Outcomes of Uveitic Macular Edema in the First-line Antimetabolites as Steroid-Sparing Treatment Uveitis Trial.

PURPOSE: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. DESIGN: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. PARTICIPANTS: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. METHODS: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group. MAIN OUTCOME MEASURES: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. RESULTS: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 µm and 342 µm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 µm (interquartile range [IQR], -132.3 to 4.0) and 54 µm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 µm (IQR, -32.3 to -0.5) and 50 µm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92). CONCLUSIONS: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.

An Algorithm for the Diagnosis of Behçet Disease Uveitis in Adults.

Purpose: To develop an algorithm for the diagnosis of Behçet's disease (BD) uveitis based on ocular findings.Methods: Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion.Results: We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis.Conclusion: This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.

Trematode Fluke Procerovum varium as Cause of Ocular Inflammation in Children, South India.

Trematodes are recognized as a group of emerging parasites in tropical countries. We identified a trematode as a cause of ocular granulomas that developed in children who bathed in ponds or rivers in South India. DNA was isolated from patients' surgically excised granulomas and from the trematode cercariae (larvae) released by the snail Melanoides tuberculata in water in which the children bathed. Real-time and conventional PCRs were performed that targeted ribosomal DNA regions spanning the internal transcribed spacer 2 and 28S sequences of this trematode. The PCR-amplified products were subjected to bidirectional sequencing. Analysis of sequences for the granuloma samples and the trematode cercariae showed maximum sequence similarity with Procerovum varium (family Heterophyidae). Our results confirmed the etiology of the ocular infection, implicating snail vectors as environmental risk factors for ocular parasitosis.

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.

Intraocular cysticercosis: case series and comprehensive review of the literature.

PURPOSE: To analyze the demographics and clinical characteristics in patients with intraocular cysticercosis. METHODS: Retrospective case series and comprehensive literature review. RESULTS: Intraocular cysticercosis was diagnosed in 21 of 21,079 patients (0.10%) seen by the uveitis service at Aravind Eye Hospital. At presentation, visual acuity was 20/200 or worse in 14 eyes (63.6%). Inflammation was unilateral in all but one patient (95.2%). The cyst was located in the vitreous cavity in 36.4% of eyes and in the subretinal space in 63.6% of eyes. In the literature review, most patients were affected unilaterally (98.5%); visual acuity at presentation was 20/200 or worse in 82.3% of eyes; and the cyst was located in the vitreous cavity in 59.5% of eyes. CONCLUSIONS: Intraocular cysticercosis usually affects young patients unilaterally. The cyst may be in either the vitreous cavity or the subretinal space, and visual acuity at presentation is often poor.

Population-based prevalence of uveitis in Southern India.

PURPOSE: To estimate the prevalence of uveitis in rural Tamil Nadu, India. METHODS: Cluster sampling identified a population-based sample of 5150 persons ages 40 years and older, representative of three districts in Tamil Nadu, India. Each received a comprehensive dilated ocular examination by an ophthalmologist, and results were registered on forms requiring responses about the presence of ocular inflammatory signs and inflammatory diagnoses. Potential uveitis cases were confirmed by consensus of two uveitis specialists, upon review of study and medical records. Crude prevalence rates and prevalence rates age-adjusted to reflect the 2001 Tamil Nadu census population were calculated. RESULTS: Crude and age-adjusted prevalence rates for endogenous uveitis were 310/100,000 and 317/100,000. The corresponding rates for all ocular inflammation were 450 and 467/100,000. Males tended to have a greater prevalence than females in this population, and older persons tended to have higher prevalence than younger persons. The majority of cases of posterior uveitis and infectious endophthalmitis were visually compromised, but few among the cases of other forms of ocular inflammation were visually impaired. CONCLUSIONS: The results suggest that nearly one in 200 persons in rural, South India has been affected by ocular inflammation in at least one eye by mid to late adulthood, about one in 330 if cases related to surgery or trauma are not included. Postsurgical endophthalmitis and posterior uveitis were associated with a high rate of vision loss. These results indicate that uveitis is an important cause of ocular morbidity and of vision loss in this population.

Ocular manifestations of systemic disease: ocular parasitosis.

PURPOSE OF REVIEW: To highlight recent advances in basic research, diagnostic as well as therapeutic advances in ocular parasitosis and to evaluate their application in medical practice. RECENT FINDINGS: Knowledge relating to immunoreactivity in ocular parasitology has grown impressively in past few years. The outcome of infection is the result of a set of interactions involving host and parasite genetic background, environmental and social factors. Immunopathogenesis of parasite-mediated host cell lysis is better understood. Studies on newer drugs with cophylogenetic techniques are in horizon. There are success stories on control of transmission in some countries. SUMMARY: Much has been achieved; however, much more effort is needed in the area of translational research from bench to bedside. There is a need to enhance the awareness of risk factors of parasitic diseases in the population. Newer molecular diagnostic techniques need to be standardized for field application. Steps needed to be taken by the ophthalmologist when a parasite is seen in ocular tissues including identification, search for systemic involvement, treatment for elimination and sequelae and public health notification. Lack of methodological uniformity in management emphasis the need for standardization including construction of management algorithm for ophthalmologists.

A shared HLA-DRB1 epitope in the DR beta first domain is associated with Vogt-Koyanagi-Harada syndrome in Indian patients.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease and sympathetic ophthalmia (SO) are two distinct entities that share common clinical and histopathological features; however, it remains unknown whether they have a common genetic susceptibility. Several studies have shown an association of human leukocyte antigen (HLA)-DR4 with VKH disease in patients of different ethnic backgrounds. We present in this paper the HLA-DRB1 genotyping analysis of a large cohort of VKH patients from southern India and compare these patients to patients with SO and to healthy individuals from the same geographic area. METHODS: VKH patients were diagnosed according to the revised criteria of the International Committee on VKH disease. Patients with granulomatous uveitis after ocular trauma or multiple eye surgeries were diagnosed as having SO. Genomic DNA was extracted from all patients and controls. Samples were analyzed for HLA-DRB1 alleles by reverse polymerase chain reaction (PCR) sequence-specific oligonucleotide (SSO) hybridization on microbeads, using the Luminex technology, and by PCR sequence-specific primers (SSP) typing for DRB1*04 allele determination. Strength of associations was estimated by odds ratios (OR) and 95% confidence intervals (CI) and frequencies were compared using the Fisher's exact test. RESULTS: HLA-DRB1 alleles were determined in 94 VKH patients, 39 SO patients, and 112 healthy controls. HLA-DRB1*04 frequency was higher in VKH patients (20.2% versus 10.3% in controls; OR=2.2, p=0.005, pc=0.067). This association was lower than the association of HLA-DRB1*04 frequency in cohorts of patients from different origins. No significant DR4 association with SO was detected. HLA-DRB1*0405 and HLA-DRB1*0410 alleles were significantly increased in VKH patients (8.5% versus 0.9% in controls; OR=10.3, 95% CI=2.34-45.5, p<0.001). These two alleles share the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DR molecule. None of the DRB1 alleles was significantly associated with SO. CONCLUSIONS: Based on the association of HLA-DRB1*0405 and HLA-DRB1*0410 alleles with VKH disease, we propose that the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DRbeta1 molecule is the relevant susceptibility epitope. This genetic component seems specific to VKH disease since no correlation could be identified in SO patients. The weaker association with HLA-DR4 in this VKH patient cohort compared to VKH patients from northern India is probably related to the lower frequency of HLA-DRB1*0405 in our study group. The HLA-DRB1 association with susceptibility to VKH syndrome seems weaker in Indian patients compared to Japanese or Hispanic patients, suggesting a different non-HLA immunogenetic background in Indian VKH patients.

Sympathetic ophthalmia following postoperative bacterial endophthalmitis: a clinicopathologic study.

PURPOSE: Clinical and histopathologic documentation of sympathetic ophthalmia (SO) development in eyes with postoperative bacterial endophthalmitis. DESIGN: Observational case series; retrospective clinicopathologic study. METHODS: All patients who presented with a clinical diagnosis of SO during 2002 to 2004 were included in the study. The diagnosis of SO was made on the basis of history of penetrating ocular injury, followed by development of bilateral intraocular inflammation, ultrasonographic detection of bilateral diffuse thickening of the choroid, or both. Patients presenting with the additional finding of hypopyon underwent an anterior chamber tap and vitreous aspirate for microbiologic detection of bacteria and fungi. Eight exciting eyes were enucleated and submitted for histologic examination. RESULTS: Of a total of 26 patients with a clinical diagnosis of SO, four also had bacterial endophthalmitis. Of these, histologic examination of three exciting eyes revealed vitreous abscess and typical features of SO. Of the five remaining enucleated globes, histologic examination showed that two eyes had phacoanaphylactic endophthalmitis, and two others revealed features of SO; the one remaining eye had nongranulomatous diffuse choroiditis. CONCLUSIONS: Bacterial endophthalmitis cannot prevent the development of SO. Early diagnosis of coexistent mixed infectious and inflammatory processes, and initiation of antimicrobial treatment directed at the infection followed by immunomodulatory agents to address the autoimmune component may improve the prognosis in such cases.

Presumed trematode-induced granulomatous anterior uveitis: a newly recognized cause of intraocular inflammation in children from south India.

PURPOSE: To describe the epidemiologic, clinical, and histopathologic features of a presumed trematode granulomatous anterior uveitis, primarily in children from south India. DESIGN: Prospective, noncomparative, case series. METHODS: Children with clinical evidence of granulomatous anterior uveitis were selected for the study. Those who presented with distinct anterior chamber nodules were evaluated. Demographic details, such as clinical findings and course of illness, were noted. Patients underwent either medical treatment or surgical aspiration of the lesion based on the size of the lesion. Aspirated materials were subjected to histopathologic analysis and cultures for bacteria and fungi. Response to treatment and final visual status were evaluated. RESULTS: One hundred thirteen patients with anterior chamber nodules were seen between 1998 and 2000. Ninety-three (82.4%) were males and 20 (17.7%) were females. The median age was 11.0 years. All patients were from south India and all gave a history of bathing or swimming in the local pond or river. All had normal systemic work ups. Of the 113 patients, 110 had anterior chamber nodules and three had both anterior chamber and subconjunctival nodules. Aspirates of the anterior chamber lesions revealed lymphocytes, intact and necrotic neutrophils, and eosinophils admixed with histiocytes. One subconjunctival nodule showed necrotizing granuloma, displaying the tegument of a trematode. Those patients who were followed had good visual recovery after medical or surgical intervention or both. CONCLUSION: The present study shows a newly recognized granulomatous anterior uveitis caused by a presumed water-borne trematode infection. This infection appears to be a common cause of pediatric granulomatous anterior uveitis in south India.