Abstract
Abstract: :
Purpose: Steroid therapy is the mainstay of ocular inflammation control for uveitis. However, controversy remains regarding the clinical efficacy of various commercial preparations. This study objectively compares glucocorticoid receptor activity with in vivo efficacy of loteprednol etabonate 0.5% (LotemaxTM), prednisolone acetate 1% (Pred Forte®, PREDF), and generic prednisolone acetate 1% (PREDA), dexamethasone Na phosphate 0.1% (DEX), and fluorometholone 0.1% (FML). Methods: Acute uveitis was induced in anesthetized New Zealand white rabbits by injection of endotoxin into the vitreous humor. All were randomly assigned to either qid topical steroid or saline treatment for 2 or 4d. Intraocular pressure (IOP), slit lamp examination and confocal microscopy were performed daily. Internalization of the glucocorticoid receptor was assayed in cornea, iris, lens and retina by Western blot, and protein in aqueous humor (AH) and ocular tissues by Bradford assay. Results: By day 2, loteprednol and PREDF significantly decreased photophobia (p<0.005). The order of reduction in corneal edema and thickness was loteprednol ≷ FML ≷ PREDF = PREDA ≷ DEX ≷≷ saline. All drugs decreased AH cells, but only loteprednol, PREDA and PREDF decreased aqueous flare and keratic punctate; PREDA, PREDF and FML decreased keratic precipitates; no drug significantly reduced fibrin. At 4d, the amount of protein in AH was loteprednol = PREDF = PREDA < DEX = FML << saline. IOP of all steroid and saline treated uveitic eyes was lower than the control eyes. IOP ranged between 42 and 54% of pre-uveitis IOP with no differences between treatment groups. Confocal microscopy indicated that IOP reduction correlated with corneal endothelial shape change. The percent glucocorticoid receptor internalization after 2d was loteprednol = DEX ≷ FML = PREDA ≷ PREDF; after 4d loteprednol ≷ FML = PREDF ≷ PREDA = DEX. Conclusions: All steroid treatments reduced uveitis to some degree. None restored IOP or reduced fibrin. Corneal thickness increased over time in untreated uveitis; this visual acuity limiting trend was counteracted most effectively by loteprednol, also the most efficacious at reducing photophobia. Western Blot analysis showed sustained glucocorticoid receptor activity by loteprednol from 2d to 4d. In general, PREDF and PREDA had similar effects. All were more effective than DEX.
Keywords: 390 drug toxicity/drug effects • 471 microscopy: confocal/tunneling • 437 inflammation