Faculty Bibliography

INTRODUCTION/UNASSIGNED:A standardized multidisciplinary treatment protocol for NVG was developed in 2020 at the University of Chicago and has been termed Salvaging the Conventional Outflow Pathway in Neovascular Glaucoma (SCOPING). We describe 9 eyes with anterior segment neovascularization and at least partially open angles that underwent the SCOPING protocol to suppress the underlying neovascular drive, control intraocular pressure, and medically or surgically salvage the angle whenever possible. METHODS/UNASSIGNED:Nine eyes from 8 patients with first-time anterior segment neovascularization, at least partially open angles, and normal or elevated IOP were treated with 6 serial monthly intravitreal bevacizumab injections interspersed with pan-retinal photocoagulation. RESULTS/UNASSIGNED:Five eyes with completely open angles without any peripheral anterior synechiae and each achieved and/or maintained physiologic IOP without requiring surgery. The other 4 eyes presented with partially open angles. Three out of these 4 eyes required subsequent IOP-lowering surgery. None of the 9 eyes developed recurrence of anterior segment neovascularization during the treatment protocol. DISCUSSION/UNASSIGNED:This protocol may be utilized to salvage the conventional outflow pathway for patients with partially or completely open angles. The etiology and diagnosis of neovascular glaucoma have been established. Current treatment strategies include reduction of neovascular drive including panretinal photocoagulation, intravitreal injections, intraocular pressure lowering medications, and filtration surgery. However, a protocol has not been developed to treat neovascular glaucoma (NVG). Our SCOPING protocol may be helpful for glaucoma specialists in treating patients with neovascular glaucoma.

Orbital arteriovenous fistulas are exceedingly rare and present a unique challenge due to difficulties with access. We report a case of a patient with an acute progressive direct orbital arteriovenous fistula causing orbital compartment syndrome and compressive optic neuropathy. He underwent medial orbital decompression followed immediately by direct cannulation of the vascular anomaly, through which two separate fistulas were embolized under fluoroscopic guidance.

PURPOSE/UNASSIGNED:To determine the characteristics of normal tension glaucoma referrals at a tertiary care center and risk factors associated with unilateral versus bilateral disease. PATIENTS AND METHODS/UNASSIGNED:Medical records were reviewed of patients who were referred to a single glaucoma provider at a tertiary care center and were given a presumptive diagnosis of normal tension glaucoma (NTG) between the years 2018 and 2021. Data collected included demographics, medical and family history, ophthalmic history, ophthalmic examination findings, neuro-ophthalmology referrals, and magnetic resonance imaging (MRI) results. RESULTS/UNASSIGNED:A total of 98 patients were included in this study. The majority of patients (82%) had bilateral disease at initial presentation. Most patients (65%) had a history of systemic disease, including hypertension (32%), cardiovascular disease (19%), diabetes (12%), obstructive sleep apnea (10%), or orthostatic hypotension (4%). Conditions associated with vascular dysregulation were identified in 24% of patients. Sixty six percent of patients had a family history of glaucoma, while nearly half (49%) were myopic. Of patients with unilateral disease, 39% had workup or consideration of other neuro-ophthalmic diagnoses compared to 13% of patients with bilateral disease (P = 0.01). CONCLUSION/UNASSIGNED:Patients referred for NTG commonly present with disc changes in both eyes. Clinicians should assess for the presence of systemic diseases associated with vascular dysregulation, myopia, and a family history of glaucoma. Patients with unilateral disease consistent with NTG may benefit from additional workup including neuroimaging or a neuro-ophthalmic evaluation.

PURPOSE/UNASSIGNED:We evaluated the efficacy of varenicline solution nasal spray (VNS) in treating dry eye disease (DED) associated with moderate to severe Sjogren's disease and analyzed tear film cytokine levels of patients with DED and Sjogren's disease before and after VNS use. METHODS/UNASSIGNED:This was a pilot study involving a single-center, single-arm investigator-initiated trial. Patients with moderate to severe Sjogren's disease were given VNS 0.03 mg twice daily for 28 days. Patients were assessed on day 0 before VNS use, day 14 and day 28. Clinical exam findings, symptomatology as measured by the eye dryness score, and tear cytokines were assessed at baseline and day 28. RESULTS/UNASSIGNED:Thirty-nine subjects were included. Between day 0 and day 28, there was a statistically significant improvement in the eye dryness score (p = 0.01), corneal staining (p < 0.001), and conjunctival staining (p = 0.04). There was a statistically significant increase in tear secretion by unanesthetized Schirmer's in subjects with a baseline Schirmer's ≤5 mm (n = 35 eyes, p = 0.02) and a non-statistically significant increase in tear secretion in subjects with a baseline Schirmer's of 6-10 mm (n = 16 eyes, p = 0.79). There was a statistically significant decrease in tear film cytokine concentration of IFNγ (p = 0.0003), IL-12p70 (p < 0.0001), IL-17a (p = 0.004), IL-1β (p = 0.007), IL-2 (p < 0.0001), IL-4 (p = 0.01), and TNF-α (p = 0.02), and no significant change in IL-6 (p = 0.56) and IL-10 (p = 0.18). CONCLUSION/UNASSIGNED:Our findings add to existing evidence that VNS improves subjective dry eye symptoms, corneal and conjunctival staining, and tear secretion in a subset of tear-deficient patients, while providing new evidence that VNS reduces concentration of pro-inflammatory cytokines in the tear film. CLINICAL TRIAL REGISTRATION NUMBER/UNASSIGNED:NCT05700422.

PURPOSE/UNASSIGNED:To determine the efficacy and safety of repetitive transorbital alternating current stimulation (rtACS) treatment by assessing vision-related quality of life and visual function outcome in subjects treated with rtACS versus sham-control. STUDY DESIGN/UNASSIGNED:Double masked, randomized, sham-controlled clinical trial (NCT03188042). SUBJECTS/UNASSIGNED:Sixteen subjects with moderate-to-advanced glaucoma (visual field [VF] mean deviation [MD] ≤-6.00 decibels) randomized into sham (9 subjects) or rtACS intervention (7 subjects) groups. METHODS/UNASSIGNED:Subjects underwent 10 rtACS sessions over 2 weeks. All subjects had comprehensive ocular examination at baseline, 1-week, and 4-weeks posttreatment. MAIN OUTCOME MEASURES/UNASSIGNED:Visual acuity (VA), contrast sensitivity (CS), VF MD, number of threshold sensitivity points that changed or were unchanged, and vision-related quality of life (VR-QoL) questionnaire scores. RESULTS/UNASSIGNED: = 0.04). No significant changes were detected with VA, CS, and VF analyses for either group. No serious adverse events were noted in either study group. CONCLUSIONS/UNASSIGNED:Repetitive transorbital alternating current stimulation therapy showed a significant beneficial effect on several domains of VR-QoL. Further studies will determine its utility in glaucoma. FINANCIAL DISCLOSURES/UNASSIGNED:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Currently there are no surgical solutions to restore vision in the irreversibly blind. Whole eye transplantation (WET), is an appealing surgical approach for restoration, replacement, and reconstruction of nonfunctioning eyes. Development of a reliable animal model to test the integrity and functionality of the transplanted eye is an essential step towards clinical whole eye transplantation. This study presents a feasible vascularized orthotopic eye transplantation preclinical rat model to study the structural and functional outcomes of whole eye transplantation. Syngeneic orthotopic transplants were performed in rats, involving anastomoses between carotid arteries, external jugular veins, and optic nerve coaptations of donors and recipients. The transplanted and recipient native eyes were assessed by ocular exam under anesthesia, optical coherence tomography (OCT), histology, magnetic resonance imaging and electroretinography. A 100% surgical survival rate of recipients with maintained long-term health demonstrated this to be a reliable and reproducible model. Assessment from clinical examination under anesthesia revealed that segments of native eyes appeared normal throughout the duration of the study, but transplanted eyes presented mild chemosis of the eye lids, mild ciliary flush of the conjunctiva, cornea neovascularization, mild engorgement of the vessels in the iris, and mild opacities in the lens in some animals. Most of these findings improved over time after transplantation. Doppler optical coherence tomography corroborated the presence of blood flow in transplanted retinas. There was no significant difference in measured IOP between native and transplanted eyes. Both histology and OCT scans demonstrated increased central corneal thickness and decreased total retinal thickness in transplanted eyes. Transplanted eyes exhibit minimal scotopic and photopic ERG responses. To date, no other vascularized orthotopic rodent WET transplantation models have been described in the literature. As functional visual return remains the ultimate goal, this model provides a foundation for future translational strategies and is ideal for testing immunomodulatory, neuroprotective, and neuroregenerative approaches either individually or in combination, as required for total human eye allotransplantation (THEA) to become a clinical reality.

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we found that the functional connectivity within the cerebellum tended to be weakened in glaucoma patients compared to healthy controls, whereas the functional connectivity between some cerebral and cerebellar regions showed opposite changes in the same glaucoma subjects. Our findings underscore the potential role of cerebellar and cerebro-cerebellar dysfunction in postural and cognitive control in glaucoma patients. Taken together, these observations implicate the widespread brain changes in glaucoma beyond the cerebral regions into the cerebellum that may underlie the neural underpinnings of impaired balance control in this disease.

In the last decade, there has been tremendous growth in the number of accelerated three-year medical pathway programs. The needs of accelerated pathway students are different from traditional students, and a robust mentoring program should be developed to address specific issues and guarantee student success. We describe a unique approach to the development of a mentoring program for accelerated three-year MD students at New York University Grossman School of Medicine.

CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention. We performed a comprehensive metabolome/reactome analysis of CYP1B1 to enlist CYP1B1-mediated processes in eye development. The identified metabolic events were classified into major pathways. Functional analysis of these metabolic pathways was performed after cloning the CYP1B1 wild-type gene and expressing the wild-type and selected novel mutants (previously reported by our group L24R, F190L, H279D, and G329D) in heterologous hosts. Stability and enzymatic functions were investigated. Structural modeling of the wild-type and the variants was also performed. Reactome analysis revealed a total of 166 metabolic processes which could be classified into four major pathways including estradiol metabolism, retinoic acid metabolism, arachidonic acid metabolism, and melatonin metabolism. Stability assay revealed rapid denaturing of mutant proteins compared to wild-type. Enzymatic assays showed functional deficit in mutant proteins in metabolizing estradiol, retinoids, arachidonate, and melatonin. Modeling revealed that the examined mutations induced structural changes likely causative in functional loss in CYB1B1 as observed in enzymatic assays. Hence, mutations in the CYP1B1 gene are associated with a functional deficit in critical pathways of eye development. These findings implicate the potential contributions of altered metabolic regulations of estradiol, retinoids, arachidonate and melatonin to the pathogenesis of PCG during the processes of the formation of ocular structures and function.