Extramacular Drusen and Progression of Age-Related Macular Degeneration: Age Related Eye Disease Study 2 Report 30.

PURPOSE: To identify the prevalence of extramacular drusen and their role in the progression of age-related macular degeneration (AMD). DESIGN: Retrospective analysis of a prospective cohort study. PARTICIPANTS: The study was conducted in 4168 eyes (2998 participants) with intermediate AMD in one or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplements. METHODS: Baseline 3-field 30-degree color photographs were evaluated for drusen characteristics outside the macular grid, including size, area, and location. The characteristics of extramacular drusen were compared with those of drusen within the macula. MAIN OUTCOME MEASURES: Progression rates to late AMD. RESULTS: Although extramacular drusen were observed in 3624 (86.9%) eyes, they represented a small area (< 0.5 mm2) in 50.3% of eyes, with only 17.5% exhibiting an area of > 1 disc area. Eyes with extramacular drusen exhibited larger macular drusen size and area than eyes without extramacular drusen (P < 0.001). Extramacular drusen were not associated with progression to late AMD. The hazard ratio adjusted for baseline age, sex, smoking, AMD severity level, and reticular pseudodrusen for 4043 eyes at risk of developing late AMD over 5 years was 1.17 (95% confidence interval [CI], 0.88-1.54; P = 0.27) for geographic atrophy and 0.96 (95% CI, 0.76-1.2; P = 0.7) for neovascular AMD. CONCLUSIONS: Extramacular drusen are commonly observed in eyes with AMD and are more frequent with an increasing drusen burden within the macula. In eyes with intermediate AMD, extramacular drusen do not confer additional risk to previously identified risk factors in progression to late AMD.

The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. METHODS: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. RESULTS: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. CONCLUSION: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.

TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1ß levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1ß levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

Progression of Geographic Atrophy with Subsequent Exudative Neovascular Disease in Age-Related Macular Degeneration: AREDS2 Report 24.

PURPOSE: To examine whether the rate of geographic atrophy (GA) enlargement is influenced by subsequent exudative neovascular age-related macular degeneration (nAMD) and hence, to explore indirectly whether nonexudative nAMD may slow GA enlargement. DESIGN: Post hoc analysis of a controlled clinical trial cohort. PARTICIPANTS: Age-Related Eye Disease Study 2 participants 50 to 85 years of age. METHODS: Baseline and annual stereoscopic color fundus photographs were evaluated for (1) GA presence and area and (2) exudative nAMD presence. Two cohorts were constructed: eyes with GA at study baseline (prevalent cohort) and eyes in which GA developed during follow-up (incident cohort). Mixed-model regression of the square root of GA area was performed according to the presence or absence of subsequent exudative nAMD. MAIN OUTCOME MEASURES: Change over time in square root of GA area. RESULTS: Of the 757 eyes in the incident GA cohort, over a mean follow-up of 2.3 years (standard deviation [SD], 1.2 years), 73 eyes (9.6%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was significantly slower (0.20 mm/year; 95% confidence interval [CI], 0.12-0.28 mm/year) compared with the other 684 eyes in which subsequent exudative nAMD did not develop (0.29 mm/year; 95% CI, 0.27-0.30 mm/year; P = 0.037). Of the 456 eyes in the prevalent GA cohort, over a mean follow-up of 4.1 years (SD, 1.4 years), 63 eyes (13.8%) demonstrated subsequent exudative nAMD. Geographic atrophy enlargement in these eyes was similar (0.31 mm/year; 95% CI, 0.24-0.37 mm/year) compared with the other 393 eyes in which subsequent exudative nAMD did not develop (0.28 mm/year; 95% CI, 0.26-0.29 mm/year; P = 0.37). CONCLUSIONS: In eyes with recent GA, GA enlargement before the development of exudative nAMD seems slowed. This association was not observed in eyes with more long-standing GA, which have larger lesion sizes. Hence, perilesional nonexudative choroidal neovascular tissue (presumably present before the development of clinically apparent exudation) may slow enlargement of smaller GA lesions through improved perfusion. This hypothesis warrants further evaluation in prospective studies.

Optical Coherence Tomography Angiography Quantitative Assessment of Macular Neovascularization in Best Vitelliform Macular Dystrophy.

Purpose: To describe quantitative characteristics of macular neovascularization (MNV) in vitelliform macular dystrophy (VMD) patients by means of optical coherence tomography angiography (OCTA). Methods: The study design was a prospective case series. All patients underwent complete ophthalmologic assessment, optical coherence tomography, and OCTA. The quantitative OCTA parameters examined included vessel tortuosity and vessel dispersion of the MNV. The primary outcome was OCTA characterization of MNV in VMD. Secondary outcomes included the evolution of MNV over the follow-up. Results: A total of 78 eyes were recruited for the study. MNV was identified in 50 eyes (64%) at baseline and in 51 eyes (65%) at the end of the follow-up (mean follow-up, 24.7 ± 9.7 months). MNV was detected in four out of the 30 eyes classified as stages 2 and 3 (13%), showing exudative manifestations and undergoing ranibizumab treatment, leading to clinical stabilization. OCTA detected MNV in 46 out of 48 eyes (96%) classified as stages 4 and 5, showing no evidence of exudative manifestation. All of the non-exudative MNVs were merely observed over the follow-up and received no treatment. At the end of the follow-up, 47 out of 48 eyes displayed MNV (98%). Non-exudative MNVs remained stable over the follow-up. Statistically significant differences were found when comparing vessel tortuosity and vessel dispersion in the two MNV subforms. Conclusions: VMD is characterized by two MNV subforms. Exudative MNV is rare and may develop in the early stages of the disease, in association with bleeding and fluid formation. Non-exudative MNV develops very commonly in the advanced stage of VMD, without any exudative manifestation.

Benefits of micronutrient supplementation for reducing the risk of wet age-related macular disease and diabetic retinopathy: An update.

Age-related macular disease and diabetic retinopathy are chronic degenerative diseases characterised by progressive visual impairment. In Europe, age-related macular disease accounts for over 15% of blindness in adults over 50 years of age, and although the burden of diabetic retinopathy in terms of vision impairment is lower, vision loss associated with diabetic retinopathy is increasing with the rising prevalence of diabetes mellitus and the ageing of the population. Late-stage age-related macular disease can be subdivided into dry (non-neovascular) or wet (neovascular or exudative) forms. The large Age-Related Eye Disease Study 2 showed that supplementation with antioxidant nutrients reduces choroids neovascularisation and reduces the risk of progression of neovascular age-related macular disease. Antioxidant micronutrient supplements have also shown promising results in preventing the pathogenesis of retinopathy in animal models of diabetes. Age-related macular disease and diabetic retinopathy are understood to share some common pathophysiological characteristics, suggesting that micronutrients have an important role in ocular health in both conditions. This article will review the current evidence for the utility of micronutrients in preventing the development and progression of neovascular age-related macular disease and diabetic retinopathy.

THE RAP STUDY, REPORT TWO: The Regional Distribution of Macular Neovascularization Type 3, a Novel Insight Into Its Etiology.

PURPOSE: To explore the regional distribution of macular neovascularization type 3 (MNV3). METHODS: Seventy-eight eyes of 78 patients were reviewed. We defined the location of each lesion after applying a modified ETDRS grid and the incidence of simultaneous MNV1 or 2. Also, we investigated the distribution of MNV3 at the outline of the foveal avascular zone and when the diameter of foveal avascular zone was less than 325 µm. RESULTS: The distribution of MNV3 was 4 lesions (5%) from the center to 500 µm, 72 (92%) from 500 µm to 1500 µm, and 2 (3%) from 1,500 µm to 3000 µm. The distribution in respect of the ETDRS fields was 7 (9%) nasal, 16 (20%) superior, 32 (40%) temporal, and 23 (31%) inferior. No additional MNV1 or 2 were found elsewhere. Most lesions tended to distribute along straight bands radiating from the perifoveal area, mainly in the temporal half (72%). None of the cases had MNV3 at the boundary of the foveal avascular zone. Only five cases had foveal avascular zone diameter of less than 325 µm, the closest lesion was 425 µm away from the center. CONCLUSION: MNV3 lesions are most likely neither symmetrical nor uniformly distributed. They have a higher affinity to distribute radially in the temporal perifoveal area.

The association between clinically diagnosed insomnia and age-related macular degeneration: a population-based cohort study.

PURPOSE: The decreased level of melatonin, the substance involved in the control of the sleep-wake cycle, has been reported among the patients with age-related macular degeneration (AMD). However, knowledge about the relationship between sleep disturbance and AMD is still limited. This longitudinal case-control study aims to investigate the risk of incident AMD among the patients with clinically diagnosed insomnia using the Taiwan National Health Insurance Research Database. METHODS: The insomnia cohort (n = 15 465) consisted of newly diagnosed insomnia cases aged ≥55 years between 2000 and 2009. Subjects without insomnia, matched for age, gender and enrolment time, were randomly sampled as the control cohort (n = 92 790). Cox proportional hazard regressions were performed to calculate the hazard ratios (HR) of incident AMD for the two cohorts after adjusting for potential confounders. RESULTS: Of the 108 255 sampled subjects, 2094 (1.9%) were diagnosed with AMD, including 214 (0.2%) with neovascular AMD, during a mean follow-up period of 5.1 ± 2.8 years. Insomnia patients were more likely to have subsequent AMD than those without insomnia (2.5% versus 1.8%, p < 0.001). Further, the incidence of exudative AMD was also higher in the insomnia cohort than the control cohort (0.3% versus 0.2%, p = 0.002). The adjusted HR was 1.33 (95% confidence interval [CI], 1.18-1.48, p < 0.001) for AMD and 1.67 (95% CI, 1.20-2.33, p = 0.002) for exudative AMD. CONCLUSIONS: Clinically diagnosed insomnia is an independent indicator for the increased risk of subsequent AMD development.

Pseudodrusen pattern and development of late age-related macular degeneration in the fellow eye of the unilateral case.

PURPOSE: To investigate whether the development of late age-related macular degeneration (AMD) in fellow eyes with pseudodrusen is associated with the pseudodrusen pattern in patients with unilateral exudative AMD. STUDY DESIGN: Retrospective observational study. METHODS: A retrospective analysis was performed on 73 patients with unilateral exudative AMD showing pseudodrusen in their fellow eyes. Eyes were classified according to pseudodrusen pattern, which was determined based on maximum pseudodrusen ribbon length. RESULTS: During the mean follow-up period of 35.5±18.6 months, 21 (28.8%) eyes developed late AMD. Among these eyes, 15 (71%) developed exudative AMD and six (29%) developed geographic atrophy (GA). Development of late AMD in fellow eyes occurred with significantly more prevalence in patients showing a ribbon-dominant type pseudodrusen pattern in their fellow eye than dot-dominant type (P=0.0005, log-rank test). Cox-regression analysis revealed that development of late AMD in fellow eyes is associated with the presence of ribbon-dominant pseudodrusen in the fellow eyes (hazard ratio 4.15, 95% confidence interval (CI) 1.59-10.8), along with older age (hazard ratio 1.10, 95% CI 1.03-1.17), a history of smoking (hazard ratio 17.2, 95% CI 1.11-263), the presence of large soft drusen in the fellow eye. (hazard ratio 5.49, 95% CI 1.29-21.1) and retinal angiomatous proliferation (hazard ratio 5.02, 95% CI 1.90-13.2) CONCLUSIONS: Fellow eyes with ribbon-dominant pseudodrusen in patients with unilateral exudative AMD are likely to develop late AMD.

Association of Dietary and Supplementary Calcium Intake With Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 39.

Importance: Previous studies of the role of dietary and supplementary calcium in age-related macular degeneration (AMD) have produced mixed results, suggesting that supplementation and decreased dietary intake are both harmful. Objective: To evaluate the association of baseline dietary and supplementary calcium intake with progression of AMD. Design, Setting, and Participants: This study involved secondary analyses of participants enrolled in the Age-Related Eye Disease Study (AREDS). The AREDS study (1992-2001) enrolled patients from academic and community-based retinal practices in the United States. Men and women with varying severity of AMD were included. Data analysis for this article occurred from September 2015 to December 2018. Exposures: Baseline self-reported dietary or supplementary calcium intake. Main Outcomes and Measures: Development of late AMD, geographic atrophy (central or noncentral), or neovascular AMD detected on centrally graded baseline and annual fundus photographs. Results: A total of 4751 participants were included (mean [SD] age, 69.4 [5.1] years); 4543 (95.6%) were white, and 2655 (55.9%) were female. Compared with those who were in the lowest quintile, the participants in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (hazard ratio [HR], 0.73 [95% CI, 0.59-0.90]), central geographic atrophy (HR, 0.64 [95% CI, 0.48-0.86]), and any geographic atrophy (HR, 0.80 [95% CI, 0.64-1.00]). The participants in the highest tertile of supplementary calcium intake had a lower risk of developing neovascular AMD (HR, 0.70 [95% CI, 0.50-0.97]) compared with those who did not take calcium supplements. When stratified by sex, women in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (HR, 0.73 [95% CI, 0.56-0.97]) compared with those in the lowest quintile. Women in the highest tertile of calcium supplementation had a lower risk of progression to neovascular AMD (HR, 0.67 [95% CI, 0.48-0.94]) compared with those who did not take calcium supplements. Similar findings were found in men for dietary calcium. Too few men took calcium supplements to allow for analyses. Conclusions and Relevance: In this secondary analysis, higher levels of dietary and supplementary calcium intake were associated with lower incidence of progression to late AMD in AREDS participants. The results may be owing to uncontrolled confounding or chance and should be considered hypothesis development requiring additional study.

Targeted Imaging of VCAM-1 mRNA in a Mouse Model of Laser-Induced Choroidal Neovascularization Using Antisense Hairpin-DNA-Functionalized Gold-Nanoparticles.

Mouse laser-induced choroidal neovascularization (mouse LCNV) recapitulates the "wet" form of human age-related macular degeneration (AMD). Vascular cell adhesion molecule-1 (VCAM-1) is a known inflammatory biomarker, and it increases in the choroidal neovascular tissues characteristic of this experimental model. We have designed and constructed gold nanoparticles (AuNPs) functionalized with hairpin-DNA that incorporates an antisense sequence complementary to VCAM-1 mRNA (AS-VCAM-1 hAuNPs) and tested them as optical imaging probes. The 3' end of the hairpin is coupled to a near-infrared fluorophore that is quenched by the AuNP surface via Förster resonance energy transfer (FRET). Hybridization of the antisense sequence to VCAM-1 mRNA displaces the fluorophore away from the AuNP surface, inducing fluorescent activity. In vitro testing showed that hAuNPs hybridize to an exogenous complementary oligonucleotide within a pH range of 4.5-7.4, and that they are stable at reduced pH. LCNV mice received tail-vein injections of AS-VCAM-1 hAuNPs. Hyperspectral imaging revealed the delivery of AS-VCAM-1 hAuNPs to excised choroidal tissues. Fluorescent images of CNV lesions were obtained, presumably in response to the hybridization of AS-hAuNPs to LCNV-induced VCAM-1 mRNA. This is the first demonstration of systemic delivery of hAuNPs to ocular tissues to facilitate mRNA imaging of any target.

Novel Association of High C-Reactive Protein Levels and A69S at Risk Alleles in Wet Age-Related Macular Degeneration Women.

Purpose: To explore the relationship between plasma C-reactive protein (CRP) levels, the main ARMS2 gene single nucleotide polymorphism (SNP), and gender in patients with neovascular age-related macular degeneration (wet AMD). Methods: Our study included 131 patients with wetAMD [age-related eye disease study (AREDS) category 4] and 153 control participants (AREDS category 1) from two Spanish retinal units. CRP levels were determined on blood samples by high-sensitivity ELISA assay. According to their CRP level, subjects were categorized into three well-established CRP categories: low (<1.00 mg/L, L-CRP), moderate (1-2.99 mg/L, M-CRP), and high (>3.00 mg/L, H-CRP). Genomic DNA was extracted from oral swabs using QIAcube (Qiagen, Hilden, Germany) and the A69S; rs10490924 of ARMS2 gene was genotyped by allelic discrimination with validated TaqMan assays (Applied Biosystems, Foster City, CA, USA). Univariate and multivariate logistic regression adjusted for age was used to analyze the genomic frequencies and to calculate odds ratio (OR) using SNPStats software. Results: Considering CRP risk categories, H-CRP group showed a significant [OR 4.0 (1.9-8.3)] association with wetAMD compared to L-CRP group. The risk genotypes of A69S (TT) SNPs showed an association with wetAMD risk [OR 14.0 (4.8-40.8)]. Interestingly, the gender stratification of the CRP categories showed a significant increase in CRP levels in wetAMD women compared with control women [OR 6.9 (2.2-22.3)] and with wetAMD men [OR 4.6 (1.3-16.9)]. In addition, the subgroup analysis of CRP within A69S genotype and gender showed a link in women between the A69S and CRP levels in the AMD group compared to controls [OR 4.2 (1.4-12.6)]. Conclusion: Our study shows, for the first time, that a different genetic association related with gender could contribute to AMD risk. As a consequence, the risk of female gender in the different CRP levels and A69S SNP frequencies could be taken into consideration to the established risk relationship of high levels of CRP and its association with risk A69S genotype.

An Evaluation of the Relationship Between Clinically Unilateral Pseudoexfoliation Syndrome and Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the relationship between age-related macular degeneration (AMD) and clinically unilateral pseudoexfoliation syndrome (XFS). PATIENTS AND METHODS: Seventy-six patients (152 eyes) with bilateral AMD and clinically unilateral XFS were included. Eyes with AMD were divided into three stages (early, intermediate, and late), based on the Beckman Initiative for Macular Research Classification Committee of fundus findings. The distribution of AMD lesions was assessed in both groups, and the subfoveal choroidal thickness (SFCT) was measured using enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT). RESULTS: There were significantly more early and intermediate-stage AMD cases in eyes with XFS than in non-XFS fellow eyes (P < .05). In contrast, there were significantly fewer wet AMD cases in XFS eyes than in non-XFS fellow eyes (P < .05). SFCT in all AMD stages was significantly lower in eyes with XFS (P < .05). CONCLUSION: XFS was associated with a lower prevalence of wet AMD. Further studies are required to elucidate this association. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:12-19.].

Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PURPOSE: To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. METHODS: We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. RESULTS: The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). CONCLUSIONS: Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended.

Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 µmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I2  = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 µmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I2  = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn.

Analysis of the Retinal Nerve Fiber Layer Thickness in Alzheimer Disease and Mild Cognitive Impairment.

PURPOSE: To compare the retinal nerve fiber layer (RNFL) as well as the macula volume and thickness in the eyes of age-matched healthy controls with no cognitive disabilities with those of elderly people with mild cognitive impairment (MCI) or Alzheimer disease (AD). We used optical coherence tomography (OCT) to determine the effectiveness of the above quantities for early diagnosis of MCI or AD. METHODS: Ninety eyes were considered in this study, split between 30 normal eyes, 30 eyes from patients with MCI, and 30eyes from patients with AD. All subjects underwent ophthalmologic and cognitive examinations, and measurements of the RNFL thickness as well as macular volume and thickness were taken for all patients using OCT. RESULTS: The mean RNFL thickness upon OCT was significantly thinner in the AD group than in the MCI group (p = 0.01). The RNFL was thinner in the superior quadrant in patients with AD when compared to the healthy controls (p = 0.03). The RNFL thicknesses in the inferior, nasal, and temporal quadrants did not differ significantly between the groups. Measurements in the 12 clock-hour zones revealed that zone 11 had a significantly thinner RNFL in the AD group as compared with the healthy control group (p = 0.02). In zone 2, the MCI group had a significantly thinner RNFL than the AD group (p = 0.03). CONCLUSIONS: Our OCT findings revealed a neuroanatomic difference in the RNFL thickness among the three groups, i.e., the AD, MCI, and healthy control groups. This suggests that a change in average RNFL thickness could be a meaningful index for diagnosing early AD.

Influence of Vitreomacular Adhesion on Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.

PURPOSE: To investigate the effect of vitreomacular adhesion (VMA) on the outcome of antiangiogenic treatment for neovascular age-related macular degeneration (AMD). METHODS: Ninety-nine eyes of 83 patients were used in our cohort study. We prospectively evaluated best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with neovascular AMD at baseline and 1, 2, 3, 6, and 12 months after treatment with anti-vascular endothelial growth factor (anti-VEGF) agents. All patients were stratified by spectral domain optical coherence tomography into 2 groups (i.e., VMA[+] and VMA[-]) according to the presence or absence of VMA, and the response to treatment was evaluated. RESULTS: Fifty-four eyes (54.5%) were included in the VMA(-) group and 45 eyes (45.5%) comprised the VMA(+) group. In paired comparisons of mean BCVA between baseline and each follow-up visit (1, 2, 3, 6, and 12 months), the VMA(-) group showed statistically significant improvement at 1, 2, and 3 months compared to baseline, and BCVA significantly improved only at 3 months in the VMA(+) group. For both groups, paired comparisons of CRT showed a statistically significant decrease when data obtained at 1, 2, 3, 6, and 12 months were compared to baseline values (p < 0.05). CONCLUSIONS: Posterior VMA is associated with a worse short-term outcome in patients with neovascular AMD treated with anti-VEGF agents.

Association between open-angle glaucoma and neovascular age-related macular degeneration: a case-control study.

PurposeTo investigate the relationship between previously diagnosed open-angle glaucoma (OAG) and neovascular age-related macular degeneration (AMD) using a routine insurance dataset.MethodsThis study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We found 3282 patients with neovascular AMD as cases and 13 128 sex- and age-matched subjects without neovascular AMD as controls. Conditional logistic regressions were performed to evaluate the association of neovascular AMD with previously diagnosed OAG among the sampled patients.ResultsOf the 16 410 sampled patients, 2.55% had previously diagnosed OAG, 5.06 and 1.92% for the cases and controls, respectively. The logistic regression analysis showed that the odds ratio (OR) of previously diagnosed OAG for cases was 2.45 (OR: 2.45; 95% confidence interval: 1.99-3.01) compared with the controls after adjusting for potential confounders. In addition, the adjusted ORs for previously diagnosed OAG were similar for patients with AMD in both genders (with an adjusted OR of 2.49 for males and 2.39 for females). Furthermore, it shows that OAG was significantly associated with neovascular AMD regardless of sex even after adjusting for monthly income, geographic region, urbanisation level, and comorbidities (with adjusted ORs of 2.49 for males and 2.39 for females).ConclusionsThis study demonstrated that patients with neovascular AMD had a higher odds of previously diagnosed OAG compared with those patients without neovascular AMD regardless of sex.