History Of Age-related Macular Degeneration Research Articles

Melatonin and Risk of Age-Related Macular Degeneration

Melatonin has been shown to oppose several processes that are known to mediate age-related macular degeneration (AMD), but whether melatonin can confer benefits against AMD remains unclear. To examine the association between melatonin supplementation and the risk of the development or progression of AMD. This retrospective cohort study accessed data from TriNetX, a national database of deidentified electronic medical records from both inpatient and outpatient health care organizations across the US, between December 4, 2023, and March 19, 2024. Patients aged 50 years or older, 60 years or older, and 70 years or older with no history of AMD (AMD-naive group) and with a history of nonexudative AMD (nonexudative AMD group) were queried for instances of melatonin medication codes between November 14, 2008, and November 14, 2023. Patients were then classified into either a melatonin group or a control group based on the presence of medication codes for melatonin. Propensity score matching (PSM) was performed to match the cohorts based on demographic variables, comorbidities, and nonmelatonin hypnotic medication use. The presence of at least 4 instances of melatonin records that each occurred at least 3 months apart. After PSM, the melatonin and the control cohorts were compared to evaluate the risk ratios (RRs) and the 95% CIs of having an outcome. For the AMD-naive group, the outcome was defined as a new diagnosis of any AMD, whereas for the nonexudative AMD group, the outcome was progression to exudative AMD. Among 121 523 patients in the melatonin-naive group aged 50 years or older (4848 in the melatonin cohort [4580 after PSM; mean (SD) age, 68.24 (11.47) years; 2588 female (56.5%)] and 116 675 in the control cohort [4580 after PSM; mean (SD) age, 68.17 (10.63) years; 2681 female (58.5%)]), melatonin use was associated with a reduced risk of developing AMD (RR, 0.42; 95% CI, 0.28-0.62). Among 66 253 patients aged 50 years or older in the nonexudative AMD group (4350 in the melatonin cohort [4064 after PSM; mean (SD) age, 80.21 (8.78) years; 2482 female (61.1%)] and 61 903 in the control cohort [4064 patients after PSM; mean (SD) age, 80.31 (8.03) years; 2531 female (62.3%)]), melatonin was associated with a reduced risk of AMD progression to exudative AMD (RR, 0.44; 95% CI, 0.34-0.56). The results were consistent among subsets of individuals aged 60 years or older (AMD-naive cohort: RR, 0.36 [95% CI, 0.25-0.54]; nonexudative AMD cohort: RR, 0.38 [95% CI, 0.30-0.49]) and 70 years or older (AMD-naive cohort: RR, 0.35 [95% CI, 0.23-0.53]; nonexudative AMD cohort: RR, 0.40 [95% CI, 0.31-0.51]). Melatonin use was associated with a decreased risk of development and progression of AMD. Although lifestyle factors may have influenced this association, these findings provide a rationale for further research on the efficacy of using melatonin as a preventive therapy against AMD.

Family History of Age-Related Macular Degeneration and Genetics Predict Progression to Advanced Age-Related Macular Degeneration Adjusting for Macular Status, Demographic, and Lifestyle Factors

To determine if a family history of age-related macular degeneration (AMD) and genetic variants identify eyes at higher risk for progression to advanced AMD (AAMD), after controlling for baseline demographics, behavioral factors, and macular status. Prospective, longitudinal cohort study. Eyes were classified using the Age-Related Eye Disease Study severity scale. Non-genetic and genetic predictors for progression to AAMD, geographic atrophy, and neovascular disease were evaluated. Cox proportional hazards models using the eye as the unit of analysis were used to calculate hazard ratios (HRs), accounting for correlated data. Discrimination between progressing and non-progressing eyes was assessed using C-statistics and net reclassification improvement (NRI). Among 4910 eyes, 863 progressed to AAMD over 12 years. Baseline AMD severity scale and status of the fellow eye were important predictors; genes provided additional discrimination. A family history of AMD also independently predicted progression after accounting for genetic and other covariates: 1 family member versus none (HR 1.21 [95% confidence interval {CI} 1.02-1.43]; P=0.03); ≥2 family members versus none (HR 1.55 [95% CI 1.26-1.90]; P < 0.001). A composite risk score calculated using β estimates of both non-genetic and significant genetic factors predicted progression to AAMD (HR 5.57; 90th vs 10th percentile; area under the receiver operating characteristic curve [AUC] = 0.92), providing superior fit compared with other models, including one with only ocular variables (NRI=0.34; P < 0.001; AUC = 0.87, ΔAUC 0.05 ± 0.005; P < 0.001). Genetic variants and family history provided additional discrimination for predicting progression to AAMD, after accounting for baseline macular status and other covariates.

Correlation between genetic and environmental risk factors for age-related macular degeneration in Brazilian patients.

To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. Cross-sectional study with a control group. We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94-22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08-5.28), low physical activity level (OR: 1.39; 95% CI: 0.82-2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84-2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81-6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47-3.35), 2.27 (95% CI: 1.52-3.37), and 2.76 (95% CI: 1.89-4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

Polypoidal Choroidal Vasculopathy Diagnosis and Neovascular Activity Evaluation Using Optical Coherence Tomography Angiography.

Purpose To examine choroidal neovascularization (CNV) characteristics in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), using swept-source optical coherence tomography angiography (SS-OCTA), and investigate agreement with OCT B-scan, fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) by two different examiners. Methods This is a retrospective multicentric study that involved patients with a history of AMD and PCV. Examiner A, who had access to OCTA, B-scan OCT, FFA, and ICGA imaging, had to differentiate between AMD and PCV, study the activity of AMD using Coscas' criteria (active vs. quiescent), and categorize PCV subtypes, while examiner B had only access to OCTA. Then, the diagnostic concordance was assessed between both examiners. Results A total of 27 patients (11 females (40.7%) and 16 males (59.3%), P = 0.231) were included in the analysis. Among those, 13 patients presented with neovascular AMD and 14 patients with PCV. There were 92.3% of correct answers regarding appropriate diagnosis and lesion characterization among AMD patients, against 61.5% of correct answers among PCV patients. The overall interrater reliability agreement between examiners, using Cohen's kappa coefficient (κ) was 0.70 (0.5082-0.8916). Disagreement was found with one active AMD misdiagnosed as inactive AMD, three inactive PCV misdiagnosed as inactive AMD, and one inactive PCV misdiagnosed as active AMD. Conclusion SS-OCTA alone remains limited in some specific phenotypes of PCV, which suggests the ongoing role of B-scan OCT associated with FFA and ICGA in the diagnosis of these conditions.

Refractive Outcomes After Immediate Sequential vs Delayed Sequential Bilateral Cataract Surgery

Approximately 2 million cataract operations are performed annually in the US, and patterns of cataract surgery delivery are changing to meet the increasing demand. Therefore, a comparative analysis of visual acuity outcomes after immediate sequential bilateral cataract surgery (ISBCS) vs delayed sequential bilateral cataract surgery (DSBCS) is important for informing future best practices. To compare refractive outcomes of patients who underwent ISBCS, short-interval (1-14 days between operations) DSBCS (DSBCS-14), and long-interval (15-90 days) DSBCS (DSBCS-90) procedures. This retrospective cohort study used population-based data from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry. A total of 1 824 196 IRIS Registry participants with bilateral visual acuity measurements who underwent bilateral cataract surgery were assessed. Participants were divided into 3 groups (DSBCS-90, DSBCS-14, and ISBCS groups) based on the timing of the second eye surgery. Univariable and multivariable linear regression models were used to analyze the refractive outcomes of the first and second surgery eye. Mean postoperative uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) after cataract surgery. This study analyzed data from 1 824 196 patients undergoing bilateral cataract surgery (mean [SD] age for those <87 years, 70.03 [7.77]; 684 916 [37.5%] male). Compared with the DSBCS-90 group, after age, self-reported race, insurance status, history of age-related macular degeneration, diabetic retinopathy, and glaucoma were controlled for, the UCVA of the first surgical eye was higher by 0.41 (95% CI, 0.36-0.45; P < .001) letters, and the BCVA was higher by 0.89 (95% CI, 0.86-0.92; P < .001) letters in the DSBCS-14 group, whereas in the ISBCS group, the UCVA was lower by 2.79 (95% CI, -2.95 to -2.63; P < .001) letters and the BCVA by 1.64 (95% CI, -1.74 to -1.53; P < .001) letters. Similarly, compared with the DSBCS-90 group for the second eye, in the DSBCS-14 group, the UCVA was higher by 0.79 (95% CI, 0.74-0.83; P < .001) letters and the BCVA by 0.48 (95% CI, 0.45-0.51; P < .001) letters, whereas in the ISBCS group, the UCVA was lower by -1.67 (95% CI, -1.83 to -1.51; P < .001) letters and the BCVA by -1.88 (95% CI, -1.98 to -1.78; P < .001) letters. The results of this cohort study of patients in the IRIS Registry suggest that compared with DSBCS-14 or DSBCS-90, ISBCS is associated with worse visual outcomes, which may or may not be clinically relevant, depending on patients' additional risk factors. Nonrandom surgery group assignment, confounding factors, and large sample size could account for the small but statistically significant differences noted. Further studies are warranted to determine whether these factors should be considered clinically relevant when counseling patients before cataract surgery.

Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration.

Inflammation is a key underlying factor of age-related macular degeneration (AMD) and inflammasome activation has been linked to disease development. Induced pluripotent stem-cell-derived retinal pigment epithelial cells (iPSC-RPE) are an attractive novel model system that can help to further elucidate disease pathways of this complex disease. Here, we analyzed the effect of dysfunctional protein clearance on inflammation and inflammasome activation in iPSC-RPE cells generated from a patient suffering from age-related macular degeneration (AMD) and an age-matched control. We primed iPSC-RPE cells with IL-1α and then inhibited both proteasomal degradation and autophagic clearance using MG-132 and bafilomycin A1, respectively, causing inflammasome activation. Subsequently, we determined cell viability, analyzed the expression levels of inflammasome-related genes using a PCR array, and measured the levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MCP-1 secreted into the medium. Cell treatments modified the expression of 48 inflammasome-related genes and increased the secretion of mature IL-1β, while reducing the levels of IL-6 and MCP-1. Interestingly, iPSC-RPE from an AMD donor secreted more IL-1β and expressed more Hsp90 prior to the inhibition of protein clearance, while MCP-1 and IL-6 were reduced at both protein and mRNA levels. Overall, our results suggest that cellular clearance mechanisms might already be dysfunctional, and the inflammasome activated, in cells with a disease origin.

A Prospective Study on Hereditary Bias of Age-Related Macular Degeneration

Purpose: This study employed a prospective survey to evaluate whether maternal family history or paternal family history is more likely to be found in patients with age-related macular degeneration (AMD). Methods: Family history of AMD was ascertained through a survey questionnaire of 346 patients who were confirmed by an ophthalmologist to have AMD. To compare proportions of maternally and paternally transmitted disease, the data were treated as pair matched and analyzed using the modified chi-squared McNemar test. Probands with either parent deceased before age 60 were excluded. Further analysis was conducted by grouping wet-AMD and dry-AMD patients. Results: Of the 346 surveys conducted, 91 (26.3%) reported at least 1 parent affected with AMD. Probands were 65.9% women and 44.1% men. The mean ± SD age for men was 74.3 ± 6.3 years and for women 72.7 ± 7.7 years. The average age of proband fathers was 75.0 ± 6.9 years and of proband mothers 80.1 ± 6.0 years. Probands with AMD had a higher proportion of affected mothers than fathers with an odds ratio (OR) of 3.00 and a 95% CI of 1.73 to 5.44, P = .0001. For wet AMD, the OR was 4.0 (95% CI 1.46 to 13.6) and for dry AMD, the OR was 2.6 (95% CI 1.35 to 5.4). Conclusions: Our results indicate that individuals with maternal history of AMD may be at a significantly increased risk for developing AMD than if their father had the disease. Owing to limitations in sample size and discrepancies in lifespan between sexes, further studies will be needed to generalize results. The maternal proclivity in our study sample correlates with literature describing a mitochondrial component in the disease process, soliciting further exploration into mitochondrial etiology and larger hereditary studies.

Significant Association Between Variant in SGCD and Age-Related Macular Degeneration.

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes—for instance, in the dystrophin-associated protein complex—might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4–5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06–3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03–3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02–0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.

Non-Dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population.

To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA) sample. Cross-sectional study. Community dwelling adults in the Republic of Ireland (ROI). 3,681 participants aged 50 years and older. TILDA is a nationally representative prospective cohort study of community dwelling adults aged 50 years and over in the ROI. Demographic and health variables were collected during a face-to-face interview carried out in the home (n=8175), and a substantial proportion of these (n=5035; 62%) also attended a study visit in a health assessment centre. Blood samples collected at baseline (wave 1, the subject of the current study), were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography, and macular pigment (MP) optical density was also measured (using customized heterochromatic flicker photometry). After excluding participants with eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with body mass index (BMI), and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p<0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants reporting lower levels of education (p<0.05, for all). Plasma L was significantly higher in participants reporting a family history of age-related macular degeneration (AMD) (p=0.001), and in the group of ≥75 years old (p<0.05). For each of these variables, the significant associations remained after controlling for other potential confounding variables. The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.

Targeting Tissue Lipids in Age-related Macular Degeneration

Targeting Tissue Lipids in Age-related Macular Degeneration

Cigarette Smoking and the Natural History of Age-Related Macular Degeneration: The Beaver Dam Eye Study

To examine the association of current cigarette smoking and pack-years smoked with the incidence and progression of age-related macular degeneration (AMD) and to examine the interactions of current smoking and pack-years smoked with complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) genotype. A longitudinal population-based study of AMD in a representative American community. Examinations were performed every 5 years over a 20-year period. A total of 4439 participants in the population-based Beaver Dam Eye Study (BDES). Age-related macular degeneration status was determined from grading retinal photographs. Multi-state models were used to model the relationship of current smoking and pack-years smoked and interactions with CFH and ARMS2 with the incidence and progression of AMD over the entire age range. Incidence and progression of AMD over a 20-year period and interactions between current smoking and pack-years smoked with CFH and ARMS2 genotype. The incidence of early AMD over the 20-year period was 24.4%, and the incidence of late AMD was 4.5%. Current smoking was associated with an increased risk of transitioning from minimal to moderate early AMD. A greater number of pack-years smoked was associated with an increased risk of transitioning from no AMD to minimal early AMD and from severe early AMD to late AMD. Current smoking and a greater number of pack-years smoked were associated with an increased risk of death. There were no statistically significant multiplicative interactions between current smoking or pack-years smoked and CFH or ARMS2 genotype. Current smoking and a greater number of pack-years smoked increase the risk of the progression of AMD. This has important health care implications because smoking is a modifiable behavior.

Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36.

Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. To describe 10-year progression rates to intermediate or advanced AMD. We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years. Treatment with antioxidant vitamins and minerals. Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits. The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200. The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.

Association between Visual Field Defects and Quality of Life in the United States

To investigate the association between visual field defects and quality of life in the United States population. Cross-sectional study. A total of 5186 participants in the 2005 through 2008 National Health and Nutrition Examination Survey 40 years of age and older without a self-reported history of age-related macular degeneration or prior refractive surgery who had undergone frequency doubling technology perimetric testing. Frequency doubling technology perimetry was performed in both eyes. Results from the better eye were used to categorize subjects as normal or having mild, moderate, or severe visual field loss. Subjects completed surveys about their visual and physical functioning ability. Disability pertaining to 6 vision-related activities, 2 visual function questions, and 5 physical functioning domains. Eighty-one percent of subjects had normal visual fields and 10%, 7%, and 2% demonstrated mild, moderate, and severe visual field defects, respectively. Subjects with greater severity of visual field defects had greater difficulty with vision-related activities. Subjects with severe visual field defects demonstrated the greatest odds of difficulty with all 6 activities. The 2 activities impacted most adversely were daytime driving in familiar places (odds ratio [OR], 12.4; 95% confidence interval [CI], 6.1-25.1) and noticing objects off to the side when walking (OR, 7.7; 95% CI, 4.7-12.7). Subjects with severe visual field defects had greater odds of worrying about eyesight (OR, 3.4; 95% CI, 2.0-5.8) and being limited by vision in the time spent on daily activities (OR, 5.1; 95% CI, 3.0-8.5). Subjects with severe visual field defects demonstrated the greatest odds of difficulty with 3 physical function domains, including activities of daily living (OR, 2.45; 95% CI, 1.37-4.38), instrumental activities of daily living (OR, 2.45; 95% CI, 1.37-4.38), as well as leisure and social activities (OR, 3.29; 95% CI, 1.87-5.77). Greater severity of visual field abnormality was associated with significantly greater odds of disability with vision-related function and physical function. These findings support the necessity of routine screening to find those who may benefit from therapy to prevent progressive glaucomatous vision loss.

CORRELATION OF FOVEAL MICROSTRUCTURAL CHANGES WITH VISION AFTER ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN AGE-RELATED MACULAR DEGENERATION

To investigate the correlation of foveal microstructural changes with vision after intravitreal ranibizumab injection in eye with choroidal neovascularization (CNV) secondary to age-related macular degeneration. We retrospectively studied 40 eyes of 40 patients with neovascular age-related macular degeneration who had no previous treatment history of age-related macular degeneration. All patients were treated with 3 monthly intravitreal ranibizumab (0.5 mg/0.05 mL) injections. One month after the third consecutive injection, best-corrected visual acuity (BCVA) was evaluated and the eyes were categorized into 2 groups according to the change in BCVA (good function group: BCVA improvement ≥ logarithm of minimum angle of resolution 0.3; poor function group: BCVA improvement < logarithm of minimum angle of resolution 0.3). Changes of foveal photoreceptor layer integrity, CNV size (diameter and thickness), central macular thickness, center point thickness, outer nuclear layer thickness, and subretinal fluid in each group were also evaluated using spectral-domain optical coherence tomography. The good function group is 20 eyes, and the poor function group is 20 eyes. No significant differences in baseline characteristics of variables including CNV type, initial BCVA, photoreceptor integrity, and CNV size were observed between the two groups. Best-corrected visual acuity in the good function group was 0.30 ± 0.17 (logarithm of minimum angle of resolution) and that in the poor function group was 0.48 ± 0.40 (logarithm of minimum angle of resolution). Decreased disrupted length of photoreceptor layer (1,020.80 ± 974.60) and decreased CNV thickness (78.86 ± 50.78) were found in the good function group at the end of follow-up. However, no significant differences in changes of CNV diameter, central macular thickness, center point thickness, outer nuclear layer thickness, and resolution of subretinal fluid were observed between the two groups. Restoration of foveal photoreceptor integrity and decreased CNV thickness are closely associated with visual improvement in neovascular age-related macular degeneration after treatment.

Risk factors of age-related macular degeneration in Argentina

To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment), smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4%) were female. Of the cases with age-related macular degeneration, 159 (45.4%) had age-related macular degeneration in their left eyes, 154 (44.0%) in their right eyes, and 138 (39.4%) in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3) and a family history of age-related macular degeneration (OR: 4.3). Other factors included hypertension (OR: 2.1), smoking (OR: 2.2), and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40). Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

Risk Alleles in CFH and ARMS2 and the Long-term Natural History of Age-Related Macular Degeneration

To describe the relationships of risk alleles in complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) to the incidence and progression of age-related macular degeneration (AMD) during a 20-year period. There were 4282 persons aged 43 to 86 years at the baseline examination in 1988-1990 enrolled in a population-based cohort study who participated in at least 1 examination spaced 5 years apart during a 20-year period and had gradable fundus photographs for AMD and genotype information on CFH and ARMS2. Low, intermediate, and high genetic risk for AMD was defined by the presence of 0 to 1, 2, or 3 to 4 risk alleles for CFH and ARMS2, respectively. Multistate models were used to estimate the progression of AMD throughout the entire age range. There were 2820 (66%), 1129 (26%), and 333 persons (8%) with low, intermediate, and high genetic risk for AMD, respectively. The 5-year incidences of early and late AMD were 9.1% and 1.6%, respectively, and increased with age but did not differ significantly by sex. Using the multistate model, of persons aged 45 years with no AMD in the low, intermediate, and high AMD genetic risk groups, 33.0%, 39.9%, and 46.5%, respectively, were estimated to develop early AMD, and 1.4%, 5.2%, and 15.3% were estimated to develop late AMD by age 80 years. These population-based data provide estimates of the long-term risk of the incidence and progression of AMD and its lesions by age and genetic risk alleles for CFH and ARMS2. They also show that when early AMD is present, knowing the phenotype contributes more to risk assessment than knowing the genetic risk based on these 2 AMD genes.

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

We hypothesized that reduction/loss of very long chain PUFAs (VLC-PUFAs) due to mutations in the ELOngase of very long chain fatty acid-4 (ELOVL4) protein contributes to retinal degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC-PUFA in the retina of these patients could provide some therapeutic benefits. Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4 protein to determine which substrates are the best precursors for biosynthesis of VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while green fluorescent protein-expressing and nontransduced cells served as controls. The cells were treated with 20:5n3, 22:6n3, and 20:4n6, either individually or in equal combinations. Both transduced and control cells internalized and elongated the supplemented FAs to C22-C26 precursors. Only ELOVL4-expressing cells synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more efficiently elongated to VLC-PUFA in the ELOVL4-expressing cells, regardless of whether it was in combination with 22:6n3 or with 20:4n6. In each FA treatment group, C34 and C36 VLC-PUFAs were the predominant VLC-PUFAs in the ELOVL4-expressing cells. In summary, 20:5n3, followed by 20:4n6, seems to be the best precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein.

ADHERENCE TO RECOMMENDATIONS OF THE AGE-RELATED EYE DISEASE STUDY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION

The purposes of this study were to determine the rate of adherence to the recommendations of the Age-Related Eye Disease Study (AREDS) regarding vitamin supplement use among patients with age-related macular degeneration (AMD) at a tertiary retina center and to identify factors associated with adherence. Consecutive patients with a history of AMD were administered an in-person survey designed to assess use of vitamin supplementation as well as to investigate factors that may influence supplementation use patterns. A retina specialist performed dilated funduscopic examinations and categorized patients' AMD severity according to the AREDS classification system. The main outcome measure was rate of adherence to AREDS recommendations. Sixty-four patients with AMD completed the survey. Sixty-three percent of patients met AREDS criteria for vitamin supplementation. Of those patients who met the criteria, only 43% reported taking AREDS vitamins in the recommended dosages. Among patients using AREDS vitamins as recommended, 100% were return patients to the tertiary retina center and reported a retina specialist as the primary recommendation source for supplement use. Of patients who met AREDS criteria for vitamin supplementation but were not taking vitamins as per AREDS recommendations, 87% were new patients to the retina service and 75% reported that vitamin supplementation had never been recommended to them. Patients with intermediate or advanced AMD in at least one eye show a low adherence rate to the AREDS recommendations for vitamin supplementation.

The Role of Spectral-Domain Optical Coherence Tomography in the Diagnosis of Retinal Angiomatous Proliferation

We present the findings of spectral-domain optical coherence tomography (OCT) in 8 patients with retinal angiomatous proliferation. Eight patients with a known history of age-related macular degeneration presented with a recent decrease of visual acuity in one eye. On fundus examination, all patients showed an elevated macular lesion associated with intra- or subretinal hemorrhage and retinal hard exudates. Fluorescein and indocyanine-green (ICG) angiography, together with spectral-domain OCT (Optopol Copernicus SOCT), were performed. Fluorescein angiography showed early hyperfluorescence with late leakage in all cases. A serous pigment epithelium detachment was present in 6 cases. ICG angiography showed a hot spot in the macular area. The OCT showed a serous pigment epithelium detachment in 6 cases and intraretinal cysts in all cases. The line crossing the ICG visible hot spot showed a greatly hyperreflective intraretinal lesion located at various depths inside the retina. Spectral-domain OCT is a useful complementary tool to confirm the diagnosis of retinal angiomatous proliferation. Its high resolution and speed enables accurate localization of the angiomatous lesion.

Resolution of a giant pigment epithelial detachment after treatment with intravitreal bevacizumab.

To describe a patient with a giant pigment epithelial detachment (PED) successfully treated with intravitreal bevacizumab. Retrospective, observational case report. The patient's records were reviewed. An 81-year-old man with history of age-related macular degeneration was seen on routine follow-up examination with an asymptomatic PED temporal to the macula in the right eye and visual acuity of 20/40. The patient was observed. Ten months later, the patient was found to have decreased vision to 20/80 and massive enlargement of the PED, with extension from the temporal equator into the macula. Optical coherence tomography of the macula showed a PED with overlying intraretinal cysts. The patient was given injections of intravitreal bevacizumab for every 4 months (1.25 mg) with complete resolution of the PED and return to baseline visual acuity of 20/40. Giant PED secondary to exudative age-related macular degeneration can be successfully treated with intravitreal bevacizumab.