Drusen Area Research Articles

Signal reduction in choriocapillaris and segmentation errors in spectral domain OCT angiography caused by soft drusen.

To analyze signal reduction in choriocapillaris (CC) and segmentation errors in spectral domain optical coherence tomography angiography (OCT-A) caused by soft drusen due to age-related macular degeneration (AMD). Twenty-four eyes of 24 patients underwent multimodal retinal imaging including central 3×3mm2 OCT-A (AngioVue, Optovue). Three drusen per study eye were randomly chosen and evaluated regarding drusen height, diameter, and accuracy of OCT-A layer segmentation in lesion proximity. Structural en-face OCT CC images were graded qualitatively and quantitatively regarding signal loss underneath the individual drusen area. Those drusen that showed no distinct signal loss in structural en-face OCT CC images were further evaluated in OCT-A. CC decorrelation signal index was measured within a 30-μm OCT-A CC slab in the exact area of drusen affection. Data were compared to healthy age-matched control subjects. Accuracy of layer segmentation, OCT CC data, and OCT-A CC data were correlated to morphological drusen parameters. Mean drusen height and diameter were 91.57 ± 19.5μm and 315.17 ± 116.7μm. OCT-A layer segmentation of the inner plexiform layer (IPL) was disturbed by more than 50μm in proximity to 26 drusen (36.1%). In these patients, drusen height was significantly higher compared to those with accurate IPL segmentation (p=0.0126). Sixty-six out of 72 drusen (91.7%) caused a distinct signal loss in the structural en-face OCT CC image. Drusen height and drusen diameter were significantly higher in this group compared to the six drusen with a sufficient signal (p=0.0276, p=0.0025). CC decorrelation signal index measured in the area of these six drusen without OCT signal loss (8.3%) was reduced compared to age-matched healthy controls (73.6 vs. 100.1; p=0.001). Signal attenuation in CC slabs and segmentation errors of the IPL depend on drusen morphology. Both are frequent artifacts in OCT-A imaging in patients with soft drusen and must be considered during image analysis.

Gender Differences in the Relationship between Sex Hormone Deficiency and Soft Drusen

ABSTRACTPurpose: To investigate the association between sex hormone deficiency and soft drusen in women and men.Materials and Methods: We retrospectively reviewed the medical records and fundus photographs of subjects who underwent a health screening for additional examination of climacterium and age-related changes including sex hormone status. In women, sex hormone deficiency was defined as cessation of menstruation that had lasted for at least 12 months and follicular stimulating hormone (FSH) levels ≥ 25 mIU/mL; in men, it was defined as testosterone levels ≤ 3.5 ng/mL. The subjects were divided into two groups—the soft drusen and control groups—based on the presence of soft drusen in the fundus photographs. The total drusen area was measured using ImageJ™ software.Results: Of total 2036 subjects, 638 (271 women; 367 men) were included. Two hundred thirteen subjects (33.4%) had soft drusen (97/271 women, 116/367 men). In women, sex hormone deficiency was more common in the soft drusen group than in the control group (P < 0.001); this was not the case in men. Multivariate logistic regression analysis revealed that sex hormone deficiency was an independent risk factor for soft drusen in women (P < 0.001; odds ratio [OR] = 3.494), as was age (P < 0.001; OR = 1.092). A long post-menopausal period was a risk factor for large soft drusen (≥ 125 μm). (P < 0.001; OR = 1.220). Age was significantly associated with total drusen area in both women (P = 0.022; β = 0.406) and men (P = 0.015; β = 0.246).Conclusions: Sex hormone deficiency and its duration were significantly associated with the development and progression of soft drusen in women but not in men. It may be necessary to assess and manage the sex hormone deficiency in women with age-related macular degeneration.

Phenotype Characteristics of Patients With Age-Related Macular Degeneration Carrying a Rare Variant in the Complement Factor H Gene

Rare variants in the complement factor H (CFH) gene and their association with age-related macular degeneration (AMD) have been described. However, there is limited literature on the phenotypes accompanying these rare variants. Phenotypical characteristics could help ophthalmologists select patients for additional genetic testing. To describe the phenotypical characteristics of patients with AMD carrying a rare variant in the CFH gene. In this cross-sectional study, we searched the genetic database of the department of ophthalmology at the Radboudumc (tertiary ophthalmologic referral center) and the European Genetic Database for patients with AMD with a rare genetic variant in the CFH gene. Patient recruitment took place from March 30, 2006, to February 18, 2013, and data were analyzed from November 30, 2015, to May 8, 2017. Phenotypical features on fundus photographs of both eyes of patients were graded by 2 independent reading center graders masked for carrier status. Differences in phenotypical characteristics between rare variant carriers and noncarriers were analyzed using univariable generalized estimated equations logistic regression models accounting for intereye correlation. Analyses included 100 eyes of 51 patients with AMD carrying a CFH variant (mean [SD] age, 66.7 [12.1] years; 64.7% female) and 204 eyes of 102 age-matched noncarriers (mean [SD] age, 67.1 [11.8] years; 54.9% female). Carrying a rare pathogenic CFH variant was associated with larger drusen area (odds ratio range, 6.98 [95% CI, 2.04-23.89] to 18.50 [95% CI, 2.19-155.99]; P = .002), presence of drusen with crystalline appearance (odds ratio, 3.24; 95% CI, 1.24-8.50; P = .02), and drusen nasal to the optic disc (odds ratio range, 4.03 [95% CI, 1.70-9.56] to 7.42 [95% CI, 0.65-84.84]; P = .003). Identification of rare CFH variant carriers may be important for upcoming complement-inhibiting therapies. Patients with an extensive drusen area, drusen with crystalline appearance, and drusen nasal to the optic disc are more likely to have a rare variant in the CFH gene. However, it is not likely that carriers can be discriminated from noncarriers based solely on phenotypical characteristics from color fundus images. Therefore, ophthalmologists should consider genetic testing in patients with these phenotypic characteristics in combination with other patient characteristics, such as early onset, cuticular drusen on fluorescein angiography, and family history of AMD.

Correlation Between Mesopic Retinal Sensitivity and Optical Coherence Tomographic Metrics of the Outer Retina in Patients With Non-Atrophic Dry Age-Related Macular Degeneration.

To determine the correlation between mesopic retinal sensitivity and optical coherence tomographic metrics of the outer retina in patients with intermediate age-related macular degeneration (AMD). Participants with nonatrophic dry AMD underwent mesopic MP-3 microperimetry (Nidek, Padova, Italy) and both Nidek and Cirrus (Carl Zeiss Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD-OCT). The volume of the outer retinal layers was measured on the Nidek SD-OCT scans using the automatic segmentation algorithm of Navis-EX software. In addition, drusen area and volume within a 5-mm circle centered on the fovea were determined using the Cirrus Advanced RPE Analysis Tool. The mean retinal sensitivity at 8° and 10° of fixation (5-mm and 6-mm circles) was calculated for every eye. The correlation between retinal sensitivity and patient age, outer retinal layer volume, drusen area, and drusen volume was assessed. Thirty-seven eyes from 25 patients with non-atrophic dry AMD were included in the study. The mean age of the patients was 76 years ± 9 years. The mean sensitivity across the whole tested retinal area was 24.9 dB ± 2.4 dB, with a sensitivity of 25.1 dB ± 2.4 dB within the central 5-mm circle. Drusen area within the central 5-mm circle was 0.7 mm2 ± 0.89 mm2 with a drusen volume of 0.03 mm3 ± 0.04 mm3. Retinal pigment epithelium and photoreceptor outer segment (RPE + OS) volume was 1.96 mm3 ± 0.1 mm3, and outer nuclear layer (ONL) volume was 1.91 mm3 ± 0.17 mm3. There was a significant correlation between RPE + OS volume and retinal sensitivity, as well as between patients' age and retinal sensitivity. There was no significant correlation between drusen area or volume and retinal sensitivity, nor between ONL volume and retinal sensitivity. In eyes with nonatrophic AMD, retinal sensitivity is correlated with the RPE + OS volume, but not the ONL volume or the area or volume of drusen. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:312-318.].

Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images.

PurposeTo introduce a novel method to segment individual drusen in spectral-domain optical coherence tomography (SD-OCT), and evaluate its accuracy, and repeatability/reproducibility of drusen quantifications extracted from the segmentation results.MethodsOur method uses a smooth interpolation of the retinal pigment epithelium (RPE) outer boundary, fitted to candidate locations in proximity to Bruch's Membrane, to identify regions of substantial lifting in the inner-RPE or inner-segment boundaries, and then separates and evaluates individual druse independently. The study included 192 eyes from 129 patients. Accuracy of drusen segmentations was evaluated measuring the overlap ratio (OR) with manual markings, also comparing the results to a previously proposed method. Repeatability and reproducibility across scanning protocols of automated drusen quantifications were investigated in repeated SD-OCT volume pairs and compared with those measured by a commercial tool (Cirrus HD-OCT).ResultsOur segmentation method produced higher accuracy than a previously proposed method, showing similar differences to manual markings (0.72 ± 0.09 OR) as the measured intra- and interreader variability (0.78 ± 0.09 and 0.77 ± 0.09, respectively). The automated quantifications displayed high repeatability and reproducibility, showing a more stable behavior across scanning protocols in drusen area and volume measurements than the commercial software. Measurements of drusen slope and mean intensity showed significant differences across protocols.ConclusionAutomated drusen outlines produced by our method show promising accurate results that seem relatively stable in repeated scans using the same or different scanning protocols.Translational RelevanceThe proposed method represents a viable tool to measure and track drusen measurements in early or intermediate age-related macular degeneration patients.

Fundus autofluorescence of choroidal nevi and melanoma

Choroidal melanoma is the most frequent primary intra-ocular tumour. Although being a malignancy of the choroidal melanocytes, it affects the retinal pigment epithelium (RPE). The resulting epitheliopathy appears as an area of atrophy, drusen, lipofuscin accumulation and localized detachment over the RPE associated with phagocytic activity that changes fundus colouration (Lavinsky et al. 2007). Lipofuscin from degraded lysosomal function accumulates in RPE cells and in macrophages of malignant choroidal tumours and generally appears as orange pigmentation over the lesion. Colour may vary from orange to brown or red brown depending on whether the tumour is melanocytic or amelanocytic. Orange pigment has also been considered a sign of malignancy. Fundus autofluorescence (FAF) photography is based on the stimulated emission of light from naturally occurring fluorophores, the most significant being lipofuscin. The recently developed Heidelberg Spectralis HRA+OCTdevice (Heidelberg Engineering, Heidelberg, Germany) enables a better assessment of autofluorescence than earlier devices, and, in addition, it evaluates the spatial distribution of lipofuscin-mediated fundus autofluorescence in vivo (Singh et al. 2010). We evaluated FAF in 100 choroidal nevi and in 65 choroidal melanomas. The mean best-corrected visual acuity (BCVA) for eyes with choroidal nevi was 20/14 ± 1.14 Snellen with a lesion thickness of 1.75 ± 0.23 μm (mean ± standard deviation); the mean BCVA of eyes with choroidal melanomas was 20/8 ± 2.61 with a mean tumour thickness of 3.67 ± 1.27 μm; all patients were of Caucasian origin. In 40 eyes with choroidal nevi, FAF showed a normal pattern of background fundus fluorescence with no corresponding areas of hyperfluorescence or hypofluorescence over the nevi (Fig. 1). Sixty eyes with choroidal nevi presented hypoautofluorescence associated with chronic RPE degenerative features and RPE atrophy. In 26 choroidal melanomas, fundus photography showed orange pigmentation, and FAF showed a plaque-like hyperautofluorescence throughout the surface of the lesion, which corresponded to the areas of increased pigment and fibrous metaplasia. Moreover, macrophages invade the highly pigmented areas in the attempt to phagocytize the accumulated material (Fig. 1). The lipofuscin overlying the choroidal melanomas is brightly hyperautofluorescent. Adjacent dark hypoautofluorescent areas surround the bright lipofuscin hyperautofluorescence. These may represent shifting and clumping of RPE cells or RPE atrophy (Lavinsky et al. 2007; Singh et al. 2010; Shields et al. 2007). Detection of lipofuscin by FAF imaging could play a role in the early detection of choroidal melanoma. Notably, orange pigment is considered one of five factors predictive of growth of small choroidal melanocytic tumours into melanoma. Subretinal fluid represents a physical barrier between the outer segments of photoreceptors and the RPE, thereby preventing normal phagocytosis of the shed outer segments of the photoreceptors. The latter subsequently accumulate on the outer retinal surface and in the subretinal space and are a source of autofluorescence. Histologically, the debris in the subretinal fluid consists of rounded or elongated densely packed multilamellar bodies that appear to result from the breakdown of outer segment discs. The retina anterior to the subretinal material shows attenuation of the photoreceptor layer. The subretinal material is bound posteriorly by the RPE (Singh et al. 2010). Shields et al. examined choroidal melanomas characterized by overlying orange pigment and subretinal fluid and found that the pigment corresponded to lipofuscin in macrophages located in the subretinal space. They also demonstrated that the fluid rim was slightly more hyperautofluorescence than the fluid centre (Shields et al. 2007; Singh et al. 2010). Following treatment (plaque radiotherapy combined with transpupillary thermotherapy), choroidal melanomas may show increased FAF due to an increase in lipofuscin and hyperpigmentation (Gündüz et al. 2007). All treated melanomas enrolled in our study showed an increase in FAF irrespective of the type of treatment (plaque radiotherapy, transpupillary thermotherapy or a combination of them) (Fig. 1). In conclusion, choroidal melanomas may be surrounded by confluent hyperautofluorescence. Most nevi are not hyperautofluorescence (Gündüz et al. 2009). Therefore, FAF studies may be a useful non-invasive tool with which to identify lipofuscin in pigmented choroidal lesions, especially nevi and small choroidal melanomas.

Surgery for cataracts in people with age-related macular degeneration.

Cataract and age-related macular degeneration (AMD) are common causes of decreased vision that often occur simultaneously in people over age 50. Although cataract surgery is an effective treatment for cataract-induced visual loss, some clinicians suspect that such an intervention may increase the risk of worsening of underlying AMD and thus have deleterious effects on vision. The objective of this review was to evaluate the effectiveness and safety of cataract surgery compared with no surgery in eyes with AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 December 2016. We included randomized controlled trials (RCTs) and quasi-randomized trials that enrolled participants whose eyes were affected by both cataract and AMD in which cataract surgery was compared with no surgery. Two review authors independently evaluated the search results against the inclusion and exclusion criteria. Two review authors independently extracted data, assessed risk of bias for included studies, and graded the certainty of evidence. We followed methods as recommended by Cochrane. We included two RCTs with a total of 114 participants (114 study eyes) with visually significant cataract and AMD. We identified no ongoing trials. Participants in each RCT were randomized to immediate cataract surgery (within two weeks of enrollment) or delayed cataract surgery (six months after enrollment). The risk of bias was unclear for most domains in each study; one study was registered prospectively.In one study conducted in Australia outcomes were reported only at six months (before participants in the delayed-surgery group had cataract surgery). At six months, the immediate-surgery group showed mean improvement in best-corrected visual acuity (BCVA) compared with the delayed-surgery group (mean difference (MD) -0.15 LogMAR, 95% confidence interval (CI) -0.28 to -0.02; 56 participants; moderate-certainty evidence). In the other study, conducted in Austria, outcomes were reported only at 12 months (12 months after participants in the immediate-surgery group and six months after participants in the delayed-surgery group had cataract surgery). There was uncertainty as to which treatment group had better improvement in distance visual acuity at 12 months (unit of measure not reported; very low-certainty evidence).At 12 months, the mean change from baseline between groups in cumulated drusen or geographic atrophy area size was small and there was uncertainty which, if either, of the groups was favored (MD 0.76, 95% CI -8.49 to 10.00; 49 participants; low-certainty evidence). No participant in one study had exudative AMD develop in the study eye during 12 months of follow-up; in the other study, choroidal neovascularization developed in the study eye of 1 of 27 participants in the immediate-surgery group versus 0 of 29 participants in the delayed-surgery group at six months (risk ratio 3.21, 95% CI 0.14 to 75.68; 56 participants; very low-certainty evidence). Quality of life was measured using two different questionnaires. Scores on the Impact of Vision Impairment (IVI) questionnaire suggested that the immediate-surgery group fared better regarding vision-related quality of life than the delayed-surgery group at six months (MD in IVI logit scores 1.60, 95% CI 0.61 to 2.59; low-certainty evidence). However, we could not analyze scores from the Visual Function-14 (VF-14) questionnaire from the other study due to insufficient data. No postoperative complication was reported from either study. At this time, it is not possible to draw reliable conclusions from the available data as to whether cataract surgery is beneficial or harmful in people with AMD after 12 months.Although cataract surgery provides short-term (six months) improvement in BCVA in eyes with AMD compared with no surgery, it is unclear whether the timing of surgery has an effect on long-term outcomes. Physicians must make recommendations to their AMD patients regarding cataract surgery based on experience and clinical judgment until large controlled trials are conducted and their findings published.There is a need for prospective RCTs in which cataract surgery is compared with no surgery in people with AMD to better evaluate whether cataract surgery is beneficial or harmful in all or a subset of AMD patients. However, ethical considerations preclude withholding surgery, or delaying it for several years, if it may be a potentially beneficial treatment. Designers of future trials are encouraged to utilize existing standardized systems for grading cataract and AMD and for measuring key outcomes: visual acuity, change in visual acuity, worsening of AMD, quality of life measures, and adverse events.

Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration: Study Design and Baseline Characteristics of the Laser in Early Stages of Age-Related Macular Degeneration Study (Report Number 1)

The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is an investigation of the safety and efficacy of subthreshold nanosecond laser treatment to slow the progression of intermediate age-related macular degeneration (AMD). This report presents the novel study design and baseline characteristics. Multicenter, double-masked, randomized controlled, medical device feasibility clinical trial. Persons with bilateral drusen >125 μm within 1500 μm of the fovea, monocular best-corrected visual acuity (BCVA) ≥20/40, and microperimetric retinal sensitivity of <25 decibels (dB) in at least 1 location within central 6° in 1 eye. Signs of late AMD; choroidal neovascularization or geographic atrophy, or anatomic end points defined on multimodal imaging (MMI) as fundus autofluorescence-defined atrophy, spectral-domain OCT (SD-OCT)-defined atrophy, or nascent GA excluded participation. Participants were randomized to nanosecond or sham laser treatment. Twelve laser or sham spots are applied to the macular region of the study eye. Participants are reviewed in visits every 6 months with functional testing and MMI for 36 months and are re-treated at each visit (until 30 months) if an end point is not reached in the study eye. Progression to late AMD or MMI-defined anatomic end points in the study eye. A total of 292 participants across 6 centers were enrolled, with 145 participants randomized to arm 1 and 147 participants randomized to arm 2. Population characteristics at baseline were as follows: median age 70 years, 73% female, 90% Anglo-Saxon, and 3% current smokers. Baseline ocular characteristics of the study eyes were BCVA of 83 letters (20/25); low luminance visual acuity (LLVA) of 68 letters (20/50); hyperpigmentation, 33%; reticular pseudodrusen, 23%; square root drusen area (SD-OCT), 0.77mm; square root drusen area (color photographs), 0.92 mm; cube root drusen volume (SD-OCT), 0.26 mm; average retinal sensitivity, 26 dB; and worst point retinal sensitivity, 20 dB. Only lutein supplement use was significantly different between treatment arms. The LEAD study uses novel inclusion/exclusion criteria and end points in an attempt to optimize our study design. Risk characteristics for progression to study end points are equally distributed between treatment arms.

Five-year progression of unilateral age-related macular degeneration to bilateral involvement: the Three Continent AMD Consortium report

PurposeTo assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors.DesignPooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver...

3D Curvelet-Based Segmentation and Quantification of Drusen in Optical Coherence Tomography Images

Spectral-Domain Optical Coherence Tomography (SD-OCT) is a widely used interferometric diagnostic technique in ophthalmology that provides novel in vivo information of depth-resolved inner and outer retinal structures. This imaging modality can assist clinicians in monitoring the progression of Age-related Macular Degeneration (AMD) by providing high-resolution visualization of drusen. Quantitative tools for assessing drusen volume that are indicative of AMD progression may lead to appropriate metrics for selecting treatment protocols. To address this need, a fully automated algorithm was developed to segment drusen area and volume from SD-OCT images. The proposed algorithm consists of three parts: (1) preprocessing, which includes creating binary mask and removing possible highly reflective posterior hyaloid that is used in accurate detection of inner segment/outer segment (IS/OS) junction layer and Bruch’s membrane (BM) retinal layers; (2) coarse segmentation, in which 3D curvelet transform and graph theory are employed to get the possible candidate drusenoid regions; (3) fine segmentation, in which morphological operators are used to remove falsely extracted elongated structures and get the refined segmentation results. The proposed method was evaluated in 20 publically available volumetric scans acquired by using Bioptigen spectral-domain ophthalmic imaging system. The average true positive and false positive volume fractions (TPVF and FPVF) for the segmentation of drusenoid regions were found to be 89.15% ± 3.76 and 0.17% ± .18%, respectively.

The association of geographic atrophy and decreased renal function in patients with age-related macular degeneration.

PurposeThe purpose of the study was to investigate the association between area and presence of geographic atrophy (GA) and renal function, as measured by glomerular filtration rate (GFR).Patients and methodsWe retrospectively identified patients aged 50-90 years who were assigned an ICD-9 diagnosis code for age-related macular generation (AMD) between January 2012 and January 2016. Patients met inclusion criteria if they had at least one macular spectral domain optical coherence tomography volume scan, one provider note, and one GFR value in the electronic medical record. Images were evaluated for the presence of GA, area of GA, drusen, and subretinal drusenoid deposits (SDD) and for subfoveal choroidal thickness (CTh) by standard criteria. Imaging findings were correlated with the most recent GFR from the patient's chart.ResultsWe identified 107 patients who met our inclusion criteria (mean age=74 years, range 50-90 years). Overall, we found a significant correlation between the presence of GA and reduced GFR (P=0.002), which was maintained even after accounting for age and other confounders. No association between GFR and GA area was found. CTh was significantly lower in patients with GA (P=0.038) and those with decreased GFR (P=0.004). Within the SDD-positive population, GA was associated with reduced GFR (P=0.007) but only trended toward significance after controlling for age.ConclusionOur study findings demonstrate an association between impaired renal function and the presence, but not area, of GA within an AMD population. These findings may shed light on common pathogenic mechanisms for these two diseases.

Age-Related Macular Degeneration and Quality of Life in Latinos: The Los Angeles Latino Eye Study.

This study found evidence of a threshold effect in which the presence of bilateral soft drusen and depigmentation of retinal pigment epithelium was associated with substantially low health-related quality of life (HRQoL) in adult Latinos from the United States. To assess the association of general and vision-specific HRQoL with age-related macular degeneration (AMD), overall and by bilaterality and severity, in adult Latinos. This cross-sectional, population-based study included 4876 participants from the general urban community in 6 US Census tracts in La Puente, California. The data for these analyses were collected as part of a population-based study of ocular diseases in adult Latinos in the Los Angeles Latino Eye Study from February 1, 2000, through May 31, 2003. The analysis was performed from November 2010 to February 2011. Additional analyses were performed in June 2014. Mean-adjusted HRQoL scores and effect sizes. Of the 4876 participants included in the analysis, 4402 (90.3%) had no AMD, and 474 (9.7%) had any AMD, with 453 having early (9.3%) and 21 (0.4%) having late stages of the disease. The mean (SD) age of the cohort was 54.8 (10.7) years. Of the 4876 participants, 2001 (41.0%) were male and 2875 (59.0%) were female. In this cohort of Latinos, participants with AMD had lower vision-specific HRQoL scores. General HRQoL was assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey and self-reported vision-related HRQoL by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Composite NEI-VFQ-25 scores were 59.5 (95% CI, 50.8-68.1) for those with late-stage AMD and 79.4 (95% CI, 72.5-86.1) for those with early-stage AMD, compared with participants without AMD 80.7 (95% CI, 73.9-82.4); P < .001. Several lesions of early AMD were associated with lower NEI-VFQ-25 composite scores and 8 to 10 individual scales. Large effect sizes and lower mean scores were observed for those with late AMD lesions, overall and specifically for geographic atrophy and neovascular AMD, compared with those without AMD. With the use of concatenated bilateral severity levels for AMD, decreases in the NEI-VFQ-25 composite and individual scale scores were observed at the transition from a unilateral to bilateral severity level of 40, which corresponds to having bilateral soft drusen (>125 μm in diameter with drusen area ≥196 350 μm2) and depigmentation of retinal pigment epithelium (slope of -19.17 for the NEI-VFQ-25 composite score). Measures of general health, as assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey, were not affected in this cohort. In this study of adult Latinos, early AMD lesions are associated with lower self-reported, vision-specific HRQoL but not general HRQoL. Severity and bilaterality of AMD are associated with measurably lower HRQoL scores, with the largest difference in scores occurring for individuals with both eyes affected. A concatenated approach to incorporate bilateral severity might be more useful and provide better insight into the association of AMD and HRQoL.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis

To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. Prospective cohort study. A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. Incident early and late AMD. The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P= 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

RETINAL ANGIOMATOUS PROLIFERATION: A Quantitative Analysis of the Fundoscopic Features of the Fellow Eye.

To quantitatively analyze and compare the fundoscopic features between fellow eyes of retinal angiomatous proliferation and typical exudative age-related macular degeneration and to identify possible predictors of neovascularization. Retrospective case-control study. Seventy-nine fellow eyes of unilateral retinal angiomatous proliferation (n = 40) and typical exudative age-related macular degeneration (n = 39) were included. Fundoscopic features of the fellow eyes were assessed using digital color fundus photographs taken at the time of diagnosis of neovascularization in the first affected eye. Grading was performed by two independent graders using RetmarkerAMD, a computer-assisted grading software based on the International Classification and Grading System for age-related macular degeneration. Baseline total number and area (square micrometers) of drusen in the central 1,000, 3,000, and 6,000 μm were considerably inferior in the fellow eyes of retinal angiomatous proliferation, with statistically significant differences (P < 0.05) observed in virtually every location (1,000, 3,000, and 6,000 μm). A soft drusen (≥125 μm) area >510,196 μm2 in the central 6,000 μm was associated with an increased risk of neovascularization (hazard ratio, 4.35; 95% confidence interval [1.56-12.15]; P = 0.005). Baseline fundoscopic features of the fellow eye differ significantly between retinal angiomatous proliferation and typical exudative age-related macular degeneration. A large area (>510,196 μm2) of soft drusen in the central 6,000 μm confers a significantly higher risk of neovascularization and should be considered as a phenotypic risk factor.

Prevalence of age‐related macular diseases in an old French population (the MONTRACHET Study)

PurposeTo describe the prevalence of age‐related macular diseases in a French population‐based study (the Montrachet study) older than 74 years.MethodsThe Three City study (3C) was a prospective study including 9294 patients aged of 65 years or more from three French cities (Dijon, Bordeaux, and Montpellier) at enrolment in 1999. After 10 years of follow‐up, an eye examination was proposed to participants of the 3C cohort in Dijon and 1153 participants were included in the so‐called Montrachet study. All patients underwent a complete eye examination including nonmydriatic color retinal photographs. The photographs were classified according to the type of abnormality (intermediate soft drusen, large soft distinct or indistinct drusen, reticular drusen or large area of soft drusen reaching 500 µm in diameter, hyperpigmentation or hypopigmentation), and their location (central or pericentral) using the classification of the Multi‐ethnic Study of Atherosclerosis (MESA) and that used in the Rotterdam Study. Patients were then classified into 3 categories: early age‐related macular degeneration (AMD), late AMD (atrophic or neovascular).ResultsData were available for 1069 patients: 396 men (37.0%) and 673 women (63.0%). The mean age was 82.2 ± 3.8 years. The prevalence of healthy subjects was 56.0%. Stages 1, 2 and 3 accounted for 32.6%, 7.7% and 1.5%, respectively. The late AMD stages represented 2.2% (24 patients). Smoking was not significantly associated with AMD categories.ConclusionsThe prevalence of AMD grading in our population is consistent with the literature. The classification of participants according to different macular abnormalities may predict the populations at risk of developing an advanced grade and can help to adapt the management. The relationship with other risk factors will be the next step of this analysis.

Drusen Quantification for Early Identification of Age Related Macular Degeneration

Age-related macular degeneration (AMD) is a degenerative disorder in people of age 50 and above, in developed nations, characterized on grading of color fundus images by the presence of pathologies such as drusen in macular area. Currently, there is no treatment which can cure irreversible blindness due to age-related macular degeneration. Therefore, the only feasible option is to prevent the incidence of age-related macular degeneration and avoid this unnecessary vision loss. This paper presents an automated method for early diagnosis of AMD by quantifying drusen on the basis of its size, number and area in macular region from standard color retinal images. Previously used methods, generating unsatisfactory results in some cases, are time consuming, complex and prone to error. Therefore, this paper provides a simple drusen detection and quantification method to detect the exact number of drusen , area and size as well as classify drusen into small, intermediate and soft or large which will further help in initial screening of early stage of age-related macular degeneration and its progression i.e. change in drusen area. The proposed method achieved 93.2% accuracy for drusen detection and 91.8% accuracy in small drusen, 98.66% in intermediate drusen and 92.91% in soft drusen quantification in order to grade the severity of AMD which outwits the other methods.

Ganglion Cell–Inner Plexiform Layer and Peripapillary Retinal Nerve Fiber Layer Thicknesses in Age-Related Macular Degeneration

To investigate changes of inner retinal layers and optic nerve head (ONH) in patients with dry age-related macular degeneration (AMD) and demonstrate the pattern of these changes. A total of 76 eyes classified as having dry AMD and 76 control eyes were included. Ophthalmologic evaluations included best-corrected visual acuity (BCVA) assessment, spectral-domain optical coherence tomography (SD-OCT), and Humphrey visual field (VF) test. The drusen area and volume were determined using the automated algorithm of the SD-OCT software. Macular ganglion cell-inner plexiform layer (mGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses and ONH parameters, as well as VF parameters, were compared between groups. Macular GCIPL thickness was significantly lower in eyes with AMD than in controls (73.83 ± 7.13 vs. 82.00 ± 4.85 μm; P < 0.001), and mGCIPL thinning was observed in a ring-shaped pattern around the fovea. The pRNFL thickness was also significantly lower in eyes with AMD than in controls (88.69 ± 6.93 vs. 93.96 ± 8.33 μm; P < 0.001), but no significant difference in ONH parameters was found. An inverse correlation between drusen area and average mGCIPL thickness was found (r = -0.3253; P = 0.0064). Best-corrected visual acuity and VF parameters were worse in AMD eyes than in controls. The pattern of VF defects was mostly consistent with foveal or parafoveal scotoma. In eyes with dry AMD, mGCIPL and pRNFL thicknesses were lower than measurements in control eyes, and the average mGCIPL thickness was negatively correlated with the drusen area. However, the pattern of these changes differed from glaucomatous abnormalities.

Incidence, Progression, and Associated Risk Factors of Medium Drusen in Age-Related Macular Degeneration: Findings From the 15-Year Follow-up of an Australian Cohort.

The natural course and prognosis of medium drusen and risk factors associated with the incidence and progression of this lesion type in age-related macular degeneration (AMD) are not well understood. To assess the 15-year incidence and progression of medium drusen and associated risk factors. Population-based cohort in the Blue Mountains region, west of Sydney, Australia. Included in the study were 3654 participants 49 years or older who attended baseline examinations of the Blue Mountains Eye Study (1992-1994), and 75.8%, 76.7%, and 56.1% of survivors who attended the 5-year, 10-year, and 15-year follow-up examinations, respectively. Color retinal fundus photographs were obtained at each examination. The incidence and progression of medium drusen (maximum diameter, 63 to <125 µm) were assessed using Kaplan-Meier product-limit survival methods, controlling for competing risk of death. Factors associated with a 15-year incidence of medium drusen were assessed using discrete logistic regression models after adjusting for age, sex, smoking status, serum lipid levels, systemic and dietary factors, and CFH rs1061170 and ARMS2 rs10490924 polymorphisms. Associations between lesion characteristics and the progression to late AMD were assessed using generalized estimating equation models and eye-specific data. Among 1317 participants at risk, the 15-year cumulative incidence of medium drusen was 13.9% (n = 281). Increasing age (per decade older) (odds ratio [OR], 1.4; 95% CI, 1.2-1.8) and the presence of at least 3 risk alleles of the CFH rs1061170 or ARMS2 rs10490924 genes (OR, 2.1; 95% CI, 1.1-4.1) were associated with a higher incidence. There was no association between past smoking (OR, 0.8; 95% CI, 0.6-1.1) or current smoking (OR, 0.6; 95% CI, 0.4-1.1) and the development of medium drusen. The progression rate to late AMD in eyes with both medium drusen and retinal pigmentary abnormalities was 4-fold higher than that in eyes with medium drusen alone. Larger total area and central location of medium drusen were associated with a greater likelihood of the progression to worse stages of AMD. Older age and the presence of CFH and ARMS2 risk alleles are 2 main risk factors associated with the development of medium drusen. The copresence of medium drusen plus retinal pigment epithelium abnormalities signals a greater risk of the progression to late AMD than the presence of medium drusen alone.

Age-related macular degeneration phenotypes associated with mutually exclusive homozygous risk variants in CFH and HTRA1 genes.

To determine age-related macular degeneration (AMD) phenotypes associated with mutually exclusive homozygotic risk variants in rs1061170 (CFH) and rs11200638 (HTRA1). Nested case-control study of 2,982 eyes (2,129 control, 809 drusen ≥125 μm, 44 advanced AMD) homozygous for CFH [TT or CC] and HTRA1 [GG or AA] were analyzed using logistic regression and generalized estimating equations specifically regards to homozygous risk variants in one but homozygous no-risk in the other gene. In early AMD, [CFH HTRA1] and [CFH HTRA1] were associated with central drusen (odds ratio [95% confidence interval] = 4.13 [2.97-5.73] and 3.65 [1.88-7.09], respectively). However, only [CFH HTRA1] was associated with central drusen occupying ≥50% area (13.9 [2.97-64.7]). In advanced AMD, [CFH HTRA1] was associated with geographic atrophy (4.04 [1.57-10.4]), whereas [CFH HTRA1] was associated with neovascular AMD (36.5 [8.3-160.9]). In doubly homozygous risk groups [CFH HTRA1], odds ratios were multiplicative. Central but not peripheral drusen location was strongly associated with both [CFH HTRA1] and [CFH HTRA1]. Only [CFH HTRA1] was significantly associated with increased central drusen area.

Small Drusen and Age-Related Macular Degeneration: The Beaver Dam Eye Study.

We tested the hypothesis that large areas of small hard drusen (diameter <63 µm) and intermediate drusen (diameter 63–124 µm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least two consecutive visits spaced five years apart over a 20-year period were included. A 6-level severity scale, including no drusen, four levels of increasing area (from minimal (<2596 µm²) to large (>9086 µm²)) of only small hard drusen, and intermediate drusen, was used. The five-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (p < 0.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p < 0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.