Dissociations of the Fluocinolone Acetonide Implant in the MUST Trial
The purpose of the Multicenter Uveitis Steroid Treatment (MUST) trial was to compare outcomes of treatment with systemic corticosteroids versus a fluocinolone implant (Retisert) in patients with noninfectious uveitis. In this current follow-up study, Holbrook et al. describe the rate of dissociation—defined as the detachment of the drug pellet from its supporting strut—in patients who received the implant.
In the MUST trial, 250 eyes (146 patients) received at least 1 implant between December 2005 and December 2008. Median follow-up time after placement was 6 years (range, 0.5-9.2 years). There were 34 dissociations reported in 30 participants; of these, 22 events (in 22 participants) were classified as spontaneous, meaning that they were identified or confirmed on clinical examination. The 12 others were found during implant removal or replacement surgery (39 procedures), and it was unknown whether the event occurred before or during the surgery.
The 6-year cumulative risk of a spontaneous dissociation was low (4.8%), and risk increased over time. The earliest spontaneous event occurred 4.8 years after placement. (By that time, the device would not have been therapeutically active.) Nine of 22 eyes with data available had a decline in visual acuity ≥5 letters temporally related to the dissociation.
The researchers concluded that there is an increasing risk of dissociation of fluocinolone implants during follow-up and that the risk is greater with removal or exchange surgeries. They found that in 22% of affected eyes, visual acuity declined by 15 or more letters. However, they commented that this rate is not unexpected in eyes with years of moderate to severe uveitis and that it is often impossible to disentangle the effect of implant dissociation from the effects of uveitis or its treatments.
Incorporating HRQOL Into Outcomes Assessment After Strabismus Surgery
The success or failure of strabismus surgery is currently assessed by standard motor and diplopia criteria. Hatt et al. studied health-related quality of life (HRQOL) after strabismus surgery in adults and found that more than half of the patients classified as surgical failures reported improved quality of life.
This prospective cohort outcomes study included 227 adult patients who had strabismus surgery at a single clinical practice and had completed Adult Strabismus-20 HRQOL questionnaires preoperatively and at 1 year after surgery. Motor and diplopia criteria were used to classify surgical outcomes as success, partial success, or failure; in 40 patients (18%) the outcome was classified as a failure. For the cases assessed as failures, the researchers reviewed the medical record from the 1-year examination to determine whether the patient had reported any subjective improvement.
The researchers also looked at improvement in HRQOL in at least 1 of the 4 Adult Strabismus-20 domains, and then compared that with the proportion of patients reporting subjective improvement versus those who did not. Of the 40 “failed” patients, 39 had reliable HRQOL tests. Overall, 21 of these 39 (54%) showed improved HRQOL. Twenty-five patients (64%) reported subjective improvement; and, of these, 16 (64%) had improved HRQOL.
The researchers concluded that many patients who were considered surgical failures according to standard criteria nevertheless reported subjective improvement, which was often reflected in improved HRQOL scores. Thus, they propose incorporating quantitative HRQOL criteria into the assessment of strabismus surgery outcomes to define success as either meeting motor and diplopia criteria or showing improvement in HRQOL.
5-Year Outcomes of Ranibizumab With Prompt or Deferred Laser vs. Laser or Triamcinolone + Laser
On behalf of the Diabetic Retinopathy Clinical Research Network (DRCR.net), Bressler et al. compared long-term visual and anatomic effects of ranibizumab with prompt or deferred laser versus laser or triamcinolone + laser with very deferred ranibizumab in diabetic macular edema (DME). Their findings suggest that initial ranibizumab therapy was likely to yield better outcomes than the other approaches.
This randomized clinical trial initially included 828 study eyes, with visual acuity (VA) of 20/32 to 20/320 and center-involving DME; 558 (67%) completed the 5-year visit. Eyes were randomly assigned to the following groups: intravitreous ranibizumab (0.5 mg) with either (1) prompt or (2) deferred laser; (3) sham injection + prompt laser; or (4) intravitreous triamcinolone (4 mg) + prompt laser. The 2 latter groups could initiate ranibizumab as early as 74 weeks from baseline for persistent DME with vision impairment.
At 5 years, the mean (± standard deviation) changes in Early Treatment Diabetic Retinopathy Study VA letter scores from baseline in the ranibizumab + deferred laser (n = 111), ranibizumab + prompt laser (n = 124), laser/very deferred ranibizumab (n = 198), and triamcinolone + laser/very deferred ranibizumab (n = 125) groups were 10 ± 13, 8 ± 13, 5 ± 14, and 7 ± 14, respectively. The difference (95% confidence interval) in mean change between ranibizumab + deferred laser and laser/very deferred ranibizumab and triamcinolone + laser/very deferred ranibizumab was 4.4 (1.2-7.6, p = .001) and 2.8 (–0.9 to 6.5, p = .067), respectively, at 5 years.
While recognizing limitations related to follow-up available at 5 years and changes in study protocol over time, the researchers concluded that eyes that received initial ranibizumab therapy for center-involving DME were likely to have better long-term vision improvements than those managed with laser or triamcinolone + laser followed by very deferred ranibizumab for persistent thickening and vision impairment. They also commented that this study showed that VA and retinal thickness improvements obtained with ranibizumab in conjunction with prompt or deferred laser are sustained over time.
American Journal of Ophthalmology summaries are written by Peggy Denny and edited by Richard K. Parrish II, MD.
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