Influence of the Vitreoretinal Interface on the Treatment with Anti-VEGF for Exudative Age-Related Macular Degeneration.

PURPOSE: To investigate the influence of the vitreoretinal interface on the outcomes of different ranibizumab regimens for exudative age-related macular degeneration. METHODS: We conducted a retrospective subanalysis of 2 prospective clinical trials. Patients were treated with ranibizumab for 12 months according to 3 different regimens: pro-re-nata (PRN), treat and extend (T&E), and monthly. Vitreoretinal interface was assessed for absence (group ON) or presence (group OFF) of posterior vitreous detachment (PVD). RESULTS: We included 64 eyes from 64 patients. Visual improvement was poorer for group ON (0.3 ± 10.7 letters) than for group OFF (9.2 ± 13.3; p = 0.007). A significant difference in letters of improvement between groups was observed in the PRN cohort (ON: -5.0 ± 12.9; OFF: 11.4 ± 11.9; p = 0.003), but not in the cohorts with monthly (ON: 5.7 ± 7.8; OFF: 7.9 ± 15.2; p = 0.735) or T&E (ON: 4.3 ± 4.3; OFF: 7.8 ± 11.1; p = 0.424) treatment. CONCLUSION: The negative impact of absence of PVD is regimen dependent, with monthly dosing providing similar outcomes to PVD patients. In the absence of PVD (group ON), PRN should be avoided, and T&E might be an alternative.

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.

Long-Term Management of RAP Lesions in Clinical Practice: Treatment Efficacy and Predictors of Functional Improvement.

PURPOSE: To evaluate the long-term efficacy of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) and to identify predictors of functional outcome. METHODS: Retrospective case series comprised 79 eyes of 68 consecutive patients with RAP followed up ≥36 months. Primary end-points were best-corrected visual acuity (BCVA) and central macular thickness (CMT) variation at 36 months and at the last visit. RESULTS: Mean follow-up time was 59.8 ± 16.0 months. All eyes were treated with pro re nata ranibizumab, with (n = 33) or without (n = 46) photodynamic therapy (PDT). Stabilization or improvement in BCVA was observed in 50.6% of the patients at 36 months, and in 40.5% at the end of the follow-up, where 20.3% preserved reading vision. A significant decrease in CMT was observed at 36 months (p < 0.001), but not at the end of the follow-up. Geographic atrophy (GA) was present in 59.5% of the eyes at the final visit. Baseline subretinal fluid was associated with better visual outcomes (p = 0.001). Results of combination treatment with intravitreal ranibizumab and PDT did not significantly differ from ranibizumab monotherapy. CONCLUSION: Modest functional outcomes can be expected from the long-term treatment of RAP lesions in clinical practice, most likely due to the advent of GA. Baseline subretinal fluid positively correlated with final BCVA.

Prevalence of Age-Related Macular Degeneration in Portugal: The Coimbra Eye Study - Report 1.

PURPOSE: To evaluate the age- and gender-specific prevalence of early and late age-related macular degeneration (AMD) in a Portuguese population-based sample. METHODS: All patients aged ≥55 years of a Portuguese primary health-care unit were recruited for a cross-sectional population-based study. Responders underwent complete ophthalmological examination and digital fundus imaging. Early and late AMD was defined according to the International Age-Related Macular Epidemiological Study Group Classification, and the adopted staging for AMD was the same as that used in the Rotterdam study. The age- and gender-adjusted prevalence of early and late forms of AMD was calculated. RESULTS: Of the 4,370 eligible subjects, 3,000 underwent study procedures (68.6% response rate) and 2,975 were included in the analysis; they had a mean age of 68.9 ± 8.6 years. The overall prevalence of early and late AMD was 15.53% (95% CI 14.25-16.88) and 0.67% (95% CI 0.41-1.04), respectively. Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.44% (95% CI 0.23-0.75) and 0.27% (95% CI 0.12-0.53) of individuals, respectively. The highest prevalence of advanced AMD was among those aged ≥75 years (1.13% for NV-AMD; 0.63% for GA). CONCLUSIONS: To our knowledge, this is the first AMD epidemiological study in a Portuguese population. The early forms of the disease had a similar prevalence to that of other large-scale population-based cohorts, but late AMD was less frequent than previously reported.

Macular atrophy development in neovascular age-related macular degeneration during first year of treatment: Incidence and risk factors.

PURPOSE: To assess the development of macular atrophy, according to the new Classification of Atrophy Meetings criteria, in patients with treatment-naïve neovascular age-related macular degeneration during the first year of treatment with ranibizumab or aflibercept, and to determine baseline factors predictive of atrophy development. METHODS: Retrospective subanalysis of three prospective clinical trials that included eyes with treatment-naïve neovascular age-related macular degeneration. Multimodal evaluation was performed with spectral-domain optical coherence tomography, fluorescein angiography, fundus autofluorescence and color fundus photography at baseline and after 12 months of treatment. The main outcome was the macular atrophy type, classified according to Classification of Atrophy Meeting criteria. Logistic regression models were built to test predictors of macular atrophy development. RESULTS: A total of 85 eyes of 85 patients (63% female; mean age: 78.5 ± 6.3 years old) were included. After 12 months of antiangiogenic therapy, all four Classification of Atrophy Meeting types of macular atrophy developed de novo. The atrophy type with highest incidence at end of follow-up was incomplete retinal pigment epithelium and outer retinal atrophy (63.6%; 95% confidence interval: 45.9%-86.0%). A significant association was observed between development at 12 months and the presence of incomplete retinal pigment epithelium and outer retinal atrophy at baseline (odds ratio (95% confidence interval): 22.4 (1.6, 323.5)). The number of injections was predictive of complete outer retinal atrophy development at end of follow-up (odds ratio (95% confidence interval) 1.5 (1.1, 2.1), p = 0.011). CONCLUSION: Predictors of atrophy development have the potential to change treatment practices. Further research is warranted.

Adherence to a Mediterranean diet, lifestyle and age-related macular degeneration: the Coimbra Eye Study - report 3.

PURPOSE: To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD). METHODS: Nested case-control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption. RESULTS: Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysis revealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p < 0.05). CONCLUSION: High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.

Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy.

PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. RESULTS: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. CONCLUSION: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PURPOSE: To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. POPULATION: A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). METHODS: Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. RESULTS: Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). CONCLUSIONS: The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location.

Sialidosis type I: ophthalmological findings.

Sialidosis is a lysosomal storage disease caused by deficit of neuraminidase. It is an autosomal recessive disease, heterogeneous in its onset, presentation and prognosis. We report a case of a male patient with molecular and enzymatic confirmation of the diagnosis. Symptoms began at age 26 with reduced visual acuity, bilateral cherry-red spots and later myoclonus. A brother, now deceased, had the same confirmed disease. We describe the symptoms and clinical findings of the patient, as well review the current knowledge on the topic. With this report, we highlight the importance of a clinical history integrating all the patient's symptoms in order to achieve the diagnosis. In the presence of a cherry-red spot, a comprehensive study is mandatory. Despite being a rare disease, sialidosis carries a significant burden for its patients and its diagnosis should always be considered in the appropriate setting.