Irene Leung

Agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula in the Reykjavik eye study

PurposeTo establish the agreement between image grading of conventional (45°) and ultra wide-angle (200°) digital images in the macula.MethodsIn 2008, the 12-year follow-up was conducted on 573 participants of the Reykjavik Eye Study. This study included the use of the Optos P200C AF ultra wide-angle laser scanning ophthalmoscope alongside Zeiss FF 450 conventional digital fundus camera on 121 eyes with or without age-related macular degeneration using the International Classification System. Of these eyes, detailed grading was carried out on five cases each with hard drusen, geographic atrophy and chorioretinal neovascularisation, and six cases of soft drusen. Exact agreement and κ-statistics were calculated.ResultsComparison of the conventional and ultra wide-angle images in the macula showed an overall 96.43% agreement (κ=0.93) with no disagreement at end-stage disease; although in one eye chorioretinal neovascularisation was graded as drusenoid pigment epithelial detachment. Of patients with drusen only, the exact agreement was 96.1%. The detailed grading showed no clinically significant disagreement between the conventional 45° and 200° images.ConclusionsOn the basis of our results, there is a good agreement between grading conventional and ultra wide-angle images in the macula.

The International Classification system and the progression of age-related macular degeneration.

Purpose: To determine whether grading based on the International Classification (IC) for age-related macular degeneration (AMD) allows recognition of change during the progression of the disease. Methods: Stereoscopic color fundus photographs of 50 eyes of 25 patients with AMD and at least 5 years of review were graded in a random and masked fashion for changes over time in the characteristics of drusen, pigmentary changes, and end-stage disease, according to the system defined by the IC for AMD, by two independent graders (F.B.S., I.L.). Fundus images were also analyzed in time sequence for clinical changes by a senior grader (I.L.) and two ophthalmologists (A.C.B., T.P.) without access to the grading forms of the IC grading. Clinical change, as recorded by the IC grading and the individual analysis, were compared. Results: There was 97.8% (κ = 0.70) concordance in identification of change. In four cases, the clinical classification differed from the IC grading: Two cases of drusen and two of end-stage disease grading. Inter-observer agreement for the IC grading was 89.4% for predominant phenotype (κ = 0.84), 89.36–91.49% for presence of choroidal neovascularization (CNV) (κ = 0.79–0.83), 87.23–89.36% for geographic atrophy (GA) (κ = 0.62–0.74) and 55.32% for area covered by drusen (κ = 0.31). Conclusions: Overall, progression from earlier stages of AMD to either of the two forms of advanced AMD were reflected accurately by the IC grading in the vast majority of cases.

Multimodal imaging in type 2 idiopathic macular telangiectasia

Background: Macular telangiectasia Type 2 is a bilateral, progressive potentially blinding retinal disease characterized by both vascular and neurodegenerative signs that have been documented using different imaging techniques. The correlation between macular telangiectasia Type 2 signs from various imaging modalities is unknown. Our aim was to investigate the relationship of various macular telangiectasia Type 2 signs using fundus fluorescein angiography, optical coherence tomography and dual-wavelength autofluorescence images. Methods: Participants were selected from the macular telangiectasia Type 2 Natural History Observation Study, based on a confirmed diagnosis and the availability of images. Signs in fundus fluorescein angiography, dual-wavelength autofluorescence, and optical coherence tomography images were graded according to standardized categories, and agreement among the multimodel imaging was assessed statistically. Results: One hundred and ninety-one eyes of 96 patients were examined. Significant correlations were found between early and late fundus fluorescein angiography (&rgr; = 0.82, P < 0.0001), luteal pigment loss and early/late fundus fluorescein angiography signs (&rgr; = 0.52, P < 0.0001 and &rgr; = 0.62, P < 0.0001, respectively), inner and outer segment break length and pigment loss (Class 1 vs. 2/3, P < 0.0001; Class 2 vs. 3, P = 0.04). Correlation between pigment loss and retinal spaces/atrophic retinal restructuring was fair (&kgr; = 0.25–0.33). Bilateral symmetry was slight to substantial (&kgr; = 0.18–0.62). Conclusion: Our data demonstrate the relative extent of neurodegenerative and vascular signs; it may be useful for designing systems for staging disease severity using multimodal imaging and may also provide clues to the pathogenesis of the disease.

A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration–Like Lesions at the Peripheral Retina

PURPOSE Our understanding of the relevance of peripheral retinal abnormalities to disease in general and in age-related macular degeneration (AMD) in particular is limited by the lack of detailed peripheral imaging studies. The purpose of this study was to develop image grading protocols suited to ultra-widefield imaging (UWFI) in an aged population. DESIGN A cross-sectional study of a random population sample in which UWFI was introduced at the 12-year review of the Reykjavik Eye Study in Iceland. PARTICIPANTS Five hundred seventy-six subjects 62 years of age or older. METHODS Ultra-widefield (up to 200°) color and autofluorescence images were obtained using the Optos P200CAF laser scanning ophthalmoscope (Optos plc, Dunfermline, Scotland). The images were graded at Moorfields Eye Hospital Reading Centre primarily based on the International Classification for AMD. Macular and peripheral changes were graded using a standardized grid developed for this imaging method. MAIN OUTCOME MEASURES Presence or absence of hard, crystalline, and soft drusen; retinal pigment epithelial changes; choroidal neovascularization (CNV); atrophy; and hypoautofluorescence and hyperautofluorescence were graded in the peripheral retina. RESULTS Of the eyes examined, 81.1% had AMD-like changes in the macula alone (13.6%), periphery alone (10.1%), and both periphery and macula (57.4%). There was no AMD-like CNV or pigment epithelial detachment in the periphery except in those cases in which these clearly originated from the macula. Seven patients had AMD-like atrophy in the periphery without end-stage disease in the macula. One patient with end-stage disease in the macula had normal periphery results on the color images. While analyzing the eyes, we detected pathologic appearances that were very reliably identified by graders. CONCLUSIONS Phenotyping the retinal periphery using the categories defined by the International Classification confirmed the presence of wide-ranging AMD-like pathologic changes even in those without central sight-threatening macular disease. Based on our observations, we propose here new, reliably identifiable grading categories that may be more suited for population-based UWFI.

Prevalence of age-related macular degeneration in Nakuru, Kenya: a cross-sectional population-based study.

Using digital retinal photography and slit lamp examination in a population-based sample in the Nakuru District of Kenya, Andrew Bastawrous and colleagues determined the prevalence of age-related macular degeneration in adults 50 years and older.

Prevalence and correlates of diabetic retinopathy in a population-based survey of older people in Nakuru, Kenya.

Abstract Purpose: To estimate the prevalence of and factors associated with diabetic retinopathy (DR) among people aged ≥50 years in Nakuru, Kenya. Methods: Probability-proportional-to-size sampling was used to select 100 clusters of 50 people aged ≥50 years during 2007–2008. Households within clusters were selected through compact segment sampling. Participants underwent dilated slit lamp biomicroscopy (SLB) by an ophthalmologist and digital retinal photography. Images were graded for DR at the Moorfields Eye Hospital Reading Centre, UK. Diagnosis of DR was based on retinal images where available, otherwise on SLB. Anthropometric measures, including random glucose, and lifestyle factors were measured. Results: We examined 4414 adults (response rate 88.1%), of whom 287 had diabetes. A total of 277 of these were screened for DR by SLB, and 195 also underwent retinal photography. The prevalence of any DR diagnosed by retinal images among diabetics was 35.9% (95% confidence interval, CI, 29.7–42.6%). The most common grade of DR was mild/moderate non-proliferative DR (NPDR; 22.1%, 95% CI 16.1–29.4%), while severe NPDR and proliferative DR were less frequent (13.9%, 95% CI 10.0–18.8%). SLB significantly underdiagnosed DR compared to retinal photography, particularly for milder grades. Of 87 individuals with DR, 23 had visual impairment (visual acuity <6/12). DR was associated with younger age, male sex, duration and control of diabetes, and treatment compliance. Coverage of photocoagulation in those needing immediate laser was low (25%). Conclusion: DR remains a threat to sight in people with diabetes in this elderly Kenyan population. Screening diabetics may enable those requiring treatment to be identified in time to preserve their sight.

The symmetry of phenotype between eyes of patients with early and late bilateral age-related macular degeneration (AMD)

BackgroundMacular degeneration is known to be a bilateral disease. This study set out to determine the symmetry of phenotype between eyes of patients with bilateral early AMD (or drusen) or late-stage AMD. This may be important information when considering the likelihood of anti-VEGF treatment.MethodsThis prospective, observational, cross-sectional study graded the color fundus photographs of both eyes of 1,114 Caucasian patients with either early or late-stage AMD. Patients were recruited from a tertiary referral UK population. The main outcomes were phenotype, comparison of number, type and overall area of drusen in early AMD and symmetry of late AMD.ResultsThe overall agreement of phenotype in the entire cohort of patients was 53%, kappa statistic (κ)=0.31, (95% CI = 0.27–0.36). Within this group, a total of 271 patients were identified with bilateral soft and hard drusen (early AMD). Symmetry of phenotype within this group was high in terms of total of area of drusen (agreement = 79%, weighted κ = 0.75) and number of drusen. In those with bilateral geographic atrophy (GA), symmetry between area of GA was moderate (agreement 72%, weighted κ = 0.54), and in those with bilateral neovascular disease (choroidal neovascularization or pigment epithelial detachment), symmetry was poor (agreement 45%, weighted κ = 0.16). Out of the entire cohort, 62% (n = 688) had neovascular disease in at least one eye and 37.5% of these had bilateral disease.ConclusionsThe observed symmetry of phenotype between eyes with drusen appears to reduce in GA and neovascular forms of AMD. Overall, 53% of the cohort had symmetrical disease in terms of phenotype, 23% had neovascular disease in both eyes, 9.3% had GA in both eyes, and 39% of patients had neovascular disease in one eye and non-neovascular disease in the other. This may have implications for the potential need for anti-VEGF treatment of AMD in second eye involvement.

Concordance of Macular Pigment Measurement Using Customized Heterochromatic Flicker Photometry and Fundus Autofluorescence in Age-Related Macular Degeneration

PURPOSE We compared macular pigment (MP) measurements using customized heterochromatic flicker photometry (Macular Metrics Densitometer) and dual-wavelength fundus autofluorescence (Heidelberg Spectralis HRA + OCT MultiColor) in subjects with early age-related macular degeneration (AMD). METHODS Macular pigment was measured in 117 subjects with early AMD (age, 44-88 years) using the Densitometer and Spectralis, as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787). Baseline and 6-month study visits data were used for the analyses. Agreement was investigated at four different retinal eccentricities, graphically and using indices of agreement, including Pearson correlation coefficient (precision), accuracy coefficient, and concordance correlation coefficient (ccc). RESULTS Agreement was poor between the Densitometer and Spectralis at all eccentricities, at baseline (e.g., at 0.25° eccentricity, accuracy = 0.63, precision = 0.35, ccc = 0.22) and at 6 months (e.g., at 0.25° eccentricity, accuracy = 0.52, precision = 0.43, ccc = 0.22). Agreement between the two devices was significantly greater for males at 0.5° and 1.0° of eccentricity. At all eccentricities, agreement was unaffected by cataract grade. CONCLUSIONS In subjects with early AMD, MP measurements obtained using the Densitometer and Spectralis are not statistically comparable and should not be used interchangeably in either the clinical or research setting. Despite this lack of agreement, statistically significant increases in MP, following 6 months of supplementation with macular carotenoids, were detected with each device, confirming that these devices are capable of measuring change in MP within subjects over time. (http://www.controlled-trials.com number, ISRCTN13894787.).

The prevalence of type 2 idiopathic macular telangiectasia in two African populations.

Purpose: Type 2 idiopathic macular telangiectasia (MacTel) is a progressive retinal disease associated with a slow deterioration of visual acuity, starting in the fifth to seventh decades of life. The etiology and pathogenesis of the disease are little known, and no effective therapy is available. We aimed to estimate the prevalence and describe the phenotype of type 2 MacTel in two African populations. Methods: From two population-based cross-sectional surveys conducted nationally in Nigeria and in the Nakuru district of Kenya, patients with fundus features of type 2 MacTel were selected. Diagnosis was based on color fundus images, grading performed according to the MacTel Study protocol and staged using the Gass and Blodi system. Disease phenotype and clinical characteristics of affected participants were assessed. Results: Of 8599 total participants, five showed a phenotype compatible with type 2 MacTel. Prevalence was estimated as 0.06% (95% confidence interval [CI] 0.02–0.21%) in Kenya, 0.06% (95% CI 0.01–0.17%) in Nigeria, and overall at 0.06% (95% CI 0.02–0.14%). Mean age was 62 years (SD 5 years), four of five affected participants were female, and none had a history of diabetes. Median corrected visual acuity was 6/12 in the better eye and 6/69 in the worse eye. Conclusions: The estimated prevalence and phenotype of type 2 MacTel in the African populations examined were similar to those in predominantly white populations. All data published so far are based on the analysis of color fundus images only and are thus likely to underestimate the true prevalence of this disease.

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial

Purpose The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. Methods In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. Results There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05). Conclusions Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).