British Journal of Ophthalmology, 1977, 61, 141-147

Senile disciform macular degeneration in the second eye Z. GREGOR, A. C. BIRD, AND I. H. CHISHOLM From Moorfields Eye Hospital and Institute of Ophthalmology, London

Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk of developing disciform degeneration in the second eye.

SUMMARY

Disciform macular degeneration is characterised by elevation of the pigment epithelium and retina by blood, serous fluid, and invasion of the subpigment epithelial space by fibrovascular tissue arising from the choroid. Drusen were first described by Donders (1885), but it was not until 1940 that they were recognised as a predisposing cause of disciform detachment of the macula (Gifford and Cushman, 1940). Subsequent experience has confirmed this association, so that now it is generally acknowledged that senile disciform macular degeneration occurs as a result of pre-existing changes in Bruch's membrane and the pigment epithelium. These changes may be the result of a genetically determined disorder (Gass, 1973) or of age alone, but the nature of the changes and the manner by which they induce the disciform response have yet to be identified precisely. With increasing age Bruch's membrane becomes thicker (Hogan, 1967; Hogan et al., 1971). Collagen fibres become electron dense, and irregularly banded structures appear which may be the result of degenerating collagen (Hogan et al., 1971). The elastic zone becomes basophilic, the elastic fibres increase in electron density, and needlelike crystals are deposited within the fibres. Accompanying the fibre changes there is deposition of PASpositive granular, vesicular, and filamentary material in the matrix of the inner collagen layer at first and later in the elastic zone. This material resembles the contents of pigment epithelial phagosomes, and the suggestion has been made that it consists of discharged phagosomal material (Hogan et al., 1971). It has also been inferred that drusen were formed by accumulation of this material between the inner Address for reprints: Dr A. C. Bird, Moorfields Eye Hospital, City Road, London EC1V 2PD

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collagen layer of Bruch's membrane and the pigment epithelial basement membrane. This material probably forms the linear deposits described by Sarks (1973) which form a patchy and then continuous layer on the inner surface of Bruch's membrane. If Bruch's membrane acts as a physical barrier to blood vessel growth, the degeneration of fibres and the distortion of fibres by accumulation of abnormal material within Bruch's membrane may allow vascular incursion into the subpigment epithelial space. Blood vessel growth may be stimulated by outer retinal ischaemia if the thickened membrane acts as a diffusion barrier. Furthermore, the presence of macrophages on the inner surface of Bruch's membrane, as described by Sarks (1976), may also stimulate blood vessel growth. It is also relevant that penetration of Bruch's membrane by choroid vessels is common in the eyes of the elderly, being multifocal and occurring throughout the fundus (Brown, 1940; Riechling and Klemens, 1940; Friedman et al., 1963), whereas recognisable disciform lesions are usually in the macular region and appear to arise from a single vascular source. From the clinical standpoint limited studies have been undertaken concerning the risk of visual loss of an eye with drusen (Teeters and Bird, 1973; Gass, 1973; Chandra et al., 1974). The exact prognostic significance of the type and number of drusen has not yet been defined, though Gass (1973) and Chandra and co-workers (1974) implied that a greater number of drusen denoted worse prognosis. Other poor prognostic signs have been suggested, including rapid increase in the number of drusen, extensive associated pigment epithelial changes, and disciform degeneration in the other eye (Gass, 1973).

Z. Gregor, A. C. Bird, and 1. H. Chisholm

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In the first part of this paper we record the incidence of second eye involvement in a group of patients with unilateral senile disciform macular degeneration who have been observed for periods varying between 1 and 5 years. In the second study reported a qualitative and quantitative assessment of predisposing changes was made, and an attempt was made to identify the type of change which put a patient at high risk of developing a lesion in the second eye.

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I. INCIDENCE Materials and methods All patients between the ages of 60 and 69 who presented initially to Moorfields Eye Hospital with visual loss due to senile disciform macular degeneration and were seen in the retinal diagnostic department from 1970 until the end of 1974 were reviewed. A large number of patients referred from other hospitals and those over 69 were not included because of difficulties of follow-up. In our group there were 172 patients. Of these, 104 had a disciform lesion in one eye only at the time of presentation and had been followed up for at least one year. All patients with a disciform lesion had serous elevation of the retina and the pigment epithelium and subretinal blood vessels were recognised on fluorescein angiography.

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Results

Twenty-nine patients developed a disciform lesion in the second eye during the period of follow-up. The results were analysed in two ways-in respect of length of follow-up and in respect of annual risk in completed years of observation.

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PATIENT RESULTS

During the first year of follow-up 9 (9 8 %) of the 104 patients developed a disciform lesion in the other eye. Of these, 74 were followed up for 2 years, and 18 (19%) developed disciform degeneration in the fellow eye during this period. The figures for incidence of involvement of the second eye for those followed up for 3 years was 17 of 53 (30%), for 4 years was 11 of 23 (48 %), and for 5 years, 5 of 11 (45%) (Fig. 1). II. YEARLY RESULTS

Of the 34 patients 5 (15%) followed up in 1972 developed a disciform lesion in the other eye. The incidence for 1973 was 6 of 49 patients (12%) and for 1974, 12 of 78 patients (15%) (Fig. 2).

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Fig. I Patient results. (a) Proportion of patients who developed a disciform lesion in the second eye over the period offollow-up (shaded section of column). (b) Same expressed as percentages. (c) Comparison with calculated incidence curve of 12 % per year

Comments In respect of yearly incidence the risk of developing disciform lesion in the second eye appears to lie between 12 and 15%. This is in agreement with the incidence of 12% found by Teeters and Bird (1973), and 35 % in 3 years by Gass (1973). The results in terms of patient follow-up suggest a constant risk of 12% per year of developing a second disciform lesion during the first 5 years. A second disciform lesion does not appear to be inevitable within any given period. It is unlikely that the risk in the 60 to 69 age group can be applied to younger patients. Equally the risk may not pertain to people witlh a

Senile disciform macular degeneration in the second eye Fig. 2. Yearly results. (a) Proportion of patients who developed a disciform lesion in the other eye each year (shaded section of column).

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143 Both drusen and pigment epithelial changes were examined on the initial colour stereophotographs. The following characteristics of drusen were assessed: Total number and distribution, whether macular or perimacular. Single dome-shaped drusen were arbitrarily divided into four categories according to their diameter: Less than 50 ,um; 50 to 150 l±m;

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bilateral drusen and pigment epithelial changes without disciform lesions. Gass (1973) has clearly shown the relatively lower risk of developing a disciform lesion in these two groups. In his series a smaller proportion of eyes in patients with no disciform lesions suffered visual loss than in those with unilateral disciform degeneration, and in the latter group the average age of patients suffering visual loss in the second eye was higher than in the original sample.

Fig. 3 The measuring grid. Inner complete ring corresponds to a diameter of 1600 tm (I DD), outer ring to 4800 j±m (3 DD). The distances between the dividing marks correspond to 200 l±m in the inner ring and 400 Ftm in the outer ring

II. SIGNIFICANCE OF PREDISCIFORM CHANGES IN THE SUBSEQUENT DEVELOPMENT OF SENILE DISCIFORM MACULAR DEGENERATION Materials and methods

All 104 patients in the original sample had a full ophthalmological examination which included fundus colour stereophotography and fluorescein angiography. All the patients have had repeated examinations during the period of follow-up (29 of these 104 patients developed a disciform lesion in the other eye during this period). A Zeiss (Oberkochen) fundus camera was used to obtain both colour photographs and fluorescein angiograms. The initial colour photographs and fluorescein angiograms of the eye with predisciform changes were examined under magnification. The Fig. 4 The measuring grid is placed on a standard fundus macular region was arbitrarily divided into sectors by photograph, centred on the fovea. The size and distances placing a grid over the photograph (Figs. 3 and 4). offundus abnormalities can be assessed

Z. Gregor, A. C. Bird, and I. H. Chisholm

144 200 to 500 ,um; 500 to 800 sum. Sheets of white subpigment epithelial material with an irregular surface were categorised as confluent. In respect of the edge of the drusen, they were separately recorded as having well-defined or blurred edges. The corresponding fluorescein angiograms were examined. The following features were noted: accumulation of dye, transmission defect or a normal appearance. All the findings were recorded on a standard form. Pigment epithelial changes were recognised either as pigment clumping on the surface of the drusen or without underlying drusen, and as pigment epithelial atrophy with or without coexisting choroidal atrophy. Although the following features were recorded, they were not used in the final analysis. The colour of drusen was difficult to assess because of variation in the quality of the original photographs or lens opacities or the likelihood of observer error. Drusen with white glistening surfaces, usually thought to denote calcification, were observed infrequently. In the presence of widespread drusen pigment epithelial atrophy without choroidal atrophy was also difficult to estimate. To minimise bias and to maintain standardisation, the following steps were adhered to: (1) The patient records were examined at random without prior knowledge of the examiner as to which patient subsequently developed a disciform lesion in that eye; (2) all findings were tape-recorded at first, so that no pattern could be observed from the record form before the investigation was completed; (3) repeatability tests were performed. After completion of the study, patients who developed a disciform lesion in the second eye were identified (group I) and compared with those patients who remained at the predisciform stage (group II). The results were analysed with the aid of a computer, using the x2 method. Results I. DRUSEN

Drusen were found in all the patients studied.

Number and distribution No significant difference in number of drusen was found between the two groups. This was so both in the macular and perimacular areas. Size Small drusen (less than 50 jum) were found more commonly and large drusen (500 to 800 ,Lm) less so in eyes which remained free of disciform lesions (group II) than those which developed a disciform lesion (group I), though at a low level of significance (P=0-0207 and 0-0844 respectively).

Patients who subsequently developed disciform degeneration (group I) had more areas of confluent drusen than patients in group II. The difference is highly significant (P

Senile disciform macular degeneration in the second eye.

British Journal of Ophthalmology, 1977, 61, 141-147 Senile disciform macular degeneration in the second eye Z. GREGOR, A. C. BIRD, AND I. H. CHISHOLM...
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