Alex Fonollosa

Treatment of Refractory Uveitis with Adalimumab: A Prospective Multicenter Study of 131 Patients

OBJECTIVE To evaluate adalimumab therapy in refractory uveitis. DESIGN Prospective case series. PARTICIPANTS A total of 131 patients with refractory uveitis and intolerance or failure to respond to prednisone and at least 1 other systemic immunosuppressive drug participated. INTERVENTION Patients received a 40 mg adalimumab subcutaneous injection every other week for 6 months. The associated immunosuppressants were tapered after administering 3 adalimumab injections (week 6). MAIN OUTCOME MEASURES Degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria), immunosuppression load (as defined by Nussenblatt et al), visual acuity (logarithm of the minimal angle of resolution [logMAR]), and macular thickness (optical coherence tomography). RESULTS There were 61 men and 70 women (mean age, 27.3 years). The most common causes were juvenile idiopathic arthritis in 39 patients, pars planitis in 16 patients, and Behçets disease in 13 patients. Twenty-seven patients had uveitis of idiopathic origin. Inflammation in the anterior chamber was present in 82% of patients and in the vitreous cavity in 59% of patients. Anterior chamber inflammation and vitreous inflammation decreased significantly (P < 0.001) from a mean of 1.51 and 1.03 at baseline to 0.25 and 0.14, respectively, at 6 months. Macular thickness was 296 (102) μ at baseline versus 240 (36) μ at the 6-month visit (P < 0.001). Visual acuity improved by -0.3 logMAR in 32 of 150 eyes (21.3%) and worsened by +0.3 logMAR (-15 letters) in 5 eyes (3.3%). The dose of corticosteroids also decreased from 0.74 (3.50) to 0.20 (0.57) mg/kg/day (P < 0.001). Cystoid macular edema, which was present in 40 eyes at baseline, showed complete resolution in 28 eyes at 6 months. The mean suppression load decreased significantly (8.81 [5.05] vs 5.40 [4.43]; P < 0.001). Six months after the initiation of the study, 111 patients (85%) were able to reduce at least 50% of their baseline immunosuppression load. Only 9 patients (6.9%) had severe relapses during the 6 months of follow-up. CONCLUSIONS Adalimumab seems to be well tolerated and helpful in decreasing inflammatory activity in refractory uveitis and may reduce steroid requirement. Further controlled studies of adalimumab for uveitis are warranted.

Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: indications, outcomes, and reinjection frequency.

PURPOSE To identify clinical outcomes and treatment patterns of intravitreal dexamethasone implant (Ozurdex; Allergan, Inc) in noninfectious uveitis in the clinical setting. DESIGN Multicenter retrospective cohort study. METHODS Eighty-two eyes (63 patients) receiving 142 implant injections over 35 months were included. Treatment indication, uveitis diagnosis, visual acuity, intraocular pressure, vitreous haze score, central retinal thickness by optical coherence tomography, phakic status, number of injections, time to reinjection, systemic treatments, and complications data were collected. Time to visual acuity and vitreous haze score improvement as per the Standardization of Uveitis Nomenclature guidelines were also determined. RESULTS The probability of visual acuity improvement (≥0.3 logarithm of the minimal angle of resolution units improvement) was 39% at 1 month, 49% at 3 months, 52% at 6 months, and 58% at 12 months. Eyes with baseline vitritis (vitreous haze score ≥+0.5, n = 45) had a probability of vitreous haze score improvement (2-step decrease or change from +0.5 to 0) at 2 weeks of 41%, at 1 month 63%, at 3 months 73%, at 6 months 79%, and at 12 months 88%. In eyes that completed 12-month follow-up (n = 54), 40.7% underwent 2 injections (mean time to second injection of 6.6 ± 1.9 months) and 11.2% required ≥3 injections (mean time to third injection of 11 ± 1.5 months). CONCLUSIONS Dexamethasone implant use in uveitis provides favorable visual acuity and vitreous haze score outcomes but requires repeated injections, an important consideration when choosing intraocular treatment as a route to controlling uveitis.

Usefulness of Adalimumab in the Treatment of Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

Purpose. To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. Design. Multicenter, prospective case series. Methods. Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13–17 years were treated with 40 mg of adalimumab every other week for 6 months and those aged 4–12 years received 24 mg/m2 body surface. Results. Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit (P < 0.001). The mean (SD) macular thickness at baseline was 304.54 (125.03) μ and at the end of follow-up was 230.87 (31.12) μ (P < 0.014). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit (P < 0.001). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02) mg (P < 0.001). No significant side effects requiring discontinuation of therapy were observed. Conclusion. Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement.

Tuberculous uveitis after treatment with etanercept.

BackgroundEtanercept is a tumor necrosis factor (TNF) inhibitor that has been licensed in the United States for the treatment of adult and juvenile rheumatoid arthritis as well as psoriatic arthritis. Reactivation of tuberculosis is a complication of its use. We report the first case of tuberculous uveitis due to etanercept.MethodsWe performed a clinical chart review.CaseA 58-year-old Caucasian woman was referred to our hospital for chronic unilateral granulomatous panuveitis of the right eye (RE). She was on etanercept and methotrexate for rheumatoid arthritis. Since the patient was immunosuppressed with etanercept and since the uveitis was granulomatous we considered tuberculosis as a possible etiology. An aqueous humor tap was performed and sent for polymerase chain reaction analyses of Herpes simplex, Herpes zoster, and Mycobacterium tuberculosis (MT). This last test was positive. Another aqueous humor sample was taken and sent for microscopic examination of sputum for acid-fast bacilli and culture, both of which were positive for MT. A diagnosis of tuberculous uveitis was established; the patient was treated with rifampin, isoniazid pyrazinamide, and ethambutol and etanercept was stopped. Four months later there were no cells in the anterior chamber and the vitreous was clear.DiscussionTo our knowledge this is the first reported case of tuberculous uveitis following treatment with etanercept. This etiology has to be considered in patients taking this drug who present with intraocular inflammation.

Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus

Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.

Sarcoid Intermediate Uveitis Following Etanercept Treatment: A Case Report and Review of the Literature

Purpose: To describe a case of sarcoid uveitis subsequent to anti-TNFα therapy and review previously reported cases. Methods: Review of the clinical records of the authors’ patient and of the literature using the PubMed database. Results: A 30-year-old woman presented with intermediate uveitis with snowballs in both eyes. She was on treatment with etanercept due to psoriatic arthritis. An ultrasound-guided biopsy of a mediastinal adenopathy showed non-necrotizing granulomas compatible with sarcoidosis. The clinical picture resolved after etanercept was withdrawn and treatment with immunosuppressants. In a literature search the authors identified six other cases of sarcoid uveitis induced by anti-TNFα therapy. The types of uveitis were anterior uveitis, posterior uveitis, or panuveitis. Management consisted of withdrawal of anti-TNFα therapy and administration of immunosuppressive agents in 5 cases. Conclusions: Sarcoid uveitis induced by TNFα antagonists is a rare complication. Appropriate management consists of withdrawing the TNFα antagonist and giving immunosuppressants.

Macular holes after rhegmatogenous retinal detachment repair: surgical management and functional outcome.

Purpose: To review the surgical management and functional outcome of macular holes (MHs) developing after rhegmatogenous retinal detachment repair. Methods: Retrospective, interventional, noncomparative case series. Twenty patients with MH developing after rhegmatogenous retinal detachment repair were included. Pars plana vitrectomy with internal limiting membrane peeling and gas tamponade was performed. Macular attachment status and number of best-corrected visual acuity lines of improvement after MH repair were evaluated. Results: The fovea had been detached in all eyes at the time of rhegmatogenous retinal detachment repair. Six MHs developed after scleral buckling surgery and 14 MHs after vitrectomy with an encircling band. In 5 of the 20 patients, ≥2 operations had been required to achieve retinal reapplication. The mean time to MH diagnosis was 38 weeks. Preoperative best-corrected visual acuity was ≤20/100 in all but one case. Single-operation MH closure rate was 100%, with a mean of 4 Early Treatment Diabetic Retinopathy Study lines of visual improvement (P < 0.001). Mean postoperative Snellen best-corrected visual acuity was 20/70 (±0.15) (P < 0.001). Conclusion: In this small retrospective study, standard surgical treatment for idiopathic MH was effective in achieving anatomical closure of these secondary MHs, but visual acuity gain was limited by the previous macula-involving rhegmatogenous retinal detachment status.

Frosted Branch Angiitis Associated with Epstein-Barr Virus Systemic Infection

Purpose: To describe the first case that the authors are aware of frosted branch angiitis associated with Epstein-Barr virus infection. Methods: Case report. Results: A 7-year-old boy presented with bilateral decreased visual acuity. Funduscopy showed a typical image of frosted branch angiitis. He was started on treatment with intravenous steroids and acyclovir. Serological testing was positive for anti-Epstein-Barr virus IgM antibodies. Anti-Epstein-Barr virus IgG antibodies tested positive later. During follow-up, the venous sheathing decreased. Three months later funduscopy showed no abnormalities. Conclusion: Epstein-Barr virus infection should be considered in patients presenting with the typical clinical manifestations of this syndrome.

Clinical Manifestations and Outcomes of Syphilis-associated Uveitis in Northern Spain

Abstract Purpose: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain. Methods: Retrospective review of clinical records in eight general uveitis referral centers. Results: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19–76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20–20/2000) and 20/22 (20/20–20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009). Conclusions: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good.

Insulin resistance and diabetic macular oedema in type 2 diabetes mellitus.

Objective To evaluate the association between insulin resistance and diabetic macular oedema in type 2 diabetes. Methods Patients with type 2 diabetes who agreed to undergo blood sampling were enrolled into this cross-sectional study. Patients who had received treatment for macular oedema within the past 3 months and those with other retinal diseases were excluded. The following data were recorded: age, sex, time of diabetes evolution, HbA1c, ophthalmologic and systemic treatment, and lens status. Optical coherence tomography (OCT) was performed to determine the morphological patterns of macular oedema. Insulin resistance was established by a McAuley index of <6.3 and fasting insulin levels of >16 mU/l. Results A total of 177 eyes from 90 patients were included; 27.1% of eyes were from insulin-resistant patients. There were no differences in age, time of evolution, sex, HbA1c level or lens status between insulin-resistant and non-resistant patients. Insulin-resistant patients were more likely to have exogenous insulin therapy (p<0.05; OR=3.8). An association was found between diabetic cystoid macular oedema and insulin resistance (Fisher exact test p=0.007; OR=2.53, 95% CI 1.52 to 4.2). There were no associations between insulin resistance and the other morphological patterns of oedema. Patients undergoing insulin therapy were found to have an association with a diffuse retinal thickening pattern on OCT (p=0.036; OR=1.4). However, no association was found between insulin therapy and the presence of cystoid macular oedema. Conclusions The findings of this study indicate a relationship between insulin resistance and cystoid macular oedema that unrelated to the use of insulin. Insulin treatment was associated with diffuse macular oedema.