Faculty Bibliography

OBJECTIVE:Our aim was to assess the acceptability and feasibility of iCare HOME tonometer (HT) and Virtual Field (VF) devices in the home monitoring of glaucoma. DESIGN/METHODS:Prospective feasibility and acceptability study. SUBJECTS/METHODS:Twenty patients (39 eyes) with primary open-angle glaucoma, open-angle glaucoma, ocular hypertension, or suspected glaucoma. METHODS:Patients were trained and instructed to bring 2 devices home for 1 week and use the HT 4 times/day for 4 days and the VF 3 times total. MAIN OUTCOME MEASURES/METHODS:For acceptability, we conducted satisfaction surveys and semistructured, qualitative interviews with a thematic analysis. Feasibility was assessed by device usage and quality of tests. RESULTS:Most patients (73.7%) felt that the HT was easy to use, and 100% of them found the HT useful. All patients (100%) felt that VF was easy to use, and 94.4% of them found the VF useful. All patients (100%) obtained acceptable intraocular pressure and completed a VF test at home. We identified 4 key themes, with 33 subthemes. The key themes include the following: (1) advantages of home monitoring; (2) difficulties with home monitoring; (3) future considerations in home monitoring; and (4) the experience of patients with glaucoma. CONCLUSIONS:The HT and VF were acceptable and feasible in a small cohort of motivated subjects. Patients were able to perform these tests proficiently at home, and they were generally enthused to obtain more data about their intraocular health, as it allowed them a heightened sense of security and insight about their chronic disease, as well as a reduction in foreseeable barriers to care. Home monitoring may also improve upon glaucoma care by enhancing patient empowerment and fostering community bonds. The VF should be further evaluated to ensure validity.

As of 2020, it is estimated that 43.3 million people are blind, and an additional 553 million have mild to severe vision impairment.⁵⁰ At least 1 billion worldwide have a vision impairment that could have been prevented or has yet to be addressed.⁵⁴ Poor health literacy may be a significant contributor to the prevalence of eye disease. With implications on disease burden, progression, and health outcomes, a greater understanding of the role health literacy plays in ophthalmology is needed. This is the first scoping review to assess the impact of health literacy on eye health outcomes and blindness, including ocular screening rates/follow-up rates, treatment adherence, and self-care practices. PubMed, Embase, and CINAHL databases were searched systematically through November 12, 2021, and we evaluated the association between health literacy and ophthalmic outcomes in 4 domains: clinical outcomes, treatment adherence rates, screening/follow-up rates, and self-care practices. There is evidence to suggest that health literacy is associated with ophthalmic outcomes in all these domains. To better understand how health literacy impacts eye health, further longitudinal studies examining the effect of health literacy (using standardized health literacy measures) on ophthalmic outcomes are needed. We believe a specific ophthalmic health literacy survey could help achieve this goal and help target interventions to ultimately improve outcomes among ophthalmology patients.

This study was registered with ClinicalTrials.gov (ID: NCT03715231). A total of 20 participants (37 eyes) who were 18 or older and had glaucoma or were glaucoma suspects were enrolled from the NYU Langone Eye Center and Bellevue Hospital. During their usual ophthalmology visit, they were consented for the study and underwent 360-degree goniophotography using the NIDEK Gonioscope GS-1. Afterwards, the three ophthalmologists separately examined the images obtained and determined the status of the iridocorneal angle in four quadrants using the Shaffer grading system. Physicians were masked to patient names and diagnoses. Inter-observer reproducibility was determined using Fleiss' kappa statistics. The interobserver reliability using Fleiss' statistics was shown to be significant between three glaucoma specialists with fair overall agreement (Fleiss' kappa: 0.266, p < .0001) in the interpretation of 360-degree goniophotos. Automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 have quality such that they are interpreted similarly by independent expert observers. This indicates that angle investigation may be performed using this automated device and that interpretation by expert observers is likely to be similar. Images produced from automated 360-degree goniophotography using the NIDEK Gonioscope GS-1 are similarly interpreted amongst glaucoma specialists, thus supporting use of this technique to document and assess the anterior chamber angle in patients with, or suspected of, glaucoma and iridocorneal angle abnormalities.

PURPOSE/OBJECTIVE:To investigate the cost-effectiveness (CE) of prophylactic laser peripheral iridotomy (LPI) in primary angle-closure (PAC) suspects (PACSs). DESIGN/METHODS:Cost-effectiveness analysis utilizing Markov models. SUBJECTS/METHODS:Patients with narrow angles (PACSs). METHODS:Progression from PACSs through 4 states (PAC, PAC glaucoma, blindness, and death) was simulated using Markov cycles. The cohort entered at 50 years and received either LPI or no treatment. Transition probabilities were calculated from published models, and risk reduction of LPI was calculated from the Zhongshan Angle Closure Prevention trial. We estimated costs of Medicare rates, and previously published utility values were used to calculate quality-adjusted life year (QALY). Incremental CE ratios (ICER) were evaluated at $50 000. Probabilistic sensitivity analyses (PSAs) addressed uncertainty. MAIN OUTCOME MEASURES/METHODS:Total cost, QALY, and ICER. RESULTS:Over 2 years, the ICER for the LPI cohort was > $50 000. At 6 years, the LPI cohort was less expensive with more accrued QALY. In PSA, the LPI arm was cost-effective in 24.65% of iterations over 2 years and 92.69% over 6 years. The most sensitive parameters were probability of progressing to PAC and cost and number of annual office visits. CONCLUSIONS:By 6 years, prophylactic LPI was cost-effective. The rate of progressing to PAC and differing practice patterns most impacted CE. With uncertainty of management of narrow angles, cost may be a decision management tool for providers. FINANCIAL DISCLOSURE(S)/BACKGROUND:The authors have no proprietary or commercial interest in any materials discussed in this article.

Plasticity in the brain is impacted by an individual's age at the onset of the blindness. However, what drives the varying degrees of plasticity remains largely unclear. One possible explanation attributes the mechanisms for the differing levels of plasticity to the cholinergic signals originating in the nucleus basalis of Meynert. This explanation is based on the fact that the nucleus basalis of Meynert can modulate cortical processes such as plasticity and sensory encoding through its widespread cholinergic projections. Nevertheless, there is no direct evidence indicating that the nucleus basalis of Meynert undergoes plastic changes following blindness. Therefore, using multiparametric magnetic resonance imaging, we examined if the structural and functional properties of the nucleus basalis of Meynert differ between early blind, late blind and sighted individuals. We observed that early and late blind individuals had a preserved volumetric size and cerebrovascular reactivity in the nucleus basalis of Meynert. However, we observed a reduction in the directionality of water diffusion in both early and late blind individuals compared to sighted individuals. Notably, the nucleus basalis of Meynert presented diverging patterns of functional connectivity between early and late blind individuals. This functional connectivity was enhanced at both global and local (visual, language and default-mode networks) levels in the early blind individuals, but there were little-to-no changes in the late blind individuals when compared to sighted controls. Furthermore, the age at onset of blindness predicted both global and local functional connectivity. These results suggest that upon reduced directionality of water diffusion in the nucleus basalis of Meynert, cholinergic influence may be stronger for the early blind compared to the late blind individuals. Our findings are important to unravelling why early blind individuals present stronger and more widespread cross-modal plasticity compared to late blind individuals.

Connecting neuronal activity to perception requires tools that can probe neural codes at cellular and circuit levels, paired with sensitive behavioral measures. In this chapter, we present an overview of current methods for connecting neural codes to perception using precision optogenetics and psychophysical measurements of synthetically induced percepts. We also highlight new methodologies for validating precise control of optical and behavioral manipulations. Finally, we provide a perspective on upcoming developments that are poised to advance the field.
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BACKGROUND:Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS:Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS:The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 μm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 μm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 μm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS:A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.

PURPOSE/UNASSIGNED:Lamina cribrosa (LC) deformations caused by elevated intraocular pressure (IOP) are believed to contribute to glaucomatous neuropathy and have therefore been extensively studied, in many conditions, from in vivo to ex vivo. We compare acute IOP-induced global and local LC deformations immediately before (premortem) and after (postmortem) sacrifice by exsanguination. METHODS/UNASSIGNED:The optic nerve heads of three healthy monkeys 12 to 15 years old were imaged with spectral-domain optical coherence tomography under controlled IOP premortem and postmortem. Volume scans were acquired at baseline IOP (8-10 mm Hg) and at 15, 30, and 40 mm Hg IOP. A digital volume correlation technique was used to determine the IOP-induced three-dimensional LC deformations (strains) in regions visible premortem and postmortem. RESULTS/UNASSIGNED:Both conditions exhibited similar nonlinear relationships between IOP increases and LC deformations. Median effective and shear strains were, on average, over all eyes and pressures, smaller postmortem than premortem, by 14% and 11%, respectively (P's < 0.001). Locally, however, the differences in LC deformation between conditions were variable. Some regions were subjected premortem to triple the strains observed postmortem, and others suffered smaller deformations premortem than postmortem. CONCLUSIONS/UNASSIGNED:Increasing IOP acutely caused nonlinear LC deformations with an overall smaller effect postmortem than premortem. Locally, deformations premortem and postmortem were sometimes substantially different. We suggest that the differences may be due to weakened mechanical support from the unpressurized central retinal vessels postmortem. TRANSLATIONAL RELEVANCE/UNASSIGNED:Additional to the important premortem information, comparison with postmortem provides a unique context essential to understand the translational relevance of all postmortem biomechanics literature.

The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease, and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here, we elucidated the transcriptomic cell fate map of 4-month-old human cornea organoids and human donor corneas. The organoids harbor cell clusters that resemble cells of the corneal epithelium, stroma, and endothelium, with subpopulations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids contain large proportions of epithelial and endothelial-like cells. These corneal organoids offer a 3D model to study corneal diseases and integrated responses of different cell types.