T. L. van der Schaft

Early stages of age-related macular degeneration: an immunofluorescence and electron microscopy study.

In subretinal neovascularisation capillaries originating from the choriocapillaris must cross Bruchs membrane to reach the subretinal pigment epithelial space. Thus gaps in Bruchs membrane have to be formed before subretinal neovascularisation. Histological examination of eyes with subretinal neovascularisation or disciform scars has shown macrophages adjacent to thin areas and ruptures in Bruchs membrane. This has been interpreted as phagocytosis of Bruchs membrane. The purpose of this study was to investigate whether immune complex depositions can be detected in maculae with early stages of age-related macular degeneration and to explain the macrophage reaction before the disciform reaction. A series of 20 human maculae were examined by direct immunofluorescence light microscopy to detect the presence of immune complexes with antibodies directed against immunoglobulins, fibrinogen, and complement factors. Transmission electron microscopy on several maculae was performed to identify the macrophages. Macrophages were observed in close relation to the readily recognisable long spacing collagen, which suggested that long spacing collagen was selectively internalised by these cells. Definite immune complex depositions were not found in basal laminar deposits or drusen. Linear deposits of fibrinogen and complement were frequently found in the outer collagenous zone of Bruchs membrane. However, because of the absence of immunoglobulins, it seems unlikely that these non-specific deposits might cause chemoattraction of macrophages and play a role in the initial phase of the development of subretinal neovascularisation and disciform macular degeneration.

Increased prevalence of disciform macular degeneration after cataract extraction with implantation of an intraocular lens.

After cataract extraction with implantation of an intraocular lens the increased transmission of ultraviolet and blue light may accelerate the development of age-related macular degeneration by producing free radicals in the retina. The maculae of 82 randomly selected postmortem human pseudophakic eyes and 16 fellow phakic eyes were examined by light microscopy. The presence of a basal laminar deposit, hard and soft drusen, thickening and calcification of Bruchs membrane, geographic atrophy, subretinal neovascularisation, and disciform scars was assessed in a standardised way. An age-matched series of 126 postmortem phakic eyes was used as control group. There was no difference between the two groups, except for a higher prevalence of hard drusen (exact trend test, p = 0.038) and disciform scars for the pseudophakic eyes (Fishers exact test, p = 0.007). There was no significant correlation between either age-related changes in the macula or disciform degeneration and the length of time between cataract surgery and death. No significant difference was found between pseudophakic eyes with or without ultraviolet filter. These findings do not confirm that disciform scar formation is caused by an increase in ultraviolet or blue light.

Basal laminar deposit in the aging peripheral human retina

A basal laminar deposit (BLD) in the human macula has been described as an early sign of age-related macular degeneration. In some eyes with a BLD in the macula, light microscopic sections of the peripheral retina revealed almost similar deposits between the retinal pigment epithelium and Bruchs membrane. Because the exact pathogenesis of age-related macular degeneration and the origin of the BLD are unknown, we studied the ultrastructure of these peripheral sub-RPE deposits. Parts of the equatorial and peripheral regions of the retina of ten human eyes, with BLD-like deposits between the retinal pigment epithelium and Bruchs membrane, were examined by electron microscopy. In eight of these ten eyes the ultrastructure of these deposits was amorphous and finely granular. Five of the eight deposits also contained small amounts of long-spacing collagen. Ultrastructurally, the deposits were similar to an early type BLD in the macula. In the remaining two eyes, the deposits appeared to consist of flat, elongated drusen. Our findings indicate that a BLD can develop not only in the macula but also in the peripheral region of the retina.