Faculty Bibliography

Vision, which requires extensive neural involvement, is often impaired in Alzheimer's disease (AD). Over the last few decades, accumulating evidence has shown that various visual functions and structures are compromised in Alzheimer's dementia and when measured can detect those with dementia from those with normal aging. These visual changes involve both the afferent and efferent parts of the visual system, which correspond to the sensory and eye movement aspects of vision, respectively. There are fewer, but a growing number of studies, that focus on the detection of predementia stages. Visual biomarkers that detect these stages are paramount in the development of successful disease-modifying therapies by identifying appropriate research participants and in identifying those who would receive future therapies. This review provides a summary and update on common afferent and efferent visual markers of AD with a focus on mild cognitive impairment (MCI) and preclinical disease detection. We further propose future directions in this area. Given the ease of performing visual tests, the accessibility of the eye, and advances in ocular technology, visual measures have the potential to be effective, practical, and non-invasive biomarkers of AD.

Saccadic eye movement abnormalities are among the earliest manifestations of Huntington's disease (HD) but are difficult to quantify at the bedside. Similarly, afferent visual pathway involvement in HD is poorly characterised. The objective was to evaluate afferent and efferent visual function in HD. Participants with manifest HD (n = 19) and healthy controls (n = 20) performed the King-Devick test, a timed test of rapid number naming. Binocular high and low-contrast (2.5% and 1.25%) acuities were measured using low-contrast Sloan letter charts, and pupillometric recordings were made using a handheld NeurOptics PLR-3000 pupillometer. The NEI-VFQ-25 questionnaire with 10-item neuro-ophthalmic supplement were also completed. Unified Huntington's Disease Rating Scale (UHDRS) motor score and other clinical and demographic variables were collected. Comparisons between manifest HD and controls were performed using linear regression adjusted for confounders. Mean King-Devick time scores were 102.9 seconds in patients with manifest HD and 48.2 seconds in controls (p < .01, t-test). In unadjusted analyses, binocular high contrast acuity was seven letters (one Snellen line equivalent) lower in manifest HD than controls (p = .043). This effect was similar for low-contrast acuity, but only low-contrast acuity remained statistically significant after adjusting for covariates. Low-contrast acuity also correlated with UHDRS motor score. There were no differences in pupillary reactivity or self-reported vision-related quality of life. In conclusion, HD is associated with reduced low-contrast acuity and abnormal performance on the King-Devick test of rapid number naming. These tests are easy to administer, providing an objective quantitative measure of visual function which could be incorporated into optimised rating scales.

OBJECTIVE:Investigations have found associations of homonymous thinning of the macular ganglion cell/ inner-plexiform layer (GCIPL) with demyelinating lesions in the post-chiasmal visual pathway among patients with multiple sclerosis (MS). Retinal thinning may also occur through retrograde trans-synaptic degeneration, a process by which lesions in post-geniculate visual pathway structures lead to thinning of the GCIPL across thalamic synapses. The purpose of our study was to determine the frequency of homonymous hemimacular thinning that occurs in association with post-chiasmal visual pathway demyelinating lesions in patients with MS and other demyelinating diseases. METHODS:Adult patients with demyelinating diseases (MS, neuromyelitis optica spectrum disorder [NMOSD], myelin oligodendrocyte glycoprotein antibody disease (anti-MOG)) who were participants in an ongoing observational study of visual pathway structure and function were analyzed for the presence of hemimacular GCIPL thinning on OCT scans. Brain MRI scans were examined for the presence of post-geniculate visual pathway demyelinating lesions. RESULTS:Among 135 participants in the visual pathway study, 5 patients (3.7%) had homonymous hemimacular GCIPL thinning. Eleven patients (8.1%) had a whole+half pattern of GCIPL thinning, characterized by hemimacular thinning in one eye and circumferential macular thinning in the contralateral eye. All but one patient with homonymous hemimacular thinning had demyelinating lesions in the post-geniculate visual pathway; however, these lesions were located in both cerebral hemispheres. CONCLUSION/CONCLUSIONS:Homonymous hemimacular thinning in the GCIPL by OCT is associated with post-chiasmal visual pathway demyelinating lesions but it appears to be a relatively uncommon contributor to GCIPL loss. Patients with this pattern of GCIPL often fail to complain of hemifield visual loss. Future studies with prospective and detailed MR imaging may be able to more closely associate demyelinating lesions in anatomically appropriate regions of the post-chiasmal visual pathways with homonymous hemimacular thinning.

OBJECTIVES/OBJECTIVE:Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN/METHODS:Retrospective, multicenter, observational cohort study. SETTING/METHODS:Four New York City hospitals that are part of the same health network. PATIENTS/METHODS:Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS:Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.