J P Sarks

Evolution of geographic atrophy of the retinal pigment epithelium

The aim of this study was to trace the evolution of geographic atrophy (GA) by clinical documentation and by clinico-morphological correlation in representative eyes. Geographic atrophy commonly commenced within a parafoveal band of incipient atrophy of varying width, characterised by semisolid drusen and a microreticular pigment pattern. Progession of atrophy mostly skirted fixation and visual acuity was a poor guide to the functional impact, an estimate of the percentage of fovea involved proving a more useful clinical parameter. The rate of progression slowed once GA had involved all the retina affected by incipient atrophy and the risk of choroidal neovascularization appeared to decline.An earlier histological classification of the evolution of GA is revised according to the ultras- tructural findings. Membranous debris was not previously recognised and its contribution to the findings in incipient atrophy and to dot-like drusen is described.

Reticular pseudodrusen. A risk factor in age-related maculopathy.

Background: Reticular pseudodrusen refer to a yellow interlacing network 125µm to 250µm wide appearing first in the superior outer macula and then extending circumferentially and beyond. Unlike true drusen, they do not fluoresce on fluorescein or indocyanine green angiography, and are best seen in red-free light or with the He-Ne laser of the scanning laser ophthalmoscope. Methods: One hundred patients have been seen in our retinal practice with this clinical feature in the past 3 years. Results: All had some manifestation of age-related maculopathy (ARM), and 66% had or subsequently developed subretinal new vessels in one or both eyes. The appearance is attributed to changes in the choroid. Conclusions: Reticular pseudodrusen are an easily recognizable clinical sign, and may be an important risk factor for choroidal neovascularization in ARM.

Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study

AIM To describe the early formation of drusen and their relation to normal aging changes at the macula and to the development of age related maculopathy (ARM). METHOD Histopathological features of 353 eyes without histological evidence of ARM are described and correlated with the clinical appearance. In addition, 45 of these eyes were examined by transmission electron microscopy. RESULTS Drusen were detected histopathologically in 177 (50%) eyes but were seen clinically in only 34% of these. Drusen were mainly small hard drusen with an occasional soft distinct drusen: no soft indistinct drusen were seen. Only those drusen deposits larger than 25–30 μm in diameter were detectable clinically. Preclinical drusen in eyes with only an occasional drusen were seen on electron microscopy as entrapment sites of coated membrane bound bodies which formed adjacent to the inner collagenous zone of Bruch’s membrane. In contrast, preclinical drusen deposits in eyes with many drusen were seen as accumulations of amorphous material which appeared hyalinised by light microscopy. A distinct feature were rows of dense hyalinised microdrusen (1–2 μm in diameter), over which larger globular hyalinised drusen formed. CONCLUSION Histological and ultrastructural examination can recognise and distinguish the earliest drusen formed as a result of normal aging from those associated with ARM. In eyes without diffuse deposits, histologically all drusen were of the hard hyalinised variety or their derivatives; no soft drusen composed of membranous debris were found. These findings support and explain those of other authors who do not consider the presence of a few small hard drusen to be a risk factor for the development of ARM.

Evolution of soft drusen in age-related macular degeneration

The pathways by which soft drusen are formed are illustrated by representative clinical and clinicopathological cases. One type is derived from small hard drusen which first tend to aggregate into clusters and then fuse, forming larger deposits termed hard clusters. Breakdown of the hard drusen results in varying degrees of softening and confluence. These soft clusters may appear in middle age and, like the preceding hard drusen, remain a focal pathology. Soft clusters commonly lead to the atrophic form of age-related macular degeneration. Another type of soft drusen is formed from membranous debris as part of a diffuse disturbance of the retinal pigment epithelium. These membranous soft drusen first appear in the seventh decade and are commonly associated with choroidal neovascularisation.

Evolution of reticular pseudodrusen

Aims To report observations relating to the clinical recognition and possible basis of reticular pseudodrusen (RPD). Methods This retrospective study reports the evolution of RPD in 166 patients who had follow-up of over 1 year using multiple imaging techniques. Mean age when first seen was 73.3 years and the mean period of observation was 4.9 years (range 1–18 years). Associated macular changes were recorded. Results RPD were first identified in the upper fundus as a reticular network, which then became less obvious, developing a diffuse yellowish appearance. RPD also faded around choroidal neovascularisation (CNV). RPD therefore could be transient but the pattern often remained visible outside the macula or nasal to the discs. Manifestations of age-related macular degeneration (AMD) were present in nearly all eyes and there was a particularly high association with CNV (52.1%). In one clinicopathological case abnormal material was found in the subretinal space. Conclusions The prevalence of RPD may be underestimated because their recognition depends upon the imaging method used, the area of fundus examined and the confusion with typical drusen. The pathology of one eye suggests that RPD may correspond to material in the subretinal space.

Morphology of early choroidal neovascularisation in age-related macular degeneration: correlation with activity.

The purpose of this study was to describe the morphology of early choroidal neovascularisation (CNV) and compare the findings in two patients, in the first of whom the vessels appeared inactive and in the second progressive. Changes common to both included a diffuse deposition of membrane coils external to the basement membrane (BsM) of the retinal pigment epithelium (RPE), and macrophages and foreign body giant cells beneath thinned segments of Bruchs membrane (BrM). In the first patient small activated vessels surrounded by enlarged pericytes were found in the choroid beneath these areas and pursued a convoluted course, bulging into or through BrM, but without spreading in the sub-RPE space. This choroidal phase of CNV may be common and unrecognised. In the second patient there was spread of CNV in the sub-RPE space with extravasation of red cells and fibrin. The tips leaking fibrin were covered by a thick BsM-like material and naked endothelial cells were not seen. Pericytes were absent here but were observed at the non-leaking edge. The difference in activity of CNV in the two patients appeared to correlate with the quantity of membranous debris present.

Adult vitelliform macular degeneration: a clinicopathological study.

AbstractAims/background The yellow lesions of adult vitelliform macular degeneration (AVMD) slowly fade, progressing to hyperpigmentation or atrophy. This study aims to provide further observations on the location and nature of the vitelliform material.Methods This report describes the clinicopathological correlation of four eyes with AVMD. A retrospective histopathological study of a further 526 aged eyes previously graded for the stage of age-related macular degeneration (AMD) found another 10 eyes with similar pathology.Results The predominant finding was a collection of extracellular material beneath the sensory retina at the fovea. This material was derived internally from photoreceptor outer segments and externally from the retinal pigment epithelium (RPE), the latter first undergoing hypertrophy and then disruption and attenuation. Fallout of foveal cones occurred over these lesions and the inner retina was thinned, which may explain macular hole formation in this condition. All affected eyes showed histopathological evidence of AMD.Conclusions This study confirms that the vitelliform lesions of AVMD lie beneath the sensory retina. In contrast to previous reports, however, it is proposed that the lesions comprise mainly extracellular material consisting of photoreceptor debris, possibly the result of faulty phagocytosis by the RPE, mixed with pigment liberated as the RPE undergoes disruption. The vitelliform lesions therefore are a marker for the area of maximal RPE disturbance.

Development of atrophy of the retinal pigment epithelium around disciform scars

Background/aims: Eyes with burnt out disciform scars secondary to age related macular degeneration (AMD) are regarded as visually stable. The aim of this study is to report the subsequent development of atrophy of the retinal pigment epithelium (RPE) around the scars and discuss the possible basis. Methods: 20 eyes from 18 patients were observed to develop atrophy around choroidal neovascularisation (CNV). A method of measuring expansion of the atrophy over time is described using the Topcon Imagenet 2000 system. An additional 10 clinicopathological examples were reviewed. Results: Clinically CNV became surrounded initially by a ring of pallor that progressed to an expanding band of atrophy of the RPE. It developed most rapidly in the first 3 years after CNV became quiescent but then continued to expand slowly to more than three times the size of the scar. Histopathological specimens showed large choroidal vessels entering the scars directly and a reduced number of small choroidal vessels beneath and around the scar Conclusions: Disciform scars may become surrounded by an expanding band of atrophy of the RPE, postulated to result from remodelling of the choroidal circulation. The ongoing enlargement of the resulting scotoma may need to be considered when planning management and assessing treatment outcomes.