In vivo macular pigment measurements:a comparison of resonance Raman spectroscopy and heterochromatic flicker photometry

To investigate whether two methods of measuring macular pigment-namely, heterochromatic flicker photometry (HFP) and resonance Raman spectroscopy (RRS)--yield comparable data.

Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

ARMS2 Increases the Risk of Early and Late Age-Related Macular Degeneration in the European Eye Study

OBJECTIVE:
To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.
DESIGN:
Population-based, cross-sectional European Eye Study in 7 countries in Europe.
PARTICIPANTS:
Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
METHODS:
Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.
MAIN OUTCOME MEASURES:
Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
RESULTS:
Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).
CONCLUSIONS:
A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.

Secondary Outcomes in a Clinical Trial of Carotenoids with Coantioxidants versus Placebo in Early Age-Related Macular Degeneration

Purpose: To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.

Design: Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).

Participants: Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2).

Intervention: An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months.

Main Outcome Measures: Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months).

Results: The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed.

Conclusions: Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Fundus autofluorescence in the diagnosis of cystoid macular oedema

Aim: To determine the sensitivity and specificity of the non-invasive imaging technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular oedema (CMO), using fluorescein angiography as the reference standard. Design: Retrospective, consecutive, observational case series. Methods: Ninety-six consecutive patients with CMO suspected clinically were selected from the AF database of the Retina Unit, Ophthalmology Department, Grampian University Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO was secondary to (1) cataract extraction, (2) inherited retinopathies, (3) inflammatory eye disease or (4) idiopathic cases were included in this study. Only patients in whom AF images had been performed within 2 weeks of FFA and, when obtained following FFA, there was a minimum gap of 4 days ("washing out" period), were considered eligible for this study. A total of 34 eyes from 34 patients were eligible and were included in this study. FFA was used as the reference test to confirm the presence of CMO, and, based on fluorescein angiography (FFA), CMO was graded as either mild or florid. AF images were examined in a masked fashion for the presence or absence of CMO. The sensitivity and specificity of AF in detecting CMO were then calculated. Results: CMO was seen on AF imaging as round or oval areas at the fovea with an AF signal similar to that of background levels. At this site (fovea), the AF signal is usually reduced compared with background, due to the blockage caused by luteal pigment. The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity when compared with the reference standard FFA. Based on the FFA, there were 12 cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes). Conclusions: AF imaging can be used as a rapid, non-invasive technique in the diagnosis of CMO.

Fundus autofluorescence in exudative age-related macular degeneration

Aim: To evaluate the distribution of fundus autofluorescence in patients with age-related macular degeneration and choroidal neovascularisation (CNV). Methods: Colour fundus photographs, fundus fluorescein angiograms (FFA) and fundus autofluorescence images were obtained from a group of 40 patients (43 eyes) with age-related macular degeneration and purely classic or occult CNV. Only patients with newly diagnosed CNV and in whom autofluorescence images were obtained within 2 weeks from FFA were included. The distribution of autofluorescence was qualitatively evaluated, and the findings compared with those from colour fundus photographs and FFA. Results: 29 (67%) eyes had classic CNV and 14 (33%) had occult CNV. In 26 (90%) eyes with classic CNV, a low autofluorescence signal was detected at the site of the CNV; in 7 (50%) eyes with occult CNV, multiple foci of low autofluorescence signal were detected. Outside the area affected by the lesion, homogeneous autofluorescence was observed in most of the cases (n = 33, 77%). Similarly, homogeneous autofluorescence was commonly observed in fellow eyes (62%). A pattern of focal increased autofluorescence was rarely seen in eyes with CNV (n = 4, 9%) or in fellow eyes (n = 4, 15%). In 11 of 43 (25%) eyes, areas of increased autofluorescence, other than a pattern of focal increased autofluorescence, were detected. In four patients, autofluorescence images had been obtained before the development of CNV; in none was any increased autofluorescence detected before the formation of CNV. Conclusions: Distinct patterns of autofluorescence were observed in eyes with pure classic and occult CNV. Increased autofluorescence was rarely seen in eyes with CNV and in fellow eyes, suggesting that increased autofluorescence, and thus, retinal pigment epithelium lipofuscin, may not play an essential part in the formation of CNV.

Fundus autofluorescence in stargardt macular dystrophy-fundus flavimaculatus

Purpose To quantify autofluorescence (AF) levels in patients with Stargardt macular dystrophy-fundus flavimaculatus (STGD-FFM), and to identify patterns of AF. Design Observational, comparative study. Methods Prospective study. Settings Patients were recruited at Moorfields Eye Hospital. Study population Forty-three STGD-FFM patients aged 20 to 40 years and 35 age-matched normal volunteers. The right eye was chosen arbitrarily for measures of AF. Intervention The AF images were obtained using a confocal scanning laser ophthalmoscope. Levels of AF across the macula were measured. The distribution of AF was also evaluated. In 36 patients (84%) pattern electroretinogram (PERG) and full-field ERG were obtained and results were evaluated with respect to levels of AF. Main outcome measures Values of AF, AF distribution, PERG, and ERG. Results Normal or high AF at the center of the macula with high AF temporally or nasally or both was detected in 17 patients (39%). In nine (21%), low AF at the center of the macula with normal or low AF temporally or nasally or both was found. Levels of AF were normal throughout the macula in six patients (14%). In 11 (26%), high, normal, and low levels of AF were found. All patients tested with low AF at the center of the macula and normal or low AF temporally or nasally or both had peripheral cone/rod dysfunction. None of the patients tested that had normal or high AF at the fovea and high AF temporally or nasally, or normal AF throughout the macula, had peripheral cone/rod dysfunction. Conclusion AF is not universally high in STGD-FFM. Some patients have normal or low AF. Autofluorescence patterns appear to relate to functional abnormalities. © 2004 by Elsevier Inc. All rights reserved.

Retinal pigment epithelial atrophy in patients with exudative age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy

PURPOSE:: To evaluate the occurrence of retinal pigment epithelial atrophy in patients with age-related macular degeneration undergoing anti-vascular endothelial growth factor therapy. METHODS:: The study is a retrospective review. Eligible were patients with age-related macular degeneration and choroidal neovascular membranes treated with anti-vascular endothelial growth factor between October 2007 and February 2011; they were followed for >3 months, with fundus photographs and fluorescein angiography at baseline and with autofluorescence and near-infrared autofluorescence images at baseline and follow-up. Demographics, visual acuity, the type of choroidal neovascular membranes, the number of treatments performed, and the length of follow-up were recorded. Autofluorescence and near-infrared autofluorescence images were evaluated for the presence or absence of areas of reduced signal. A multilevel logistic regression model was used to investigate the factors that may be associated with progression of atrophy at follow-up, which was the primary outcome of this study. RESULTS:: Sixty-three patients (72 eyes) were followed for a median of 16 months (range, 3-36 months). Atrophy at baseline was observed in 47% (34/72) of eyes; progression of atrophy occurred in 62% (45/72) of eyes at the last visit. The number of anti-vascular endothelial growth factor injections received was statistically significantly associated with the progression of atrophy at follow-up (odds ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). CONCLUSION:: Atrophy was frequently observed in patients with age-related macular degeneration and choroidal neovascular membranes undergoing anti-vascular endothelial growth factor therapy.

In vivo safety of trypan blue use in vitreoretinal surgery

Purpose: The purpose of this study was to evaluate "in vivo" safety of trypan blue (TB) in patients undergoing TB-assisted internal limiting membrane or epiretinal membrane peeling. Methods: Prospective study including 21 patients (21 eyes) with full-thickness macular hole and/or epiretinal membrane undergoing TB-assisted internal limiting membrane/epiretinal membrane peeling. Main outcome measures included distance visual acuity, near visual acuity, amplitude of P50 and N95 of the pattern electroretinogram, and fundus autofluorescence; these were assessed preoperatively, at 6 months (n = 21) and 12 months (n = 10) postoperatively. Results: There was a statistically significant improvement in distance visual acuity, near visual acuity, P50, and N95 amplitude at 6 months and 12 months postoperatively. The mean logarithm of the minimum angle of resolution distance visual acuity and near visual acuity improved from baseline by 0.31 (SD 0.37) and 0.17 (SD 0.31) at 6 months, respectively, and by 0.4 (SD 0.25) and 0.35 (SD 0.28) at 12 months, respectively. The mean P50 and N95 component amplitudes improved by 28% compared with baseline at 6 months (P50 0.4 [SD 0.8]; N95 0.53 [SD 1.07]) and by 63% at 12 months (P50 0.9 [0.85]; N95 1.04 [1.34]). Autofluorescence did not demonstrate damage to the retinal pigment epithelium attributable to TB. Conclusion: No deleterious effects of TB were observed in this study. Copyright © 2011 Lippincott Williams &Wilkins.

Socio-economic deprivation and visual acuity at presentation in exudative age-related macular degeneration

Aim: To evaluate the influence of socio-economic factors on visual acuity (VA) at presentation in exudative age- related macular degeneration (AMD). Methods: The medical records of all consecutive patients with newly diagnosed exudative AMD examined at the Ophthalmology Departments of Grampian University Hospitals-NHS Trust, Aberdeen, and Gartnavel General Hospital, Glasgow, between July 2004 and June 2005, were reviewed. Demographics, duration of symptoms, VA in study and fellow eye, exudative AMD characteristics, status of fellow eye and patient home address, used to determine the Scottish Index of Multiple Deprivation (SIMD) score, were recorded. The effect of these parameters on VA at presentation was investigated using general linear modelling. Results: Two-hundred and forty patients (median age 79 years) were included in this study; 44 (18.3%) belonged to the lowest 20% SIMD score (most deprived). Age and location and type of the choroidal neovascular- isation were statistically significantly associated with VA at presentation (p = 0.003, p

Classification of fundus autofluorescence patterns in early age-related macular disease

PURPOSE. To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS. FAF images were recorded in eyes with early AMD by confocal scanning laser ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and emission above 500 or 521 nm (barrier filter). A standardized protocol for image acquisition and generation of mean images after automated alignment was applied, and routine fundus photographs were obtained. FAF images were classified by two independent observers. The ? statistic was applied to assess intra- and interobserver variability. RESULTS. Alterations in FAF were classified into eight phenotypic patterns including normal, minimal change, focal increased, patchy, linear, lacelike, reticular, and speckled. Areas with abnormal increased or decreased FAF signals may or may not have corresponded to funduscopically visible alterations. For intraobserver variability, ? of observer I was 0.80 (95% confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84). For interobserver variability, ? was 0.77 (95% CI, 0.67-0.87). CONCLUSIONS. Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast to a nonspecific aging process. The results indicate that the classification system yields a relatively high degree of intra- and interobserver agreement. It may be applicable for determination of novel prognostic determinants in longitudinal natural history studies, for identification of genetic risk factors, and for monitoring of future therapeutic interventions to slow the progression of early AMD. Copyright © Association for Research in Vision and Ophthalmology.

Internal Limiting Membrane Peeling in Vitreo-retinal Surgery

Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver. © 2008 Elsevier Inc. All rights reserved.