Carol A. Applegate

Visual Function Abnormalities and Prognosis in Eyes with Age-related Geographic Atrophy of the Macula and Good Visual Acuity

PURPOSE Geographic atrophy (GA) may cause significant compromise of visual function, even when there still is good visual acuity (VA), because of parafoveal scotomas and foveal function abnormalities antedating visible atrophy. This study evaluates the visual function abnormalities at baseline and the 2-year worsening of VA and reading rate for eyes with GA compared with a group of eyes with drusen only. METHODS Seventy-four eyes with GA and VA greater than or equal to 20/50 from a prospective natural history study of GA were included, as were 13 eyes with only drusen. Baseline visual function testing and 2-year VA and maximum reading rate are reported. RESULTS The worsening of VA in decreased luminance and foveal dark-adapted sensitivity showed severe abnormalities for the GA group. Contrast sensitivity was significantly reduced for the eyes with GA. Half the eyes with GA, but none of the drusen eyes, had maximum reading rates below 100 words per minute. A scanning laser ophthalmoscope (SLO) measure of the scotoma near fixation combined with a measure of residual foveal function accounted for 54% of the variability in maximum reading rate in the eyes with GA. Of 40 eyes with GA observed for 2 years, half lost greater than or equal to 3 lines of VA and one quarter lost greater than or equal to 6 lines. The nine eyes with drusen with follow-up had no significant change in VA. Low foveal dark-adapted sensitivity, SLO measures of the scotoma within 1 degree of fixation, and low maximum reading rate were statistically significant risk factors for doubling of the visual angle. Significant reduction in maximum reading rates at 2 years was present for the eyes with GA. CONCLUSIONS The eyes with GA with good VA have profound decreases in visual function, particularly in dim lighting and in reading. Half the eyes with GA had doubling in visual angle at 2 years after the baseline examination, whereas the drusen eyes remained essentially unchanged. Impaired visual function at baseline was predictive of an adverse outcome for the eyes with GA.

The development of choroidal neovascularization in eyes with the geographic atrophy form of age-related macular degeneration.

OBJECTIVE To determine the rate of developing choroidal neovascularization (CNV) in eyes with geographic atrophy (GA) from age-related macular degeneration (AMD) and the characteristics of the CNV in these eyes. DESIGN Prospective natural history study with cohort analysis. PARTICIPANTS One hundred fifty-two patients with GA and no CNV by fluorescein angiography in at least 1 eye, with annual follow-up. MAIN OUTCOME MEASURES The development of CNV. RESULTS Thirteen eyes with GA developed CNV. For patients with bilateral GA and no CNV at baseline, 2% developed CNV by 2 years and 11% by 4 years. For patients with CNV in the fellow eye, 18% developed CNV in the study eye with GA by 2 years and 34% by 4 years. The eyes that developed CNV experienced more acuity loss than did the eyes with only GA. Within the fellow eye CNV group, those study eyes with GA that had less central atrophy (and better acuity) at baseline were more likely to develop CNV. The CNV developed at a peripheral border of GA in nine eyes, in the spared foveal region in two eyes, and in both center and border in one eye. No eye developed CNV in the area of atrophy itself. The appearance of CNV was evanescent in some cases and had a final appearance of an enlarged area of GA. Twelve other eyes had hemorrhages without definite evidence of CNV; three were thought to be suspicious for CNV and the remainder were thought to be hemorrhages that may be seen in elderly patients. CONCLUSION An eye with GA whose fellow eye has CNV is at significant risk for the development of CNV in the GA eye. A patient with bilateral GA and no evidence of CNV is at relatively low risk for developing CNV. The CNV may be evanescent and may not be detected. Intraretinal hemorrhages unrelated to CNV are relatively common in this older population.

Issues in quantifying atrophic macular disease using retinal autofluorescence.

Purpose: To demonstrate the potential and limits of autofluorescence imaging in identifying and delineating areas of atrophy. Methods: Fundus photographs and infrared scanning laser ophthalmoscope (SLO) imaging, SLO macular perimetry, and SLO autofluorescence imaging results were compared for two patients with geographic atrophy (GA) from age-related macular degeneration, one patient with pigmentary alteration of the retina, and two patients with Stargardt disease. The main outcome measure in this case series was the presence of reduced autofluorescence. Results: Drusen may become undetectable during autofluorescence imaging for some patients, allowing simple identification of areas of GA with areas of reduced autofluorescence. In other patients, drusen themselves have decreased autofluorescence, despite having intact retinal function in the retina overlying them. Some patients may have areas of reduced autofluorescence that persist for many years, without evidence of the development of atrophy. In Stargardt disease, decreased autofluorescence can easily detect and delineate areas of scotoma. Areas with mottled autofluorescence may have overlying function, but the function may not be adequate to support a fixation locus in that area. Conclusions: Using decreased autofluorescence to delineate areas of atrophy may be helpful in atrophic macular disorders. For GA, correlation with fundus photographs or macular perimetry findings may be necessary to differentiate between drusen and atrophy. For Stargardt disease, the nature of areas of decreased autofluorescence may help explain visual function of those areas.

Improvement of visual acuity over time in patients with bilateral geographic atrophy from age-related macular degeneration.

Purpose: To study the improvement in visual acuity over time in patients with central scotomas. Methods: In a prospective natural history study of geographic atrophy (GA) from age‐related macular degeneration (ARMD) with annual follow‐up, 36 patients with bilateral GA completed 3 years of follow‐up. Protocol visual acuity (VA) measurements were performed. Scanning laser ophthalmoscopy (SLO) was performed, and the areas of GA were measured from fundus photographs. Results: Six eyes of six patients with VA ranging from 20/80 to 20/500 had a VA improvement of two or more lines (mean, 3.2 lines). This was found only in the worse‐seeing eyes of the patients and was contemporaneous with the deterioration in VA of the better‐seeing eyes. Four of six eyes that improved in acuity had an improvement in the ability to find and hold the fixation target in an area of seeing retina, as assessed by SLO at follow‐up, and a fifth eye changed from one fixation site that had little functional retina to another site. Conclusions: Spontaneous improvement in VA in eyes with bilateral GA and central scotomas may occur. It appears to be related to deterioration in VA of the better‐seeing fellow eye and is associated with improvement of fixation in the worse‐seeing eye. The worse‐seeing eye of a patient with bilateral ARMD may have the potential for better vision than measured VA indicates. This finding may have implications for the choice of patients in treatment trials, for interpretation of long‐term results, and for planning and assessment of low vision intervention.

Automated Image Alignment And Segmentation To Follow Progression Of Geographic Atrophy In Age-related Macular Degeneration

Purpose: To develop a computer-based image segmentation method for standardizing the quantification of geographic atrophy (GA). Methods: The authors present an automated image segmentation method based on the fuzzy c-means clustering algorithm for the detection of GA lesions. The method is evaluated by comparing computerized segmentation against outlines of GA drawn by an expert grader for a longitudinal series of fundus autofluorescence images with paired 30° color fundus photographs for 10 patients. Results: The automated segmentation method showed excellent agreement with an expert grader for fundus autofluorescence images, achieving a performance level of 94 ± 5% sensitivity and 98 ± 2% specificity on a per-pixel basis for the detection of GA area, but performed less well on color fundus photographs with a sensitivity of 47 ± 26% and specificity of 98 ± 2%. The segmentation algorithm identified 75 ± 16% of the GA border correctly in fundus autofluorescence images compared with just 42 ± 25% for color fundus photographs. Conclusion: The results of this study demonstrate a promising computerized segmentation method that may enhance the reproducibility of GA measurement and provide an objective strategy to assist an expert in the grading of images.

MAPPING THE DENSE SCOTOMA AND ITS ENLARGEMENT IN STARGARDT DISEASE.

Purpose: To describe the enlargement of the dense scotoma over time in Stargardt disease and to highlight methodologic issues in tracking enlargement. Methods: Retrospective study of patients with full mapping of the border of the dense scotoma using the MP-1 for at least two visits. Results: 14 eyes of 7 patients met this criterion. Patients had median of 3 visits (range 2–5), with median total follow-up of 4.5 years (range 1.5–8). Mean baseline visual acuity was 20/56 (range 20/25–20/200), mean baseline dense scotoma area was 2.23 mm2 (range 0.41–5.48), and mean dense scotoma enlargement rate was 1.36 mm2/year (range 0.22–2.91). The younger patients tended to have more rapid loss of visual acuity, which tended to plateau when the visual acuity was 20/100 or worse. The patients who developed Stargardt before age 20 years, and the single patient who developed Stargardt disease after age 40 years, had more rapid enlargement rates, with preservation of central vision in the oldest patient. The ability to precisely define the dense scotoma area was dependent on the density location of the points tested; this led to significant variability in the assessment of the scotoma enlargement rate in three of the seven patients. The dense scotoma was not described adequately by the extent of the homogeneous dark area on fundus autofluorescence imaging. Conclusion: Microperimetry is necessary for mapping the scotoma in patients with Stargardt disease, because current imaging is not adequate. Standardized grid testing, plus a standardized procedure for refining the border of the dense scotoma, should allow more precise testing and longitudinal assessment of enlargement rates.