Dataset Information

Noninfectious Intermediate, Posterior, or Panuveitis: Results from the Retrospective, Observational, International EyeCOPE Study.

ABSTRACT:

Introduction

The EyeCOPE study characterized noninfectious intermediate posterior, or panuveitis (NIIPPU) before biologic agents were widely available.

Methods

This retrospective, observational study included adults with NIIPPU attending a routine ophthalmological visit. Data were collected from the study visit and medical records.

Results

Of 565 patients, 58.8% were female, and the mean age was 41.3 years; 33.8% had idiopathic uveitis and 45.8% had panuveitis. The median time from symptom onset to diagnosis and treatment was 27.0 and 30.5 days, respectively. Patients received immunosuppressants and systemic/local corticosteroids. Most patients experienced substantial decline in ocular function (mean best corrected visual acuity, 0.4 logMAR). Mean total work productivity impairment among employed patients was 31.0%. Most patients reported ocular complications (70.8%) such as vision loss and cataracts.

Conclusions

Despite treatment, most patients with NIIPPU experienced a decline in ocular function and ocular complications. There is an unmet need for additional NIIPPU treatment, such as targeted monoclonal antibodies.

SUBMITTER: Kramer M

PROVIDER: S-EPMC8319263 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAdalimumab was recently approved for the treatment of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.ObjectiveTo assess the effect of adalimumab on the visual functioning and quality of life in patients with corticosteroid-dependent noninfectious intermediate uveitis, posterior uveitis, and panuveitis.DesignA post hoc analysis of clinical trials of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate uveitis, posterior uveitis, and panuveitis was conducted in the United States, Canada, Europe, Israel, Australia, Latin America, and Japan. A total of 217 patients (110 adalimumab, 107 placebo) in VISUAL-1 and 226 patients (115 adalimumab, 111 placebo) in VISUAL-2 were studied using intent-to-treat analyses. The clinical trials were conducted between August 10, 2010, and May 14, 2015.InterventionsIn VISUAL-1 and VISUAL-2, patients were randomized to receive adalimumab, 80-mg, subcutaneous loading dose followed by 40 mg every other week or placebo for 80 weeks. All patients underwent prednisone tapering, with patients in VISUAL-1 receiving an initial prednisone burst.Main outcomes and measuresThe 25-item National Eye Institute Vision Function Questionnaire (NEI VFQ-25) composite score questionnaire assessed the impact of visual impairment from the patient's perspective; scores on the questionnaire range from 0 to 100, with higher scores indicating better vision-related quality of life. The change in NEI VFQ-25 from best state achieved prior to week 6 (VISUAL-1) and from baseline state (VISUAL-2) to the final or early termination visit was determined in each group and statistically compared using analysis of variance. The temporal effects of adalimumab and placebo on NEI VFQ-25 were investigated using a longitudinal model.ResultsOf the 217 patients in VISUAL-1, 124 (57.1%) were women; the mean (SD) age was 42.7 (14.9) years. Of the 226 patients in VISUAL-2, 138 (61.1%) were women; the mean (SD) age was 42.5 (13.4). In VISUAL-1, the change from final score to best score in NEI VFQ-25 was -1.30 for adalimumab and -5.50 for placebo-a difference of 4.20 (95% CI, 1.04 to 7.36; P = .01) associated with adalimumab compared with placebo. In VISUAL-2, the change from baseline NEI VFQ-25 was 3.36 for adalimumab and 1.24 for placebo-a difference of 2.12 (95% CI, -0.81 to 5.04; P = .16). In both trials, the longitudinal models showed a significant difference in NEI VFQ-25 between adalimumab and placebo of 3.07 (95% CI, 2.09 to 4.06; P < .001) and 4.66 (95% CI, 0.05 to 9.26; P = .048) in the VISUAL-1 (74.15 vs 71.08) and VISUAL-2 (82.39 vs 77.73) trials, respectively.Conclusions and relevanceThis post hoc analysis suggests that adalimumab is associated with statistically significant and clinically meaningful improvements in patient-reported visual functioning for patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis.Trial registrationclinicaltrials.gov Identifiers: NCT01138657 (VISUAL-1) and NCT01124838 (VISUAL-2).

Project description:BACKGROUND:This study aims to determine if the intravitreal dexamethasone implant (DEX implant, Ozurdex; Allergan, Inc., Irvine, California) is effective for treating intermediate, posterior, and panuveitis as a monotherapy or adjunctive treatment to systemic immunomodulatory therapies. METHODS:A systematic review using MEDLINE, EMBASE, and PubMed database searches was conducted with the Oxford Centre for Evidence-based Medicine Levels of Evidence criteria to select publications. Available background information and patient data from each study was tabulated. Outcomes studied were central retinal thickness (CRT), best corrected visual acuity, intraocular inflammation (anterior chamber cells, vitreous haze), number of patients with prior and concomitant immunomodulatory treatments, intraocular pressure (IOP) elevation (? 25?mmHg), and other adverse effects associated with the implant. RESULTS:One hundred ninety-five (61.51%) patients had previous immunomodulatory treatment while 232 (64.8%) were treated with concomitant immunomodulatory therapy with the DEX implant. CRT decreased by an average of 198.65??m (42.74%). Visual acuity improved to an average of 0.451 (logMAR) or 20/57 (Snellen) which is a 43.11% improvement from baseline. One hundred seventy-three (59%) of eyes were quiescent at the end of the trials, of which 40 (13.7%) previously inflamed eyes became quiescent. Elevated IOP occurred in 91 (20.6%). The most common adverse events were cataract/posterior subcapsular opacities in 47 (11.03%) patients and conjunctival hemorrhage in 24 (5.44%) patients. CONCLUSIONS:The DEX implant is an effective medication for the treatment of posterior segment uveitis, uveitic macular edema, and results in improved visual acuity. Development of elevated IOP and cataract should be closely monitored as they are tangible risks associated with the DEX implant. This study was not able to determine whether the DEX implant was more effective as a monotherapy or as an adjunctive therapy to systemic immunomodulatory treatment.

Project description:PurposeTo compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate uveitis, posterior uveitis, and panuveitis.DesignAdditional follow-up of a randomized comparative effectiveness trial cohort.ParticipantsTwo hundred fifty-five patients with intermediate uveitis, posterior uveitis, or panuveitis randomized to implant or systemic therapy.Main outcome measuresBest-corrected visual acuity (BCVA), visual field mean deviation (MD), activity of uveitis, and presence of macular edema (per reading center grading) ascertained prospectively.MethodsTrial participants were followed-up for 54 months from original randomization.ResultsThe visual function trajectory in uveitic eyes demonstrated a similar (P = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months, 2.4 and 3.1 letters in the implant and systemic groups, respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry MD score remained similar to baseline throughout 48 months of follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (P < 0.016), although most eyes in the systemic therapy arm also showed substantial improvement, achieving complete control or low levels of inflammation. Although macular edema improved significantly more often with implant treatment within the first 6 months, the systemic group gradually improved over time such that the proportions with macular edema converged in the 2 groups by 36 months and overlapped thereafter (P = 0.41 at 48 months).ConclusionsVisual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate uveitis, posterior uveitis, and panuveitis were similarly favorable through 54 months. The implant maintained a clear advantage in controlling inflammation through 54 months. Nevertheless, with systemic therapy, most patients also experienced greatly improved inflammatory status. Macular edema improved equally with longer follow-up. Based on cost effectiveness and side-effect considerations, systemic therapy may be indicated as the initial treatment for many bilateral uveitis cases. However, implant therapy is a reasonable alternative, especially for unilateral cases and when systemic therapy is not feasible or is not successful.

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