The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer’s disease (AD), as classified by cerebral spinal fluid (CSF) Aβ₄₂/Tau ratio. Individuals with normal retinal morphology ascertained by spectral-domain optical coherence tomography were enrolled. Full-field ERG, pattern PERG, and photopic negative response (PhNR) were performed in 29 adult participants (58 eyes). Amplitude and implicit times of the ERG wave components were analyzed. Preclinical AD participants showed marked retinal ganglion cell dysfunction relative to controls. The PhNR was significantly diminished in preclinical AD relative to controls. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity. These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. Retinal ganglion cell dysfunction, as detected by ERG, may be a clinically useful, non-invasive in vivo biomarker for early disease detection, which is necessary for ultimately pursuing early intervention.

Introduction: Previous in vivo optical coherence tomography studies have proposed the retinal choroid as a potential oculovascular biomarker for Alzheimer's disease (AD). However, the clinical use of the choroid as a purported surrogate marker remains poorly understood. We pursued a histopathological approach to assess choroidal thickness and vascular morphology in severe disease.Methods: Human postmortem tissues from 8 patients with AD (mean age: 80.1 ± 12.7 years) and from 11 age‐matched controls (mean age: 78.4 ± 16.57 years) were analyzed. Thickness, area, and vascularity of the retinal choroid and its sublayers were measured from the nasal and temporal quadrants of the superior retina.Results: Nasally, the choroid was thinner in the patients with AD than in the controls (22% thickness reduction; P < .001), but to our surprise, the choroid was thicker in the patients with AD than in the controls (~60% increase; P < .03) within the macula, temporally. The choroidal area was also significantly greater in the patients with AD than in the controls (~60% increase; P < .03). Choroidal thickening in AD was strongly correlated with the stromal vessel number (R² = 0.96, P < .001).Discussion: We found significant differences in the retinal choroid by layer and by region, nasally and temporally with respect to the optic nerve. Intriguingly, the choroid was markedly thicker in the central macular region and was strongly associated with vessel number in the stromal vascular layer. These quantified histological findings in severe disease expand our understanding of vascular pathology in AD and suggest vascularity as a potential biomarker supplementary to thickness when evaluating the retinal choroid in AD.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease involving immune system over-activation leading to hemophagocytosis. HLH requires early diagnosis and prompt treatment initiation, especially in patients with Acquired Immunodeficiency Syndrome (AIDS). We present a case of a middle-aged male with AIDS and renal failure, who developed HLH secondary to disseminated histoplasmosis. Etoposide chemotherapy as recommended by the HLH 2004 Guidelines was deferred and treatment focused instead on anti-fungal therapy. Anti-retroviral therapy followed thereafter.

Optical coherence tomography angiography (OCTA) is an emerging technique for non-invasively imaging the ocular vasculature, enabling quantitative measurements of retinal vascular anatomy. As extensions of the central nervous system, the optic nerve and the retina share many vascular characteristics with the brain. Measuring the structural and functional changes within the ocular vasculature may be useful as an objective approach for non-invasively evaluating the cerebrovascular architecture. The current article reviews the most recent applications of OCTA imaging at the eye-brain interface and highlights the emerging vascular biomarkers for neurodegenerative optic neuropathies, as reported in Alzheimer’s disease, Parkinson’s disease, schizophrenia, and mitochondrial optic neuropathies. These ophthalmologic findings offer objective measures of a more accessible clinical marker and may improve our understanding of neurodegenerative disease.