Miaoling Li1,2, Rosa Dolz-Marco3,4,5, Jeffrey D Messinger2, Daniela Ferrara6, K Bailey Freund3,4,7, Christine A Curcio8. 1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. 2. Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 3. Vitreous Retina Macula Consultants of New York, New York, NY, USA. 4. LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY, USA. 5. Unit of Macula, Oftalvist Clinic, Valencia, Spain. 6. Genentech, South San Francisco, CA, USA. 7. Department of Ophthalmology, New York University School of Medicine, New York, NY, USA. 8. Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. christinecurcio@uabmc.edu.
Abstract
BACKGROUND: To analyse cellular and spatiotemporal factors of neurodegeneration and gliosis in a patient with submacular haemorrhage (SMH) secondary to type 1 macular neovascularization in neovascular age-related macular degeneration (nAMD). METHODS: This is a case study and clinicopathologic correlation of an 84-year-old white man with nAMD treated with antiangiogenic drugs and photodynamic therapy during a 6-year follow-up. Eyes were recovered for histology 8.23 h after death. In vivo multimodal imaging including optical coherence tomography (OCT) and en face modalities was compared with ex vivo OCT and high-resolution histologic images, using a custom image registration procedure. SMH components were defined (intraretinal, subretinal, sub-retinal pigment epithelium (RPE), and dehemoglobinized blood). Neurodegenerative changes in each of these areas were described. One anonymous donor eye with haemorrhagic nAMD was also reviewed as a comparator. RESULTS: By in vivo OCT, progressive resolution of the haemorrhage and gradual transformation of sub-RPE fluid to fibrous hyperreflective tissue, progressive macular atrophy, and variation in external limiting membrane (ELM) visibility were observed. Histology showed intense photoreceptor loss with preservation and self-adhesion of macular Müller glia resulting in ELM condensation. The comparator eye exhibited shed cone inner segments among subretinal erythrocytes. CONCLUSION: This is the most detailed clinicopathologic correlation of nAMD with SMH resolution to date, and the first in the OCT era. Our results reveal profound macular neurodegeneration and gliosis, signified by condensed ELM, soon after haemorrhage begins. Intensified OCT reflectivity of the ELM, an important retinal barrier, has potential as a biomarker for severe photoreceptor loss and gliosis.
BACKGROUND: To analyse cellular and spatiotemporal factors of neurodegeneration and gliosis in a patient with submacular haemorrhage (SMH) secondary to type 1 macular neovascularization in neovascular age-related macular degeneration (nAMD). METHODS: This is a case study and clinicopathologic correlation of an 84-year-old white man with nAMD treated with antiangiogenic drugs and photodynamic therapy during a 6-year follow-up. Eyes were recovered for histology 8.23 h after death. In vivo multimodal imaging including optical coherence tomography (OCT) and en face modalities was compared with ex vivo OCT and high-resolution histologic images, using a custom image registration procedure. SMH components were defined (intraretinal, subretinal, sub-retinal pigment epithelium (RPE), and dehemoglobinized blood). Neurodegenerative changes in each of these areas were described. One anonymous donor eye with haemorrhagic nAMD was also reviewed as a comparator. RESULTS: By in vivo OCT, progressive resolution of the haemorrhage and gradual transformation of sub-RPE fluid to fibrous hyperreflective tissue, progressive macular atrophy, and variation in external limiting membrane (ELM) visibility were observed. Histology showed intense photoreceptor loss with preservation and self-adhesion of macular Müller glia resulting in ELM condensation. The comparator eye exhibited shed cone inner segments among subretinal erythrocytes. CONCLUSION: This is the most detailed clinicopathologic correlation of nAMD with SMH resolution to date, and the first in the OCT era. Our results reveal profound macular neurodegeneration and gliosis, signified by condensed ELM, soon after haemorrhage begins. Intensified OCT reflectivity of the ELM, an important retinal barrier, has potential as a biomarker for severe photoreceptor loss and gliosis.
Authors: Karen B Schaal; K Bailey Freund; Katie M Litts; Yuhua Zhang; Jeffrey D Messinger; Christine A Curcio Journal: Retina Date: 2015-07 Impact factor: 4.256
Authors: Rosa Dolz-Marco; Katie M Litts; Anna C S Tan; K Bailey Freund; Christine A Curcio Journal: Ophthalmology Date: 2017-04-26 Impact factor: 12.079
Authors: Kunal K Dansingani; Orly Gal-Or; Srinivas R Sadda; Lawrence A Yannuzzi; K Bailey Freund Journal: Clin Exp Ophthalmol Date: 2017-12-26 Impact factor: 4.207
Authors: Manuela Völkner; Felix Wagner; Lisa Maria Steinheuer; Madalena Carido; Thomas Kurth; Ali Yazbeck; Jana Schor; Stephanie Wieneke; Lynn J A Ebner; Claudia Del Toro Runzer; David Taborsky; Katja Zoschke; Marlen Vogt; Sebastian Canzler; Andreas Hermann; Shahryar Khattak; Jörg Hackermüller; Mike O Karl Journal: Nat Commun Date: 2022-10-19 Impact factor: 17.694