Visual Function in Eyes with Intermediate AMD with and without Retinal Pigment Abnormalities

May 2005 at a Glance

To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol. Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (≥90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors. Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01). Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (≥90%), may improve consistency. Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.

PurposeTo determine if increasing drusen height correlates with predictive optical coherence tomography (OCT) biomarkers of atrophy.MethodsRetrospective cross-sectional study that enrolled patients with drusen associated with intermediate AMD. Macular drusen were classified as small, intermediate, large, or very large based on OCT quartile measurement of height. Drusen diameter was also tabulated. The presence and localization of the OCT biomarkers of atrophy were assessed: disruption of the external limiting membrane and ellipsoid zone, intraretinal hyper-reflective foci, RPE disruption, choroidal hypertransmission, and presence of hyporeflective cores. Predictive OCT biomarkers of atrophy were correlated with drusen height.ResultsA total of 155 eyes from 104 patients met the inclusion and exclusion criteria. The mean age was 75.7 ± 8.7 years, and patients were predominantly female (74.0%). The mean visual acuity was logMAR 0.2 ± 0.2 (Snellen equivalent 20/32). The average drusen height was 134.6 ± 107.5 µm and the greatest horizontal diameter was 970.7 ± 867.4 µm. Disruption of the external limiting membrane and ellipsoid zone, RPE thickening or thinning, intraretinal hyper-reflective foci, choroidal hypertransmission, and presence of hyporeflective cores (P < 0.05) were more common in eyes with large drusen and very large drusen versus small or intermediate drusen. All biomarkers were positively correlated with drusen height. OCT biomarkers of atrophy were predominantly located at the apex of the drusen.ConclusionsPredictive OCT biomarkers of atrophy, specifically signs of RPE breakdown and disruption, occur more commonly in large or very large drusen, especially in drusen with greater height and separation of the RPE from the underlying choroid.

Reticular Pseudodrusen and Their Association with Age-Related Macular Degeneration: The Melbourne Collaborative Cohort Study

To explore the association of AMD with long-term average blood pressure (BP) parameters, including pulse pressure (PP). The ALIENOR study is a population-based study on age-related eye diseases in 963 residents of Bordeaux, France, aged 73 years or older. AMD was graded from nonmydriatic color retinal photographs, in three exclusive stages: no AMD (1015 eyes), large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, 276 eyes), and late AMD (66 eyes). BP parameters were measured at four occasions over a 7-year period. PP was defined as systolic BP minus diastolic BP. Associations of AMD with BP parameters were estimated using generalized estimating equation logistic regressions. Statistical analyses included 702 subjects (1357 eyes) with complete data. After adjustment for age, sex, educational level, smoking, body mass index, plasma HDL and LDL cholesterol, CFH Y402H, ApoE2, ApoE4, and ARMS2 A69S polymorphisms, elevated PP was significantly associated with an increased risk of late AMD (odds ratio [OR] = 1.37 for a 10-mm Hg increase, 95% confidence interval [CI]: 1.03-1.82). Associations were similar for late atrophic and late neovascular AMD (OR = 1.39, 95% CI: 1.01-1.92, P = 0.04, and OR = 1.43, 95% CI: 0.90-2.23, P = 0.13, respectively). Association with early AMD was in the same direction but did not reach statistical significance (OR = 1.12, 95% CI: 0.98-1.28). Early and late AMD were not significantly associated with systolic or diastolic BP, hypertension, or use of antihypertensive medications. This study suggests that high PP may be associated with increased risk for AMD.

Background and Objectives: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses light in the infrared spectrum. The laser light penetrates into the deep retinal layers and the choroid. Retromode images are captured with a laterally displaced aperture, and the detector captures only the scattered light. The result is a high-contrast pseudo-three-dimensional image. Age-related macular degeneration (AMD) is a disabling retinal disease. AMD is characterized in its early stage by small and intermediate drusen formation, while the signs of intermediate AMD are large drusen and/or pigmentary abnormalities. Late AMD has two forms, geographic atrophy, which is the advanced form of dry AMD, and wet AMD. Most of the lesions of AMD are located in the outer layers of the retina. This new imaging method can provide a glimpse of the deep retinal layers’ topographic changes in a non-invasive, fast, and effective way that can match the other imaging tools available. Materials and Methods: The literature review was performed by searching the PubMed database using the following combination of keywords: retromode imaging and age-related macular degeneration. Relevant images similar to the ones in the literature were identified and used as models. Results: The purpose of this article is to highlight the utility of incorporating retromode imaging into the multimodal evaluation of the retina in patients with AMD and to gather and integrate these findings into a brief but comprehensive paper. Conclusions: Retromode imaging is a good screening, diagnosis, and monitoring tool for patients with AMD.

This Issue at a Glance

To investigate the relationship between photoreceptor layers overlying and adjacent to large drusen in intermediate nonneovascular AMD. Patients with AMD (n = 41; aged 53-83 years) and elderly control subjects without eye disease (n = 10; aged 51-79 years) were studied with spectral-domain optical coherence tomography. Characteristics of large drusen (≥125 μm) were measured and the thickness of photoreceptor laminae overlying drusen and in retinal regions neighboring the drusen were quantified. There were 750 large drusen in 63 intermediate AMD eyes studied. The width of the drusen sampled averaged 352 μm (SD = 153) and the height averaged 78 μm (SD = 31). There was significant reduction of the photoreceptor outer nuclear layer (ONL) thickness overlying 92% of the drusen. The thickness of the layer corresponding to photoreceptor inner and outer segments above drusen was also reduced, and the reduction was proportional to ONL thickness. In a substantial fraction (~20%) of normally laminated paradrusen locations sampled within ~300 μm of peak drusen height, ONL thickness was significantly increased compared with age and retinal location-matched normal values. Topographical analyses of the macula showed ONL thickening occurring in paradrusen regions as well as retinal locations distant from drusen. Reductions in the photoreceptor laminae overlying drusen were detectable and this is consistent with histological studies revealing neuronal degeneration in AMD. ONL thickening in some macular areas of AMD eyes has not been previously reported and may be an early phenotypic marker for photoreceptor stress, as it has been speculated to be in hereditary retinal degenerations.

PIGMENTARY MOSAICISM: AN UPDATE

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. 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). 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. 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.

Retinal safety evaluation of photoacoustic microscopy

A low glycemic diet protects disease-prone Nrf2-deficient mice against age-related macular degeneration

Previous psychophysical studies have reported conflicting results concerning the effects of short-term visual deprivation upon tactile acuity. Some studies have found that 45 to 90 minutes of total light deprivation produce significant improvements in participants' tactile acuity as measured with a grating orientation discrimination task. In contrast, a single 2011 study found no such improvement while attempting to replicate these earlier findings. A primary goal of the current experiment was to resolve this discrepancy in the literature by evaluating the effects of a 90-minute period of total light deprivation upon tactile grating orientation discrimination. We also evaluated the potential effect of short-term deprivation upon haptic 3-D shape discrimination using a set of naturally-shaped solid objects. According to previous research, short-term deprivation enhances performance in a tactile 2-D shape discrimination task – perhaps a similar improvement also occurs for haptic 3-D shape discrimination. The results of the current investigation demonstrate that not only does short-term visual deprivation not enhance tactile acuity, it additionally has no effect upon haptic 3-D shape discrimination. While visual deprivation had no effect in our study, there was a significant effect of experience and learning for the grating orientation task – the participants' tactile acuity improved over time, independent of whether they had, or had not, experienced visual deprivation.