Systemic immunosuppressive therapies for uveitis in developing countries.

There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides.

Observer-masked trial comparing efficacy of topical olopatadine (0.1%), bepotastine (1.5%), and alcaftadine (0.25%) in mild to moderate allergic conjunctivitis.

Purpose: With increasing environmental pollution, the incidence of allergic conjunctivitis is increasing. Newer anti-allergic medications with combined anti-histaminic and mast cell stabilization action can help reducing the use of topical steroids for milder form of disease. There is no study directly comparing olopatadine (0.1%), bepotastine (1.5%), and alcaftadine (0.25%) for mild to moderate allergic conjunctivitis cases. Hence, we decided to methodically study the efficacy of three topical medications. Methods: Prospective, observer-masked clinical trial enrolled 45 patients with 15 patients in each of the three groups. Patients with mild to moderate allergic conjunctivitis were sequentially assigned to respective groups, and relief of symptoms and signs were noted upto 1-month follow-up. Results: All three topical medications faired almost equally in resolving symptoms of the patients with mild to moderate allergic conjunctivitis, and most of them reported complete relief after 1 week of use of medication. Few cases with limbal or palpebral papillae reported symptomatic relief after use of medication, but the resolution of these signs was not noted in all three groups. Conclusion: We concluded similar efficacy of three medications in relieving symptoms and inefficacy in regressing palpebral and limbal papillae in cases of allergic conjunctivitis.

Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing Antimetabolites for Intermediate, Posterior, and Panuveitis.

PURPOSE: To evaluate the changes in quality of life in noninfectious uveitis patients treated with 2 of the most commonly prescribed antimetabolite treatments. DESIGN: Secondary analysis of a multicenter, block-randomized clinical trial. METHODS: Eighty patients at Aravind Eye Hospitals in Madurai and Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best-corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at enrollment and at 6 months (or prior, in the event of early treatment failure). RESULTS: IND-VFQ scores, on average, increased by 9.2 points from trial enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001). Although the SF-36 physical component summary score did not significantly differ over the course of the trial, the mental component summary score decreased by 2.3 points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5 points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ between treatment arms. Linear regression modeling showed a 3.2-point improvement in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9, 4.3; P < .001). CONCLUSIONS: Although uveitis treatment was associated with increased vision and vision-related quality of life, patient-reported physical health did not change after 6 months of treatment, and mental health decreased. Despite improved visual outcomes, uveitis patients receiving systemic immunosuppressive therapy may experience a deterioration in mental health-related quality of life.

A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis.

PURPOSE: To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. METHODS: A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome. RESULTS: A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis. CONCLUSIONS: A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

Outcomes of Vogt-Koyanagi-Harada Disease: A Subanalysis From a Randomized Clinical Trial of Antimetabolite Therapies.

PURPOSE: To report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies. DESIGN: Subanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis. METHODS: setting: Clinical practice at Aravind Eye Hospitals, India. PATIENT POPULATION: Forty-three of 80 patients enrolled (54%) diagnosed with VKH. INTERVENTION: Patients were randomized to either 25 mg oral methotrexate weekly or 1 g mycophenolate mofetil twice daily, with a corticosteroid taper. MAIN OUTCOME MEASURES: Primary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment). RESULTS: Twenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P = .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P = .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation. CONCLUSIONS: The majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher rate of controlled inflammation.

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

OBJECTIVE: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Algorithmic approach in the diagnosis of uveitis.

Uveitis is caused by disorders of diverse etiologies including wide spectrum of infectious and non-infectious causes. Often clinical signs are less specific and shared by different diseases. On several occasions, uveitis represents diseases that are developing elsewhere in the body and ocular signs may be the first evidence of such systemic diseases. Uveitis specialists need to have a thorough knowledge of all entities and their work up has to be systematic and complete including systemic and ocular examinations. Creating an algorithmic approach on critical steps to be taken would help the ophthalmologist in arriving at the etiological diagnosis.

Congenital bilateral sternocleidomastoid contracture: a case report.

Unilateral sternocleidomastoid muscle contracture causing torticollis and other secondary deformities such as facial scoliosis, plagiocephaly and scoliosis of cervical spine are well known. The aetiology and pathogenesis is still intriguing. Although unilateral contracture of sternocleidomastoid is seen quite often, bilateral sternocleidomastoid contracture is almost unheard of. A review of the English literature revealed no cases of bilateral congenital sternocleidomastoid contracture being reported. We present a case report of a 19-year-old girl with congenital bilateral sternocleidomastoid contracture.

Compartment syndrome in a free fibula osteocutaneous flap donor site.

Donor site morbidity for free fibula microvascular flaps is generally reported to be low and considered to be minor. We describe a case where the major complication of compartment syndrome occurred in a 15-year-old boy when the donor site defect was closed primarily after taking a skin paddle with a width of 4 cm. We recommend that when harvesting free fibula flaps in children, skin grafting of donor site should be considered irrespective of the width of the flap, if there is any doubt about the tightness of the closure.

Vertebro-carotid anastomosis as a cause of uncontrollable epistaxis.

Uncontrolled epistaxis may require a long hospital stay, multiple blood transfusions and multiple arterial ligations. This case report highlights vertebro-carotid anastomosis as a rare cause of uncontrolled epistaxis. The importance of angiography in the identification of rare arterial anastomoses is stressed.