Early Age-related Maculopathy Research Articles

The prevalence and risk factors for age-related macular degeneration in rural-urban India, Sankara Nethralaya Rural-Urban Age-related Macular degeneration study, Report No. 1.

PurposeTo report the age- and gender-adjusted prevalence rates of early and late age-related maculopathy (ARM) and associated risk factors in rural and urban Indian population.MethodsA population-based cross-sectional study was carried out in South India between 2009 and 2011. Of the 6617 subjects ≥60 years enumerated ones, 5495 (83.04%) participated in the eye examination. A detailed history including data on demographic, socioeconomic, and ocular history was obtained. Participants underwent detailed ophthalmic evaluation including 30° 3-field photograph as per Age-Related Eye Disease Study protocol. The ARM was graded according to the International ARM Epidemiological Study Group.ResultsAge- and gender-adjusted prevalence of early ARM was 20.91% (20.86-20.94) in the rural population and 16.37% (16.32-16.42) in the urban population. Similarly, the prevalence of late ARM was 2.26% (2.24-2.29) and 2.32% (2.29-2.34) in the rural and urban population, respectively. In both rural and urban populations, risk factors that were related to both early and late ARM were age, per year increase (OR, range 1.00-1.08); middle socioeconomic status (OR, range 1.05-1.83); and smokeless tobacco (OR, range 1.11-2.21). Protective factor in both was the presence of diabetes mellitus in all ARM (OR, range 0.34-0.83). Risk factors, only in the rural arm, were female gender (OR, range 1.06-1.64), past smoker (OR, 1.14), and serum low-density lipoprotein cholesterol level (OR, 1.03).ConclusionsThe study reports smokessless tobacco as a risk factor for both early and late ARM and identified a higher prevalence of early ARM in the rural population compared with urban population.

Differential Vulnerability of Retinal Layers to Early Age-Related Macular Degeneration: Evidence by SD-OCT Segmentation Analysis

We evaluated layer-by-layer retinal thickness in spectral-domain optical coherence tomography (SD-OCT), determined by automated segmentation analysis (ASA) software in healthy and early age-related maculopathy (ARM) eyes. There were 57 eyes (specifically, 19 healthy eyes under 60 years old, 19 healthy eyes over 60, and 19 ARM eyes) recruited into this cross-sectional study. The mean ages were 36.78 (SD, ±13.82), 69.89 (SD, ±6.14), and 66.10 (SD, ±8.67) years, respectively, in the three study groups. The SD-OCT scans were transferred into a dedicated software program that performed automated segmentation of different retinal layers. Automated layer segmentation showed clear boundaries between the following layers: retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), inner nuclear layer plus outer plexiform layer (INL+OPL), outer nuclear layer (ONL), and RPE complex. The thickness of the RNFL, ONL, and RPE layers did not show a statistically significant change across the three groups by ANOVA (P = 0.10, P = 0.09, P = 0.15, respectively). The thickness of GCL+IPL and INL+OPL was significantly different across the groups (P < 0.01), being reduced in the ARM eyes compared to healthy eyes, under and over 60 years old. The early morphologic involvement of the GCL+IPL and INL+OPL layers in ARM eyes, as revealed by the ASA, could be related to early anatomic changes described in the inner retina of ARM eyes. This finding may represent a morphologic correlation to the deficits in postreceptoral retinal function in ARM eyes.

Differences in spectral absorption properties between active neovascular macular degeneration and mild age related maculopathy

This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for...

The Role of Optical Coherence Tomography in the Diagnosis of Early Age-related Maculopathy

There has been increasing interest in improving imaging technologies to identify and grade early age-related maculopathy (ARM). Recently, advances in optical coherence tomography (OCT) has allowed a virtual biopsy of the retina and identification of different types of drusen in relation to early ARM. Several investigators have improved our understanding of both the qualitative and quantitative analyses of drusen, the clinical hallmark of ARM. The purpose of this article is to critically review the current literature in OCT in the evaluation of early ARM. Although seemingly useful and ideal, the current analysis of the retina using OCT is highly complex and lacking. It is currently too premature to use OCT as a grading tool for early ARM. However, the authors are hopeful that the rapid progress in this field will enable the use of an OCT-defined outcome measure in early ARM clinical trials in the foreseeable future.

COMPARISON OF CHOROIDAL THICKNESS AMONG PATIENTS WITH HEALTHY EYES, EARLY AGE-RELATED MACULOPATHY, NEOVASCULAR AGE-RELATED MACULAR DEGENERATION, CENTRAL SEROUS CHORIORETINOPATHY, AND POLYPOIDAL CHOROIDAL VASCULOPATHY

To compare choroidal thicknesses among eyes with early age-related maculopathy (ARM), neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous chorioretinopathy. Patients with age-related maculopathy (37 eyes), neovascular age-related macular degeneration (24 eyes), polypoidal choroidal vasculopathy (12 eyes), and central serous chorioretinopathy (31 eyes) underwent spectral-domain optical coherence tomography evaluations using a choroid scanning protocol. A horizontal linear section comprising 50 averaged scans was obtained of each macula. The choroidal thickness was measured from the outer border of the retinal pigment epithelium to the inner scleral border. Twenty-nine subjects with healthy eyes served as a control group. Analysis of covariance tests were performed to evaluate the effects of various diagnoses on choroidal thickness after removal of variance (covariates = gender, age, and refractive error). Among the different covariates, age was associated with choroidal thickness (fovea: F = 12.067, P = 0.001). After controlling for age differences, the choroid was thicker in polypoidal choroidal vasculopathy (319.92 ± 68.66 μm) and central serous chorioretinopathy (367.81 ± 105.56 μm) patients than in controls (241.97 ± 66.37 μm) and age-related maculopathy patients (186.62 ± 64.02 μm). However, there were no significant differences in mean choroidal thickness between neovascular age-related macular degeneration (226.46 ± 102.87 μm) and any of the other diagnoses. The choroid was thicker in eyes with polypoidal choroidal vasculopathy or central serous chorioretinopathy than in control or age-related maculopathy groups.

Age-Related Macular Degeneration and Risk Factors for the Development of Choroidal Neovascularisation in the Fellow Eye: A 3-Year Follow-Up Study

Introduction: The presence of large-sized drusen (≧125 µm), soft indistinct drusen, pigmentary changes, a large area of drusen and a choroidal neovascular membrane in one eye have been found to be predictive risk factors of late exudative age-related macular degeneration (AMD). Multimodal imaging potentially increases the possibility of indentifying further potential risk factors of developing wet AMD. Purpose: To identify morphological and/or functional baseline risk factors for the development of choroidal neovascularization (CNV) in a multimodal set of images from fellow eyes of patients with exudative AMD. Methods: Single-center, prospective, observational, longitudinal 2-year plus 1-year extension study of 62 patients with neovascular AMD in one eye (the nonstudy eye) and early age-related maculopathy (ARM) in the fellow eye (study eye). Best-corrected ETDRS visual acuity, fluorescein angiography (FA) and indocyanine green angiography (ICG), fundus photography, retinal leakage analysis, fundus autofluorescence imaging and optical coherence tomography (OCT Stratus 4.0.2, Carl Zeiss Meditech Inc.) were performed at baseline and every 6 months in order to identify both conversion to CNV as well as possible predictive features present before conversion. A semiautomated computer-assisted grading system was used for classifying fundus color images. Only eyes with 3 years of follow-up were considered for statistical analysis. Results: Fifty-two patients completed the 3-year study follow-up: 26 men and 26 women aged from 56 to 92 years (mean ± SD: 76 ± 6 years). CNV confirmed with FA developed in 46% of the 52 study eyes during the 3-year follow-up (24 converted eyes: 7 in the first year, 11 in the second and 6 in the third). A significantly higher risk for conversion to wet AMD was found only for leakage on a retinal leakage analyzer (odds ratio, OR = 5.0; 95% confidence interval, CI = 1.5–16.4; p = 0.006) detected at least in one visit before the onset of exudative lesions, for baseline ICG hot spots (OR = 7.2; 95% CI = 2.0–25.7; p = 0.002), baseline late ICG hot spots (OR = 4.7; 95% CI = 1.4–15.4; p = 0.009) and baseline early ICG hypofluorescent spots (OR = 3.7; 95% CI = 1.2–12.1; p = 0.025). The total area of drusen, the area of drusen in subfield 1, inner circle or outer circle, the total number of drusen and the number of drusen ≧125 µm, fundus autofluorescence patterns, OCT findings and the severity of ARM at baseline did not show any correlation with an increased risk of conversion to wet AMD. Conclusion: At 3 years, progression from early to late exudative AMD was superior to the expected rate (44%). ICG early and late hyperfluorescent spots or areas, ICG early hypofluorescent spots or areas and early leakage detected with the retinal leakage analyzer, but not pigmentary changes, large drusen, number and area of drusen at any location or a greater severity of ARM at baseline, showed to be a predictive parameter of conversion to wet AMD.

The prevalence and analysis of risk factors for age-related macular degeneration: 18-year follow-up data from the Speedwell eye study, United Kingdom

To determine the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in men aged 65-83 years living in the Speedwell region of Bristol, United Kingdom and identify modifiable risk factors. A total of 2348 men recruited to the Speedwell prospective cohort study in 1979 were followed up in 1997 with an eye questionnaire and had retinal photographs that were assessed using the International Classification System for ARM. In all, 934 men (66.8% response rate) attended with a mean of 17.9 years (15.3-20.6 years) follow-up. Early ARM (grades 2-3) was found in 9.2% (95% confidence interval (CI) 7.4%, 11.4%) and late age-related maculopathy (grade 4, AMD) in 0.5% (95% CI 0.2%, 1.2%). The risk of ARM (grades 2-4) was increased with raised C-reactive protein and consumption of lard and solid fats, whereas triglyceride levels were associated with a lower risk. The latter were confirmed in multivariable analyses and in addition, haemodynamic measures also predicted risk (eg mean arterial pressure odds ratio (OR) per z-score 1.37, 95% CI 1.04, 1.79). In a representative cohort of men aged 65-83 from Bristol, United Kingdom, many had macular changes that put them at higher risk of developing AMD. Various modifiable exposures were associated with an increased risk ARM/AMD. Opportunities for screening and undertaking secondary prevention interventions need to be explored to prevent progression of the disease and blindness.

The decline in visual acuity in elderly people with healthy eyes or eyes with early age-related maculopathy in two Scandinavian population samples

This study aimed to analyse the decline in visual acuity (VA) during normal ageing in two Scandinavian population samples of subjects aged ≥ 70 years and to study the age-specific decline in VA in eyes with early age-related maculopathy (ARM). We carried out a cross-sectional analysis of data pertaining to VA in the better eye in one population sample from Oulu (OU), Finland (aged 70-82 years) and a second population sample from Gothenburg (GG), Sweden (aged 82 or 88 years). The change in VA with age was evaluated in healthy eyes (OU, n = 119; GG, n = 40) and in eyes with early ARM (OU-ARM, n = 22; GG-ARM, n = 114) using linear regression or logistic regression. The results were compared with those of previous reports. Our population samples showed a significant decrease with age in VA in healthy eyes in subjects aged ≥ 44 years using both statistical models. Comparisons with previous reports demonstrated a homogeneity in the decline in VA with age. On average, 0.3 logMAR are lost from middle age up to 88 years, presumably as a result of physiological ageing. In early ARM, the rate of age-specific decline in VA more than doubled and the prevalence of VA < 0.5 markedly increased. Visual acuity in healthy eyes declines with age from middle age onwards. The decrease in VA possibly accelerates in subjects aged > 70 years, although no significant evidence for this was found. An age-specific decline in VA is shown in eyes with early ARM. These results are important for the evaluation of age-specific treatment results.

Usefulness of Brachial-Ankle Pulse Wave Velocity and Ankle-Brachial Index as Predictors of Early Age-Related Maculopathy

Usefulness of Brachial-Ankle Pulse Wave Velocity and Ankle-Brachial Index as Predictors of Early Age-Related Maculopathy

Early Markers of Choroidal Neovascularization in the Fellow Eye of Patients with Unilateral Exudative Age-Related Macular Degeneration

Objective: To identify morphological and/or functional early markers of choroidal neovascularization (CNV) development in fellow eyes of patients with exudative age-related macular degeneration (AMD). Design: This is a single-center, prospective, observational, longitudinal 2-year study. Patients: Patients were enrolled with the diagnosis of neovascular AMD in 1 eye and early age-related maculopathy (ARM) in the fellow eye. Intervention or Methods: All patients completed the baseline assessment and were followed up for up to 24 months with repeated ophthalmic and imaging assessments performed at 6-month intervals. Main OutcomeMeasures: Each patient underwent a detailed ocular and medical history, a complete ophthalmologic examination with color fundus photography, fluorescein angiography, indocyanine green angiography (ICG), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging and retinal leakage analysis (RLA). Results: Sixty-two patients were enrolled in the study. Large or intermediate drusen were present in 100% of the study eyes and hyperpigmentation in 46% (24 eyes). Fifty-two patients completed the 2-year study follow-up. Large soft drusen (>125 µm) were observed in 15 out of 17 eyes (88%) that converted and developed CNV during the study and in 25 out of 35 eyes (71.4%) that did not develop CNV. Among the 17 eyes that developed CNV, 9 (53%) showed abnormal findings before conversion, on ICG. No particular FAF pattern was found to be correlated with conversion to wet AMD. OCT was able to document the presence of intra- or subretinal fluid at the time of conversion in all 17 eyes that developed CNV during the study. Alterations of the blood-retinal barrier were identified by RLA before conversion in 76% of the eyes that converted and 23% of the eyes that did not convert during the study. Conclusions: Characterization of early ARM phenotypes is challenging. By combining different imaging modalities of the macula and correlating this information, we were able to determine the presence of functional macular alterations in the fellow eye of patients with this disease before development of CNV.

Relationship between macular pigment and mesopic visual function in early age‐related maculopathy

Abstract Purpose Psychophysical studies have demonstrated that several parameters of visual function deteriorate in the early stages of age‐related maculopathy (ARM). This study was performed to analyze whether the variability in high (HC) and low (LC) ‐contrast visual acuity (VA) and contrast sensitivity (CS) at mesopic light level is attributable to differences in macular pigment optical density (MPOD) in early ARM patients. Methods Measurements were obtained from 40 eyes of adults (65 ± 7 years) with early ARM and 34 age‐matched healthy control eyes (67 ± 6 years). MPOD was estimated at the fovea using the Metropsis Test (Cambridge Research System). Visual acuity (VA) was measured with the best spectacle correction using high‐contrast (96%) and low‐contrast (10%) logMAR letter charts under mesopic luminance conditions (0.1 to 0.2 cd/m2). Mesopic contrast sensitivity (CS) was determined using the Pelli‐Robson chart. Results Foveal MPOD was 0.25 ± 0.14 in eyes without ARM and 0.29 ± 0.22 in eyes with early ARM. Mean mesopic high and low contrast logMAR VA and log CS were significantly worse in the ARM group than in the control group. There was no significant relationship between high HC‐VA and MPOD, LC‐VA and MPOD and between log CS and MPOD in both early ARM and control group. Conclusion No differences in MP optical density were found between eyes with and without early ARM. Mesopic visual function was unrelated to foveal macular pigment optical density in early age‐related maculopathy.

Is foveal thickness correlated with macular pigment optical density and with Intraocular light scatter in early age‐related maculopathy?

Abstract Purpose The purpose of this study was to investigate the relationship of foveal thickness with macular pigment optical density (MPOD) and intraocular light scatter (IOLS) in Early Age Related Maculopathy (ARM) subjects. Methods Forty eyes of adults (age mean: 65 ± 7 years) with early Age Related Maculopathy (ARM) were investigated. All patients had undergone a complete ophthalmic examination to select the subjects. Foveal thickness parameters were obtained using optical coherence tomography (OCT: Topcon 3D OCT‐1000). Macular pigment optical density at the fovea was measured with the Metropsis Test (Cambridge Research Systems. Ltd. UK) and intraocular light scatter was measured using the C‐Quant straylight meter (Oculus AG, Germany). Results Mean foveal thickness was 226.44 ± 22.56 microns, mean MPOD was 0.22 ± 0.29 log units and mean IOLS was 1.14 ± 0.18 log units. With the regression analysis of linear model, we did not find a significant correlation between foveal thickness and MPOD and neither between foveal thickness and IOLS in early ARM subjects. Conclusion No correlation was found between foveal thickness and macular pigment optical density and between foveal thickness and intraocular light scatter in early ARM subjects.

Prevalence and prospective risk factors for age‐related macular degeneration: The Bristol Speedwell cohort, UK

Abstract Purpose Age‐related macular degeneration (AMD) is a progressive eye disease, with a pre‐clinical stage of age‐related maculopathy (ARM), and is the leading cause of blindness in the Western world. This study aimed to determine the population prevalence in a representative group of men (65‐83 years) and identify prospective risk factors for ARM/AMD. Methods 2348 men (45‐63 years from Speedwell, Bristol) were enlisted into a cohort study in 1979. At phase V (mean of 17.9 years follow‐up) they had retinal photographs taken which were assessed using the Wisconsin Age‐related Maculopathy Grading System. Results Data were obtained on 934 men from a potentially eligible sample of 1394 (67%). Early ARM was found in 9.2% of all men and late ARM in 0.5%; the rates increased with age. Baseline risk factors collected in 1979 that were associated with increased risk of AMD (ARM stage 2‐4) seen in 1997 were: diastolic blood pressure, C‐reactive protein, and increased consumption of lard, oils and fats whilst triglycerides were associated with a reduced risk. In multivariable analyses, elevated mean arterial pressure (OR per z‐score 1.37, 95% CI 1.04, 1.79) and fat consumption were significant predictors of increased risk, whilst triglycerides had reduced risk (OR 0.68, 95% CI 0.47, 0.99). Conclusion Whilst the prevalence of AMD was only 0.5%, almost 10% of elderly men in this UK sample were at high risk of developing AMD over the next 5 years. Our observation that elevated triglycerides is associated with reduced risk, if replicated, may provide insights into pathophysiological pathways. Early detection and possible risk factor modification should be explored to prevent ARM progression and blindness.

Mesopic visual function as a prognostic indicator of early age‐related maculopathy

Abstract Purpose Rod photoreceptors, which mediate night vision, are vulnerable early in age‐related maculopathy (ARM) pathogenesis. This study was performed to analyze mesopic visual function of early ARM subjects. Methods The samples were 40 early ARM eyes of adults (65 ± 7 years), and 34 age‐matched healthy control eyes (67 ± 6 years). The selected criteria in both samples were: Best‐corrected VA of at least 0.9 decimal. Under photopic (80 cd/m2) and mesopic (0.1 to 0.2 cd/m2) luminance conditions and with the best‐optical correction, the logMAR VA was measured using high‐contrast (HC‐96%) and low‐contrast (LC‐10%) logMAR Bailey‐Lovie letter charts, and the mesopic contrast sensitivity (CS) was assessed with Pelli‐Robson Test Results Photopic high and low‐contrast VA showed no statistically differences between the two groups. Under mesopic conditions, the HC logMAR VA was 0.54 ± 0.13 in ARM group and 0.46 ± 0.10 in Control group. The ARM LC logMAR VA was 0.72 ± 0.11 and the Control LC logMAR VA was 0.99 ± 0.13. Differences in mesopic high and low contrast logMAR VA between the Control and ARM group were statistically significant; the Control group showing best logMAR VA at high and low contrast (p&lt; 0.00). The mesopic ARM logCS was 0.99 ± 0.21 and the mesopic Control logCS was 1.19 ± 0.14. In ARM group, the mean mesopic log CS was 0.2 ± 0.08 log units lower (p&lt; 0.00) than in the Control group. Conclusion The results indicated that assessment of the mesopic high and low contrast logMAR VA and log CS might potentially predict the mesopic visual function and the first night‐vision problems of the early ARM disease process

Nutrition and age-related eye diseases: The Alienor (Antioxydants, lipides essentiels, nutrition et maladies oculaires) study

Worldwide, degenerative eye diseases (age-related maculopathy (ARM), cataract, glaucoma) are the main causes of visual impairment and blindness, which contribute to disability in the elderly. Mainly three types of nutritional factors are investigated for their potential protection against eye ageing: antioxidants; lutein and zeaxanthin (carotenoids which accumulate specifically in the eye); omega 3 polyunsaturated fatty acids. Few epidemiological studies have been conducted in this field, particularly in Europe. The Alienor (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) Study aims at assessing the associations of eye diseases with nutritional factors, determined from plasma measurements and estimation of dietary intakes. Subjects were recruited in Bordeaux (France) from the ongoing population-based 3C study. In 2006-2008, 963 subjects from the 3C Study, aged 73 years or more, had an eye examination and will have follow-up eye examinations every 2 years. Vascular, genetic and nutritional factors were assessed at baseline (1999-2001) and follow-up examinations of the 3C Study. Eye diseases were classified according to international classifications. Nutritional status and vascular disease and risk factors were similar between participants and non participants, except for a slight difference in plasma triglycerides and HDL-cholesterol. As expected, the prevalence of eye diseases was high: early and late ARM (28.4 % and 5.6 %, respectively), open-angle glaucoma and treated ocular hypertension (4.8 % and 10.0 %, respectively), cataract extraction (45.2 %), retinopathy (8.4 %), retinal vein occlusion (1.1 %), epiretinal membrane (3.9 %), current use of artificial tears (17.3 %). This study confirms the high prevalence of eye diseases in the elderly. Its main strength is the combination of nutritional, vascular and genetic information, collected over a 7 year period of time before the first eye examination. It may help design future interventional studies, which might be common with other age-related disorders, because of common nutritional factors.

Klinische Manifestationen von Funktionsstörungen des retinalen Pigmentepithels

The retinal pigment epithelium (RPE) serves a variety of different functions and impairment of these functions can lead to a multitude of different diseases of the posterior segment of the eye. The RPE plays an important role as an ion and fluid pump for the reabsorption of subretinal fluid in retinal detachment. On the other hand, defects in this pump function and in the outer blood-retinal barrier formed by the RPE, lead to fluid retention in inflammatory diseases. Metaplasia of RPE cells to myofibroblasts can lead to proliferative vitreoretinopathy and tractive retinal detachment. Early age-related maculopathy is caused by disturbances of phagocytosis and metabolism of the RPE. Imbalance of the physiological equilibrium between vasoproliferative and vasoinhibitory factors secreted by the RPE is probably involved in the development of atrophic or neovascular forms of advanced age-related macular degeneration. Mutations in the different steps involved in regeneration of the visual pigment (visual cycle) may lead to retinal dystrophy. Finally, immunoregulatory properties of the RPE are responsible for the phenomenon of immunological privilege, which may facilitate clinical interventions such as gene therapy and RPE transplantation.

Functional deficits in early stage age‐related maculopathy

Background: It is of interest to examine paracentral functional deficits in early age‐related maculopathy (ARM), as histopathological studies indicate that this is where the earliest changes occur. The purpose of this study is to detect the sensory functional deficits at chosen retinal areas around the fovea and at the fovea itself in patients with early age‐related maculopathy and to determine the type of functional losses that are more pronounced in early ARM.Methods: Ten participants with early ARM and 10 age‐matched controls took part. Crowded and uncrowded visual acuity and static and transient contrast sensitivity were measured in the same selected eye of each participant at eight predetermined retinal locations plus the fovea in patients with early ARM and controls. All measurements were made using computer‐generated targets.Results: A significant difference between the controls and subjects with ARM was found in low spatial frequency static contrast sensitivity (p = 0.05) but not for transient contrast sensitivity (p = 0.586). Visual acuity (uncrowded VA and crowded VA) showed a borderline difference (p = 0.072 and p = 0.084, respectively). Compared to controls, there was no evidence of increased contour interaction effects in early ARM (p = 0.595).Conclusion: The subjects with very early ARM showed significant loss of low spatial frequency static contrast sensitivity before the loss of high contrast VA, indicating that static contrast sensitivity may be one of the earliest functional losses in early ARM and this loss was found to extend across the central 10 degrees of the retina.

Psychophysical Function in Age-related Maculopathy

Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

Sunlight-Related Factors and the 10-Year Incidence of Age-Related Maculopathy

Purpose: To examine the associations among iris, skin, or hair color, and skin sun sensitivity and the 10-year incidence of age-related maculopathy (ARM). Methods: The Blue Mountains Eye Study (BMES) recruited 3654 participants aged 49+ years at baseline (1992–1994, 82.4% participation rate). Re-examinations of 2335 participants (75.1% of survivors) were done after 5 years (1997–1999) and 1952 (76.5% of survivors) after 10 years (2002–2004). Retinal photographs were graded using the Wisconsin ARM Grading System and incident ARM confirmed using the side-by-side grading method. Iris, skin, and hair color, and sun-related skin damage were assessed and skin sun-sensitivity questions were asked at baseline. Ten-year ARM incidence was calculated using Kaplan Meier methods and discrete logistic models were used to assess associations after adjusting for age, sex, and smoking. Results: After adjustment, no significant associations were found between iris or hair color and either late- or early-incident ARM. Compared to persons with fair skin, those with very fair skin had an increased risk of developing geographic atrophy (multivariate adjusted risk ratio, RR = 7.6; 95% confidence interval, CI = 3.0–19.6). In contrast, compared to persons with average skin sun sensitivity, persons who reported that their skin would usually burn and tan with difficulty had a reduced risk of neovascular ARM (RR = 0.2, 95% CI = 0.0–0.7). Sun-related skin damage was not associated with late or early ARM. Conclusions: In this older cohort, we did not find a consistent pattern of association between sunlight-related factors and ARM incidence, except that persons with very fair skin might have an increased risk of geographic atrophy, consistent with our 5-year incidence data. The protective association between skin sensitivity to sun damage and neovascular ARM could have be the result of confounding by sun-avoidance behavior among persons sensitive to sunburn.

Age-related maculopathy – Linking aetiology and pathophysiological changes to the ischaemia hypothesis

Age-related maculopathy (ARM) has remained a challenging topic with respect to its aetiology, pathomechanisms, early detection and treatment since the late 19th century when it was first described as its own entity. ARM was previously considered an inflammatory disease, a degenerative disease, a tumor and as the result of choroidal hemodynamic disturbances and ischaemia. The latter processes have been repeatedly suggested to have a key role in its development and progression. In vivo experiments under hypoxic conditions could be models for the ischaemic deficits in ARM. Recent research has also linked ARM with gene polymorphisms. It is however unclear what triggers a person's gene susceptibility. In this manuscript, a linking hypothesis between aetiological factors including ischaemia and genetics and the development of early clinicopathological changes in ARM is proposed. New clinical psychophysical and electrophysiological tests are introduced that can detect ARM at an early stage. Models of early ARM based upon hemodynamic, photoreceptor and post-receptoral deficits are described and the mechanisms by which ischaemia may be involved as a final common pathway are considered. In neovascular age-related macular degeneration (neovascular AMD), ischaemia is thought to promote release of vascular endothelial growth factor (VEGF) which induces chorioretinal neovascularisation. VEGF is critical in the maintenance of the healthy choriocapillaris. In the final section of the manuscript the documentation of the effect of new anti-VEGF treatments on retinal function in neovascular AMD is critically viewed.