Faculty Bibliography

Light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) quantifies these fluctuations to provide marginal brain sensitivity for CBFi in adult humans, new techniques have emerged to improve diffuse light throughput and brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to the number of independent channels, camera duty cycle and full well capacity, incident laser power, noise and artifact mitigation, and data processing. We build the system on a cart and define conditions for stable operation. We show pulsatile CBFi monitoring at 4-4.5 cm source-collector separation in adults with moderate pigmentation (Fitzpatrick 4). We also report preliminary clinical measurements of patient CBFi in the Neuro Intensive Care Unit (Neuro ICU). These results push the boundaries of iDWS CBFi monitoring performance beyond previous reports.

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.

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.

The XEN®45 Glaucoma Treatment System (gel stent; Allergan, an AbbVie company, Irvine, CA, USA) is a minimally invasive bleb-forming surgical device that was originally approved to lower intraocular pressure by diverting the aqueous humor from the anterior chamber to the subconjunctival space (like trabeculectomy) following ab-interno placement. Since approval of the gel stent in multiple countries, the implantation technique has evolved considerably, being performed ab interno or ab externo with open or closed conjunctiva, based on patients' needs and/or surgeons' preferences. Additional technical variations that can facilitate gel stent placement and/or improve outcomes have also emerged. This article aims to increase awareness of these developments to facilitate informed decision-making and improve surgical success and outcomes for patients.

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.