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New developments in retinal drusen.

Retinal drusen are an important manifestation of age-related maculopathy, and increase with ageing. Recent studies have shown that gentle laser photocoagulation can lead to resolution of soft drusen and may lessen the high risk of development of choroidal neovascularisation in these cases. Laser induced regression of retinal drusen appears to be a safe technique, but no long term results are yet available. Retinal drusen may also occur as a dominantly inherited disorder and current evidence suggests that these represent more than one disorder. Misclassification of retinal drusen as retinal exudates is an important cause of false positive referral in diabetic retinopathy screening programmes.

Aged↗

Prevalence of age-related maculopathy. The Beaver Dam Eye Study.

PURPOSE: The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study. METHODS: The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P less than 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (greater than or equal to 125 microns, 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1%), and geographic atrophy (2.0% versus 0%). CONCLUSION: These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health problem.

Adult↗

Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study.

PURPOSE: The aim of the study was to describe the 10-year incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. DESIGN: Population-based cohort study. PARTICIPANTS: The study included 4926 persons, 43 to 86 years of age at the time of a baseline examination from 1988 through 1990, living in Beaver Dam, Wisconsin, of whom 3684 participated in a 5-year follow-up examination and 2764 participated in a 10-year follow-up. METHODS: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOMES MEASURES: Incidence of drusen type and size, pigmentary abnormalities, geographic atrophy, and exudative degeneration. RESULTS: The 10-year incidence of early age-related maculopathy was 12.1% and of late age-related maculopathy it was 2.1%. There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older at baseline had significantly (P < 0.01) higher 10-year incidences of the following characteristics than people 43 to 54 years of age: larger sized drusen (125 micro m-249 micro m, 26.3% vs. 3.3%; > or =250 micro m, 16.2% vs. 1.0%), soft indistinct drusen (22.2% vs. 2.2%), retinal pigment abnormalities (19.5% vs. 0.8%), exudative macular degeneration (4.1% vs. 0%), and pure geographic atrophy (3.1% vs. 0%). Compared with those with small numbers of only small, hard drusen (1-2), those with large numbers of only hard drusen (8 or more) had an increased 10-year incidence of both soft drusen (12.3% vs. 6.7%) and pigmentary abnormalities (4.9% vs. 1.7%). Eyes with soft indistinct drusen or retinal pigmentary abnormalities at baseline, were more likely to develop late age-related macular degeneration at follow-up than eyes without these lesions (15.1% vs. 0.4% and 20.0% vs. 0.8%, respectively). CONCLUSIONS: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older. Our findings demonstrate that large numbers of hard drusen predict the incidence of soft drusen and pigmentary abnormalities and that the presence of the latter lesions significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.

Adult↗

The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. POPULATION: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period. METHODS: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. CONCLUSIONS: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.

Adult↗

Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression.

PURPOSE: To evaluate apolipoprotein (Apo) gene expression in native human retinal pigment epithelium (RPE) and neurosensory retina and to detect apolipoproteins within age-related, extramacular drusen. METHOD: Drusen were isolated manually from 10 eyes of 10 donors (age range, 58-93 years) with grossly normal maculas that were preserved in 4% paraformaldehyde within 6 hours of death. In cryosections of druse-enriched pellets (6-57 drusen per eye), the Apos A-I, A-II, B, C-I, C-II, C-III, E, and J were detected by indirect immunofluorescence. Two graders assessed the prevalence and pattern of immunoreactivity. mRNA transcripts were detected by reverse-transcription polymerase chain reaction (RT-PCR), with human hepatoma HepG2 cells as the positive control. RESULTS: Extramacular drusen were classified in two groups on gross appearance: transparent with a reflective shell and cloudy. The proportion of the latter increased significantly with age. All Apos examined were detectable, in descending order of prevalence: ApoE (99.5%), J (99.5%), C-I (93.1%), B (80.4%), A-I (61.0%), A-II (59.2%), C-II (57.7%), and C-III (16.6%). Immunoreactivity was either diffusely distributed throughout the drusen (56.7%), confined to the druse rim (16.0%), or both (21.2%). Six percent displayed evidence of organized substructure reminiscent of active remodeling. The proportion of diffusely labeled drusen decreased significantly with age for ApoE (P=0.034) and ApoE/C-I combined (P=0.027). RT-PCR products for Apos C-I, C-II, E, and J were found in retina and RPE; for ApoA-II in the retina only. The ApoC-III message was undetectable. CONCLUSIONS: To an emerging model of an RPE-secreted large lipoprotein particle implied by previous work, this study adds ApoC-I and ApoC-II, major modulators of lipoprotein lipase activity, and confirms previously demonstrated Apos A-I, B-100, and E. It is possible that a neutral lipid-rich druse shell containing Apos will be visible in the living fundus.

Aged↗

[Central chorioretinal dystrophy with drusen and retinal crystals].

4 patients out of 2 pedigrees present an association of dominant drusen, central chorioretinal dystrophy and retinal crystals. It seems to be transmitted in an autosomal dominant mode. Drusen have also been found in 4 patients (3rd generation) at the age of 40 years. Central chorioretinal dystrophy and retinal crystals have not been found prior to the age of 60 years. Visual acuity and central scotoma depend on the central chorioretinal dystrophy. Electro-oculograms and electroretinograms exhibited relatively little changes. 2 patients showed phenotype II and IV of Fredriksen.

Adult↗

Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa.

PURPOSE: To determine the frequency and characteristics of optic disc and parapapillary nerve fiber layer drusen in patients with retinitis pigmentosa and to attempt to document any differences in the frequency within different genetic subtypes of retinitis pigmentosa. METHODS: This retrospective case series reviewed 117 patients with autosomal-dominant, 84 with autosomal-recessive, and 61 with X-linked recessive forms of retinitis pigmentosa. Color fundus photographs were reviewed independently by three investigators. The presence of optic disc or parapapillary nerve fiber layer drusen was documented only when all three observers concurred as to their presence. The number (isolated or multiple), site (disc, parapapillary, or both), and bilaterality (unilateral or bilateral) were noted in each patient. RESULTS: Optic disc or parapapillary nerve fiber layer drusen or both were observed in 11 patients (9.4%) with autosomal-dominant, 6 patients (7.1%) with autosomal-recessive, and 7 patients (11.5%) with X-linked recessive types of retinitis pigmentosa. The differences in the observed frequencies were not statistically significant (P = 0.67). Overall, the frequency of optic nerve head or parapapillary drusen or both in 262 patients with retinitis pigmentosa was 9.2%. CONCLUSION: In a large population of patients with retinitis pigmentosa, our findings suggest that approximately 10% are likely to show optic nerve fiber layer drusen involving the optic disc or parapapillary regions or both. The frequency does not vary significantly between different genetic subtypes.

Adolescent↗

Bilateral midperipheral large drusen and retinal pigment epithelial detachments associated with multifocal areas of choroidal neovascularization: a histopathologic study.

PURPOSE: The ocular histopathologic features of a patient with bilateral multiple midperipheral areas of choroidal vascularization, large drusen, and detachments of the retinal pigment epithelium (RPE) are presented. METHODS: The eyes were obtained at autopsy and fixed in 4% buffered formaldehyde. Serial sections through the macula area and inferior segments were prepared. Light as well as electron microscopy was performed. RESULTS: Microscopic examination disclosed numerous large drusen measuring up to 200 micro m in height and 280 micro m in diameter and areas of serous RPE detachments in the midperiphery of both eyes. Some of the large drusen had choroidal vascularization. Areas of sub-RPE neovascularization that measured up to 6.5 mm in diameter were present in the midperiphery of both eyes. The choroidal origin for neovascularization was evident in 10 areas. A 1-mm area of hemorrhagic detachment of the RPE contiguous with choroidal neovascularization (CNV) was present in the immediate postequatorial area temporally in the left eye. No drusen, basal deposit, or CNV was present in the macular area. CONCLUSION: Multifocal midperipheral RPE detachments and CNV can occur in the absence of significant age-related macular disease.

Choroidal Neovascularization↗

Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration.

BACKGROUND: Clinicopathologic studies of eyes lead to a better understanding of the nature of the ophthalmoscopic and fluorescein angiographic features of drusen. A study was conducted to provide clinicopathologic correlation of drusen and present a classification of drusen based on clinical and histopathologic features. METHODS: The macular areas of three eyes from two patients were serially sectioned and studied, and features were depicted in a two-dimensional map and compared with clinical findings. RESULTS: All three tyes had large drusen (> 63 microns) with soft morphologic characteristics (poorly demarcated borders) documented on fundus photographs. In both eyes from one patient, these large drusen corresponded to areas of focal retinal pigment epithelium hypopigmentation overlying Bruch's membrane, which was diffusely thickened throughout the macula. Similar findings were noted in another eye from a second patient, and additionally, where there was relatively marked fluorescein staining of large drusen on the late phase of an angiogram, the pathologic correlation demonstrated detachment of the thickened inner aspect of Bruch's membrane from the remainder of Bruch's membrane. Focal hyperpigmentation corresponded to areas of hypertrophy of the retinal pigment epithelium and to clusters of pigmented cells in the subretinal space and outer nuclear area. CONCLUSION: Diffuse thickening of the inner aspect of Bruch's membrane is associated with retinal pigment epithelial hypopigmentation, focal atrophy, and soft (large) drusen formation.

Aged↗

Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalities. Waterman study.

PURPOSE: To obtain 5-year longitudinal data on age-related macular degeneration (AMD) that might be useful for disease prognosis, public health planning, and clinical trial development. PATIENTS AND METHODS: Baseline (1985) and 5-year follow-up (1990) fundus photographs of 483 watermen over 30 years of age who participated in a cohort study conducted on the eastern shore of Maryland were graded independently in a reliable, standardized fashion. Eyes in which AMD appeared or disappeared also were graded in a side-by-side fashion. RESULTS: Development of definite choroidal neovascularization and/or disciform scarring occurred in one of 50 participants over 70 years of age, specifically one of 15 participants over 70 years of age with AMD-3 (defined as large or confluent drusen focal hyperpigmentation of the retinal pigment epithelium [RPE], and/or nongeographic atrophy of the RPE). Appearance of large drusen, focal hyperpigmentation, or AMD-3 was age related, occurring in 5%, 1%, and 7%, respectively, of participants aged 50 to 59 years; 17%, 3%, and 14%, respectively, of participants aged 60 to 69 years; and 17%, 9%, and 26%, respectively, of participants aged 70 years or more. Disappearance of large drusen, hyperpigmentation, or AMD-3 occurred in 16 (34%) of 47 participants, 11 (58%) of 19 participants, and 17 (28%) of 61 participants, respectively, who had each feature photographically present in 1985. Among the 47 eyes identified in which AMD-3 developed by independent gradings, 38 cases of AMD-3 (81%) were confirmed on side-by-side grading. Among the 16 eyes identified as having AMD-3 that disappeared, nine disappearances (56%) were confirmed. Borderline differences in appearance of pigment, drusen size, drusen location, or photographic quality may have accounted for disappearance in seven cases (44%). CONCLUSIONS: Prospective studies on the nonneovascular features of AMD (including large drusen and abnormalities of the RPE) must account for the appearance and disappearance of these features and support the idea that side-by-side gradings can complement independent gradings identifying appearance or disappearance of features of AMD.

Adult↗

Mapping of a macular drusen susceptibility locus in rhesus macaques to the homologue of human chromosome 6q14-15.

Rhesus macaques (Macaca mulatta) are a natural model for retinal drusen formation. The present study aimed at clarifying whether chromosomal regions homologous to candidate genes for drusen formation and progression in humans are also associated with a drusen phenotype in rhesus macaques. Some 42 genetic markers from seven chromosomal regions implicated in macular degeneration syndromes in humans were tested for whether they identified homologous, polymorphic sequences in rhesus DNA. This was found to be the case for seven markers, all of which were subsequently screened for the presence of potentially disease-predisposing alleles in 52 randomly chosen adult animals from the Cayo Santiago population of rhesus macaques (Caribbean Primate Research Center, PR, USA). The high drusen prevalence expected in the Cayo Santiago colony was confirmed in our sample in that 38 animals were found to have drusen (73%). Logistic regression analysis revealed that some alleles of the rhesus homologue of anonymous human marker D6S1036 were consistently over-represented among affected animals. Of two candidate genes located in the respective region, allelic variation in one (IMPG1) showed strong association with drusen formation. We conclude that one or more genes located at the rhesus homologue of human 6q14-15 are likely to play a role in retinal drusen formation, a finding that represents a first step towards the identification of genetic factors implicated in macular drusen formation in rhesus macaques. This is an important tool for the separation of genetic and environmental factors which must occur before satisfactory management methods can be developed.

Animals↗

Alcohol consumption and the 5-year incidence of age-related maculopathy: the Beaver Dam eye study.

OBJECTIVE: This study evaluated alcohol consumption as a risk factor for incidence of age-related maculopathy (ARM). DESIGN: Persons aged 43 to 86 years in 1988 in Beaver Dam, Wisconsin, were examined from 1988 through 1990 and 1993 through 1995, n = 3684. The presence and severity of ARM at both examinations were determined from gradings of stereoscopic fundus photographs using the Wisconsin Age-related Maculopathy Classification System. Alcohol consumption was determined by self-report. RESULTS: Men drinking at least 78 g/week of alcohol from beer had a higher 5-year age-adjusted incidence of early ARM (10.6%) than did men who did not drink beer (6.9%), but the test for trend was only borderline significant (P = 0.08). However, incidence of soft indistinct drusen (P = 0.01), increased drusen area (P < 0.01), and confluent drusen (P = 0.02) are all associated with beer drinking in men. Increased retinal pigment and retinal pigment epithelial depigmentation are not associated with beer drinking in men or women nor are any lesions associated with total alcohol consumption or consumption from liquor or wine in either men or women. CONCLUSIONS: Except for an association of beer drinking with retinal drusen in men, consumption of alcoholic beverages is not likely to be an important risk factor for incidence of ARM.

Adult↗

[Differentiation and prognosis of colloidal retinal dystrophy].

The authors investigated in a prospective investigation 27 patients of different age groups for 5 to 12 years with symmetrical, bilateral non-hereditary retinal drusen. The examination was focused on assessment of different types of drusen, on evaluation of the development and incidence of risk factors leading to complications and loss of central vision. The latter include the part of the spectrum of pathological manifestations in higher age groups which are included in the category of senile macular degeneration.

Adult↗

North Carolina macular dystrophy, revisited.

Progression of the maculopathy in North Carolina macular dystrophy (NCMD) was not well documented. Thus, the author recently examined 22 affected members of the original kindred. Evidence of progression of the macular disease was sought through comparison of the recent fundus findings with old fundus photographs and from subjective complaints of worsening visual acuity. Only 1 of the 22 affected subjects had evidence of such change. Additionally, two new findings of NCMD were observed: (1) severe macular lesions which were staphylomatous or excavated in appearance, not flat, and atrophic as previously described; and (2) peripheral retinal drusen variably present in affected subjects, in contrast to the "normal peripheral retina" originally described. These new findings, along with the generally stable course of the disease would seem to alter our understanding of the relationship of NCMD to other dominant macular dystrophies.

Adolescent↗

Serum antioxidants and age-related macular degeneration in a population-based case-control study.

OBJECTIVE: To investigate relationships between levels of tocopherols and carotenoids in the serum and age-related macular degeneration (ARMD). DESIGN: A nested case-control study within a population-based cohort. PARTICIPANTS: Cases included a sample of subjects with retinal pigment abnormalities with the presence of soft drusen (n = 127) or with late ARMD (geographic atrophy [n = 9]) or neovascular and exudative macular degeneration (n = 31). An equal number of controls (167 pairs) were selected from among participants in the Beaver Dam Eye Study. The controls had no photographic evidence of soft drusen, retinal pigment abnormalities, or late ARMD and were matched with cases for age, sex, and current smoking status. DATA COLLECTION: Presence and severity of ARMD were determined from masked grading of fundus photographs obtained from 1988 to 1990. Levels of individual carotenoids and tocopherols were determined in serum collected at the same time. RESULTS: Average levels of individual carotenoids were similar in cases and controls. Average levels of vitamin E (alpha-tocopherol) were lower in people with exudative macular degeneration (P = .03). However, the difference was no longer statistically significant after controlling for levels of cholesterol in the serum. Persons with levels of lycopene, the most abundant carotenoid in the serum, in the lowest quintile were twice as likely to have ARMD. Levels of the carotenoids that compose macular pigment (lutein with zeaxanthin) in the serum were unrelated to ARMD. CONCLUSIONS: Very low levels of one (lycopene) but not other dietary carotenoids or tocopherols were related to ARMD. Lower levels of vitamin E in subjects with exudative macular degeneration compared with controls may be explained by lower levels of serum lipids.

Adult↗

Smoking, alcohol intake, estrogen use, and age-related macular degeneration in Latinos: the Los Angeles Latino Eye Study.

PURPOSE: To assess the association between smoking, alcohol intake, estrogen use, and both early age-related macular degeneration (AMD) (soft indistinct drusen, retinal pigment abnormalities) and advanced AMD (exudative AMD, geographic atrophy) in the Latino community. DESIGN: Population-based, cross-sectional study. METHODS: Complete ophthalmic examination included stereoscopic macular photographs graded with a modified Wisconsin Age-related Maculopathy Grading System. A history of smoking, alcohol intake, and exogenous estrogen use was obtained by interview. Logistic regression was performed, and odds ratios (OR) were calculated with each AMD lesion as a dependent variable. RESULTS: There were 5875 participants (92.4%) with gradable photographs. Having ever smoked was associated with a higher risk of having advanced AMD (OR, 2.4). Heavy consumption of alcohol (>5 drinks per session) was significantly associated with a greater risk of having exudative AMD (OR, 5.8) and geographic atrophy (OR, 12.7) Beer drinking was associated with a higher risk of having advanced AMD (OR, 2.9), whereas wine drinking appeared to be protective for increased retinal pigment (OR, 0.7). Exogenous estrogen use also appeared to be protective from soft indistinct drusen (OR, 0.5) and increased retinal pigment (OR, 0.6), but power was limited in the assessment of its association with advanced AMD. CONCLUSION: Smoking and heavy alcohol consumption, particularly beer, was associated with a greater risk of having advanced AMD; exogenous estrogen use appeared to have a weak protective effect in Latino participants. Similar modifiable risk factors have been identified previously in non-Hispanic white patients, which suggests that common pathogenic mechanisms may be associated with AMD in persons of different ethnicities.

Adult↗