Age-related macular degeneration.

Age-related macular degeneration is a leading cause of visual impairment and severe vision loss. Clinically, it is classified as early-stage (medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic). Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids). Progression from early-stage to late-stage disease can be slowed with high-dose zinc and antioxidant vitamin supplements. Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab, aflibercept, or bevacizumab) is highly effective at treating neovascular age-related macular degeneration, and has markedly decreased the prevalence of visual impairment in populations worldwide. Currently, no proven therapies for atrophic disease are available, but several agents are being investigated in clinical trials. Future progress is likely to be from improved efforts in prevention and risk-factor modification, personalised medicine targeting specific pathways, newer anti-vascular endothelial growth factor agents or other agents, and regenerative therapies.

Visual acuity after cataract surgery in patients with age-related macular degeneration: age-related eye disease study 2 report number 5.

OBJECTIVE: To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. METHODS: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. RESULTS: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). CONCLUSIONS: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity.

The incidental findings of age-related macular degeneration during diabetic retinopathy screening.

BACKGROUND: The purpose of this study was to determine the reliability of detecting age-related macular degeneration (AMD) during screening for diabetic retinopathy (DR). METHODS: This prospective study included 2,003 subjects with diabetes mellitus who underwent photographic screening for DR. The reliability of detecting AMD lesions was tested by interobserver and intraobserver agreement, and the sensitivity and specificity of diagnosing AMD at different grades of severity were tested using the consensus grading of a group as the reference standard. RESULTS: DR affected 24.7% of the subjects. The age-standardized prevalence of early AMD was 17.9%, and late AMD was 0.1%. The interobserver and intraobserver agreement for grading AMD was substantial (k = 0.72 and 0.71 respectively, p < 0.001). It was equally good in those with different severities of DR. There was also no difference in sensitivity and specificity of detecting AMD in those with different levels of DR (sensitivity 62-68% and specificity 97-98%). CONCLUSION: Intermediate- and high-risk AMD that warrant treatment with zinc and anti-oxidant supplements could be reliably detected during screening for diabetic retinopathy.

Determinants of macular pigment optical density and its relation to age-related maculopathy: results from the Muenster Aging and Retina Study (MARS).

PURPOSE: The controversial protective effect of macular pigment (MP), consisting of lutein (L) and zeaxantin (Z), in age-related maculopathy (ARM) and its late-stage, age-related macular degeneration (AMD) is discussed. Determinants of MP optical density (MPOD) and its relation to ARM were investigated. METHODS: MPOD was accessed at eccentricities of 0.5° and 2.0° from the fovea in 369 participants in the 2.6-year follow-up examination of the prospective Muenster Aging and Retina Study using dual-wavelength analysis of autofluorescence images. ARM was graded from standardized fundus photographs according to the International Classification System. RESULTS: MPOD at 0.5° and 2.0° between pairs and within single eyes was strongly correlated (P < 0.001). Smoking and body mass index showed moderately inverse associations with MPOD at 2.0°, and age was positively related to MPOD at both eccentricities. Serum L, measured at the baseline examination, was significantly associated with MPOD measured at follow-up. Likewise, use of L/Z-containing supplements raised MPOD. Crude mean MPOD increased with ascending stage of ARM. However, adjustment for influential factors and exclusion of L supplement users removed differences of mean MPOD between ARM stages. Considering further the accompanying eye, study eyes with ARM had significantly higher MPOD when the contralateral eye had AMD. CONCLUSIONS: MPOD levels showed a high degree of intraindividual concordance and interindividual variability. Long-standing serum L levels, and in particular L supplementation, were the strongest determinants of MPOD. The hypothetical inverse association between MPOD and ARM stage was not confirmed.

Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration.

PURPOSE: To measure zinc and copper levels in the retinal pigment epithelium (RPE) and choroid complex and in the neural retina in subjects with and without age-related macular degeneration (AMD). DESIGN: Laboratory investigation. METHODS: Eighty-eight donor eyes (44 subjects) were analyzed. After retinal dissection, the RPE and choroid complex was photographed. Using the Minnesota Grading System (MGS), the RPE and choroid complex was classified into 1 of 4 stages as defined by the Age-Related Eye Disease Study. Subjects without AMD were defined as both eyes having MGS stage 1; subjects with AMD were defined as both eyes having MGS stages 2 through 4. Zinc and copper levels were determined by using an inductively coupled plasma-mass spectrometer. Metal levels from two eyes of the same subject were averaged and treated as one observation. Differences in metal levels were examined by using Wilcoxon rank-sum tests. RESULTS: The mean RPE and choroid complex zinc level in subjects with AMD (+/- standard deviation, 223.7 +/- 94.0 microg/g; n = 15) was reduced 24% when compared with that of subjects without AMD (292.1 +/- 98.5 microg/g; n = 29; P = .01). The mean RPE and choroid complex copper level in subjects with AMD (5.1 +/- 1.1 microg/g) was reduced 23% when compared with that of subjects without AMD (6.6 +/- 1.4 microg/g; P = .002). No difference was detected in retinal zinc and copper levels in subjects with and without AMD (P > .09). CONCLUSIONS: Reduced RPE and choroid complex zinc and copper levels in AMD eyes combined with previous information that oral supplementation of zinc plus copper reduces the risk of progression of AMD suggests that metal homeostasis plays a role in AMD and in retinal health.

[Age-related macular degeneration]. / La dégénérescence maculaire liée à l'âge.

PURPOSE: Age-related macular degeneration is the commonest overall cause of irreversible blindness in patients aged 50 or over in the Western world. CURRENT KNOWLEDGE AND KEY POINTS: Because of the interaction of genetic and environmental origin, the pathogenesis of this affection remains imperfectly elucidated. The disease has been traditionally classified into early and late stages with its dry and wet forms. In association with fluorescein angiography, essential for diagnosis, green indocyanin angiography and optical coherence tomography made it possible to better know the clinical forms of the disease. Patients with age-related maculopathy should consider taking a dietary supplement such as that used in the age-related eye disease study. Exudative age-related macular degeneration is approached depending on the type and localisation of the choroidal new vessels. Laser photocoagulation has only been shown to be beneficial for extra and juxtafoveal classic lesions. Photodynamic therapy with verteporfin is effective in the management of eyes with subfoveal predominantly classic lesions. The encouraging results of new therapeutic with antiangiogenic aiming against vascular endothelial growth factor are a hope to preserve the sight of our patients. FUTURE PROSPECTS AND PROJECTS: In the future, many therapeutics inhibiting neo-vessels will widen our therapeutic options in the treatment of exsudative age-related macular degeneration.

Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration.

PURPOSE: The purpose of this study was to investigate the association of age-related macular degeneration (AMD) with plasma homocysteine, vitamin B12, and folate levels. METHODS: Sixty patients diagnosed with AMD at our clinic between March 2004 and September 2004 were assessed in a prospective cross-sectional study. Plasma homocysteine, vitamin B12, and folate levels taken after 8 h of fasting from 30 patients with exudative AMD and 30 patients with dry AMD were compared with the results of 30 age- and sex-matched healthy participants. RESULTS: Patients with both exudative and dry types of AMD had significantly higher plasma homocysteine levels (mean 14.19+/-3.11 micromol/l; 13.07+/-2.90 micromol/l respectively) compared with the controls (mean 10.79+/-2.56 micromol/l; (p=0.000 and p=0.008 respectively). Homocysteine levels were higher in the exudative AMD group compared with the dry AMD group, but the difference was not statistically significant (p=0.290). Plasma vitamin B12 levels were found to be significantly lower in the exudative AMD group (289.14+/-113.44 pg/l) compared with the controls (436.17+/-204.12 pg/l) and dry AMD group (443.47+/-190.83 pg/l; (p=0.000). Plasma folate levels were comparable among groups (p=0.106). CONCLUSION: This study suggests an association between elevated plasma homocysteine and AMD regardless of the subtype. Further controlled prospective studies are needed to investigate the possible role of homocysteine in AMD and the effect of vitamin B12 and folate supplementation in this process.

Comparing age-related macular degeneration phenotype in probands from singleton and multiplex families.

PURPOSE: To compare age-related macular degeneration (AMD) phenotype between probands in singleton and multiplex families to determine whether data from these two groups may be combined for consolidated genetic analyses. DESIGN: Retrospective case-control study. METHODS: Individuals 55 years of age or older with AMD were identified. Complete histories and examinations were recorded, 35-mm fundus photographs obtained, and macular findings graded. Detailed information was recorded, including the presence of extramacular and peripheral drusen, peripheral reticular pigmentary change, posterior vitreous detachment, and iris color. Comparisons were performed between probands from singleton and multiplex families. RESULTS: There was no statistically significant difference in grade between the 411 singleton and 125 multiplex probands (P = .52), and the distribution of grades was similar between the two groups. No statistically significant difference was found between proband groups with respect to the presence or extent of small (P = .48), intermediate (P = .72), and large drusen (P = .74) and retinal pigment epithelium hyper- (P = .76) and hypopigmentation (P = .55); in the presence or grade of peripheral reticular pigment change; the presence of geographic atrophy in exudative disease, extramacular drusen, or posterior vitreous detachment; lens status; iris color; visual acuity; intraocular pressure; optic nerve cupping; and body mass index. A statistically significant difference between the two groups was noted in the presence of peripheral drusen (P = .0001). CONCLUSIONS: Singleton and multiplex AMD probands share a similar phenotype. This suggests that multiplex and singleton data can be combined for consolidated genetic analyses.

The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study Report Number 6.

PURPOSE: To describe the system for grading age-related macular degeneration from fundus photographs in the Age-Related Eye Disease Study. This is a prospective multicenter cohort study of the course of age-related macular degeneration and a placebo-controlled clinical trial of the effect of high-dose vitamin and mineral supplements on development of advanced age-related macular degeneration. METHODS: Standardized stereoscopic 30-degree color fundus photographs are taken at 11 clinical centers and evaluated by graders at a reading center for quality and age-related macular degeneration abnormalities. Macular subfields are defined by a grid, and presence and severity of various age-related macular degeneration abnormalities are graded using standard/example photographs and measuring circles. Advanced age-related macular degeneration abnormalities (presence/absence) include retinal pigment epithelial detachment, serous (or hemorrhagic) sensory retinal detachment, hard exudates, subretinal/subretinal pigment epithelial hemorrhage, subretinal fibrous tissue, and photocoagulation scars. Other abnormalities (multistep scales) include retinal pigment epithelial abnormalities (geographic atrophy, depigmentation, and increased pigment), and drusen (size, type [hard versus soft distinct or indistinct], and total area). Contemporaneous variability is tested by having different graders evaluate samples of photographs, and temporal variability by annual regrading of a dedicated subset. RESULTS: In a cumulative sample of 1230 eyes for contemporaneous reproducibility, agreement on advanced age-related macular degeneration was 96% (kappa = 0.88) and for four-step age-related macular degeneration level was 83% (kappa = 0.77). Agreement was moderate for pigment epithelial detachment (kappa = 0.54) and substantial for serous sensory retinal detachment, hard exudates, subretinal/subretinal pigment epithelial hemorrhage, subretinal fibrous tissue, and central geographic atrophy (kappa = 0.73-0.82). For pigment abnormalities, agreement was substantial for geographic atrophy (kappa = 0.63; kappa(weighted) = 0.71, 0.75 weight for one-step disagreements), and moderate for depigmentation (kappa = 0.41, kappa(weighted) = 0.51) and increased pigment (kappa = 0.54, kappa(weighted) = 0.71). For drusen, agreement was moderate to substantial for presence/maximum size (kappa = 0.50, kappa(weighted) = 0.68), type (kappa = 0.61, kappa(weighted) = 0.69), and area (kappa = 0.56, kappa(weighted) = 0.77). Six annual regrades of 119 eyes showed little temporal drift in grading of various age-related macular degeneration abnormalities, except for drusen type. CONCLUSIONS: The Age-Related Eye Disease Study has demonstrated satisfactory reliability for detecting onset of advanced age-related macular degeneration in a cohort, and moderate to substantial agreement on various abnormalities across the age-related macular degeneration spectrum. The Age-Related Eye Disease Study system for classification of age-related macular degeneration is suitable for longitudinal multicenter studies.

Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy.

In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.

[Statistical analysis of age-related macular degeneration (AMD) in the differentiation of symptoms and signs].

Ninety-eight individuals according with entry criterion were allowed to participate in the study. Their clinical symptoms and signs were classified to seven symptoms by means of epidemiology. The results indicated syndrome of vital energy in patient group had more significant than controlled group, the others had not. In the syndrome of deficiency of vital energy, the frequency that the corpalent tongue or margin and tip of the tongue look jagged and the pulse lost its vitality emerged in the patient group surpassed significantly the controlled group. So, we initially considered that traditional Chinese medicine syndrome of AMD patient is mainly the deficiency of vital energy. The happening and development of AMD is probably related to the physique of deficiency of vital energy, it is a key point of determination of treatment with traditional chinese medicine based on differentiation of symptoms and signs.