ABSTRACT
BACKGROUND: The National Eye Institute 39-Question Visual Function Questionnaire (NEI VFQ-39) is an indicator of vision-related quality of life (QoL). The NEI VFQ-39 is used to assess the QoL in patients with non-infectious posterior uveitis, intermediate uveitis, or panuveitis, treated with subconjunctival (SCJ) or intravitreal (IVT) sirolimus as an immunomodulatory therapeutic (IMT) agent, delivered subconjunctivally (SCJ) or intravitreally (IVT) (the SAVE Study). Thirty subjects with non-infectious uveitis were randomized (SCJ:IVT, 1:1) for a prospective clinical trial. The 39-Question Visual Function Questionnaire (VFQ-39) was administered at baseline (BL), month 6 (M6), and month 12 (M12) visits. The survey measures self-reported vision health status for patients with chronic eye disease and assesses the effects of visual impairment on both task-oriented visual function and general health domains. In accordance to the NEI-VFQ Manual, each patient's questionnaire was converted to a scaled score between 0 (worst) and 100 (best), and median scores were calculated for each of the subcategories and overall composite score at BL, M6, and M12. Wilcoxon signed-rank test was performed. RESULTS: Twenty-six patients completed the VFQ-39 at BL and M6, whereas 23 patients completed it at M12. Patients showed a significant improvement in pooled composite scores from BL to M6 and BL to M12. Analysis by treatment groups showed that intravitreal injection of sirolimus is better tolerated. CONCLUSIONS: Sirolimus has demonstrated bioactivity as an IMT and corticosteroid-sparing agent to treat non-infectious uveitis. Patients receiving intravitreal injection of sirolimus showed overall improvement of vision-related health while those receiving subconjunctival injections did not. Larger randomized control trials with sirolimus are indicated to validate these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00908466.
ABSTRACT
PURPOSE: To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE) Study. METHODS: Open-label, prospective, and randomized interventional clinical trial in which 30 patients with noninfectious intermediate, posterior, or panuveitis were randomized 1:1 to receive sirolimus 352-µg intravitreal or 1320-µg subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month 6, all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12. Changes in vitreous haze (VH), visual acuity (VA), and retinal thickness at month 12 were compared with baseline. RESULTS: Of patients with active uveitis at baseline (n = 20), 70% showed greater than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and 43% (n = 12) showed no change. At the end of 1 year, no statistical differences in efficacy were found between intravitreal and subconjunctival groups. No serious adverse events were determined to be secondary to sirolimus. CONCLUSIONS: Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months. Results from the index study suggest that sirolimus may provide benefits to patients with uveitis. Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy. The intravitreal route, however, was better tolerated. TRANSLATIONAL RELEVANCE: The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.
ABSTRACT
BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 µg sirolimus or subconjunctival injections of 1,320 µg at days 0, 60, and 120, with primary endpoint at month 6. RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug. CONCLUSION: Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.
ABSTRACT
BACKGROUND: The aim of this retrospective study was to review our practice of the management of open tibial fractures in children. METHODS: Twenty-seven children aged 3-15 years (mean 9.5) with open fractures of the tibia were treated with early aggressive wound debridement and lavage. Gustilo grading was used. The wounds were graded as follows: I (13 patients), II (6 patients), IIIa (3 patients), IIIb (5 patients). Open wounds were treated as appropriate, 30% of patients required a plastic surgical procedure. RESULTS: Five patients were treated by initial external fixation of the tibia; the remainder was treated by cast immobilisation. The mean period for fracture healing was 6 months (1.5-48 months). There were no cases of non-union or deep infection. The incidence of complications where external fixation was applied was significant: one malunion required osteotomy, there were 2 cases of delayed union and four cases of pin track infection. In the group treated in casts, the most significant complication was loss of reduction of the fracture (five cases), requiring conversion to external fixation in 2 and screw and wire fixation in another; the remaining cases of displaced fractures responded to re-manipulation and plaster application. CONCLUSIONS: We conclude from our results hat majority of isolated open tibial fracture in children can be treated by wound debridement and plaster cast immobilisation. There is still a role for the use of external fixation especially where there is a grossly unstable fracture or extensive soft tissue injury requiring a flap procedure.
