Macular Degeneration: Young TA

Bourla DH, Young TA. · Jules Stein Eye Institute, Retina Division, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA. · J Am Geriatr Soc. · Pubmed #16866687 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in older North Americans. The clinical spectrum, risk factors, pathophysiology, and potential therapeutic options for AMD warrant a careful review. Despite the growth in treatment options for this disease, there is no current curative therapy. Of critical importance is attention to modifiable risk factors--improvements in cardiovascular status, including smoking cessation, and routine ophthalmic monitoring for opportunities to provide early intervention. In addition, a low-vision assessment to investigate the potential use of visual assistive devices may be beneficial to any patient who has experienced a decrease in vision. Finally, education regarding the clinical course of age-related macular degeneration and accurate information with respect to the known benefits of available treatments will impart a better understanding of this disease to patients.

Oliver SC, Young TA, Kobe LH, Leu MY, Lee SP, Chun MW, Straatsma BR. · Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7000, USA. · Am J Clin Oncol. · Pubmed #18838887 No free full text.

Abstract: OBJECTIVES: To prospectively report standardized visual function and macular structural assessment in patients undergoing iodine-125 brachytherapy for choroidal and ciliary body melanoma. MATERIALS AND METHODS: Patients were enrolled for pretreatment and annual posttreatment assessment. Evaluations included ophthalmic history; standardized refraction; visual acuity, contrast sensitivity, and color vision measurement; comprehensive ophthalmic examination; fundus photography; fluorescein angiography; optical coherence tomography; and ultrasonography. Radiation doses to the foveola and optic disc margin were calculated. RESULTS: Forty-two patients were enrolled. Melanoma location included 3 in the ciliary body, 7 anterior, 11 equatorial, 13 posterior, and 8 macular tumors. Mean apical tumor height was 4.45 mm (range 1.79-9.83 mm) and mean longitudinal tumor diameter was 9.41 mm (range 4.52-4.73 mm).Pretreatment mean best-corrected Ferris-Bailey early treatment diabetic retinopathy study visual acuity was 50 (standard deviation +/- 15) letters (Snellen equivalent 20/32, range 20/15 to hand motions). The mean Pelli-Robson contrast threshold percentage was 4.1% (+/- 2.5%). The mean Hardy-Rand-Rittler color vision score was 13/14 (+/- 2.7). Mean distances from the posterior edge of the tumor to the foveola and the optic disc margin were 6.99 mm (+/- 6.22 mm) and 7.28 mm (+/- 5.98 mm), respectively. At the foveola, median total radiation dose was 36.2 Gy (+/-50.6 Gy) and median dose rate was 31.6 cGy/h (+/- 39.8 cGy/h). At the optic nerve, median total radiation dose was 42.8 Gy (+/- 30.8 Gy) and median dose rate was 36.2 cGy/h (+/- 21.4 cGy/h). CONCLUSION: This prospective assessment of macular structure and function will provide more complete understanding of the ocular effects of radiation therapy for ocular melanoma.

Matsubara A, Nakazawa T, Noda K, She H, Connolly E, Young TA, Ogura Y, Gragoudas ES, Miller JW. · Angiogenesis and Laser Laboratories, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17898299 links to  free full text

Abstract: PURPOSE: To investigate the mechanism of cell death in laser-induced choroidal neovascularization (CNV) after photodynamic therapy (PDT). METHODS: PDT was performed in Brown-Norway rats using laser light at a wavelength of 689 nm, irradiance of 600 mW/cm(2), and fluence of 25 J/cm(2) after intravenous injection of verteporfin at the doses of 3, 6, and 12 mg/m(2). Apoptotic cells in CNV were detected by TUNEL assay at 1, 3, 6, 15, 24, and 48 hours after PDT. Caspase activation at 1, 3, 6, 15, and 24 hours after PDT was determined by immunohistochemistry (IHC) with a cleaved caspase-3 or -9 antibody. Akt activity was determined by Western blot and IHC with a phosphorylated-Akt (pAkt) antibody. To investigate the roles of Akt in PDT-induced apoptosis, insulin-like growth factor (IGF)-1, an Akt activator, with or without wortmannin, an inhibitor of PI3K-Akt pathway, was injected into the vitreous before PDT. RESULTS: The number of TUNEL-positive cells in CNV increased at 3 hours after PDT and peaked at 6 hours, showing a dose dependence of verteporfin. Caspase activation was detected in TUNEL-positive cells. Dephosphorylation of Akt in CNV occurred within 1 hour. IGF-1 significantly activated Akt and suppressed the number of TUNEL-positive cells in CNV, and the effects of IGF-1 were diminished by wortmannin. CONCLUSIONS: PDT induced caspase-dependent apoptosis in CNV. These results suggest that PDT leads to dephosphorylation of Akt and subsequent activation of the caspase-dependent pathway. Understanding the intracellular signaling mechanisms of apoptosis in PDT may lead to more selective and effective treatment of CNV secondary to age-related macular degeneration.