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J. Torrent, A. Wagner, S. Grisanti, S. Vogt, R. Read, C. Curcio, M. Rudolf; Morphometry of Cell Phenomena in Histological Sections of Geographic Atrophy Due to Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4943.
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© ARVO (1962-2015); The Authors (2016-present)
Background: New clinical high resolution imaging technologies like spectral domain OCT are useful tools in the evaluation of GA due to ARMD. The GA junctional zone includes changes in RPE-Bruch’s membrane (BrM) complex that are difficult to interpret. We measured and evaluated characteristic RPE cell changes in histological sections of GA eyes to provide a better basis for interpreting clinical GA imaging data.
Ten µm macular sections of 7 GA donor eyes fixed with 4% paraformaldehyde were evaluated by light microscopy with differential interference contrast. In 3 sections/eye, zones of RPE alterations were graded (0 = normal; 1 = irregular cells, but intact layer; 2 = rounded, enlarged, and/or heaping cells; 3 = migrating cells in retina; 4 = RPE absent). Per graded zone, we measured and statistically evaluated A) the total height of RPE cell layer, B) the height of individual RPE cells, and C) the height of basal laminar deposits (BlamD).
We defined zones from the outer macula towards the central RPE atrophic area in which the RPE passed almost steadily upward through the grades of increased pathology. A) Zone 2 exhibited variable total RPE height (16.9 µm ± 5.6) with hypertrophic and heaping cells next to atrophic ones. In comparison, Zone 0 (10.9 µm ± 2.6) and Zone 1 (11.8 µm ± 2.8) showed significantly less variability and total RPE height (p<0.001). If present, Zone 3 was found close to the atrophy margin, and migrating cells/cell debris were seen across all retinal layers. B) Individual cell height of Zone 0 and 1 equals total RPE height, but in Zone 2, the size of altered RPE cells varied widely (12.4 µm ± 5.2, minimum 5.1, maximum 27.5). C) In Zone 0, sporadic BlamD was thin (3.5 µm ± 1.1) with progressing cell alteration becoming progressively continuous and thicker from Zone 1 (5.0 µm ± 2.3) to Zone 4 (9.5 µm ± 4.3).
Our histological measurements provide information about GA typical alterations of the RPE-Bruch’s membrane complex and are useful for interpreting clinical imaging data. BlamD thickness is related to the degree of RPE alteration, with areas of advanced RPE alterations are most likely to exhibit recognizable thickening of the RPE-Bruch’s membrane complex in OCT images. Individual large or heaping cells are large enough to be detected by clinical imaging.
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