Subject(s)
Alzheimer Disease/diagnosis , Fluorescein Angiography/methods , Fovea Centralis/diagnostic imaging , Psychometrics/methods , Retinal Vessels/diagnostic imaging , Aged , Alzheimer Disease/cerebrospinal fluid , Amyloid/cerebrospinal fluid , Artificial Intelligence , Biomarkers/cerebrospinal fluid , Disease Progression , Female , Follow-Up Studies , Fundus Oculi , Humans , Male , Microvessels/diagnostic imaging , Pilot Projects , Time Factors , Tomography, Optical CoherenceABSTRACT
PURPOSE: To report the occurrence of bilateral choroidal detachments due to the use of ipilimumab and pembrolizumab immunochemotherapeutics to treat widely metastatic cutaneous melanoma and to raise awareness about this potentially vision-threatening adverse drug event. METHODS: A 77 year-old man presented with acute onset, painless, and bilateral blurry vision. He had started ipilimumab and pembrolizumab 2 weeks prior for Stage IV metastatic cutaneous melanoma. RESULTS: Clinical examination revealed bilateral choroidal detachments. After discussion with the patient's medical oncologist, the patient discontinued both medications and began oral prednisone to expedite visual recovery. The choroidal detachments subsequently resolved, and visual acuity improved 2 weeks later. CONCLUSION: Ipilimumab and pembrolizumab have been reported both in monotherapy and in combination to cause a wide variety of ophthalmic adverse events. This is the first report of choroidal detachments as a complication.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Choroid Diseases/chemically induced , Drug-Related Side Effects and Adverse Reactions/etiology , Ipilimumab/adverse effects , Aged , Choroid Diseases/physiopathology , Humans , Male , Melanoma/drug therapy , Rupture , Skin Neoplasms/drug therapy , Vision Disorders/chemically induced , Vision Disorders/physiopathology , Visual Acuity/physiology , Melanoma, Cutaneous MalignantSubject(s)
Angiogenesis Inhibitors/administration & dosage , Anterior Chamber/diagnostic imaging , Macular Degeneration/drug therapy , Female , Humans , Intraocular Pressure/physiology , Intravitreal Injections , Macular Degeneration/diagnosis , Macular Degeneration/physiopathology , Male , Middle Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
Importance: Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD. Objective: To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing. Design, Setting, and Participants: This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017. Main Outcomes and Measures: Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome. Results: Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] µm; P = .03). Conclusions and Relevance: This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.