Faculty Bibliography

BACKGROUND: Over the past decade, several new medical therapies have become available for the treatment of primary open-angle glaucoma (POAG). A systematic evidence-based approach for identifying an optimal therapeutic agent is lacking. OBJECTIVES: The aims of this review were to critically evaluate published treatment recommendations for POAG and, based on a systematic review of the literature, to develop criteria that would define a 'gold standard' medical therapy that reflects new treatment advances and established therapeutic goals. METHODS: A MEDLINE search spanning the years 1966 to 2002 and using the search terms gold standard, drug of choice, agent of choice, benchmark, ophthalmology, eye, and glaucoma was conducted and the results reviewed by a panel of 15 experts in the field of glaucoma. Published treatment recommendations for POAG were discussed. Criteria, anchored to medical evidence, for distinguishing a standard of medical therapy for POAG were defined. RESULTS: The terms connoting a gold standard therapy were found in only 258 of approximately 368,000 ophthalmology-related citations and 53 of almost 23,000 glaucoma citations, validating the need to define therapeutic standards. The lack of recommendations for the use of new classes of ocular hypotensive agents was acknowledged. Criteria identified to evaluate intraocular pressure (IOP)-lowering agents as gold standards included the following: efficacy in reducing IOP consistently over a 24-hour period to a level that will preserve the visual field and protect the optic nerve without inducing tachyphylaxis and tolerance, paucity of local and systemic adverse effects, promotion of patient compliance, and applicability in diverse patient populations. CONCLUSIONS: These criteria should be employed as measures for evidence-based analyses to evaluate available and future IOP-lowering medical therapies for POAG. The conceptual framework presented may be applicable to other therapeutic areas

PURPOSE: To determine the association of prostaglandins E1 (PGE1), E2 (PGE2), and F2-alpha (PGF2-alpha) with proliferative diabetic retinopathy (PDR) in human vitreous. METHODS: We collected human vitreous samples from eyes undergoing pars plana vitrectomy for proliferative diabetic retinopathy with vitreous hemorrhage (N=13) and for other reasons including macular gliosis and Stage IV idiopathic macular holes (N=7). Vitreal prostaglandins E1, E2, and F2-alpha were measured by radioimmunoassay. RESULTS: Eyes with PDR had significantly lower vitreal levels of PGE1 (74.77 pg/ml +/- 15.70) compared to those without PDR (91.86 pg/ml +/- 13.36) (p=0.025) using t-test analysis. Eyes with PDR also had significantly lower levels of PGE2 (127.52 pg/ml +/- 70.52) compared to those eyes without PDR (194.43 pg/ml +/- 57.10) (p=0.045). In addition, eyes with PDR had significantly lower levels of PGF2-alpha (34.62 pg/ml +/- 11.56) compared to those eyes without PDR (51.43 pg/ml +/- 18.44) (p=0.021). Panretinal photocoagulation in diabetic eyes did not have an effect on vitreal concentrations of PGE1 (p=0.588). PGE2 (p=0.460) and PGF2-alpha (p=0.351), but sample size was too small. CONCLUSIONS: Diabetic eyes with PDR had significantly lower vitreal levels of PGE1, PGE2 and PGF2-alpha compared to controls consistent with decreased production of these prostaglandins by the endothelial cells of diabetic eyes. Laser treatment did not appear to have a significant effect on vitreal concentrations of these prostaglandins, but sample size was small. The lower concentration of these vasodilatory prostaglandins may reflect the vasculature's inability to produce these substances and the vasoconstrictive state of the end-stage diabetic eye with PDR