Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes.

IMPORTANCE: Geographic atrophy (GA) is a progressing atrophy of the neuroretina with no treatment option. BACKGROUND: Age-related malfunction of retinal microglia amplifies response towards age-related tissue stress in age-related macular degeneration. Here, we investigated monocyte CD200 expression - the circulating middleman negotiating retinal microglial activity - in a poorly understood subtype of age-related macular degeneration. DESIGN: Prospective case-control study. PARTICIPANTS: Forty-six patients with GA and 26 healthy controls were included. METHODS: All participants were subjected to a structured interview and detailed retinal examination. Controls were recruited from patient's spouses accompanying them in the clinic to match the groups best possibly. Participants had no history of immune disorders or cancer, and did not receive any immune-modulating medication. Patients did not have any history or sign of choroidal neovascularization in either eye. Fresh drawn blood was stained with monoclonal antibodies and prepared for flow cytometry to evaluate CD200 expression in monocytes and their functional subsets. MAIN OUTCOME MEASURES: The percentage of CD200+ monocytes in patients and controls. RESULTS: We found that monocytes were more CD200 positive in patients with GA compared to healthy age-matched controls. Then, we explored the potential relationship between CD200 expression and important fundus autofluorescence patterns that predict disease progression. Patients with a high risk of progression (patients with high degree of hyperautofluorescence) had distinctly increased CD200 expression compared to other patients with GA. CONCLUSIONS AND RELEVANCE: Our data reveals that abnormal monocytic CD200 expression is present in GA, and in particular among those identified as fast progressors.

The Impact of the COVID-19 Pandemic on Tele-ophthalmology-Based Retinal Screening.

INTRODUCTION: This study reports our experiences with systematic retinal screening in Denmark through optometrists with access to tele-ophthalmological services before, during, and after the COVID-19 pandemic. METHODS: We evaluated an optometrist-based retinal screening system with a referral option for tele-ophthalmological service by a consultant ophthalmologist within the time period of August 1, 2018 to September 30, 2023. The optometrist collected patient history, refraction, best-corrected visual acuity, intraocular pressure, basic slit-lamp examination, 4-in-1 visual field report, and retinal imaging using color fundus 45° photography. Tele-ophthalmological services were provided by consultant ophthalmologists. Within pre-defined periods of pre-COVID-19, COVID-19, and post-COVID-19, we evaluated the rate of referrals to the tele-ophthalmological service, diagnoses made, and referrals to the public healthcare system. RESULTS: A total of 1,142,028 unique individuals, which corresponded to 19.1% of the entire population of Denmark, underwent screening by the optometrists; 50,612 (4.4%) of these individuals were referred to the tele-ophthalmological examination by consultant ophthalmologists. A referral for further ophthalmic examination, either at hospital or at an ophthalmic practice, was made for 10,300 individuals (20.4% of those referred for tele-ophthalmology, corresponding to 0.9% of the population screened). The referral rate from the screening to the tele-ophthalmological service increased from before COVID-19 (3.4%) to during COVID-19 (4.3%) and further after COVID-19 (6.4%). This increase coincided with an increasing prevalence of conditions seen in the tele-ophthalmological service. CONCLUSION: During a period of 5 years, 19.1% of the entire population of Denmark underwent retinal screening. This provided an adjunctive health service during a period of severe strain on the public healthcare system, while limiting the number of excessive referrals to the public healthcare system. Temporal trends illustrated an increased pattern of use of a large-scale tele-ophthalmological system.

Increased expression of CD200 on circulating CD11b+ monocytes in patients with neovascular age-related macular degeneration.

OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both the ligand and the receptor are expressed on a broad spectrum of cell types, we set out to study the expression of CD200 and CD200R on CD11b+ monocytes, granulocytes, and subsets of T lymphocytes. DESIGN: Prospective, case-control study. PARTICIPANTS: The study population consisted of 62 patients with neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview, and detailed retinal imaging was performed: fundus autofluorescence imaging, digital color fundoscopy, and spectral-domain optical coherence tomography. Fluorescein and indocyanine green angiography were performed in patients with suspected neovascular AMD. Visual acuity was measured in both eyes. Fresh venous blood was obtained and stained with monoclonal antibodies and analyzed using flow cytometry within 6 hours of phlebotomy. MAIN OUTCOME MEASURES: The percentage of CD11b+ monocytes, granulocytes, and CD4+/CD8+ T lymphocytes positive for CD200 or CD200R in patients and controls, respectively. RESULTS: Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes was observed in controls with healthy eyes, but not in patients with neovascular AMD. We did not find any differences in CD200 and CD200R expression between patients with subretinal fibrosis and patients without subretinal fibrosis. CONCLUSIONS: The surface expression of CD200 on circulating CD11b+ monocytes was found to be increased in patients with neovascular AMD compared with controls with healthy eyes. This novel finding supports the notion that altered regulation of the inflammatory response plays an integral role in the pathogenesis of AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.