Autofluorescence imaging in age-related macular degeneration complicated by choroidal neovascularization: a prospective study.

PURPOSE: To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. METHODS: Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. MAIN OUTCOME MEASURES: Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. RESULTS: Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. CONCLUSION: Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment.

Autofluorescence imaging of choroidal neovascularization due to age-related macular degeneration.

OBJECTIVE: To describe the autofluorescence (AF) characteristics of choroidal neovascularization (CNV) in patients with age-related macular degeneration. METHODS: Autofluorescence images of 65 consecutive eyes with CNV at various stages of evolution were analyzed. Twenty images were of recent-onset CNV (group 1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were late-stage CNV (group 3). Autofluorescence images from groups 1 and 2 were compared with fundus fluorescein angiographic images. RESULTS: Group 1 showed areas of hyperfluorescence on fundus fluorescein angiography corresponding to areas of normal AF in 16 of 20 cases, with adjacent areas of increased AF in 13 cases. The main areas of abnormal AF were larger than the main areas of abnormal fluorescence on fundus fluorescein angiography in 18 of the 20 cases. Groups 2 and 3 showed areas of decreased AF corresponding to areas of previous leakage on fundus fluorescein angiography (in group 2) or atrophy. CONCLUSIONS: Preserved AF in group 1 indicates viable retinal pigment epithelium initially, which has implications for visual prognosis. Decreased AF in groups 2 and 3 indicates loss of retinal pigment epithelium and photoreceptors. Autofluorescence imaging may increase our understanding of CNV in age-related macular degeneration.

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

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

What is lost by digitizing stereoscopic fundus color slides for macular grading in age-related maculopathy and degeneration?

OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN: Comparative observational case series. PARTICIPANTS: Twenty-five patients (50 eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least 1 eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral United Kingdom population. Retinal photography was performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on Ektachrome slide transparency film. The images were centered on the macula. The color transparencies were then digitized. The grading process has been set up based on the International ARM Epidemiology Study Group. All images were independently graded by 3 retinal specialists. Both kappa statistics and exact agreement were calculated to assess agreement between and within observers and between the 2 master copies derived from the gradings of the color slides and digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies derived from the gradings obtained from stereoscopic slide transparencies and digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93% (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was 94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93% (kappa, 0.78) for the area covered. For the presence of choroidal neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was 95% (kappa, 0.83) for the area covered. For individual features of CNV, exact agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and 2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because of the close agreement for most categories between the grading of stereoscopic color slides and digitized images, digitized nonstereoscopic color images prove to be useful for grading ARM and AMD.

Photopic and scotopic fine matrix mapping of retinal areas of increased fundus autofluorescence in patients with age-related maculopathy.

PURPOSE: To investigate photopic and scotopic sensitivity of retinal areas that show increased fundus autofluorescence (FAF) in patients with age-related maculopathy (ARM). METHODS: FAF was imaged with a modified confocal scanning laser ophthalmoscope (cSLO). Fine matrix mapping (FMM) was performed with a modified field analyzer. Photopic and scotopic thresholds were obtained at 100 locations on a 9 degrees x 9 degrees matrix with 1 degrees spacing, centered on a macular area of increased FAF. Inclusion criteria included ARM fundus changes, areas of increased FAF, central and stable fixation, and visual acuity of 20/40 or better. RESULTS: FAF images were reviewed in 436 patients with age-related maculopathy (ARM), of whom 38 met the inclusion criteria. FMM was performed in seven eyes of seven patients. Areas of increased FAF in patients with late ARM (choroidal neovascularization or geographic atrophy) showed normal or only mildly abnormal photopic, but severely reduced scotopic, sensitivity. The central area of increased FAF corresponding to a large foveal druse in a patient with ARM showed moderately reduced photopic and severely reduced scotopic sensitivity. In the other patients with ARM with drusen, areas of increased FAF showed normal or near-normal photopic sensitivity, but moderately reduced scotopic sensitivity. CONCLUSIONS: In retinal areas of increased FAF in patients with ARM, scotopic sensitivity loss considerably exceeded photopic sensitivity loss. This finding is in line with histologic data that have demonstrated a preferential loss of rods in ARM, but does not explain the magnitude of sensitivity loss. The study shows that increased FAF in ARM has a functional correlate.

Retinopathy of incontinentia pigmenti: a case report with thirteen years follow-up.

A spectrum of retinal features has been recognised in association with incontinentia pigmenti. The majority of reported cases describe a rapidly progressive proliferative retinopathy, often leading to retinal detachment, emphasizing the potentially blinding nature of the disease. In some instances, the retinopathy has been noted to be less severe but follow-up has been short. We describe a young girl with incontinentia pigmenti in whom the retinopathy has shown a fluctuating but stable course over 13 years without treatment.