas facing ophthalmologists both during and following the pandemic. DESIGN/METHODS:Perspective METHODS: Case presentations drawn from actual clinical scenarios were presented during a virtual Ophthalmology Grand Rounds and discussed with the Director of Clinical Ethics at Columbia University Irving Medical Center. RESULTS:It has become routine to expect an ophthalmologist to be involved in many levels of care for critically ill patients with COVID-19. Ophthalmology patients - even those with chronic, progressive conditions - are being triaged, and vision-saving interventions are being postponed. Four questions were applied to each scenario allowing for ethical conclusions to be reached. These questions were; What is the imminence and the severity of the harm expected without intervention? What is the efficacy of the intervention under consideration? What are the risks of treatment for the patient? What are the risks of treating the patient for the healthcare team? CONCLUSION/CONCLUSIONS:During this pandemic and for months, perhaps years, to come, it is critical to reconsider the ethical principles underlying modern medicine and ophthalmic care as well as the ramifications of our decisions and actions. ABSTRACT/UNASSIGNED:Perspective.

Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma.

PURPOSE/OBJECTIVE:To investigate central visual field (VF) defects among four phenotypes of glaucomatous optic discs. DESIGN/METHODS:Cross-sectional study. METHODS:Optic disc phenotypes were determined in eyes with definite or suspected glaucoma that had a 24-2 VF with mean deviation (MD) better than -12 dB and a 10-2 VF. 10-2 VFs were classified as abnormal based on a cluster criterion. Additionally, the average of the total deviation values at each 10-2 test point was compared by optic disc phenotype. RESULTS:Four glaucomatous optic disc phenotypes were identified in 448 eyes of 309 patients: focal ischemic (FI)(n=121), generalized cup enlargement (GE)(n=109), myopic glaucoma (MY)(n=66), and senile sclerotic (SS)(n=152). Although VF 24-2 MD values were similar among optic disc phenotypes, GE eyes had higher VF 10-2 MD(p=0.004), as well as lower VF 24-2 pattern standard deviation(PSD)(p<0.001) and VF 10-2 PSD(p<0.001) compared to other phenotypes. The prevalence of an abnormal VF 10-2 was highest in FI eyes (78.5%) and lowest in GE eyes (50.5%)(p<0.001). In glaucoma suspects, the prevalence of an abnormal 10-2 VF was highest in the MY (31.2%) eyes and FI (23.5%) eyes and lowest in GE eyes (8.6%). In mild glaucoma, the prevalence of abnormal 10-2 VF tests was highest in FI eyes (79.2%) and lowest in GE eyes (44.4%)(p=0.013). CONCLUSION/CONCLUSIONS:The severity and prevalence of central visual field loss vary among different glaucomatous optic disc phenotypes. Glaucomatous eyes with FI and MY optic disc phenotypes are more likely to have 10-2 VF loss, particularly in early disease, and especially may benefit from testing with both 10-2 and 24-2 VF tests.

PURPOSE/OBJECTIVE:To use optical coherence tomography (OCT) to 3D characterize optic nerve head (ONH) peripapillary scleral bowing in non-highly myopic healthy eyes. DESIGN/METHODS:Cross-sectional, multicenter study. METHODS:362 non-highly myopic (+6 diopters (D) > spherical equivalent > -6D) eyes of 362 healthy subjects aging from 20-90 years underwent OCT ONH radial B-scan imaging. Bruch's membrane (BM), BM opening (BMO), ASCO and the peripapillary scleral surface were segmented. BMO and ASCO planes were fit and their centroids, major axes, ovality, area and offset were determined. Peripapillary scleral bowing was characterized by two parameters: peripapillary scleral slope (ppSS) of three anterior peripapillary scleral segments (0-300, 300-700 and 700-1000 μm from the ASCO centroid); and ASCO depth relative to a peripapillary scleral reference plane (ASCOD-ppScleral). Peripapillary choroidal thickness (ppCT) was calculated relative to the ASCO as the minimum distance between the anterior scleral surface and BM. RESULTS:ppSS and ASCOD-ppScleral both ranged from slightly inward through profoundly outward in direction. Both parameters increased with age and were independently associated with decreased ppCT. CONCLUSIONS:In non-highly myopic healthy eyes outward peripapillary scleral bowing achieved substantial levels, was markedly increased with age and was independently associated with decreased peripapillary choroidal thickness. Our findings provide a normative foundation for characterizing this anatomy in high myopia and glaucoma and in eyes with optic disc tilt, torsion and peripapillary atrophy.

PURPOSE/OBJECTIVE:This report examines the relationship between glaucomatous macular damage and facial recognition. Additionally, it assesses the role of contrast sensitivity (CS) as an intermediary step in the causal pathway between macular damage and impairment of facial recognition. DESIGN/METHODS:Prospective cross-sectional study METHODS: . SETTING/METHODS:Tertiary care center STUDY POPULATION: 144 eyes of 72 participants with a diagnosis of open angle glaucoma in one or both eyes and a visual acuity of 20/40 or better in each eye. The presence or absence of macular damage was determined by comparing corresponding regions of the retinal nerve fiber layer and the retinal ganglion cell layer spectral domain optical coherence tomography (SD-OCT) with the 10-2 visual field (VF). Better and worse eye was determined by 10-2 VF mean deviations (MD). INTERVENTION/METHODS:(1) Macular function as measured by 10-2 VF. (2) CS as measured by the Freiburg Visual Acuity and Contrast Test (FrACT). MAIN OUTCOME MEASURE/METHODS:Cambridge Face Memory Test scores (CFMT) RESULTS: Regardless of eye, there was a significant correlation between facial recogntion and 10-2 VF MD (p<0.0001 better, worse eye). The 10-2 VF MD remained a significant predictor of facial recogntion after adjusting for potential confounders including glaucoma severity, CS, age and visual acuity (p=0.004 better eye, p=0.019 worse eye). CONCLUSIONS:Even with good central visual acuity, patients with glaucomatous macular damage exhibit diminished facial recognition, which is partly mediated through diminished CS.

PURPOSE/OBJECTIVE:To test the hypothesis that a recently proposed pattern standard deviation (PSD) metric, based upon the 24-2 visual field (VF) test, as well as the PSD of the 10-2 VF, will miss central glaucomatous damage confirmed with an objective structure-function method. DESIGN/METHODS:Cross-sectional case-control study METHODS: A glaucoma (G) group (70 eyes/patients) diagnosed as glaucoma, with a 24-2 mean deviation better than -6 dB, and a healthy (H) group (45 eyes/patients) had 24-2 and 10-2 VFs, and optical coherence tomography (OCT) scans twice within 4 weeks. The PSD (C24-2), based upon the central 12 points of the 24-2, was compared to the PSD(10-2). To evaluate central damage (CD) in G eyes with normal PSD(C24-2) values, a post hoc analysis was combined with a reference standard for central damage (CD-RS), which was based upon an objective, topographical comparison between abnormal points on the 10-2 VF and OCT probability maps. RESULTS:The 115 PSD(C24-2) and PSD(10-2) values were significantly correlated (Spearman's CC: rho = 0.55; p < 0.001) and the number of G eyes, 19, identified as abnormal by the PSD(C24-2) was not significantly different from the number, 22, identified by the PSD(10-2) (P=0.15). However, based upon the CD-RS, 44 of the 70 G eyes were classified as abnormal. The PSD(C24-2) missed 27 (61%) of these 44 eyes, and the PSD(10-2) missed 23 (52%). Post-hoc analysis revealed clear central damage in most of these eyes. CONCLUSION/CONCLUSIONS:Neither the PSD(C24-2) nor the PSD(10-2) metric is good measure of early central damage. Instead we recommend a topographical approach based upon OCT probability maps, and a 10-2 VF.