HISTOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION

Retina - Tập 38 Số 10 - Trang 1937-1953 - 2018
Feng Wen1,2, Carrie Huisingh1, Jeffrey D. Messinger1, J. Fernando Arévalo3,4,5, Daniela Ferrara6, K. Bailey Freund7,3,5, Christine A. Curcio1
1Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
3LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York
4Oftalvist Clinic, Valencia, Spain
5Vitreous Retina Macula Consultants of New York, New York
6Genentech, South San Francisco, California; and
7Department of Ophthalmology, New York University School of Medicine, New York, New York

Tóm tắt

Purpose: To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane—choriocapillaris complex and associated extracellular deposits. Methods: Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models. Results: On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased. Conclusion: The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick deposits impede therapeutic intervention.

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Tài liệu tham khảo

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Retina

Tập 38 Số 10

1937-1953

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