Purpose To identify factors associated with best-corrected visual acuity (BCVA) presentation and two-year outcome in 479 intermediate, posterior, and panuveitic eyes. Design Cohort study using randomized controlled trial data Methods Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and 2 years’ follow-up used gold standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and two-year change in BCVA. Results Baseline factors significantly associated with reduced BCVA included: age ≥50 vs. <50 years; posterior vs. intermediate uveitis; uveitis duration >10 vs. <6 years; anterior chamber (AC) flare > grade 0; cataract; macular thickening; and exudative retinal detachment. Over two years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (p=0.52) and 10 letters (p<0.001) respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6–10 or >10 vs. <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening. Conclusions Intermediate, posterior and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.

The cytokine interleukin-1 beta (IL-1beta) is an evolutionarily conserved molecule that was originally identified in the immune system. In addition to regulating peripheral immune responses, IL-1beta plays an important role in mediating neural-immune interactions and regulating glial activities during healing and repair in the damaged nervous system. Active IL-1beta is produced by interleukin-converting enzyme (ICE), a caspase thought to be involved in the induction of apoptosis. We report that, in the developing frog, Xenopus laevis, IL-1beta and the IL-1 type 1 receptor proteins are coexpressed in specific neurons that comprise early sensory-motor circuits. IL-1beta and IL-1 type 1 receptor proteins are colocalized in specific midbrain and hindbrain reticular cells, including Mauthner's neuron; specific cells in the trigeminal (fifth), lateral line (seventh), and vestibular (eighth) cranial ganglia; oculomotor neurons; and the primordial Purkinje cells of the lateral cerebellar auricle. In the spinal cord, Rohon-Beard sensory neurons, dorsal root ganglion cells, and primary motoneurons are immunopositive. Anteriorly, the olfactory pits, olfactory nerves, and olfactory bulbs are labeled, as are retinal cells, especially photoreceptor inner segments. With regard to the function of IL-1beta during neural development, IL-1beta and its type 1 receptor are present throughout the course of neural development in identifiable, long-lived neurons, such as Mauthner's neuron. These and other data suggest that IL-1beta and its type 1 receptor may be involved in the maintenance of cell survival rather than induction of neuronal death.

No abstract

Purpose To describe fluocinolone acetonide implant dissociations in the Multicenter Uveitis Steroid Treatment (MUST) Trial. Design Randomized clinical trial with extended follow-up. Methods Review of data collected on the first implant in the eye(s) of participants. Dissociation was defined as the drug pellet no longer being affixed to the strut and categorized as spontaneous or surgically-related. Results 250 eyes (146 patients) had at least one implant placed. Median time follow-up time after implant placement was 6 years (range 0.5 to 9.2). Thirty-four dissociations were reported in 30 participants. There were 22 spontaneous events in 22 participants; 6-year cumulative risk of a spontaneous dissociation was 4.8% (95% confidence interval (CI): 2.4%–9.1%). The earliest event occurred 4.8 years after placement. Nine of 22 eyes with data had a decline in visual acuity ≥5 letters temporally related to the dissociation. 39 implant removal surgeries were performed, 33 with replacement. Twelve dissociations were noted during implant removal surgeries in 10 participants (26%, 95% CI 15%–48%); 5 of these eyes had a decline in visual acuity ≥5 letters after surgery. The time from implant placement to removal surgery was longer for the surgeries at which dissociated implants were identified than for those without one (5.7 vs 3.7 years, p < 0.001). Overall, visual acuity declined 15 or more letters from pre-implant values in 22% of affected eyes; declines were frequently associated with complications of uveitis or it’s treatment. Conclusion There is an increasing risk of dissociation of Retisert implants during follow-up, the risk is greater with removal/exchange surgeries, but both the risk of spontaneous and surgically related events increase with longevity of the implants. In 22% of affected eyes visual acuity declined by 15 letters. In the context of eyes with moderate to severe uveitis for years, this rate is not unexpected.