Macular Degeneration: Flaxel CJ

Flaxel CJ. · Doheny Retina Institute of the Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. · Ophthalmol Clin North Am. · Pubmed #12515075 No free full text.

Abstract: In this century, macular degeneration is likely to reach epidemic proportions. New treatment modalities are being evaluated for wet or neovascular age-related macular degeneration (AMD) and include radiation treatment. Radiation is known to potentially destroy vascular tissue, and low-dose radiation has been shown to inhibit new blood vessel growth. Potential advantages to radiation therapy in treating AMD include the absence of iatrogenic mechanical or laser damage, the absence of systemic side effects, and the absence of local side effects caused by periocular and intraocular injection. An additional advantage is that eyes with primarily large, occult choroidal neovascularization are potentially eligible for treatment, and only one treatment would be necessary. The major potential side effect is radiation retinopathy, which is dose dependent.

Lim JI, Walonker AF, Levin L, Mahmoud M, Sadda S, Flaxel CJ, Humayun M, deJuan E, Labree L. · Doheny Retina Institute of the Doheny Eye Institute, Los Angeles, CA, USA. · Retina. · Pubmed #16508432 No free full text.

Abstract: PURPOSE: To evaluate the safety and evidence of efficacy for oral 13-cis retinoic acid as a treatment for patients with subfoveal occult choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD). METHODS: Patients with active, subfoveal occult CNV with no prior treatment of the subfoveal component were eligible for inclusion. Patients received 40 mg of 13-cis retinoic acid twice daily for 5 months, stopped treatment for 2 months, and then resumed treatment for 5 months. Patients were observed monthly with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA), clinical examination, fluorescein angiography, and laboratory testing. RESULTS: Eleven patients, aged 64 to 88 years, were enrolled and followed for 1 year. Initial VA ranged from 55 (20/40) to 5 (20/400) ETDRS letters (median 48 letters). Mild drug-related side effects (dry skin, chapped lips) occurred in all 11 patients. Three patients experienced more severe side effects (muscle aches, mood swings) and did not resume treatment after the drug holiday. Moderate VA loss occurred in 36% at both 6 and 12 months. CONCLUSIONS: Oral 13-cis retinoic acid is too toxic to be useful in patients with ARMD. Oral 13-cis retinoic acid did not improve vision although it may have slowed visual acuity loss in patients with ARMD with occult subfoveal CNV.

Flaxel CJ, Friedrichsen EJ, Smith JO, Oeinck SC, Blacharski PA, Garcia CA, Chu HH. · Department of Ophthalmology, Loma Linda University Medical Center, California, USA. · Eye. · Pubmed #10845009 No free full text.

Abstract: PURPOSE: To assess the safety and potential toxicity of proton beam radiation in the treatment of subfoveal choroidal neovascular membrane (CNVM) due to age-related manner degeneration (ARMD) in a prospective, non-randomised study. METHODS: Forty-eight eyes of 46 consecutive patients with subfoveal CNVM due to ARMD, not amenable to laser photocoagulation, were treated prospectively with a single proton beam exposure. Two dose regimens were evaluated: 8 CGE (Cobalt Gray Equivalent) and 14 CGE. Patients were followed for an average of 22.1 months after proton beam treatment. RESULTS: At the 12 month follow-up, 44% of eyes in the 8 CGE group and 75% of the eyes in the 14 CGE group had stabilized or improved visual acuity. Complex size in the 8 CGE group as measured on standard fluorescein angiography (FA), decreased or had no change initially but showed less effect over time, while the eyes treated with 14 CGE maintained decreased leakage over the follow-up period of 12 months. However, 11 eyes in the 14 CGE group experienced radiation retinopathy, with the onset between 3 and 30 months. Seven of these 11 eyes have demonstrated some visual loss but only 1 eye developed severe visual loss at 15 months after proton treatment. CONCLUSIONS: To date, 14 CGE has suggested a favourable influence on visual function and growth inhibition of CNVM. Proton beam irradiation appears to inhibit CNVM growth. The 14 CGE dose regimen appears to have a longer effect of CNVM growth than does 8 CGE, with overall stabilisation of visual function and growth inhibition. Radiation retinopathy has developed over time, but severe visual loss has been limited. On the basis of the incidence of radiation retinopathy, adjustments in the total radiation dosage and/or fractionation of the dosage should be considered.

Ip MS, Bressler SB, Antoszyk AN, Flaxel CJ, Kim JE, Friedman SM, Qin H, Anonymous00381. · University of Wisconsin Fundus Photograph Reading Center, Madison, WI, USA. · Retina. · Pubmed #18698292 No free full text.

Abstract: PURPOSE: To compare baseline demographic, systemic, and ocular characteristics within age and racial subgroups among participants in this Diabetic Retinopathy Clinical Research Network clinical trial and to compare this cohort with other cohorts enrolled in phase 3 clinical trials for diabetic retinopathy. METHODS: Thirty-six month, randomized, controlled, multicenter clinical trial of 693 participants with diabetic macular edema enrolled at 88 clinical sites in the United States. Participants were categorized into self-reported race/ethnicity subgroups and into one of three age groups: 18 to <60, 60 to <70, and 70 and older. RESULTS: Mean age of participants was 63 years, 72% were white, and median visual acuity letter score was 62 (approximately 20/63). No substantial difference was identified between racial subgroups for any baseline variable. Older participants were more likely to have Type 2 diabetes mellitus and longer duration disease. The most frequent levels of diabetic retinopathy among 840 study eyes were moderate (level 43) to moderately severe (level 47) nonproliferative disease. CONCLUSION: While the racial composition of this cohort does not differ from other cohorts in large phase 3 trials that have evaluated participants with diabetic retinopathy, the inclusion of many subjects over age 70 and a better level of glycemic control are distinguishing features.

Davis MD, Bressler SB, Aiello LP, Bressler NM, Browning DJ, Flaxel CJ, Fong DS, Foster WJ, Glassman AR, Hartnett ME, Kollman C, Li HK, Qin H, Scott IU, Anonymous00289. · Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18316700 links to  free full text

Abstract: PURPOSE: To explore the correlation between optical coherence tomography (OCT) and stereoscopic fundus photographs (FP) for the assessment of retinal thickening (RT) in diabetic macular edema (DME) within a clinical trial. METHODS: OCT, FP, and best corrected visual acuity (VA) measurements were obtained in both eyes of 263 participants in a trial comparing two photocoagulation techniques for DME. Correlation coefficients (r) were calculated comparing RT measured by OCT, RT estimated from FP, and VA. Principal variables were central subfield retinal thickness (CSRT) obtained from the OCT fast macular map and DME severity assessed by a reading center using a seven-step photographic scale combining the area of thickened retina within 1 disc diameter of the foveal center and thickening at the center. RESULTS: Medians (quartiles) for retinal thickness within the center subfield by OCT at baseline increased from 236 (214, 264) microm in the lowest level of the photographic scale to 517 (455, 598) microm in the highest level (r = 0.67). However, CSRT interquartile ranges were broad and overlapping between FP scale levels, and there were many outliers. Correlations between either modality and VA were weaker (r = 0.57 for CSRT, and r = 0.47 for the FP scale). OCT appeared to be more reproducible and more sensitive to change in RT between baseline and 1 year than was FP. CONCLUSIONS: There was a moderate correlation between OCT and FP assessments of RT in patients with DME and slightly less correlation of either measure with VA. OCT and FP provide complementary information but neither is a reliable surrogate for VA.

Chang LK, Flaxel CJ, Lauer AK, Sarraf D. · Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles 90095, USA. · Retina. · Pubmed #17891009 No free full text.

Abstract: PURPOSE: To describe retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) status post pegaptanib (Macugen) injection. METHODS: Six eyes from six patients who developed RPE tears while undergoing treatment with pegaptanib for AMD-related fibrovascular pigment epithelial detachment (PED) and occult choroidal neovascularization (CNV) were identified retrospectively. Diagnosis of pre-pegaptanib fibrovascular PED and post-pegaptanib RPE tears were made by clinical examination, fluorescein angiography (FA), and optical coherence tomography (OCT) imaging of the macula. RESULTS: Four patients developed an RPE tear within 8 weeks after the first pegaptanib injection, while RPE tears were found in two patients following a second injection. Only one of the patients reported acute vision loss, although three of six eyes had a decrease in objective visual acuity in the affected eye to the count fingers level. All six cases displayed the classic clinical and angiographic appearance of RPE tears. In addition, OCT imaging showed an irregular, hyperreflective RPE layer with a focal defect. CONCLUSIONS: RPE tears are known to occur in the setting of PED spontaneously or after laser treatment, but have only recently been described in association with intravitreal pegaptanib. OCT imaging of eyes status post pegaptanib therapy may be helpful in identifying this complication. Patients with AMD, especially those with occult CNV and fibrovascular PED, receiving pegaptanib therapy should be monitored for RPE tears, which may warrant deferral of further injections.

Emerson GG, Flaxel CJ, Lauer AK, Stout JT, Emerson MV, Nolte S, Wilson DJ, Klein ML. · Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA. · Retina. · Pubmed #17621181 No free full text.

Abstract: BACKGROUND: To evaluate macular thickness measured by optical coherence tomography (OCT) during pegaptanib therapy for neovascular age-related macular degeneration (AMD). METHODS: For this prospective, nonrandomized, observational case series, 41 eyes from 41 patients with neovascular AMD received intravitreous pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure was central foveal thickness measured by OCT. Secondary outcomes were fluorescein angiographic leakage and visual acuity. RESULTS: Mean thickness of the central area on OCT decreased from 340 +/- 24 microm to 299 +/- 14 microm after 12 weeks of pegaptanib injections. This represents a reduction in thickening of 32%. Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean visual acuity decreased from 20/116 to 20/120. CONCLUSIONS: Intravitreal injections of pegaptanib at 6-week intervals result in a moderate reduction of central foveal thickness in eyes with subfoveal neovascular AMD. This presents a modest effect relative to that reported with other anti-angiogenic agents.

Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, Emerson GG, Schlesinger TK, Nolte SK, Klein ML. · Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. · Retina. · Pubmed #17420695 No free full text.

Abstract: PURPOSE: To report the change in visual acuity and central retinal thickness by optical coherence tomography (OCT) after intravitreal injections of bevacizumab for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A retrospective case series in a university-based practice evaluated patients with subfoveal choroidal neovascularization (CNV) due to AMD. Patients received intravitreal injections (1.25 mg) of bevacizumab and were monitored monthly with determination of best-corrected ETDRS visual acuity and OCT for persistence of retinal thickening. Eyes were retreated on an "as needed" basis, defined by presence of intraretinal or subretinal fluid. Patients were monitored every 2 months to 3 months for persistence of angiographic leakage. RESULTS: Seventy-nine eyes of 74 consecutive patients received the initial injection of bevacizumab between August 1, 2005, and January 30, 2006. Sixty-eight eyes (86%) of 64 patients had at least 3 months of follow-up. Mean central retinal thickness +/- SD decreased from 304 +/- 83 microm at baseline to 237 +/- 105 microm at 3 months (P = 0.00002). Mean ETDRS visual acuity gained 4 letters from 20/100 at baseline to 20/80-1 at 3 months (P = 0.040). Twenty eyes (25%) appeared to have a sustained response to a single injection and did not require further injections through 3 months. Two patients had a potentially drug-related adverse event (ischemic stroke and myocardial infarction). No serious injection-related adverse events occurred. CONCLUSIONS: Intravitreal bevacizumab injection affects a rapid decrease in retinal thickness to normal or near-normal levels and improvement in visual acuity in eyes with CNV due to AMD. The sustainability of changes in retinal thickness and visual acuity in response to bevacizumab treatment warrant further investigation and long-term follow-up.

Koh HJ, Freeman WR, Azen SP, Flaxel CJ, Labree LD, Cheng L, Wills M, Jones TR. · Joan and Irwin Jacobs Retina Center, Department of Ophthalmology, Shiley Eye Center, University of California at San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946, USA. · Retina. · Pubmed #16467679 No free full text.

Abstract: PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A 6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A 6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A 6 dose (monthly group) or 4 22.25-mg A 6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A 6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A 6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A 6 in therapy for human CNV associated with age-related macular degeneration.