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S H Sarks

Publications and source records attributed to S H Sarks.

At least 19 recordsLinked to original sources
PubMed2003

Adult vitelliform macular degeneration: a clinicopathological study.

AIMS/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.

Adult↗
PubMed2000

Swelling and loss of photoreceptors in chronic human and experimental glaucomas.

OBJECTIVE: To determine whether outer retinal changes occur in chronic, presumed primary open-angle glaucoma (POAG). METHODS: The outer retinas from 128 human eyes with a diagnosis of chronic glaucoma (presumably POAG in most cases) and 90 control eyes were examined histologically by 3 masked observers for photoreceptor swelling and loss. Retinas from 9 rhesus monkeys with glaucoma induced experimentally by laser trabecular destruction were compared with 7 fellow (control) eyes. The mean pressure elevations in the eyes with laser trabecular destruction ranged from 26.6 to 53.6 mm Hg with durations varying from 7 to 33 weeks. RESULTS: Swelling of the red- and green-sensitive cones was observed in a statistically significantly greater proportion of human eyes with presumed POAG compared with the control eyes. Patchy loss of red/green cones and rods was also found in some of the glaucomatous retinas. In a subset of the human eyes with end-stage disease, cone swelling was a variable finding. Although no photoreceptor loss was found in the 9 monkey eyes with experimental glaucoma, 8 had swelling of their red/green cones that was remarkably similar to that seen in the human eyes. Swelling was not present in any of the control monkey eyes. CONCLUSIONS: The photoreceptors are affected by chronically elevated intraocular pressure. CLINICAL RELEVANCE: These findings may explain some of the abnormalities of color vision and the electrophysiological effects that have been observed in patients with POAG.

Aged↗
PubMed1999

Distribution of cathepsin D in human eyes with or without age-related maculopathy.

Cathepsin D is a ubiquitous enzyme which plays an important role in the catabolism of proteins. Enzymatic studies showed that cathepsin D is the most important lysosomal enzyme in the proteolysis of opsin. The importance of cathepsin D in the lysosomal digestion of phagocytosed photoreceptor outer segments by the retinal pigment epithelium suggests that a decrease in cathepsin D activity might contribute to the development of hyalinized drusen and to the development of age-related maculopathy. The aim of this project was to study the immunohistochemical localization of cathepsin D in human eyes and particularly to compare the immunoreactivity of cathepsin D normal retinal pigment epithelial cells and in cells surrounding hyalinized drusen or lesions of age-related maculopathy. Following clinicopathological examinations the eyes were fixed, paraffin embedded and individual sections were subjected to Picro-Mallory staining for histopathological examination. Bleaching was performed then immunohistochemistry was carried out using a monoclonal mouse anti-human cathepsin D antibody. On the basis of the appearance of basal laminar deposit the eyes were divided into five groups corresponding to levels of progression in age-related maculopathy development. Following optimization of bleaching cathepsin D immunostaining was clearly visible in the iris epithelium, ciliary body and the retinal pigment epithelial layer of all eyes with the highest immunoreactivity present in the RPE cells. Within the neural retina the ganglion cells demonstrated a weak signal. Retinal pigment epithelial cathepsin D immunoreactivity was not impaired by age, geographical location or by age-related maculopathy status. There was a small increase in cathepsin D immunoreactivity around hyalinized drusen. The maintenance of cathepsin D immunoreactivity in eyes with hyalinized drusen or in samples with age-related maculopathy suggest that down-regulation of cathepsin D expression in the affected locations does not precede the development of these conditions. However, further studies are required to establish if the immunoreactive cathepsin D represents the fully processed biologically active enzyme.

Adolescent↗
PubMed1999

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 microns 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 microns 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.

Aged↗
PubMed1997

Indocyanine green angiography of drusen.

PURPOSE: To analyze the indocyanine green angiographic findings of drusen in the early stages of age-related macular degeneration. METHODS: Sixty-nine eyes of 53 consecutive patients with drusen but without exudative complications of age-related macular degeneration were studied. Drusen were classified into four groups: hard drusen, drusen derived from clusters of hard drusen (hard cluster-derived drusen and soft cluster-derived drusen), membranous drusen, and regressing drusen. An additional category was constituted by reticular pseudodrusen that could be associated with drusen of either the inner or outer macula. Results of contact lens biomicroscopy and fluorescein angiography were compared with findings on indocyanine green angiography. RESULTS: Hard drusen, either isolated hard drusen or hard cluster-derived drusen, were hyperfluorescent during indocyanine green angiography; in contrast, all sizes of soft drusen derived from clusters of hard drusen were hypofluorescent throughout the angiogram. Membranous drusen, visible on biomicroscopy and fluorescein angiography, were not visible during indocyanine green angiography. Regressing drusen may have showed hyperfluorescence at the early stages of indocyanine green angiography, but associated calcium and pigmentation were hypofluorescent. Reticular pseudodrusen were visible on red-free photographs; on midphase and late-phase indocyanine green angiography using the scanning laser ophthalmoscope only, reticular pseudodrusen were seen as a pattern of hypofluorescent dots. CONCLUSION: The indocyanine green angiographic findings add to and support the clinicopathologic classification of drusen. Indocyanine green angiography may help to distinguish the different types of drusen and may thus be of use in evaluating the risk of progressive age-related macular degeneration in patients with drusen.

Adult↗
PubMed1997

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 Bruch's 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.

Aged↗
PubMed1996

Prophylactic perifoveal laser treatment of soft drusen.

PURPOSE: To assess the efficacy and safety of perifoveal laser to cause drusen to resorb, and establish a treatment protocol. METHODS: Treatment technique was determined by the outcome in one patient with 15-year follow-up. In an uncontrolled series a perifoveal ring of gentle laser was applied to 30 eyes of 28 patients, 18 with bilateral drusen and 10 with exudative disease in the fellow eye. Comparison was made between treated and untreated eyes in 14 patients with bilateral drusen. Mean follow-up was 16.8 months (range, three to 42 months). RESULTS: Soft drusen resorbed in all treated eyes in the vicinity of laser and within the fovea. Large soft confluent drusen (> 500 microns) responded most rapidly. Visual acuity improved one or more lines in 12 (40%) treated eyes, was unchanged in 16 (53%) and deteriorated in two (7%). In 14 patients with bilateral drusen in whom only one eye was treated, VA remained unchanged in 10 eyes and improved in four treated eyes while none of the untreated eyes improved (P = 0.03, chi 2) and decreased in four eyes. Atrophic expansion of laser burns was minimal. CNV developed in two of 30 eyes (7%). CONCLUSION: Perifoveal laser treatment appears to expedite the regression of soft drusen within the fovea. The risks of complications may be reduced by treating eyes early, before pigment changes develop and by applying a minimum number of burns at a distance greater than 750 microns from the foveal centre. Treatment should currently be administered only in the context of a prospective clinical trial, which is required to assess whether this treatment results in lowered risk of visual loss from CNV or geographic atrophy.

Aged↗
PubMed1995

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

BACKGROUND: Reticular pseudodrusen refer to a yellow interlacing network 125 microns to 250 microns 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.

Adult↗
PubMed1994

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.

Adult↗
PubMed1993

Treatment of choroidal neovascularisation in age-related macular degeneration with interferon alfa-2a and alfa-2b.

Forty eight eyes of 42 patients with choroidal neovascular membranes and age-related macular degeneration who received three different dose regimens of systemic interferon alfa-2 were studied retrospectively. The response to treatment of 41 eyes of the 37 patients who received at least 4 weeks' treatment was analysed with respect to the change in size of the choroidal neovascular membrane and the visual acuity compared with pretreatment levels. The size of the membrane at the end of the course of treatment had decreased in seven (17%) eyes overall, not changed in 16 (39%), and increased in 18 (44%). At the end of treatment, the visual acuity had improved in seven (17%) eyes, not changed in 27 (66%), and deteriorated in seven (17%). With an average follow up of 10 months after treatment, the visual acuity had deteriorated compared with the pretreatment value in 21 out of 41 (51%) eyes. Vision improved in some fellow eyes with disciform scars. Side effects were common and often severe. The data suggest that one of the major effects of interferon alfa may be to decrease vascular permeability. While further research may identify a place for interferon alfa in the treatment of choroidal neovascularisation, we were unable to demonstrate that the treatment regimens of systemic interferon alfa we used caused a dramatic benefit to patients with exudative age-related macular degeneration.

Aged↗
PubMed1990

Macrophages related to Bruch's membrane in age-related macular degeneration.

This report describes focal thinning of Bruch's membrane in age-related macular degeneration and suggests a role for macrophages in this process. Electron microscopy was performed on four eyes ranging from normal ageing to age-related macular degeneration with early subretinal neovascularisation. As degeneration progressed multiple segments of thinning of Bruch's membrane were observed and macrophages appeared to engulf fragments of the outer collagenous zone. An associated finding at this stage was the shedding of membranous debris by the retinal pigment epithelium and its deposition within Bruch's membrane. This debris forms the basis of soft drusen but in the presence of this material thinning of Bruch's membrane was also observed beneath hard drusen. It is suggested that the widespread accumulation of phospholipid-containing membranes together with the focal concentration of lipid in hard drusen attract macrophages.

Aging↗
PubMed1990

Adult vitelliform macular degeneration: a clinical spectrum.

Adult vitelliform macular degeneration (adult Best's disease) has a spectrum of clinical appearances which may include focal macular pigment clumps as well as the more typical small, yellow lesions. We surveyed 81 patients with this diagnosis retrospectively. Ages ranged from 36 to 87 years, with an average age of 67 years. Males and females were almost equally represented. Median visual acuity at presentation was 6/12 for eyes with yellow lesions, and 6/9 for eyes with pigment clumps. Of 17 cases followed for an average of 3.6 years, there was a decrease in visual acuity of two lines or more in five cases. A significant proportion of patients also had other manifestations of age-related macular degeneration. Adult vitelliform macular degeneration probably falls within the spectrum of age-related macular degeneration.

Adult↗
PubMed1988

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. Progression 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 ultrastructural findings. Membranous debris was not previously recognised and its contribution to the findings in incipient atrophy and to dot-like drusen is described.

Aged↗
PubMed1986

Senile macular degeneration. The involvement of giant cells in atrophy of the retinal pigment epithelium.

Senile macular degeneration (SMD) is a leading cause of registered blindness in the United States and other Western countries. Loss of central vision develops as a result of atrophy of the retinal pigment epithelium or subretinal neovascularisation. The histopathology of the atrophic form of SMD has not been extensively studied. This paper illustrates at the light and electron microscope level the involvement the atrophic form of SMD. Additional features including pigment clumping and detachment of the retinal pigment epithelium at the advancing edge of the lesion are illustrated. Giant cells and MPS cells are typical features of granulomatous inflammation, and results suggest that they may play a role in the pathogenesis of SMD.

Aged↗
PubMed1985

Senile macular degeneration: the involvement of immunocompetent cells.

Senile macular degeneration (SMD) is a leading cause of legal blindness in western countries. The role of immunocompetent cells in the pathogenesis of this disease has not been widely recognised. In this work specimens were studied by electron microscopy to provide ultrastructural details of the role of immunocompetent cells in early, intermediate and late stages of the disease. Additionally, we have analysed the frequency and distribution of inflammatory cellular infiltrates using wax histology. The results illustrate the involvement of macrophage-series cells, fibroblasts, lymphocytes and mast cells in neovascularisation, atrophy of the retinal pigment epithelium and the breakdown of Bruch's membrane. These observations, together with previous clinicopathological studies, have led us to suggest that SMD has a chronic inflammatory component.

Adult↗
PubMed1982

Drusen patterns predisposing to geographic atrophy of the retinal pigment epithelium.

This report discusses the recognition of drusen referred to as "hard" which appear to predispose the eye to the development of geographic atrophy of the retinal pigment epithelium. When numerous, small hard drusen tend to become arranged in clusters. On the temporal side in particular, this grouping may be so close as to resemble larger confluent drusen within which the small drusen can only be distinguished by fluorescein angiography. The approximate interval before geographic atrophy involves the fovea can be estimated by noting the distribution of drusen and the state of the pigment epithelium between the drusen. A stage of incipient atrophy can be recognised as an area of diffuse hyperfluorescence in which pigment clumping or reticular pigment figures and fading of drusen occur.

Adult↗
PubMed1980

Council Lecture. Drusen and their relationship to senile macular degeneration.

This study is based on the clinico-pathological examination of 512 eyes. As senile macular degeneration developed drusen appeared to alter in consistency and become more fluid. This resulted in a spectrum of clinical appearances classified as hard, semisolid, soft or serous, and regressing. Histologically the hyaline contents of the drusen changed to a pale-staining amorphous material which electron microscopy showed to consist of vesicles. This membranous debris first appeared beneath the pigment epithelium in normal aged eyes but its later accumulation led to a widespread shallow separation of the basement membrane. The softening of drusen was most evident in group IV in which subretinal neovascularization was first detected. At this stage the retinal pigment epithelium also showed its greatest proliferative activity and the formation of abnormal basement membrane material.

Adult↗