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.
Communication is an important factor for bacterial survival, growth, and persistence. Much work has examined both inter-and intraspecies interactions and their effects on virulence. Now, researchers have begun to explore the ways in which host-modulated factors can impact bacterial interactions and subsequently affect patient outcomes. In this issue, two papers discuss how the host environment alters interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus, largely in the context of cystic fibrosis. MICROSCOPIC SOCIETY Just as macroscopic creatures must communicate in order to survive and thrive in the macroscopic world, so too do microorganisms "talk" with each other at the microscopic level. Instead of audio calls and visual cues, bacteria instead rely on the language of signaling molecules. As this method of cellular communication involves large numbers of cells coming to a "consensus" on subsequent group actions, researchers dubbed this behavior "quorum sensing." Classical quorum sensing has been largely focused on autoinduction, wherein a single species produces a signaling molecule unable to induce gene expression until the population grows to a threshold concentration. This phenomenon was first characterized in bioluminescence produced by Aliivibrio (formerly Vibrio) fischeri and has since been identified in a variety of clinically relevant human pathogens. More recent cell-cell communication research has revealed that other kinds of molecules, including metabolites and nutrients present in the growth environment, serve as cues that impact bacterial interactions (1-3). Additionally, interactions between different species have been found to occur in polymicrobial infections where they often form synergistic, virulence-enhancing relationships (4). MICRONUTRIENTS/MICROORGANISMSAs pathogenic bacteria prey upon their host as a living source of nourishment, it is not surprising that available nutrients in the host environment can have a major impact on microbial gene expression. It also follows, then, that such an important regulatory factor might also affect the ways in which bacteria interact within the host. Therefore, a key question is whether the in vitro systems primarily used to study microbial interactions provide relevant insights into the ways in which microbes interact in the host.This issue of the Journal of Bacteriology features two papers that explore the impact of host-provided nutrients further in the context of iron's ability to modulate Pseudomonas aeruginosa/Staphylococcus aureus interactions in the cystic fibrosis (CF) lung. Iron is a micronutrient vital for bacterial growth but relatively scarce in most infection sites, acting as a limiting factor (5). In contrast, iron levels have been found to be high in CF sputum and correlate negatively with patient outcomes (6). Additionally, pathogen lung colonization in CF patients displays a conserved pattern of succession, with S. aureus predominating early on before being displaced by P. aeruginosa (7). Although it has b...
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.
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