Macular Degeneration: Peto T

Klein R, Peto T, Bird A, Vannewkirk MR. · Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin 53726, USA. · Am J Ophthalmol. · Pubmed #15013873 No free full text.

Abstract: PURPOSE: To review the epidemiology of age-related macular degeneration (AMD). DESIGN: Evidence from epidemiologic data regarding the natural history of AMD and its risk factors are presented. RESULTS: Large, soft drusen associated with pigmentary abnormalities increase the risk of progression to advanced AMD. Large soft drusen may fade over time. Advanced AMD is more likely to be present in whites than blacks, despite the similar prevalence of soft drusen in both groups. Neovascular AMD is more frequent than geographic atrophy in most population-based studies in whites in America, Australia, and the Netherlands than in similar population-based studies in Iceland and Norway. After age and family history, there are few consistent relationships of risk factors to AMD. Of these, the relationship of smoking, hypertension, and cataract surgery to advanced AMD have been most consistent. CONCLUSIONS: Long-term epidemiologic studies have provided information on the distribution and the natural history of AMD and its associated risk factors. It is not known what effect reduction of blood pressure and the cessation of smoking might have on the incidence and progression of AMD.

Jonasson F, Arnarsson A, Sasaki H, Peto T, Sasaki K, Bird AC. · Department of Ophthalmology, University Iceland, Reykjavik, Iceland. · Arch Ophthalmol. · Pubmed #12617709 No free full text.

Abstract: OBJECTIVE: To examine the age- and sex-specific prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of Reykjavik, Iceland, who were 50 years and older. DESIGN: Random sample, cross sectional. MATERIALS AND METHODS: Response rate was 75.8%. The presence and severity of various characteristics of drusen and pigmentary changes that are typical of ARM and AMD were determined by grading stereoscopic color fundus photographs, using the international classification and grading system for ARM and AMD. RESULTS: We were able to evaluate 1021 right-eye and 1020 left-eye macular photographs. There was no statistically significant difference between right and left eyes. In people aged 50 to 59 years, 4.8% of participants (95% confidence interval [CI], 2.6-7.0) were found to have intermediate soft drusen measuring 63 to 125 micro m in either eye; 1.2% (95% CI, 0.0-2.3) had large soft distinct drusen larger than 125 micro m; and 0.6% (95% CI, 0.0-1.4) had large soft, crystalline, or semisolid drusen. The same figures for those 80 years and older were 18.2% (95% CI, 9.8-26.6), 10.9% (95% CI, 4.0-17.8), and 25.5% (95% CI, 18.4-32.6), respectively. Geographic atrophy was found in either eye in 9.2% of those participants 70 years and older (95% CI, 5.6-12.7), and exudative macular degeneration was found in 2.3% of participants 70 years and older (95% CI, 0.5-4.1). CONCLUSION: Geographic atrophy was found to be more common in our study than in other population-based studies.

Sallo FB, Peto T, Leung I, Xing W, Bunce C, Bird AC. · Department of Research and Development, Moorfields Eye Hospital, London, United Kingdom. · Curr Eye Res. · Pubmed #19274532 No free full text.

Abstract: PURPOSE: To determine whether grading based on the International Classification (IC) for age-related macular degeneration (AMD) allows recognition of change during the progression of the disease. METHODS: Stereoscopic color fundus photographs of 50 eyes of 25 patients with AMD and at least 5 years of review were graded in a random and masked fashion for changes over time in the characteristics of drusen, pigmentary changes, and end-stage disease, according to the system defined by the IC for AMD, by two independent graders (F.B.S., I.L.). Fundus images were also analyzed in time sequence for clinical changes by a senior grader (I.L.) and two ophthalmologists (A.C.B., T.P.) without access to the grading forms of the IC grading. Clinical change, as recorded by the IC grading and the individual analysis, were compared. RESULTS: There was 97.8% (kappa = 0.70) concordance in identification of change. In four cases, the clinical classification differed from the IC grading: Two cases of drusen and two of end-stage disease grading. Inter-observer agreement for the IC grading was 89.4% for predominant phenotype (kappa = 0.84), 89.36-91.49% for presence of choroidal neovascularization (CNV) (kappa = 0.79-0.83), 87.23-89.36% for geographic atrophy (GA) (kappa = 0.62-0.74) and 55.32% for area covered by drusen (kappa = 0.31). CONCLUSIONS: Overall, progression from earlier stages of AMD to either of the two forms of advanced AMD were reflected accurately by the IC grading in the vast majority of cases.

Andersen MV, Rosenberg T, la Cour M, Kiilgaard JF, Prause JU, Alsbirk PH, Borch-Johnsen K, Peto T, Carstensen B, Bird AC. · Department of Ophthalmology, Rigshospitalet, University Hospital of Copenhagen and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. · Ophthalmology. · Pubmed #18267341 No free full text.

Abstract: PURPOSE: To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland. DESIGN: Population-based cross-sectional study. PARTICIPANTS: All > or =60-year-olds born in Greenland and living in the communities of Nuuk and Sisimiut, Greenland. METHODS: The presence and form of early (ARM) and late age-related macular disease (AMD) were determined by grading color fundus photographs using the international classification and grading system for ARM and AMD. MAIN OUTCOME MEASURES: Prevalences of ARM and AMD were assessed by masked grading of fundus photographs. RESULTS: Overall, 695 persons were included in the study (response rate, 74.8%). Prevalence of any ARM was 52.3%. Age-related maculopathy was present in the worse eye in 50.0%, 58.8%, and 44.7% of age groups 60 to 69, 70 to 79, and > or =80, respectively. Prevalence of any AMD was 9.5%. Any AMD was present in the worse eye in 3.9%, 14.6%, and 43.2% of age groups 60 to 69, 70 to 79, and > or =80. Prevalences of pure geographic atrophy (GA) in one or both eyes, exudative degeneration in one or both eyes, and GA in one eye and exudative degeneration in the other eye were 2.3%, 6.1%, and 1.1%, respectively. CONCLUSIONS: The prevalence of ARM is higher than in most other populations studied, and the prevalence of AMD in the oldest age group is higher than in most other populations studied. The prevalence of exudative degeneration is higher than the prevalence of GA, in contrast to findings in some of the Nordic countries-particularly Iceland-and earlier observations in Greenland.

Vaclavik V, Vujosevic S, Dandekar SS, Bunce C, Peto T, Bird AC. · Moorfields Eye Hospital, London, United Kingdom. · Ophthalmology. · Pubmed #17599415 No free full text.

Abstract: PURPOSE: To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. METHODS: Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. MAIN OUTCOME MEASURES: Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. RESULTS: Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. CONCLUSION: Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment.

Vujosevic S, Vaclavik V, Bird AC, Leung I, Dandekar S, Peto T. · Fondazione G.B. Bietti per l'Oftalmologia, IRCCS, Via Livenza 3, 00198 Roma, Italy. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17429674 No free full text.

Abstract: BACKGROUND: Patients with age-related macular degeneration (ARMD) have several imaging techniques carried out regularly. In this study we introduce a new grading model of autofluorescence images (AF), compare it with fluorescein angiography (FFA) and digital colour fundus photos (COL) and test for inter- and intraobserver reliability. METHODS: A total of 71 eyes of 54 patients with bilateral or unilateral CNV had COL, FFA and AF, fulfilling the inclusion criterion of having all 3 types of imaging carried out on the same day or within 14 days. The grading of COL was performed by a trained grader based on the International ARM classification; FFA and AF images were independently graded by two trained retinal specialists in order to assess inter-observer reliability. Overall, 30% of all images were regraded after at least 14 days interval to assess intra-observer variability. RESULTS: The intergrader agreement was exact for classification of CNV (k = 1.00); almost perfect for FFA features (k = 0.83) and correspondence of decreased AF to COL (k = 0.94); substantial for patterns of decreased and increased AF (k = 0.80, k = 0.78), correspondence of patterns of increased AF to FFA and to COL (k = 0.78, k = 0.74) and background AF (k = 0.72); moderate for CNV diameter in FFA (k = 0.45), FFA pattern (k = 0.43), dimension of increased and decreased AF (k = 0.5, k = 0.56); fair for quality of FFA and AF images (k = 0.21, k = 0.26) respectively. The intragrader agreement varied from exact to substantial for all categories. Diffuse and reticular patterns of decreased AF and reticular pattern of increased AF correlated well, with visual acuity worse than 6/24. CONCLUSION: The combined grading system was reliable for evaluating the three imaging techniques, and might be suitable for epidemiological studies and therapeutic trials where such grading is warranted. Certain AF patterns seem to predict VA outcome better than one might have predicted based on FFA. Further studies are needed to evaluate its usefulness in clinical settings for predicting outcomes for patients receiving therapy for end-stage disease.

Lengyel I, Flinn JM, Peto T, Linkous DH, Cano K, Bird AC, Lanzirotti A, Frederickson CJ, van Kuijk FJ. · Division of Pathology, Institute of Ophthalmology, 11-43 Bath Street, University College London, and Department of Research and Development, Moorfields Eye Hospital, London EC1V 9EL, UK. · Exp Eye Res. · Pubmed #17313944 No free full text.

Abstract: One of the hallmarks of age-related macular degeneration (AMD), the leading cause of blindness in the elderly in Western societies, is the accumulation of sub-retinal pigment epithelial deposits (sub-RPE deposits), including drusen and basal laminar deposits, in Bruch's membrane (BM). The nature and the underlying mechanisms of this deposit formation are not fully understood. Because we know that zinc contributes to deposit formation in neurodegenerative diseases, we tested the hypothesis that zinc might be involved in deposit formation in AMD. Using zinc specific fluorescent probes and microprobe synchrotron X-ray fluorescence we showed that sub-RPE deposits in post-mortem human tissues contain unexpectedly high concentrations of zinc, including abundant bio-available (ionic and/or loosely protein bound) ions. Zinc accumulation was especially high in the maculae of eyes with AMD. Internal deposit structures are especially enriched in bio-available zinc. Based on the evidence provided here we suggest that zinc plays a role in sub-RPE deposit formation in the aging human eye and possibly also in the development and/or progression of AMD.

Björnsson OM, Syrdalen P, Bird AC, Peto T, Kinge B. · Department of Ophthalmology, Rikshospitalet, Oslo, Norway. · Acta Ophthalmol Scand. · Pubmed #16965494 No free full text.

Abstract: PURPOSE: To examine the prevalence of early and late age-related maculopathy (ARM) in citizens aged 51 years and older in the city of Oslo and its surroundings. METHODS: We selected a random sample of 800 subjects, using a cross-sectional study design. A total of 459 of the 770 eligible subjects agreed to participate, giving an attendance rate of 59.6%. Stereoscopic colour digital photographs were obtained and graded at a certified reading centre using the International Classification Grading System for ARM. RESULTS: Early ARM in either eye was found in 43.1% (95% CI 38.5-47.7) of subjects aged 51 years and older. This was due to a much higher prevalence of pigmentary changes, predominantly hyperpigmentation in all age groups, than previously reported; 37.5% of people aged 51-60 years of age had pigmentary changes > or = 63 microm, increasing to 66.0% in the oldest age group. In people aged 71 years and older, geographic atrophy (GA) was found in either eye in 3.6% (95% CI 0.4-6.8) and exudative macular degeneration (AMD) was found in either eye in 2.9% (95% CI 0.0-5.7) of subjects. CONCLUSION: To our knowledge, this is the first published study to rely solely on digital photography for grading purposes in a population-based study. Early ARM was found to have a higher prevalence than previously reported in other populations. Exudative AMD and GA had similar prevalences to those described in the literature, although the prevalence of GA tended to be higher than previously reported in some surveys.

Dandekar SS, Jenkins SA, Peto T, Bird AC, Webster AR. · Professorial Unit, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK. · Br J Ophthalmol. · Pubmed #16597668 links to  free full text

Abstract: AIMS: To assess the influence of smoking on the type of age related macular degeneration (AMD) lesion causing visual impairment in a large cohort of patients with AMD at a tertiary referral UK centre. METHODS: Prospective, observational, cross sectional study to analyse smoking data on 711 subjects, of western European origin, in relation to the type of AMD lesion present. Colour fundus photographs were graded according to a modified version of the international classification. Multiple logistic regression analysis was performed, adjusting for age and sex using the statistical package SPSS ver 9.0 for Windows. chi(2) tests were also used to assess pack year and ex-smoker data. RESULTS: 578 subjects were graded with neovascular AMD and 133 with non-neovascular AMD. There was no statistically significant association found between smoking status or increasing number of pack years and type of AMD lesion. The odds of "current smokers" compared to "non-smokers" developing neovascular rather than non-neovascular AMD when adjusted for age and sex was 1.88 (95% CI: 0.91 to 3.89; p = 0.09). CONCLUSIONS: Smoking is known to be a risk factor for AMD and this study suggests that smokers are at no more risk of developing neovascular than atrophic lesions.

Dandekar SS, Jenkins SA, Peto T, Scholl HP, Sehmi KS, Fitzke FW, Bird AC, Webster AR. · Moorfields Eye Hospital and Institute of Ophthalmology, London, England. · Arch Ophthalmol. · Pubmed #16286612 No free full text.

Abstract: OBJECTIVE: To describe the autofluorescence (AF) characteristics of choroidal neovascularization (CNV) in patients with age-related macular degeneration. METHODS: Autofluorescence images of 65 consecutive eyes with CNV at various stages of evolution were analyzed. Twenty images were of recent-onset CNV (group 1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were late-stage CNV (group 3). Autofluorescence images from groups 1 and 2 were compared with fundus fluorescein angiographic images. RESULTS: Group 1 showed areas of hyperfluorescence on fundus fluorescein angiography corresponding to areas of normal AF in 16 of 20 cases, with adjacent areas of increased AF in 13 cases. The main areas of abnormal AF were larger than the main areas of abnormal fluorescence on fundus fluorescein angiography in 18 of the 20 cases. Groups 2 and 3 showed areas of decreased AF corresponding to areas of previous leakage on fundus fluorescein angiography (in group 2) or atrophy. CONCLUSIONS: Preserved AF in group 1 indicates viable retinal pigment epithelium initially, which has implications for visual prognosis. Decreased AF in groups 2 and 3 indicates loss of retinal pigment epithelium and photoreceptors. Autofluorescence imaging may increase our understanding of CNV in age-related macular degeneration.

Jonasson F, Arnarsson A, Peto T, Sasaki H, Sasaki K, Bird AC. · Department of Ophthalmology, University of Iceland, Reykjavik, Iceland. <> · Ophthalmology. · Pubmed #15629833 No free full text.

Abstract: PURPOSE: To examine the age- and gender-specific 5-year incidence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of Reykjavik. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: The cohort was a population-based random sample of citizens 50 years and older. Of 1379 eligible subjects, 1045 had a baseline examination in 1996; 846 of the 958 survivors (88.2%) had a 5-year follow-up examination in 2001. METHODS: The incidence of various characteristics of drusen and pigmentary changes that are typical of ARM were determined using the international classification and grading system for ARM and AMD. MAIN OUTCOME MEASURES: Early ARM and AMD were assessed by masked grading of stereo fundus photographs. RESULTS: Hypopigmentation developed at 5 years in 10.7% of people 50 to 59 years of age (95% confidence interval [CI], 6.9-14.4) and in 25.7% those 70 to 79 years of age (95% CI, 18.4-33.0) at baseline. Age-related macular degeneration developed in no one who was 50 to 59 years of age at baseline. Geographic atrophy (GA) developed in 4.6% (95% CI, 1.2-7.9) and exudative AMD in none of those who were 70 years and older at baseline. CONCLUSIONS: Geographic atrophy is the predominant type of AMD in Iceland, and the ratio of GA to neovascular AMD is higher than in racially similar populations.

Scholl HP, Dandekar SS, Peto T, Bunce C, Xing W, Jenkins S, Bird AC. · Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom. · Ophthalmology. · Pubmed #14711724 No free full text.

Abstract: OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN: Comparative observational case series. PARTICIPANTS: Twenty-five patients (50 eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least 1 eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral United Kingdom population. Retinal photography was performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on Ektachrome slide transparency film. The images were centered on the macula. The color transparencies were then digitized. The grading process has been set up based on the International ARM Epidemiology Study Group. All images were independently graded by 3 retinal specialists. Both kappa statistics and exact agreement were calculated to assess agreement between and within observers and between the 2 master copies derived from the gradings of the color slides and digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies derived from the gradings obtained from stereoscopic slide transparencies and digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93% (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was 94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93% (kappa, 0.78) for the area covered. For the presence of choroidal neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was 95% (kappa, 0.83) for the area covered. For individual features of CNV, exact agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and 2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because of the close agreement for most categories between the grading of stereoscopic color slides and digitized images, digitized nonstereoscopic color images prove to be useful for grading ARM and AMD.

Scholl HP, Peto T, Dandekar S, Bunce C, Xing W, Jenkins S, Bird AC. · Institute of Ophthalmology, Moorfields Eye Hospital, 162 City Road, EC1 V2PD, London, UK. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #12545291 No free full text.

Abstract: PURPOSE. To introduce a revised version of the grading system established by the International ARM Epidemiological Study Group for identifying and quantifying abnormalities of age-related maculopathy (ARM) and age-related degeneration (AMD) and to investigate its reliability, specifically the inter- and intra-observer variability. METHODS. Fifty eyes of 25 patients with ARM or AMD in at least one eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral UK population. Stereoscopic color fundus photographs were taken with a 30 degrees fundus camera and were centered on the macula. Presence and severity of fundus abnormalities in ARM and AMD were graded using a grid to define macular subfields and standard circles to define the size of lesions. Inter-observer variability was assessed by having three retinal specialists evaluate the color slides and intra-observer variability by re-grading the same set. RESULTS. The inter-observer agreement for all subfields was fair to substantial for small hard drusen (70-89%; kappa=0.26-0.63) and intermediate soft drusen (76-94%; kappa=0.27-0.69). Agreement ranged between 87% and 100%, between 50% and 92%, and between 78% and 100% for larger drusen, the presence of hyperpigmentation, and the presence of hypopigmentation, respectively. Agreement was moderate to almost perfect for the presence of geographic atrophy (88-98%; kappa=0.60-0.95) and substantial to almost perfect for the presence of choroidal neovascularization (84-100%; kappa=0.62-1.00). The intra-observer variability for the grading of drusen characteristics and pigmentary changes was similar in magnitude, but slightly greater for features of advanced AMD. CONCLUSION. Reproducibility was achieved using a revised version of the grading system established by the International ARM Epidemiological Study Group. This grading system may therefore be used for phenotyping of ARM and AMD.