Macular Degeneration: Applegate CA

Sunness JS, Applegate CA, Gonzalez-Baron J. · Lions Vision Research and Rehabilitation Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Retina. · Pubmed #10783949 No free full text.

Abstract: 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.

Sunness JS, Rubin GS, Broman A, Applegate CA, Bressler NM, Hawkins BS. · The Richard E Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Ophthalmology. · Pubmed #18486216 No free full text.

Abstract: OBJECTIVE: To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD). DESIGN: Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute. PARTICIPANTS: Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination. METHODS: Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm(2) circle centered on the fovea. MAIN OUTCOME MEASURES: Visual acuity loss at 2 years and risk factors for visual loss. RESULTS: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13-7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39-12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11-5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm(2) than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm(2). The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate. CONCLUSIONS: Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials.

Sunness JS, Applegate CA, Bressler NM, Hawkins BS. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Retina. · Pubmed #17290203 No free full text.

Abstract: PURPOSE: To derive information from the Geographic Atrophy (GA) Natural History Study that is relevant to recruiting patients and designing clinical trials for GA. METHODS: A prospective natural history study with annual follow-up enrolled patients with GA and no choroidal neovascularization (CNV) in at least one eye. Characteristics of recruited and enrolled patients are analyzed, in the context of progression data from the study. RESULTS: The data show that GA from age-related macular degeneration (AMD) was seen in 82% of the referred patients, there was an attrition rate of 14%, and 60% of the patients with GA from AMD had bilateral GA without CNV. Within the 83 patients in the bilateral GA group with follow-up, 50 patients (60%) met both the proposed visual acuity and the proposed GA area criteria for a treatment trial in one or both eyes. CONCLUSION: These data should be helpful in planning future treatment trials for GA.

Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, Hawkins BS, Bressler NM. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, Greater Baltimore Medical Center, Baltimore, Maryland 21204, USA. · Ophthalmology. · Pubmed #17270676 links to  free full text

Abstract: PURPOSE: To report the enlargement rate of geographic atrophy (GA) over time, its relationship to size of atrophy at baseline and to prior enlargement rate, and the implications for designing future treatment trials for GA. DESIGN: Prospective natural history study of GA resulting from age-related macular degeneration. PARTICIPANTS: Two hundred twelve eyes of 131 patients were included in the analysis. METHODS: Annual follow-up included stereo color fundus photographs. The areas of GA were identified and measured, and the rate of enlargement of the atrophy was assessed. Sample sizes for clinical trials using systemic treatment and uniocular treatment were determined. MAIN OUTCOME MEASURE: Rate of enlargement of the atrophy. RESULTS: The median overall enlargement rate was 2.1 mm2/year (mean, 2.6 mm2/year). Eyes with larger areas of atrophy at baseline tended to have larger enlargement rates, but knowledge of prior rates of enlargement was the most significant factor in predicting subsequent enlargement rates. There was high concordance between the enlargement rates in the 2 eyes of patients with bilateral GA (correlation coefficient, 0.76). To detect a 25% reduction in enlargement rate for a systemic treatment (alpha, 0.05; power, 0.80; losses to follow-up, 15%), 153 patients each in a control and treatment group would be required for a trial with a 2-year follow-up period for each patient. For a uniocular treatment, 38 patients with bilateral GA would be required, with the untreated eye serving as a control for the treated eye. CONCLUSIONS: Treatment trials for GA with an outcome variable of change in enlargement rate are feasible.

Sunness JS, Ziegler MD, Applegate CA. · Richard E. Hoover Rehabilitation Services for Low Vision and Blindness, the Greater Baltimore Medical Center, Maryland 21204, USA. · Retina. · Pubmed #16829810 No free full text.

Abstract: 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.

Sunness JS, Applegate CA. · Greater Baltimore Medical Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21204, USA. · Am J Ophthalmol. · Pubmed #16376656 links to  free full text

Abstract: PURPOSE: To study whether fixation patterns changed over time in patients with central scotomas from geographic atrophy from age-related macular degeneration. DESIGN: Prospective cohort study. METHODS: setting: Institutional. patient or study population: Prospective natural history study of geographic atrophy included 34 eyes of 25 patients with baseline acuity between 20/80 and 20/200 and with subsequent follow-up. observation procedures: Baseline and annual follow-up visits included best-corrected visual acuity, scanning laser ophthalmoscope macular perimetry, reading rate, and clinical evaluation. main outcome measures: Location of eccentric preferred retinal locus for fixation (PRL). RESULTS: At baseline, 77% of study eyes had a PRL. At the final visit (median follow-up, 5.3 years), 91% of study eyes had a PRL, with 81% of the eyes retaining the baseline PRL location. Fixation with the scotoma to the right and fixation with the scotoma superior were the first and second most common fixation patterns, respectively. Reading rates of <50 words/min were present in 54% of eyes. Eyes fixating with the scotoma to the left tended to have lower reading rates than eyes fixating with right or superior patterns. CONCLUSION: Fixation with right pattern remained the most common fixation pattern, both in patients with a PRL at baseline and in patients who had a PRL during follow-up. Eyes with a PRL at baseline generally retained this pattern. The reading rate data suggest an advantage of fixation with right or superior pattern, rather than left. Reading rate declined further during follow-up in most patients.

Sunness JS, Gonzalez-Baron J, Applegate CA, Bressler NM, Tian Y, Hawkins B, Barron Y, Bergman A. · Wilmer Ophthalmological Institute, Lions Vision Research and Rehabilitation Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #10485549 No free full text.

Abstract: OBJECTIVE: To describe the progression of geographic atrophy (GA) from age-related macular degeneration (AMD) with respect to visual acuity (VA) loss and enlargement of atrophy. DESIGN: A prospectively observed case series. SETTING: Tertiary retinal referral center. PARTICIPANTS: One hundred twenty-three patients with GA due to AMD who completed at least 1 year of follow-up (median follow-up, 3 years) were examined annually. METHODS: At each examination, a protocol best-corrected VA of each eye was measured, a clinical examination was performed, and color fundus photographs were taken. The areas of atrophy were drawn and measured. MAIN OUTCOME MEASURES: Visual acuity loss and enlargement of total and central atrophy. RESULTS: At baseline, median VA was poorer with larger areas of atrophy, but there was wide variation related to sparing of the fovea. Thirty-one percent of all study eyes suffered a three-line VA loss from baseline by 2 years, and 53% had a three-line loss by 4 years. Those eyes with VA better than 20/50 had the highest rate of acuity loss; 27% of these eyes had acuities of 20/200 or worse at 4 years. Visual acuity loss in the GA study eye was similar in patients with bilateral GA and in those with choroidal neovascularization in the fellow eye. Total atrophy enlarged a median of 1.8 Macular Photocoagulation Study disc areas (DA) at 2 years; atrophy within a 4-DA circle centered on the fovea enlarged a median of 0.9 DA. Two (22%) of nine patients with GA in one eye and only drusen without advanced AMD in the fellow eye developed GA in the fellow eye at 2 years. CONCLUSIONS: Geographic atrophy is associated with a significant decline in VA over time in many eyes. Areas of atrophy continue to enlarge over time, even when already large at baseline. The combination of reduced VA with enlargement of atrophy, occurring bilaterally in most patients, can lead to significant impairment of visual function.

Sunness JS, Bressler NM, Tian Y, Alexander J, Applegate CA. · Lions Low Vision Center, The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. · Invest Ophthalmol Vis Sci. · Pubmed #10393046 links to  free full text

Abstract: PURPOSE: To present a method developed for measuring areas of geographic atrophy (GA) in advanced age-related macular degeneration, METHODS: A microfilm reader projected the 30 degrees fundus photograph of the macula. Retinal landmarks, atrophic areas, and spared areas within the atrophy were traced, without access to drawings of other years. The total atrophic area was calculated, as was the atrophy within a four-disc-area circle entered on the estimated foveal center. The configuration of the atrophy was documented. RESULTS: Avoidable sources of discrepancy included variability in peripapillary atrophy seen on the photograph, and variability seen in the extent of the field. Reproducibility studies found a median absolute difference of 0.19 Macular Photocoagulation Study disc areas (DA) in total atrophy between repeat drawings, with 75% of repeat drawings having a difference of less than 0.33 DA. For central atrophy measures, there was a median difference of 0.08 DA, with 75% of pairs having a difference of less than 0.18 DA. Features making the definition of borders of GA difficult include the presence of drusen and pigmentary alteration, a fundus in which choroidal vessels are easily visible, and variation in the appearance of GA within a single area of atrophy. CONCLUSIONS: This method provides a reliable means of measuring the size of atrophic areas in GA and will be useful for measuring longitudinal change. It may be difficult to determine whether central spared areas are present, and correlation with visual acuity and macular perimetry may be helpful.

Sunness JS, Gonzalez-Baron J, Bressler NM, Hawkins B, Applegate CA. · Lions Vision Research and Rehabilitation Center, Baltimore, Maryland, USA. · Ophthalmology. · Pubmed #10328389 No free full text.

Abstract: 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.