Macular Degeneration: Alexander J

Marcus DM, Peskin E, Maguire M, Weissgold D, Alexander J, Fine S, Followill D, Anonymous00162. · University of Pennsylvania, Department of Ophthalmology, Philadelphia, Pennsylvania, USA. · Am J Ophthalmol. · Pubmed #15531318 No free full text.

Abstract: PURPOSE: To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 x 4 Gy fractions among patients having age-related macular degeneration (AMD). DESIGN: A multicenter prospective randomized controlled pilot study. METHODS: Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41]) or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or >/=50% of the lesion [N = 13]). The primary outcome measure was loss of >/=3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects. RESULTS: At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost >/=3 lines of visual acuity (P = .04; stratified chi(2) test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost >/=3 visual acuity lines (P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy. CONCLUSIONS: External beam radiation at 5 x 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.

Marcus DM, Sheils WC, Young JO, McIntosh SB, Johnson MH, Alexander J, Samy CN. · Department of Ophthalmology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912, USA. · Br J Ophthalmol. · Pubmed #14693787 links to  free full text

Abstract: AIMS: To report the safety and visual outcome data of external beam irradiation for recurrent choroidal neovascularisation complicating age related macular degeneration. METHODS: Eighteen consecutive eyes received external beam irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16 consecutive eyes received external beam irradiation with five fractions of 3 Gy (total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of distance visual acuity at the three and six month follow up. At one year follow up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes. At one year follow up a decrease in visual acuity of three or more lines (moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes (p<0.36). At one year follow up a decrease in visual acuity of six or more lines (severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23). At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%) to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02). There were no significant differences in contrast sensitivity loss or fluorescein angiographic stabilisation rates. No evidence of radiation toxicity was observed. CONCLUSION: Our results are consistent with trends for a palliative benefit with higher fraction sizes and doses. The radiobiologic differences between low and high fraction size groups in this study are modest and correlate with the modest and short term difference in visual outcomes. These trends support further investigation of radiotherapy using fraction sizes of 4 Gy or higher.

Marcus DM, Sheils W, Johnson MH, McIntosh SB, Leibach DB, Maguire A, Alexander J, Samy CN. · Medical College of Georgia, Department of Ophthalmology, 1120 15th St, Augusta, GA 30912, USA. · Arch Ophthalmol. · Pubmed #11176977 No free full text.

Abstract: OBJECTIVES: To determine the effects of low-dose external beam irradiation compared with observation on the visual function of eyes with subfoveal choroidal neovascularization (CNV) complicating age-related macular degeneration (ARMD). DESIGN: Prospective, double-masked, randomized clinical trial. Patients randomized to the radiation group received external beam irradiation at a dose of 14 Gy in 7 fractions of 2 Gy. Patients randomized to the observation group received sham radiation. SETTING: Tertiary care retinal referral practice. PATIENTS: Individuals with classic, mixed, or occult subfoveal CNV secondary to ARMD. MAIN OUTCOME MEASURES: Change in visual acuity from baseline to specified time periods. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: Forty-two eyes were randomized to observation; 41 eyes, to radiation. Baseline characteristics and demographics did not differ between groups. The median distance visual acuity (DVA) in radiation-treated eyes decreased from 20/80 at baseline to 20/320 (mean loss rate, 4.14 lines) at 1-year follow-up. The median DVA in observation group eyes decreased from 20/125 at baseline to 20/250 (mean loss rate, 3.39 lines) at 1-year follow-up. There were no statistically significant differences in changes in DVA, contrast sensitivity, or fluorescein angiographic progression from baseline between groups at any follow-up period. CONCLUSIONS: At 1-year follow-up, low-dose external beam irradiation at 14 Gy in 7 fractions of 2 Gy is neither beneficial nor harmful for subfoveal CNV complicating ARMD.

Jefferys JL, Alexander J, Hiner CJ, Javornik NB, Smith RE, Bressler NM, Hawkins BS. · The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Ophthalmic Epidemiol. · Pubmed #18569815 No free full text.

Abstract: PURPOSE: To assess the reproducibility of the evaluation of color photographs and fluorescein angiograms of the macula of each eye for patients enrolled in the Macular Photocoagulation Study (MPS) trials of laser photocoagulation of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: A total of 65 pre-enrollment and 26 posttreatment sets of photographs were regraded. The two gradings were compared on selected items judged to be of primary importance with respect to the role of the MPS Reading Center. RESULTS: Agreement on eligibility of the neovascular lesion for an MPS trial was 88% (kappa statistic = 0.59); agreement on the size of the lesion was 86% (kappa statistic = 0.80); agreement on whether the lesion was covered by heavy treatment was 69% (kappa statistic = 0.35); and agreement on whether the treatment was in compliance with the study protocol was 73% (kappa statistic = 0.06). CONCLUSIONS: Interpretation of photographs of eyes with CNV secondary to age-related macular degeneration for eligibility and size of the lesion was reproducible in the MPS. However, adequacy of laser photocoagulation treatment could not be determined reliably from photographs.

Maguire MG, Alexander J, Fine SL, Anonymous00321. · Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-3309, USA. · Ophthalmology. · Pubmed #18486222 No free full text.

Abstract: OBJECTIVE: To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). DESIGN: Cross-sectional descriptive study within a multicenter, randomized clinical trial. PARTICIPANTS: Patients who developed CNV during CAPT follow-up. METHODS: Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. MAIN OUTCOME MEASURES: Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. RESULTS: Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were <or=2 MPS disc areas. Visual acuity was >or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. CONCLUSIONS: When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

Bressler SB, Silva JC, Bressler NM, Alexander J, Green WR. · No affiliation provided · Retina. · Pubmed #16049367 No free full text.

This publication has no abstract.

Yang Y, Vitale S, Ding Y, O'Connell SR, Alexander J, Bressler NM, Schachat AP, Zeimer R. · Department of Ophthalmology, Wonkwang Medical Science Center, Wonkwang University School of Medicine, Korea. · Ophthalmic Surg Lasers Imaging. · Pubmed #12569999 No free full text.

Abstract: OBJECTIVE: To evaluate the ability of a retina specialist's grading of 30 degrees color stereoscopic fundus photographs to identify areas of significant retinal thickening as assessed by the Retinal Thickness Analyzer (RTA) and to determine whether this ability was affected by the presence of retinal pathology. MATERIALS AND METHODS: Thirty-two eyes in 29 patients clinically diagnosed as having diabetic macular edema underwent RTA scanning and nonsimultaneous 30 degrees color stereoscopic fundus photography. Retinal thickness maps of the macular area were generated, and regions with significant retinal thickening (> or = 2 SD above normal values) were identified. A retina specialist reader, masked to the RTA measurements, identified areas with macular edema on the stereoscopic fundus photographs, which subsequently were overlaid on the retinal thickness maps. The sensitivity (percent of significant retinal thickening areas identified by the retina specialist grading the stereoscopic fundus photographs) was calculated separately for areas with and without retinal pathology. Specificity of the stereoscopic fundus photograph grading was assessed similarly. RESULTS: The retina specialist's stereoscopic fundus photography grading identified 78.8% of areas with significant retinal thickening (range over eyes: 20.4%-100%) and was slightly more likely to identify significant retinal thickening when pathology was present (89.6%) than when pathology was not present (78.4%; pooled risk ratio, 1.14 [95% CI = 0.54, 2.42]). Specificity of stereoscopic fundus photography grading was 58%, ie, 42% of areas without significant retinal thickening were (incorrectly) identified as edematous by the stereoscopic fundus photograph grading. This misidentification was more likely if pathology was present (76.9%) than if pathology was not present (41.1%; pooled risk ratio, 1.87 [95% CI = 1.28, 2.73]). CONCLUSION: This study shows the determination of macular edema by a retina specialist reading color stereoscopic fundus photographs is sensitive but not specific with reference to edema identified by the RTA. Furthermore, the presence of retinopathy tends to cause false-positive readings with reference to edema identified by the RTA. These findings indicate the need to use objective, quantitative methods in clinical studies to detect and monitor macular edema.

Kaiser RS, Berger JW, Williams GA, Tolentino MJ, Maguire AM, Alexander J, Madjarov B, Margherio RM. · Retina Service, Wills Eye Hospital, 9th and Walnut Streets, Philadelphia, PA 19107, USA. · Retina. · Pubmed #12476092 No free full text.

Abstract: OBJECTIVES: To investigate the variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration. METHODS: Eight graders, who included two TAP-certified ophthalmologists, three other retinal specialists, two fellows in vitreoretinal diseases, and a senior fundus photograph grader, evaluated fluorescein angiograms of six patients treated according to the Treatment for ARMD With Verteporfin (TAP) protocol at a single center. Each patient's baseline angiogram was evaluated to determine whether the CNV lesion was predominantly (> or =50%) classic. For each follow-up angiogram, at 3, 6, 12, and 24 months, the grader was required to determine whether fluorescein leakage was present. Six months after the initial gradings, each reader was again presented with the baseline angiogram for each patient and once again asked to determine whether the CNV lesion was predominantly classic without knowledge of the previous grading. All gradings were performed without knowledge of the clinical course. RESULTS: In grading initial visit and follow-up visit angiograms, the overall concordance rates were 81% and 82%, respectively. Concordance rates were not statistically different between the group as a whole when compared with the gradings of the two TAP-certified ophthalmologists. When initial visit angiograms were regraded, an intraobserver variability of 17% was noted. Overall, gradings were discordant with the majority opinion in approximately 19% of decisions. CONCLUSIONS: Considerable variability can be expected in fluorescein angiography interpretation as the results of the TAP investigation are applied to clinical practice.

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.