Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia.

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. DESIGN: Pooled analysis of cross-sectional data. PARTICIPANTS: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. METHODS: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. MAIN OUTCOME MEASURES: AMD features and stage; lipid measurements. RESULTS: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10-6 and P = 1.6 × 10-4). CONCLUSIONS: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. DESIGN: Meta-analysis of prevalence data. PARTICIPANTS: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. METHODS: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: Prevalence of early and late AMD, BCVA, and number of AMD cases. RESULTS: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. CONCLUSION: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

Occult macular dystrophy in an Italian family carrying a mutation in the RP1L1 gene.

Occult macular dystrophy (OMD) is an inherited macular disease characterized by progressive visual decline with the absence of visible retinal abnormalities. Typical alterations of the retinal structure are detectable by spectral domain optical coherence tomography (SD­OCT). Mutations in the RP1L1 gene have been identified to be responsible for the disease in Asian subjects. The present study assessed the role of mutations in the RP1L1 gene in an Italian family with OMD. One patient with OMD and five related subjects (two male offspring affected by progressive visual decline and three asymptomatic siblings of the patient) were subjected to complete ophthalmological examination. SD­OCT was also performed. All subjects were screened for OMD­associated genetic mutations in the RP1L1 gene. The OMD patient and the two symptomatic offspring presented with a reduced best­corrected visual acuity. Although no fundus abnormalities were observed, SD­OCT examination showed that the external limiting membrane and the inner segment/outer segment band were not clearly identifiable and a focal disruption of the photoreceptor layer was present. The degree of photoreceptor alterations was correlated with the severity of visual impairment. Clinical and tomographic results in the three asymptomatic relatives were normal. A p.Arg45Trp mutation in the RP1L1 gene was identified in the OMD patient, in the two symptomatic offspring and also in two of the asymptomatic siblings of the patient. The identification of RP1L1 mutations in subjects with OMD may improve the accuracy of diagnosis of this rare condition and may aid in enhancing the efficacy of genetic counseling.

Risk Factors and Age-Related Macular Degeneration in a Mediterranean-Basin Population: The PAMDI (Prevalence of Age-Related Macular Degeneration in Italy) Study--Report 2.

AIM: To investigate the association of diet and other modifiable risk factors with the prevalence of age-related macular degeneration (ARMD) in rural and urban communities of a Mediterranean population in the northeast of Italy. METHODS: A cross-sectional population-based study was conducted among subjects aged over 60 years. A food frequency questionnaire (FFQ) was used to assess the consumption of different food categories, i.e., protective (P), risky (R), lutein-rich (L) and neutral (N). Smoking habit and alcohol intake were also examined. Macular pigment was measured by Raman spectroscopy. RESULTS: P food intake reduced the risk of large drusen (ARM2; OR 0.93; 95% CI 0.89-0.96) within the rural community. In this sub-group, R foods resulted in a slight association with large drusen, though the R/P food ratio was highly correlated with ARM2 (OR 1.21; 95% CI 1.12-1.31). Raman measures showed an age-dependent decrease but did not correlate with lutein intake. Smoking habit showed a positive association with ARM2 among women (OR 2.40; 95% CI 1.54-3.75), whereas alcohol consumption resulted in protective odds (OR 0.72; 95% CI 0.60-0.86). CONCLUSION: FFQ analysis confirmed the role of P and R foods and the benefit of a Mediterranean diet in ARMD. Moderate alcohol consumption showed a beneficial effect, whereas the deleterious role of a smoking habit was more evident in females.

Combined effects of genetic and non-genetic risk factors affect response to ranibizumab in exudative age-related macular degeneration.

PURPOSE: To investigate whether genetic and non-genetic risk factors influence 12-month response to ranibizumab treatment for exudative age-related macular degeneration (AMD). METHODS: A cohort of 94 Caucasian patients with unilateral exudative AMD received intravitreal ranibizumab. After a three-injection loading phase, a PRN regimen was followed. Patients were genotyped for three single-nucleotide polymorphisms: CFH rs1061170, ARMS2 rs10490924 and C3 rs2230199. Non-genetic risk factors [choroidal neovascularization (CNV) phenotype, smoking habit, hypertension and body mass index] were considered. The selected end-point was the 12-month variation of number of ETDRS letters. RESULTS: Complement factor H (CFH) risk alleles, smoking history and arterial hypertension each independently influenced treatment response, with worse 12-month BCVA outcomes (p = 0.036, 0.037, 0.043, respectively). A significant cumulative effect of these risk factors was also observed: patients homozygous for the CFH risk alleles and with a positive smoking history showed a mean loss of 8.0 ETDRS letters (p = 0.010). Patients with CFH risk alleles, smoking history and hypertension had a mean loss of 13.9 ETDRS letters (p = 0.013). CNV phenotypes did not influence visual outcomes, nor were they associated with other genetic/non-genetic risk factors. CONCLUSIONS: Complement factor H risk alleles, smoking history and hypertension affect the mid-term response to ranibizumab in exudative AMD.

The prevalence of age-related macular degeneration in Italy (PAMDI) study: report 1.

PURPOSE: The present study aimed to estimate prevalence and risk factors associated with age-related macular degeneration (ARMD) in an Italian population and to analyze differences between urban and rural communities. METHODS: We conducted a population-based cross-sectional study among elderly residents in Northeast Italy. Participants were divided into urban and rural groups based on whether they lived in the city of Padova or the villages of Teolo and Torreglia, respectively. Fundus photographs were graded according to the International Classification for Age-related Maculopathy. RESULTS: A total of 1162 randomly selected subjects aged 61 years or more were invited to participate in the study. We examined 885 subjects, and 845 were eligible for fundus photograph grading. ARMD was estimated to affect 62.7% of the whole population (drusen 63-124 µm = 48.3%; drusen ≥125 µm = 10.4%; advanced ARMD = 4.1%). Age was confirmed as a risk factor for drusen ≥125 µm and advanced ARMD (Odds Ratio [OR] = 1.47, 95% Confidence Interval [CI] 1.28-1.69 and OR = 1.62, 95% CI 1.28-2.05, respectively, for a 5-year increase in age). The rural group appeared to be at a higher risk of developing large drusen compared to the urban sample (OR = 1.61, 95% CI 1.01-2.63) when adjusting for age and gender. CONCLUSIONS: The results confirmed that ARMD affects a high percentage of the elderly population in Italy. This study does not support the hypothesis that living in a rural environment or belonging to a population of the Mediterranean basin may be protective against the intermediate stages of the disease.

Combination of photodynamic therapy and intraocular triamcinolone for exudative age-related macular degeneration and long-term chorioretinal macular atrophy.

OBJECTIVE: To evaluate the long-term effect of intravitreal triamcinolone acetonide (IVT) treatment combined with photodynamic therapy (PDT) vs PDT alone for neovascular age-related macular degeneration. METHODS: Prospective randomized study. Eighty-four patients were enrolled to receive PDT (n = 41) or IVT treatment followed by PDT (n = 43) within approximately a 7- to 15-day interval. All patients were naive to treatment. At baseline and each follow-up visit at 3, 6, 12, and 24 months, measurement of best-corrected visual acuity (VA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed. Mean changes in VA and retreatment rate were considered as primary outcome indicators. Analysis of vascular choroidal changes documented by indocyanine green angiography and fundus autofluorescence measurements were also performed. RESULTS: Mean VA increased at 1 month of follow-up but decreased progressively by the 24-month point in both groups (P = .74). The retreatment rate was significantly lower (P < .001) in the combined therapy group. Choroidal hypoperfusion/nonperfusion (P < .001) and areas with decreased/absent fundus autofluorescence within the PDT spot area were significantly greater with combined therapy (P < .001). CONCLUSIONS: Combination IVT treatment with PDT seemed to be more effective for managing neovascular age-related macular degeneration, but long-term analysis failed to demonstrate functional benefits.

Choroidal vascular changes after transpupillary thermotherapy for choroidal melanoma.

OBJECTIVE: To evaluate choroidal vascular alterations after transpupillary thermotherapy used as the sole treatment for choroidal melanoma. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Forty-five eyes of 45 patients affected by malignant choroidal melanoma treated with transpupillary thermotherapy alone with more than 1 year of follow-up. INTERVENTION: Transpupillary thermotherapy was performed through a panfunduscopic contact lens using an 810-nm diode laser. MAIN OUTCOME MEASURES: Dynamic/static fluorescein and indocyanine green angiography were performed at scheduled intervals (24 hours, at 3-month intervals during the first year, and every 6 months thereafter) after transpupillary thermotherapy. Visual acuity, clinical evaluation, fundus photographs, and ultrasonographic examination were also performed. RESULTS: The mean follow-up was 30.5 months (range, 12-54 months). Changes in the choroidal circulation were always confined within the treatment margins (except in one case) and characterized by occlusion of choriocapillaris (100%), patent medium and/or large choroidal vessels (76%), retinochoroidal anastomosis (11%), and progressive choroidal vascular remodeling (42%). Forty-one cases (91%) showed persistent clinical regression, and four cases (9%) recurred; recurrent cases showed retinochoroidal anastomosis. CONCLUSIONS: Transpupillary thermotherapy is suggested as a new single therapeutic modality in the treatment of selected choroidal melanomas, but more precise eligibility criteria and longer follow-up are mandatory. Patent choroidal circulation, choroidal vascular remodeling, and anastomosis after transpupillary thermotherapy might be helpful to detect recurrent tumors.

Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration.

PURPOSE: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration. DESIGN: Cohort study. METHODS: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane. RESULTS: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy. CONCLUSION: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments.