Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms.

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-ß inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.

Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.

Age-related macular degeneration (AMD) is a prevalent degenerative disorder of the central retina, which holds global significance as the fourth leading cause of blindness. The condition is characterized by a multifaceted pathophysiology that involves aging, oxidative stress, inflammation, vascular dysfunction, and complement activation. The complex interplay of these factors contributes to the initiation and progression of AMD. Current treatments primarily address choroidal neovascularization (CNV) in neovascular AMD. However, the approval of novel drug therapies for the atrophic and more gradual variant, known as geographic atrophy (GA), has recently occurred. In light of the substantial impact of AMD on affected individuals' quality of life and the strain it places on healthcare systems, there is a pressing need for innovative medications. This paper aims to provide an updated and comprehensive overview of advancements in our understanding of the etiopathogenesis of AMD. Special attention will be given to the influence of aging and altered redox status on mitochondrial dynamics, cell death pathways, and the intricate interplay between oxidative stress and the complement system, specifically in the context of GA. Additionally, this review will shed light on newly approved therapies and explore emerging alternative treatment strategies in the field. The objective is to contribute to the ongoing dialogue surrounding AMD, offering insights into the latest developments that may pave the way for more effective management and intervention approaches.

Association of autoantibody levels with different stages of age-related macular degeneration (AMD): Results from the population-based Gutenberg Health Study (GHS).

PURPOSE: Anti-retinal autoantibodies are assumed to be associated with age-related macular degeneration (AMD). To our knowledge, this is the first evaluation of autoantibodies in human sera of participants with different stages of AMD in a large population-based, observational cohort study in Germany. METHODS: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. Amongst others, non-mydriatic fundus photography (Visucam PRO NM™, Carl Zeiss Meditec AG, Jena, Germany) was performed. Fundus images of the first 5000 participants were graded based on the Rotterdam Eye Study classification. Sera of participants with AMD (n=541) and sera of age-matched participants without AMD (n=490) were analyzed by antigen-microarrays. Besides descriptive statistics, autoantibody-levels were compared by Mann-Whitney-U test and the associations of level of autoantibodies with AMD were calculated by logistic regression analysis. Likewise, possible associations of the autoantibodies and both clinical and laboratory parameters on AMD subjects were analyzed. RESULTS: Autoantibodies against transferrin (p<0.001) were significantly downregulated in participants with early AMD and soft, distinct drusen (≥63 µm) or pigmentary abnormalities only compared to Controls. Mitogen-activated protein kinase 3 (p=0.041), glutathione peroxidase 4 (p=0.048), clusterin (p=0.045), lysozyme (p=0.19), protein kinase C substrate 80K-H (p=0.02), heat shock 70 kDa protein 1A (p=0.04) and insulin (p=0.018) show a trend between Control and participants with early AMD and soft, distinct drusen (≥63 µm) or pigmentary abnormalities only. CONCLUSIONS: This study contributes to a growing knowledge of autoantibodies in association with different AMD stages compared to controls in the context of a large population-based study in Germany. Especially autoantibodies against inflammatory proteins were downregulated in participants with early AMD and soft, distinct drusen (≥63 µm) or pigmentary abnormalities only.

Serum Autoantibodies in Patients with Dry and Wet Age-Related Macular Degeneration.

BACKGROUND: To assess the serum autoantibody profile in patients with dry and exudative age-related macular degeneration compared with healthy volunteers to detect potential biomarkers, e.g., markers for progression of the disease. MATERIALS AND METHODS: IgG Immunoreactivities were compared in patients suffering from dry age-related macular degeneration (AMD) (n = 20), patients with treatment-naive exudative AMD (n = 29) and healthy volunteers (n = 21). Serum was analysed by customized antigen microarrays containing 61 antigens. The statistical analysis was performed by univariate and multivariate analysis of variance, predictive data-mining methods and artificial neuronal networks were used to detect specific autoantibody patterns. RESULTS: The immunoreactivities of dry and wet AMD patients were significantly different from each other and from controls. One of the most prominently changed reactivity was against alpha-synuclein (p ≤ 0.0034), which is known from other neurodegenerative diseases. Furthermore, reactivities against glyceraldehyde-3-phosphat-dehydrogenase (p ≤ 0.031) and Annexin V (p ≤ 0.034), which performs a major role in apoptotic processes, were significantly changed. Some immunoreacitvities were antithetic regulated in wet and dry-AMD, such as Vesicle transport-related protein (VTI-B). CONCLUSIONS: Comparison of autoantibody profiles in patients with dry and wet AMD revealed significantly altered immunoreactivities against proteins particularly found in immunological diseases, further neurodegenerative, apoptotic and autoimmune markers could be observed. A validation study has to explore if these antibody pattern can help to understand the underlying differences in pathogenesis, evaluate their prognostic value and if those could be possibly useful as additional therapeutic targets.

Intravitreal fluocinolone acetonide implant for chronic postoperative cystoid macular edema - two years results.

PURPOSE: We report visual and anatomical outcomes of chronic postoperative macular edema treated with a fluocinolone acetonide intravitreal implant. METHOD: Retrospective study of chronic, post-surgical CME treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed over 24 months. The need for IOP lowering treatment, top-up therapy during follow-up, and complications were also assessed. RESULTS: We analyzed 16 consecutive eyes of 16 patients with chronic, post-surgical CME treated with fluocinolone acetonide intravitreal implant. Surgical indications included cataract surgery, vitrectomy plus membrane peeling and combined phaco-vitrectomy. Baseline mean BRVA of 0.8 ± 0.65 logMAR improved to 0.60 ± 0.4 logMAR (p = 0.02) at 12 months and to 0.7 ± 0.5 logMAR (p = 0.32) at 24 months. At month 12, BRVA improved in 11 eyes, stabilized in 4 eyes, and decreased in 1 eye. At month 24, VA remained improved in 5 eyes, remained stabilized in 5 eyes, and decreased in 1 eye. Mean CRT decreased from 524 ± 132 µm at baseline to 389 µm at month 3, 347 µm at month 6, 355 ± 106 µm (p = 0.0003) at month 12, and 313 ± 83 µm (p = 0.0001) at month 24. At 12 months, CRT improved in 13 eyes and remained unchanged in 2 eyes. At 24 months, CRT improved further in 8 eyes, and stabilized in 3 eyes. Increased IOP (≥21 mmHg) was observed only in 4 eyes, all successfully managed with topical medication. No further side effects were observed in any patient. CONCLUSION: Visual and anatomic improvements were achieved by a single fluocinolone acetonide implant with few side effects up to 24 months in CME eyes with a long and heavy prior treatment history.

RETINAL THICKNESS AND FOVEAL HYPOPLASIA IN ADULTS BORN PRETERM WITH AND WITHOUT RETINOPATHY OF PREMATURITY: The Gutenberg Prematurity Eye Study.

PURPOSE: This study analyses whether prematurity, retinopathy of prematurity (ROP), and associated factors lead to altered foveal shape in adulthood and whether these alterations are associated with visual acuity. METHODS: The Gutenberg Prematurity Eye Study is a German cohort study with a prospective ophthalmologic examination (participants aged 18-52 years) of individuals born preterm and full-term that were examined with spectral domain optical coherence tomography. Participants were grouped according to gestational age (GA) and postnatal ROP status. Multivariable linear regression analyses for foveolar retinal thickness, foveal hypoplasia, and posterior vitreous status were performed. RESULTS: A total of 755 eyes of 414 preterm and full-term individuals were included (aged 28.6 ± 8.6 years, 233 female individuals). Central foveal retinal thickness increased as GA decreased. The prevalence of foveal hypoplasia was 2% (control group), 9% (GA 33-36), 18% (GA 29-32), 48% (GA ≤28), 50% (ROP without treatment), and 82% of eyes (with ROP requiring treatment). In multivariable analyses, central foveal thickness was independently associated with GA and advanced stages of ROP requiring treatment while foveal hypoplasia was only associated with GA. Posterior vitreous was more frequently visible as partially detached in full-term than in preterm individuals. Lower distant-corrected visual acuity correlated with increased foveolar thickness (rho = 0.08; P = 0.03) and with foveal hypoplasia (rho = 0.15, P < 0.001). CONCLUSION: Our findings indicate that there are fetal origins affecting foveal shape, resulting in foveal hypoplasia potentially affecting the visual acuity in adulthood.

A Randomized, Double-Masked, Active-Controlled, Crossover Phase III Equivalence Study of Generic Dorzolamide 2% versus Innovator Trusopt® Eye Drop Solution in Subjects with Open-Angle Glaucoma or Ocular Hypertension.

Background: The aim of this study was to demonstrate the equivalence of generic dorzolamide 2% eye drops solution versus the innovator formulation (Trusopt® eye drops solution) in patients with open-angle glaucoma or ocular hypertension. Methods: This prospective, monocentric, double-masked, active-controlled crossover phase III study included 32 patients. After washout, patients were randomized to reference product (Trusopt®) or test product (dorzolamide 2% eye drops, Rompharm Company SRL) for a 4-week period. Subsequent washout and crossover were performed. Drops were applied t.i.d. The primary efficacy endpoint was the difference in mean diurnal IOP. Goldmann applanation tonometry was performed at 8 am, 12 pm, and 4 pm at each visit, and safety was assessed by documentation of adverse events (AEs). Therapy adherence was documented by self-reporting and eye drop bottle weighing. An ANOVA with treatment, sequence, study period, and patient within the sequence as effects was performed and an additional post hoc ANCOVA including the baseline IOP was also performed. Results: 34 patients were randomized and analyzed in the safety population. The per-protocol population included 32 patients. According to the self-report, all patients were >80% compliant. Under the ANCOVA model, the 90% confidence interval for the average change of the IOP -0.27 mmHg (-1.17 mmHg-0.64 mmHg) is included by the acceptance range -1.5 mmHg to +1.5 mmHg after excluding 2 patients, which had falsely reported high therapy adherence. No clinically relevant difference was observed in frequency or severity of the AEs between both treatments. Conclusions: This study showed the equivalence of the tested generic dorzolamide 2% eye drops solution to the reference product Trusopt® eye drops solution. Trial Registration. This trial is registered with (ClinicalTrials.gov (identifier: NCT00878917) on April 9, 2009).

Five-Year Cumulative Incidence and Progression of Myopic Maculopathy in a German Population.

PURPOSE: To investigate the 5-year cumulative incidence and progression of myopic maculopathy in the general population in Germany and to analyze potential risk factors. DESIGN: The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants aged 35 to 74 years at baseline. PARTICIPANTS: A total of 494 eyes of 323 participants (mean age, 50.2 ± 9.2 years; median, -7.25 diopters [D] myopic refractive error) without myopic maculopathy at baseline and 34 eyes of 27 subjects (mean age, 56.7 ± 9.1 years; median, -8.75 D myopic refractive error) with myopic maculopathy met the inclusion conditions, phakic eyes with spherical equivalent ≤-6 D (baseline), and had gradable fundus photographs at baseline and 5-year follow-up. METHODS: Myopic maculopathy incidence and progression were assessed by grading of fundus photographs according to a recent international photographic classification system (META-PM). Multivariable logistic regression analysis was used to assess risk factors for progression of myopic maculopathy. MAIN OUTCOME MEASURES: Estimates for incidence and progression of myopic maculopathy. RESULTS: The 5-year cumulative incidence of myopic maculopathy was 0.3% (95% confidence interval [CI], 0.02-1.99; n = 1). Progression occurred in 17 of 34 eyes (50%) with prior myopic maculopathy over 5 years with 4 changes in category. The most common types of progression were enlargement of diffuse and patchy chorioretinal atrophy; a new pathology was present in 8 eyes. Higher intraocular pressure (IOP) (odds ratio [OR], 1.62; 95% CI, 1.51-1.59; P = 0.035) was associated with progression of myopic maculopathy. Female gender (OR, 5.54; 95% CI, 0.93-32.92; P = 0.060) and higher myopic refractive error (OR, 1.62 per diopter; 95% CI, 0.99-1.49; P = 0.063) showed a tendency toward progression. CONCLUSIONS: Incidence of myopic maculopathy is rare in highly myopic eyes in the general population aged 35 to 74 years in Germany. Progression of myopic maculopathy in the German population occurred in 50% of highly myopic eyes. We presented population-based 5-year follow-up data on incidence and progression of myopic maculopathy in Europe.

Switching to intravitreal fluocinolone acetonide implant for refractory diabetic macular edema: 12- and 24-month results.

PURPOSE: To report visual and anatomical outcomes of chronic/refractory diabetic macular edema (DME) treated with intravitreal fluocinolone acetonide implant. SETTING: Retrospective, one arm, multicentric study. METHOD: Between 2013 and 2018, 27 consecutive eyes of 25 patients with chronic/refractory DME were treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed at 12 and 24 months. The need for IOP lowering treatment as well as top-up therapy during the follow-up were also assessed. RESULTS: The duration of DME prior to treatment in our study was 54 ± 24 months. The baseline mean BRVA of 0.7 ± 0.34 logMAR improved to 0.5 ± 0.3 (p = 0.01) at 12 months and 0.46 ± 0.3 (p = 0.04) at 24 months. At 12 months, BRVA improved in 14 eyes (52%), stabilized in 5 eyes (20%), and decreased in 3 eyes (11%). At 24 months, BRVA improved further in 6 eyes (24%), stabilized in 3 eyes (12%), and decreased in 6 eyes (24 %). Mean CRT decreased from 497 ± 176 to 349 ± 186 µm at 12 months (p = 0.0005) and to 267 ± 104 µm at 24 months (p = 0.001). Only five eyes required additional treatment for DME and only three eyes required treatment for raised IOP. DISCUSSION: Our results show that the visual and the anatomical improvements achieved by a single injection of a fluocinolone acetonide implant were maintained up to 24 months with minimal additional therapy even in eyes with a long and heavy history; however, IOP monitoring remains essential.

Five-year cumulative incidence and progression of age-related macular degeneration: results from the German population-based Gutenberg Health Study (GHS).

PURPOSE: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age. The baseline examination, including fundus photography, was conducted between 2007 and 2012, and the 5-year follow-up examination was performed between 2012 and 2017. AMD grading of fundus photographs was performed according to the Rotterdam Eye Study classification. The 5-year cumulative incidence and progression of AMD were calculated. Poisson regression analysis was conducted to investigate factors associated with the cumulative incidence and progression of AMD. RESULTS: Six-thousand-eight-hundred-eighty-eight participants (49.8%, n = 3427 female) were included in the analysis. AMD prevalence was 8.5% [95% CI: 7.9-9.2%] at baseline and 10.3% [95% CI: 9.6-11.1%] at follow-up. The cumulative 5-year-incidence was 2.0% [1.7-2.4%]. AMD progression within 5 years was seen in 18.1% [95% CI: 15.1-21.5%] of the participants. AMD incidence and AMD progression were associated with higher age, for each 10-year increase in age, the risk of AMD doubles (RR = 2.30), and the risk of progression of the disease is increased by 1.6. while AMD incidence also with pseudophakic status. CONCLUSIONS: In summary, this population-based sample provides substantial epidemiologic data from a large German cohort, including data on progression and cumulative incidence of macular degeneration in younger age groups. AMD progression over 5 years is common in the German population, 18.1% of subjects with AMD showed progression in at least one eye in this time frame and is associated with higher age. Nevertheless, although usually defined to occur over the age of 50, in this cohort AMD occurred in 0.5% and AMD progression occurred in 5.4% of those already affected in the youngest age group before 50 years of age.

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease.

BACKGROUND: Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD. METHODS: To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants. RESULTS: Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 × 10- 8), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism). CONCLUSIONS: Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.

Prevalence and new onset of depression and anxiety among participants with AMD in a European cohort.

To investigate the prevalence and new onset of depression and anxiety among subjects with age-related macular degeneration (AMD) and its association with AMD in a large European cohort with relatively good visual acuity. 11,834 participants enrolled in the German population-based Gutenberg Health Study were studied. AMD was diagnosed by grading of fundus photographs. Depression and anxiety were assessed with the Patient Health Questionnaire and the Generalized Anxiety Disorder-2 Scale, respectively. Logistic regression analyses were performed and adjusted for several parameters. 1,089 (9.2%) participants were diagnosed having AMD. Prevalence of depression in AMD and non-AMD participants was 7.2% and 8.0%, respectively and prevalence of anxiety was 4.2% and 7.0%, respectively. New onset of depression and anxiety at 5-year follow-up in AMD subjects was 2.6% and 3.6%, respectively. AMD was not associated with depression (OR 0.93; CI 95% 0.70-1.20; p = 0.62). AMD was associated with less anxiety (OR 0.67; CI 95% 0.47-0.93; p = 0.02). This is the first study analyzing both prevalence and new onset of depression and anxiety in AMD subjects. AMD- and non-AMD participants had a similar prevalence and new onset of depression in our population-based sample. Participants without AMD had a higher prevalence of anxiety. AMD was not associated with depression.

Prevalence of myopic maculopathy in the German population: results from the Gutenberg health study.

AIMS: To determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors. DESIGN: The Gutenberg Health Study is a population-based study, including 15 010 participants aged 35-74 years. METHODS: Myopic maculopathy was graded in phakic eyes with spherical equivalent ≤-6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associated factors with myopic maculopathy. RESULTS: Myopic maculopathy was present in 10.3% (95% CI 7.9 to 13.3) study participants. The prevalence was 8.6% (95% CI 6.1% to 11.9%) in the 397 right eyes and 8.7% (95% CI 6.2% to 12.0%) in the 404 left eyes. The most common type of pathology was diffuse atrophy (8.1%), followed by patchy atrophy (1.3%) and macular atrophy (0.5%); plus lesions were present in 3% (right eyes). Age (OR 1.07 per year, 95% CI 1.03 to 1.11, p<0.001), higher myopic refractive error (p<0.001), and male gender (p=0.02) were associated with myopic maculopathy, while cardiovascular risk factors and socioeconomic factors were not. CONCLUSIONS: The prevalence of myopic maculopathy in the German population was 0.5%, and 10% in high myopic participants, aged 35-74 years. These population-based data are the first in Europe. Myopic maculopathy was related to severity of myopic refractive error and age.

Characteristics and pathologies of the vitreo-macular interface-results from the Gutenberg Health Study.

PURPOSE: We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. METHODS: The Gutenberg Health Study is a population-based study in Germany, including an ophthalmological examination with refraction, biometry and optical coherence tomography (OCT) imaging. Characteristics of the vitreo-macular interface were graded on volume scans including visibility of an epiretinal membrane, full-thickness macular hole, lamellar hole and pseudohole. Overall and age-specific prevalences including 95% confidence intervals [95%-CI] were calculated. Association analyses were conducted to determine systemic and ocular factors that are associated with epiretinal membranes (the most common pathology) using multivariable logistic regression. RESULTS: A total of 1890 people aged 40-80 years were included in the study. Of these, 4.7% (95%-CI: 3.8%-5.8%) had an epiretinal membrane in at least one eye, 0.1% a full-thickness macular hole, 0.6% a lamellar hole and 0.6% a pseudohole. The presence of an epiretinal membrane was associated with higher age, myopic refractive error and prior retinal laser therapy, but not with gender, body height, body weight, smoking, prior cataract surgery or intraocular pressure. CONCLUSIONS: Epiretinal membranes are more frequent in older and myopic subjects and in those with prior retinal laser therapy.

Low Birth Weight Is Linked to Age-Related Macular Degeneration: Results From the Population-Based Gutenberg Health Study (GHS).

Purpose: This study analyzed whether low birth weight is linked to prevalence and incidence of age-related maculopathy (AMD) in adulthood. Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany. GHS participants at an age from 35 to 74 years were included. An ophthalmologic examination with fundus photography was carried out. Fundus photographs were graded according to the Rotterdam Grading Scheme for AMD at baseline and at the 5-year follow-up examination. Participants were divided into three different birth weight groups (low: <2500 g; normal: 2500-4000 g; and high: >4000 g). Poisson regression analysis with adjustment for several confounders was used to assess associations between birth weight and AMD prevalence (overall, early, late AMD) and 5-year cumulative incidence. Results: Overall, 6492 participants were included (3538 female, aged 50.7 ± 10.4 years). Prevalence of total AMD was highest in the low birth weight group (11.2%; 40/358) compared to the normal birth weight group (6.5%; 346/5328) and the high birth weight group (8.4%; 68/806). Low birth weight was associated with overall AMD prevalence (prevalence ratio [PR] = 1.54, P = 0.006), and in particular with early AMD prevalence (PR = 1.52; P = 0.01). No association was observed between low birth weight and cumulative 5-year incidence of AMD. Conclusions: Our analyses indicate that low birth weight may lead to higher prevalence of retinal diseases in later life, as we observed for AMD. Our results are limited due to missing data and loss to follow-up, but may be a first hint that AMD has one of its origins in early life.

Hypertension and multiple cardiovascular risk factors increase the risk for retinal vein occlusions: results from the Gutenberg Retinal Vein Occlusion Study.

OBJECTIVE: Although several risk factors for retinal vein occlusion (RVO) are known, what triggers RVO is unclear in many cases. We aimed to evaluate the relevance of multiple risk factors in patients with RVO. METHODS: The Gutenberg RVO Study is an observational case-control study that assessed thrombophilic, cardiovascular, ophthalmic, and drug-related risk factors in participants with RVO and the same number of matched controls. Conditional logistic regression analysis was chosen to estimate the risk of RVO due to several risk factors. RESULTS: Of 92 patients with RVO, 46 (50%) had central RVO, 31 (33.7%) had branch RVO, and 15 (16.3) had hemi-RVO. Systemic hypertension was associated with RVO [any RVO: odds ratio (OR): 1.81; 95% confidence interval (CI): 1.14-2.88; branch RVO: OR: 2.56; 95% CI: 1.08-6.10]. The most frequent combinations of risk factors were hypertension with dyslipidemia (33 of 92, 35.9%) and hyperhomocysteinemia and high levels of factor VIII (10 of 92, 10.9%). An increase in the risk sum score by one additional risk factor corresponded to ORs of 1.74 (95% CI: 1.31-2.32) for cardiovascular risk factors, 1.38 (95% CI: 1.04-1.82) for thrombophilic risk factors, and 1.43 (95% CI: 1.20-1.70) for the total number of risk factors for RVO. CONCLUSION: Cardiovascular risk factors are more important than other risk factors for the presence of RVO. The risk of RVO increased by approximately 40% with any additional risk factor and by 70% with any additional cardiovascular risk factor.

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.

Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial.

PURPOSE: To compare standard-of-care grid laser photocoagulation versus intravitreal ranibizumab (IVR) versus a combination of both in the treatment of chronic (>3 months) macular oedema secondary to branch retinal vein occlusion. METHODS: Prospective, randomized, multicentre clinical trial. Thirty patients with a best-corrected visual acuity (BCVA) between 20/320 and 20/40 were randomized 1:1:1 to receive grid laser or three monthly injections of 0.5 mg IVR or both followed by 3 months of observation. RESULTS: Mean change from baseline BCVA at month 6 was +2 letters [laser; 0.04 logMAR, 95% confidence interval (-0.17; 0.25)], +17 letters [IVR; 0.34 (0.19; 0.5)] and +6 letters [combination; 0.12 (0.01; 0.24)] (IVR versus laser p = 0.02 and IVR versus combination p = 0.02). At month 3, mean improvement in central retinal thickness (CRT) was 90.6 µm (laser) (-18.65; 199.8), 379.5 µm (IVR) (204.2; -554.8), and 248 µm (167.2; -328.8) (combination) (IVR versus laser p = 0.005, laser versus combination p = 0.02). During the observation period, CRT improved in laser [37.6 µm (-66.82; 142.0)], but deteriorated in IVR [-142.4 µm (-247.6; -37.16)] and combination [-171.7 µm (-250.4; -92.96)] (laser versus IVR p = 0.01, laser versus combination p = 0.002) indicating recurrent oedema. Less laser retreatments (at 8 weeks) were required in combination group (2/10) than grid group (7/10). CONCLUSION: Six-month results suggest that ranibizumab may be superior to grid laser in improving visual acuity. Grid combined with IVR neither enhanced functional and morphological improvement of IVR nor did it prevent or prolong recurrence of oedema. In IVR groups, CRT increased slowly after stopping injections, whereas improvement in visual acuity was sustained, indicating that morphological changes occur prior to functional impairment.

Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg Health Study.

BACKGROUND: The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort. METHODS: We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD). RESULTS: Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 µm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD. CONCLUSIONS: In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

Series of fibrinous inflammation after implantation of capsular tension rings.

PURPOSE: To analyze the cause of fibrinous inflammation in eyes with capsular tension rings (CTRs) after cataract surgery. SETTING: Department of Ophthalmology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany. DESIGN: Retrospective case series. METHODS: High-performance liquid chromatography was implemented to eliminate impurities. One CTR was explanted for microbiologic examination. The pH values of the CTR and the storage solution were analyzed, Seldi and Maldi tests were performed, as well as toxicity tests with immortal cell lines. Material batches were analyzed. The organic carbon content of CTRs, detergents, and storage solutions was checked. The presence of endotoxins was excluded with the limulus amoebocyte lysate test. Gas chromatography with mass selective detector excluded the presence of extractable organic substances. An inductively coupled plasma analysis scanned for inorganic substances. The microbial count in operating rooms, smear tests, and microbiologic examinations of technical devices were initiated. RESULTS: Analyses found no pathological findings. After intensive systemic and topical treatment with antibiotics and steroids, clinical findings improved. The implantation of CTRs was stopped immediately. No further cases occurred. CONCLUSIONS: Fibrinous inflammations after implantation of CTRs were unknown until now. Contamination and/or irritation by detergents or the material CTR itself were excluded, indicating mechanical or toxic irritation by the CTR. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.