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.
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Funding
This work was supported by Genentech/Hoffman-LaRoche. The funding organisation had no role in the design and conduct of this study. Purchase of the slide scanner was made possible by the Carl G. and Pauline Buck Trust.
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No conflicting relationship exists for ML, JDM. RD-M is consultant to Heidelberg Engineering, Novartis and Allergan and receives research support form Genentech, Heidelberg Engineering, Novartis, and Roche. KBF is a consultant for Optovue, Heidelberg Engineering, Zeiss, Genentech, Novartis, and Allergan. He receives research support from Genentech/Roche. DF is an employee of Genentech and has stock/stock options of Roche. CAC receives research support from Heidelberg Engineering and owns stock of MacRegen.
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Li, M., Dolz-Marco, R., Messinger, J.D. et al. Neurodegeneration, gliosis, and resolution of haemorrhage in neovascular age-related macular degeneration, a clinicopathologic correlation. Eye 35, 548–558 (2021). https://doi.org/10.1038/s41433-020-0896-y
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DOI: https://doi.org/10.1038/s41433-020-0896-y
