Unilateral Neovascular Age-related Macular Degeneration Research Articles

Changes in Retinal Layer Thickness in the Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD). Longitudinal study. We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe. The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis. Change in thickness of retinal layers and change in measures of vision. In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 ± 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 μm vs. 34.09 μm; P= 0.03). Low-luminance deficit was significantly worse at the final visit (P < 0.001) and correlated with PRL outer segment thickness (r= 0.33; P=0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 μm vs. 28.64 μm; P= 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs. The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD.

Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data

AimsTo evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related...

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10−5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10−9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10−7 and 9.73 × 10−7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.

Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.

To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Pseudodrusen and Incidence of Late Age-Related Macular Degeneration in Fellow Eyes in the Comparison of Age-Related Macular Degeneration Treatments Trials

To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD). Cohort study within the Comparison of AMD Treatments Trials (CATT). Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline. Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection. Incident nAMD and GA. Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43-2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13-3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51-2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60-4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69-11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

Dynamic Drusen Remodelling in Participants of the Nutritional AMD Treatment-2 (NAT-2) Randomized Trial.

PurposeTo evaluate the dynamic remodeling of drusen in subjects with unilateral neovascular age-related macular degeneration (AMD) receiving a three-year course of oral docosahexaenoic acid (DHA) or placebo.SettingInstitutional setting.MethodsThree hundred subjects with age-related maculopathy and neovascular AMD in the fellow eye were randomly assigned to receive either 840 mg/day DHA or placebo for 3 years. Main outcome measures of this post-hoc sub-group analysis were progression of drusen number, total diameter, and total area on fundus photography, and their association with DHA supplementation, socio-demographic and genetic characteristics.ResultsDrusen progression was analyzed in 167 subjects that did not develop CNV (87 that received DHA and 80 that received placebo). None of the drusen remodeling outcomes were significantly associated with DHA supplementation. Total drusen diameter reduction in the inner subfield was significantly associated with age (older patients: r = -0.17; p = 0.003). Women showed a tendency to decreased total drusen diameter in the inner subfield with CFH polymorphism (p = 0.03), where women with TT genotype tended to have a greater reduction in drusen diameter than other genotypes (CC and CT). Drusen area in the inner subfield was more reduced in older patients (r = -0.17) and in women (p = 0.01). Drusen number showed no significant trends.ConclusionsDynamic drusen remodeling with net reduction in drusen load over three years was found in patients with exudative AMD in one eye and drusen in the other eye (study-eye). This reduction was correlated with increased age and female gender, and showed a tendency to be influenced by CFH genotype, but did not appear to be affected by DHA supplementation.Trial RegistrationControlled-Trials.com ISRCTN98246501

Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration: A Meta-Analysis.

ImportanceThe fellow eye of patients with unilateral neovascular age-related degeneration (nAMD) is at increased risk of developing late AMD. Several cohort studies have evaluated the prevalence of pseudodrusen and the association between pseudodrusen and late AMD in the fellow eye of patients with unilateral nAMD. However, these studies have limited sample sizes and their results are inconsistent.ObjectiveTo evaluate the prevalence rate of pseudodrusen, and the association between pseudodrusen and incidence of late AMD (nAMD and geographic atrophy (GA)) in the fellow eye of patients with unilateral nAMD.Data SourcesThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to July 2015, as well as other systematic reviews.Study SelectionAll cohort studies for pseudodrusen with late AMD in the fellow eye of patients with unilateral nAMD.Data Extraction and SynthesisThe numbers of patients with and without pseudodrusen at baseline and the numbers of incident nAMD and GA during follow up among patients with and without pseudodrusen were independently extracted by 2 authors. The results were pooled using random-effects meta-analysis. Heterogeneity was assessed using the I2 test.Main Outcome MeasuresPrevalence rate of pseudodrusen, risk ratios (RRs) and their 95% confidence intervals (95% CIs) for associations between pseudodrusen and the incidence of nAMD and GA in the fellow eye.ResultsFive cohort studies (N = 677 patients) from 8 countries across 4 continents were included. The pooled prevalence rate of pseudodrusen in the fellow eye was 48.1% (95% Cl: 36.7–59.5%, I2 = 87%). Pseudodrusen were associated with an increased risk of nAMD (RR = 1.54, 95% Cl: 1.10–2.16, I2 = 42%), GA (RR = 4.70, 95% Cl: 1.22–18.1, I2 = 64%), and late AMD (RR = 2.03, 95% Cl: 1.35–3.06, I2 = 60%).ConclusionsFor patients with unilateral nAMD, pseudodrusen were present in about half of the fellow eyes. The presence of pseudodrusen was associated with a 1.5 times higher risk of developing nAMD, a 4.7 times higher risk of developing GA, and a 2 times higher risk of developing late AMD. Pseudodrusen should be considered in evaluating the risk of late AMD development; however, due to considerable heterogeneity across these studies, a larger study is needed to validate these findings.

Clinical Characteristics of Reticular Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

To describe associations between reticular pseudodrusen, individual characteristics, and retinal function. Cohort study. We recruited 105 patients (age range, 52-93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe. Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts. Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume. Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline. Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease.

Fixation Control before and after Treatment for Neovascular Age-Related Macular Degeneration

We studied changes in visual acuity (VA), fixation stability, and location of the preferred retinal locus (PRL) after treatment for unilateral neovascular age-related macular degeneration (AMD) for previously untreated eyes. Concomitant changes in fixation stability, PRL, and VA in the untreated fellow eye were also analyzed. Pre- and posttreatment tests of visual acuity, fixation stability, and PRL location in both the treated and the untreated eyes were performed on 13 patients undergoing three monthly intravitreal injections of ranibizumab in one eye. For the treated eyes there were improvements in VA and fixation stability but no changes in the location of the PRL. No significant changes in any of the three variables were found in the untreated eye. For previously untreated eyes, the improvement in visual acuity after intravitreal ranibizumab injections was accompanied by improvement in fixation stability.

Second eye of patients with unilateral neovascular age-related macular degeneration: Caucasians vs Chinese

To investigate the correlation between morphological features of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) in the first eye and the severity of age-related maculopathy (ARM) in the fellow eyes in two racial groups: Caucasians and Chinese. A total of 135, fluorescein angiograms of patients with unilateral neovascular AMD and ARM in the fellow eyes were included in the study: 38 Caucasians from King's College Hospital, UK; 45 Caucasians from West Kent Eye Centre, UK; 52 Chinese from Hong Kong Eye Hospital, Hong Kong. CNV subtype in the affected eye and ARM severity in the second eyes. Although the proportion of CNV subtypes in the three groups were similar, the Chinese cohort showed significantly less ARM severity compared to the Caucasian cohorts (P < 0.05). Although drusen and retinal pigmentary changes may be prognostic indicators of CNV, this study suggest that other factors contribute significantly to the pathogenesis of CNV in AMD.

LONG-TERM DRUSEN STUDY

Purpose: To determine the yearly incidence of visual loss in the fellow eyes of patients with unilateral neovascular age-related macular degeneration (ARMD) and to assess the drusen characteristics portending the greatest risk for this outcome. Methods: A total of 101 patients with unilateral exudative ARMD and drusen only in the fellow eye were entered into the study and prospectively followed up to 9 years. Visual acuity, color fundus photography, fluorescein angiography, and grading of drusen characteristics were obtained for each patient on entry into the study. Patients were followed at annual intervals with color fundus photography. The study endpoint was the development of choroidal neovascularization (CNV) or geographic atrophy (GA) in the fellow eye. Results: Yearly incidence rates for the development of an endpoint lesion were between 5 and 14%. The risk of CNV peaked at 4 years and dissipated thereafter. Longer follow-up was associated with a slightly increased incidence of GA. Greater drusen number was most highly associated with the development of an endpoint lesion. Drusen size and confluence were also significant. Conclusions: The risk of CNV in patients with ARMD is heralded by an increase in the number, size, and confluence of drusen. This risk eventually declines and is followed by later increased risk of GA.

THE EFFECT OF A LOWER BLOOD PRESSURE ON CHOROIDAL FILLING IN AGE-RELATED MACULAR DEGENERATION

To determine whether the occurrence of delayed choroidal filling or a slower foveal electroretinogram (ERG) implicit time is related to systemic blood pressure in patients with age-related macular degeneration. We assessed delayed choroidal filling by fluorescein angiography and foveal ERG implicit time with a hand-held stimulator-ophthalmoscope for the fellow eye of 67 patients with unilateral neovascular age-related macular degeneration. Blood pressure, measured by ascultation, was converted to mean arterial pressure. The relations of delayed choroidal filling and foveal ERG implicit time to the mean arterial pressure were assessed by logistic and linear regression, respectively, controlling for age, gender, and intake of hypertensive medication. The probability of having delayed choroidal filling decreased with increasing mean arterial pressure (P = 0.01). The foveal ERG implicit time was also inversely related to the mean arterial pressure (P = 0.009). Delayed choroidal filling and foveal ERG implicit time are related to blood pressure in patients with age-related macular degeneration.

High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration

Objective This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye. Design The study design was a prospective cohort study. Participants One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated. Intervention Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time. Main outcome measure The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured. Results On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10–1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06– 2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time. Conclusions A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.

Foveal electroretinograms and choroidal perfusion characteristics in fellow eyes of patients with unilateral neovascular age-related macular degeneration.

A prolonged choroidal filling phase on fluorescein angiography has been reported to be a common finding and associated with visual function abnormalities in patients with age-related macular degeneration (AMD). This investigation was carried out to determine whether this perfusion defect was related to the slowing of foveal cone electroretinogram (ERG) implicit time seen in patients with AMD. Fluorescein angiograms and foveal cone ERGs were evaluated in the fellow eyes of 67 patients with unilateral neovascular AMD. Twenty eight (42%) of the eyes had a choroidal perfusion defect. ERG implicit times averaged 1 ms slower (p = 0.0167) and were more likely to be delayed (p = 0.0078) in eyes with abnormal choroidal perfusion than in eyes with normal choroidal filling; significant relations were found also after controlling for age. ERG implicit time was also inversely related to ETDRS visual acuity and positively related to the extent of macular drusen; and the latter showed a borderline significant tendency to be more prevalent in eyes with prolonged choroidal perfusion. However, an association of a delayed ERG implicit time with prolonged choroidal filling remained after controlling for age, acuity, and the extent of drusen. These findings further establish prolonged choroidal perfusion as a common finding in AMD and link it to retinal malfunction.

Slow photostress recovery and disease severity in age-related macular degeneration.

To determine whether photostress recovery time varies with severity of disease in age-related macular degeneration. Photostress recovery time, visual acuity, and foveal retinal pigment epithelial atrophy were evaluated for the fellow eyes of 133 patients with unilateral neovascular age-related macular degeneration. Recovery times were measured by a method that flashed letters on a computer screen in random order before and after a 10 second bleach. Recovery times were delayed in 62% of the patients (including 47% of those with normal visual acuity), ranged up to 6 times the normal limit, and increased with advancing age (P < 0.0001). Photostress recovery time was inversely correlated with visual acuity (P < 0.0001) and longer in eyes with visible atrophy than in eyes without atrophy (P = 0.0007). Significant relationships between these two pairs of measures were also found after controlling for age. These findings support previous evidence that the time for visual recovery after exposure to a glare source is commonly slowed in age-related macular degeneration even among patients with normal visual acuity and further show that it can vary with age and extent of disease.

Age-related Macular Degeneration and Choroidal Neovascularization

The neovascular variant of age-related macular degeneration is amenable to laser photocoagulation treatment within well-defined guidelines established by clinical trials. However, only a limited number of patients meet eligibility criteria for this form of treatment, principally because of the ill-defined, or occult nature, of the choroidal neovascularization commonly seen. Previous studies have estimated that one half of patients with neovascular age-related macular degeneration have occult neovascularization at initial manifestation of the disease. We examined the initial findings of 67 patients with newly diagnosed unilateral neovascular age-related macular degeneration. Eighty-seven percent of these patients (58 of 67) had disease that did not meet Macular Photocoagulation Study Group guidelines for laser photocoagulation treatment. As so few patients are eligible for laser photocoagulation, further research into new techniques of diagnosis and treatment for this disorder is warranted.