Reduction of apoptosis in ischemic retinas of two mouse models using hyperbaric oxygen treatment.

PURPOSE: To investigate the effect of hyperbaric oxygen (HBO) chamber treatment in mouse models of retinal ischemia. METHODS: Unilateral central retinal artery occlusion (CRAO) or optic nerve crush (ONC) was induced in 50 mice each, of which 30 were treated with 100% oxygen at 2 atm for 90 minutes immediately after injury and then daily for up to 14 days. Mice were euthanatized on days 1, 3, and 21 for histologic analysis, apoptosis assay, and quantitative real-time polymerase chain reaction test. Findings were analyzed by injury and by treatment. RESULTS: HBO treatment reduced cell loss from 58% to 30% in the CRAO model and from 52% to 32% in the ONC model. In both models, it was associated with significantly increased cell survival in the retinal ganglion cell layer. Expression levels of the proapoptosis genes (bax, caspase-3) decreased minimally in the HBO-treated CRAO mice on day 1, but this trend was reversed on day 3. In the ONC group, levels of caspase-3, bax, and bcl-x increased on day 1 and dropped below baseline on day 3. The pattern of changes in the expression levels of the ischemia- and oxidative-stress-related genes (HO-1, SOD-1, GPX-1, NOX-2) and the effectiveness of HBO treatment varied by model. Overall, however, gene expression levels that increased in the untreated mice increased further with HBO treatment and levels that decreased, decreased further with treatment. CONCLUSIONS: HBO treatment protects injured neuronal cells from apoptosis. Response to treatment differs molecularly after ONC or CRAO. These results should prompt clinical trials of acute ischemic retinal damage.

Treatment modalities for Graves' ophthalmopathy: systematic review and metaanalysis.

BACKGROUND: Graves' ophthalmopathy (GO) is a common cause of morbidity in patients with Graves' disease. Optimal treatment of GO remains unclear, and an evidence-based approach may improve patients' outcome. METHODS: A systematic review and metaanalysis of randomized, controlled trials comparing treatment modalities for GO vs. placebo, no intervention, or other treatments. Primary outcome was the clinical activity score (CAS). RESULTS: Thirty-three trials evaluating 1367 patients fulfilled inclusion criteria. In patients with moderate to severe GO, iv pulse corticosteroids were significantly better than oral corticosteroids in reducing CAS [standardized mean difference -0.64, 95% confidence interval (CI) -1.11 to -0.17, chi(2) 7.91, I(2) 62%, random effect], with lower rate of adverse events. Somatostatin analogs showed a minor but statistically significant advantage over placebo (mean difference -0.63, 95% CI -0.98 to -0.28). There was no advantage of orbital radiotherapy over sham radiation in CAS, but radiotherapy was superior for response rates of diplopia (odds ratio 4.88, 95% CI 1.93-12.34, two trials). Treatment with combination of orbital radiotherapy and corticosteroids was significantly better than with either treatment alone (standardized mean difference -1.05, 95% CI -1.62 to -0.48). CONCLUSIONS: Current evidence demonstrates the efficacy of iv corticosteroids in decreasing CAS in patients with moderate to severe GO. Intravenous pulse corticosteroids therapy has a small but statistically significant advantage oral therapy and causes significantly fewer adverse events. Somatostatin analogs have marginal clinical efficacy. The efficacy of orbital radiotherapy as single therapy remains unclear, whereas the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral corticosteroids alone.