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ORIGINAL ARTICLE
Year : 2002  |  Volume : 50  |  Issue : 3  |  Page : 201-204

Age-related changes in the macula. A histopathological study of fifty Indian donor eyes


Medical and Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006, India

Correspondence Address:
J Biswas
Medical and Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006
India
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Source of Support: None, Conflict of Interest: None


PMID: 12355694

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  Abstract 

PURPOSE: Age-related macular degeneration (ARMD) is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, and the macula. Six sections, 6 microns thick, were cut from three levels in the macula at a distance of 140 microns. These were stained with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains. The presence of basal laminar deposits, drusen and thickening and calcification of Bruch's membrane in the macula were assessed at 400 x magnification using a modified version of Sark's classification. RESULTS: Twenty-four donor eyes (48%) had some form of age-related macular change. These included basal laminar deposits, hard drusen, soft drusen, extensive retinal pigment epithelium atrophy of the macula, and disciform degeneration of macula. A combination of changes was often seen. Age-related changes were more common in the seventh and eighth decade. CONCLUSION: Our study shows that histological changes characteristic of the early stages of age-related macular degeneration are fairly common in the Indian population. However, advanced macular changes are significantly rare.

Keywords: Age-related macular degeneration, histopathology, Indian donor eyes, basal laminar deposit, drusen, calcification of Bruch′s membrane


How to cite this article:
Biswas J, Raman R. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes. Indian J Ophthalmol 2002;50:201-4

How to cite this URL:
Biswas J, Raman R. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes. Indian J Ophthalmol [serial online] 2002 [cited 2019 May 26];50:201-4. Available from: http://www.ijo.in/text.asp?2002/50/3/201/14786



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Age-related macular degeneration (ARMD) is one of the most common causes of loss of central vision in Western Countries in persons over 50 years of age.[1],[2] The disease was believed to be less common in African and Asian countries. However, with the increase in life expectancy, such age-related macular changes are becoming common all over the world. In India, to the best of our knowledge, no data is available on the histopathologic features of age-related macular changes in Indian eyes.

Sequential changes in retinal pigment epithelium and Bruch's membrane have been studied by Sarks, describing the normal ageing changes in the macula leading to progressive development of age-related macular degeneration and advanced changes.[3] We wished to determine whether such changes occur as frequently as in Indian eyes as in the Western population.

We studied 50 consecutive human donor eyes received by the Sankara Nethralaya Eye Bank for corneal grafting to determine the gross, microscopic, histochemical age-related changes in the macula of different age groups in the Indian population.


  Materials and Methods Top


Fifty consecutive human donor eyes (25 pairs) received for corneal grafting were studied. The age, gender, systemic and ocular problems of the donor eyes were recorded. Immediately after removing the corneal button, the eyes were fixed with a mixture of glutaraldehyde (1% volume/volume) and a formaldehyde solution (4% volume/volume).

After 24 hours of fixation, the eyeball was sectioned coronally at the equator and examined under a dissecting microscope. Any positive findings were documented by photographs, using a specialised camera with a zoom lens and a shadow-free lighting system. (Wild M3C, Leica instruments, Switzerland) A longitudinal flat piece of retina and choroid measuring 6 mm x 2 mm was taken around the optic nerve and macula. One half of the section was preserved in Karnovsky's fixative. The macula and the remaining part of the block were embedded separately in paraffin using routine procedures.

From three levels in the macula, at an intervening distance of 140 μm, 6 sections 6 μm thick were cut using a Leica microtome. The sections were stained with haemotoxylin and eosin, periodic acid-schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains.

The presence of basal laminar deposits, drusen and thickening and calcification of Bruch's membrane in the macula were assessed at 400 x magnification using a modified version of Sark's classification.[3]


  Results Top


Twenty four donor eyes (48%) showed some form of age-related macular changes ranging from basal laminar deposits to disciform scar over the macula. The age distribution of 50 donor eyes and number of cases with age-related macular changes are presented in the [Table - 1]. Various types of age-related changes are noted in [Table - 2]. These range from early changes like basal laminar deposits or folding of internal limiting membranes to extensive age-related macular changes with disciform scar over the macula. These changes correlated with age and were significantly higher in the >60 years age group. In the <60 years age group, changes were seen in less than 30 % of eyes, while in the seventh, eighth, and ninth decade they occurred in 56.3 %, 58.3 % and 71.5 % of the eyes respectively. Changes were symmetrical in 63.6 % eyes, while some asymmetry was seen in 36.4 % of eyes.

Basal laminar deposits (BLD) constituted the most common age-related macular change seen histologically, in 11 eyes (22%) [Figure - 1]. BLD were seen more commonly with drusen (4%), but were seen alone in 4% cases and with folding internal limiting membrane in 2% cases [Figure - 2]. They were seen on the basal side of the RPE and ranged from small solitary patches (Class I), to a thin continuous layer (Class II) in a majority of cases. One eye had a thick layer of BLD along with drusen. Basal laminar deposits stained positive with periodic acid-Schiff stain, Mallory stain and Massontrichrome stain.

Hard drusen were characterised by their discrete appearance [Figure - 3] and stained positive with periodic acid-Schiff and Mallory stain. They were seen with BLD in 8 (16%) eyes, alone in 4 (8%) eyes and with soft drusen in one (2%) eye. Most of these drusen were large and extended over 2-3 RPE cells. Overlying RPE showed flattening or depigmentation. [Figure - 3] Hard drusen did not correlate with age.

Soft drusen had indistinct edges and were granular in appearance [Figure - 4]. Overlying RPE showed extensive degeneration and atrophy. There was marked degeneration of the Bruch's membrane underlying the soft drusen. They were seen alone in 5 (10%) eyes and with hard drusen and basal laminar deposits in 8 (16%) eyes.

Various stages of thickening of Bruch's membrane were observed. Extensive thickening was seen more commonly in the elder age group. One eye had calcific changes in the Bruch's membrane over the macula. Calcification was identified with positive von-Kossa stain. [Figure - 5]. Extensive RPE atrophy was seen in 2 eyes. Disciform degeneration of the macula with fibrovascular scar was seen in one eye [Figure - 6].


  Discussion Top


Genetic, environmental and dietetic factors are known to play an important role in age-related macular disease.[4] The incidence of age-related macular degeneration is higher and the progression is more rapid in the white. Age-related macular degeneration is noted to be lower in African and Japanese subpopulation.[2]

Our study provides quantitative evidence that the presence of basal laminar deposits, both hard and soft drusen as well as thickening and calcification of the Bruch's membrane are attributable to ageing and that the extent of these changes increase with age.

Our study showed that age-related histopathologic changes in macula is seen in 48 % of donor eyes. Various other age-related changes in the macula occurred to a lower extent than a similar study done in the white. It is possible that age-related changes in the macula occur less commonly than in the white. In a population-based study done by Dandona and co-workers only 1.9 % of Indian population in an urban area had blindness (distance visual acuity at presentation 6/60 or central visual field of less than 20 % in the better eye) due to macular scar. This indicates that in the Indian population, age- related changes occur less commonly in the macula is much than in the white.[5]

The most common histologic change observed was basal laminar deposits [Table - 3]. The BLD are located between the plasma membrane and the basement membrane of retinal pigment epithelium. Such BLD though not seen ophthalmoscopically can contribute to the pathogenesis of ARMD.[6] Pauleikhoft and co-workers found that prolonged choroidal filling occurs angiographically in diffuse thickening of Bruch's membrane.[7] This could account for the scotopic function associated with age-related macular diseases.[8] We found that such BLD occur more often in eyes over 60 years. Sarks observed that such BLD tend to develop in the seventh decade as a result of normal ageing process.[3] Pauleikhoft and co-workers have observed progressive accumulation of lipids in the Bruch's membrane with relation to age, leading to destruction of its architecture. This is more commonly observed with drusen.[9] In a recent study, Crucio and Milican observed that basal linear deposits combined with large drusen are specific to early age-related maculopathy.[6] We noted internal limiting membrane folding with basal laminar deposits in an eye of a 70-year-old man. Hard drusen were seen in 13 (26%) eyes. They were more commonly seen with basal laminar deposits. In a study by Green et al the BLD was the most common finding (54.7%) followed by disciform scar (40%) in their study of 760 eyes with ARMD from 450 patients, (94.7% Caucasians, 5.7% blacks). Other findings included neovascularization (38.2%), basal linear deposits (27.6%) nodular drusen (6.2%), and serous and haemorrhagic pigment epithelial detachments (10.8%). The most common finding observed in blacks was areolar atrophy.

RPE Atrophy may follow a spontaneous resolution of the retinal pigment epithelial detachments. Passage of molecules between the chorio capillaries and pigment epithelium are impeded by the interpositioning of debris. Complexes containing molecules essential for the receptor function do not pass freely from the RPE, leading to atrophy.

Though much is known about the clinical course of age-related macular degeneration, other details pertaining to pathogenesis of drusen, change at level of Bruch's membrane with aging and pathogenesis of chroidal neovascular membrane formation are unclear. A histopathological study of age-related changes in the macula provides a better understanding of this disease[11].

 
  References Top

1.
Blanks CN, Hutson WK. Blindness in New South Wales: An estimate of the prevalence and some of the contributing factors. Aust J Ophthalmol 1982;9:285-88.  Back to cited text no. 1
    
2.
Klein BE, Klein R. Cataracts and macular degeneration in older Americans. Arch Ophthalmol 1982;100:571-73.  Back to cited text no. 2
[PUBMED]    
3.
Sarks. SH. Aging and degeneration in the macular region - a clinicopathological study. Br J Ophthalmol 1976;60:324-41.  Back to cited text no. 3
    
4.
Bird AC. Age related macular disease. Br J Ophthalmol 1996;80:2.  Back to cited text no. 4
[PUBMED]    
5.
Dandona L, Dandona R, Naduvilath TJ, McCarty CA, Nanda A, Srinivas A, et al. Is current eye care policy focus almost exclusively on cataract adequate to deal with blindness in India? Lancet 1998;351:1312-16.  Back to cited text no. 5
    
6.
Crucio CA, Millican CL. Basal linear deposits and large drusen are specific for age related maculopathy. Arch Ophthalmol 1999;117:329-39.  Back to cited text no. 6
    
7.
Pauleikhoff D, Chen JC, Chisholm IH and Bird AC. Choroidal perfusion abnormality with age related Bruch's membrane changes. Am J Ophthalmol 1990;109:211-17.  Back to cited text no. 7
    
8.
Sunness JS, Johnson MA, Massoff RW, Marcus S. Retinal sensitivity over drusen and non-drusen areas. A study using fundus perimetry. Arch Ophthalmol 1984;96:375.  Back to cited text no. 8
    
9.
Pauleikhoff. D, Alex Harper. C, Marshall. J, Bird. A - Aging changes in Bruch's membrane. Ophthalmology 1990;97:171-78.  Back to cited text no. 9
    
10.
Green WR, Enger C. Age related macular degeneration histopathologic studies. Ophthalmology 1993;100:1519-35.  Back to cited text no. 10
[PUBMED]    
11.
van der Schaft TL, Mooy CM, de Bruijn WC, Oron FG, Mulder PG, de Jong PT. Histologic features of the early stages of age-related macular degeneration. Ophthalmology 1992;99:278-86.  Back to cited text no. 11
[PUBMED]    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]


This article has been cited by
1 Imaging maculopathy in post-mortem human eyes
Curcio, C.A.
Vision Research. 2005; 45(28): 3496-3503
[Pubmed]



 

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