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To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. 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. Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. 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). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editors discuss studies on intraocular tuberculosis (IOTB).

An introduction to articles published within the issue is presented, including two articles on the pathogenesis, clinical presentation, diagnosis and management of Vogt-Koyanagi-Harada (VKH) disease, another on a study which examined the serum interleukin (IL)-25 levels in patients in the acute uveitic phase and those with chronic/recurrent inflammation, and a case of a woman diagnosed with Holmes-Adie syndrome.

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. [ABSTRACT FROM AUTHOR]

The article presents information on leptospiral uveitis in developing countries. It explores the epidemiology of the disease, which is known to occur mostly in developing countries with tropical climates. The manifestations of ocular involvement in leptospirosis involve discharge or subconjunctival hemorrhage. Worldwide strategies for fighting leptospirosis, particularly the creation of a website providing updates on leptospirosis incidents, diagnosis, and control, are discussed.

The article discusses the treatment of uveitis in developing countries. It notes on the multifacetedness of the challenges of treating uveitis in developing countries. It describes how developing countries provide an opportunity for the medical profession to learn more information on the epidemiology, pathogenesis and treatment of uveitis. The medical, socioeconomic and ethical issues surrounding uveitis treatment are explored.

The article reviews the available epidemiologic data on uveitis from developing countries and compares it with the available data from developed countries. It notes on the demographic differences of uveitis in developing and developed countries. It reveals that posterior uveitis is more common in developing countries, while infectious uveitis is more common in developed countries. The importance of conducting regional studies on the epidemiology of uveitis in developing countries is emphasized.

The article presents information on leprosy uveitis in developing countries. It explores the epidemiology of leprosy, which is described as a chronic communicable disease caused by Mycobacterium leprae, and common in the tropical and subtropical countries. It notes that ocular leprosy occurs due to several factors, including nerve damage and aging complications such as glaucoma and cataract. Also discussed are the involvement of ocular damage in lepromatous leprosy and tuberculoid leprosy.

The article discusses visual complications resulting from human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). Health data shows that the main cause of blindness associated with HIV infection is cytomegalovirus retinitis. Other complications resulting from HIV infection and AIDS include Kaposi sarcoma, molluscum contagiosum and conjunctival microvasculopathy. Recommendations to prevent HIV- and AIDS- induced blindness are presented.

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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Purpose Method Results Conclusions Chikungunya is a re-emerging viral infection across the globe. The purpose of this article is to review the systemic and ophthalmic manifestations associated with chikungunya fever.A review of literature was conducted using online databases.In this report, we have reviewed the presently available literature on uveitis caused by chikungunya and highlighted the current knowledge of its clinical manifestations, imaging features, laboratory diagnostics, and the available therapeutic modalities from the systemic and ophthalmic standpoint.Ocular involvement in chikungunya infection may occur at the time of systemic manifestations or it may occur as a delayed presentation many weeks after the fever. Treatment relies on a supportive therapy for systemic illness. Treatment of ocular manifestation depends on the type of manifestations and usually includes a combination of topical and oral steroids. [ABSTRACT FROM AUTHOR]

A response by Jon D. Wender and colleagues to a letter to the editor regarding their article on intraocular cysticercosis in the 2012 issue is presented.

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. [ABSTRACT FROM AUTHOR]

The article discusses strategies to diagnose ocular tuberculosis (TB). Symptoms associated with optical TB are presented. The use of sputum microscopic examination, histologic examination, radiological imaging, nucleic acid amplification (NAA) methods, mycobacteriophage assay and mycobacterial antigens detection technique in the diagnosis of the disease is discussed.

To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose. The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment. [ABSTRACT FROM AUTHOR]

The article discusses the diagnoses, characteristics, treatment and outcomes of uveitis or eye inflammation, following a mosquito-borne viral infection. Topics include ocular infection by Zika virus, cases of Purtscher-like retinopathy after dengue fever and association of chikungunya virus infection with blurred vision.

Purpose: To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale versus the existing 6-step ordinal scale. Design: Evaluation of diagnostic test (interobserver agreement study). Participants: A total of 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at 1 of 3 large uveitis centers. Methods: Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. Main Outcome Measures: Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within 1 or 2 grades). Results: The scales correlated well (Spearman's ρ = 0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ = 0.46 (range, 0.28-0.81) and κ = 0.40 (range, 0.15-0.63), respectively. Within 1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ = 0.75 (range, 0.66-0.96) and κ = 0.62 (range, 0.38-0.87), respectively. Within 2-grade agreement for the 9-step scale also was excellent (κ = 0.85; range, 0.79-0.92). Two-fold more cases were potentially clinical trial eligible on the basis of the 9-step than the 6-step scale (P<0.001). Conclusions: Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (≥2- and ≥3-step differences for the 6- and 9-step scales, respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting that Reading Center grading may be preferable for clinical trials. [ABSTRACT FROM AUTHOR]

The article reviews information available about human immunodeficiency virus or acquired immunodeficiency syndrome (HIV/AIDS) from developing countries, including Africa, Asia and Latin America. It notes the demographics of HIV/AIDS in Sub-Saharan Africa, which is considered the epicenter of the disease. The common ocular manifestations of HIV/AIDS are also noted. The prevalence of the disease in Asia, Latin America and the Caribbean Area is explored.

Purpose: To evaluate the reproducibility of new criteria for grading the site and activity of intraocular inflammation. Design: Cross-sectional agreement study. Methods: Grading of 202 eyes of 101 patients with uveitis was conducted by pairs of uveitis subspecialists at three uveitis subspecialty clinics. Agreement in grading location of inflammation, anterior chamber (AC) cells, AC flare, vitreous cells (present or absent), and vitreous haze was calculated. Results: Proposed criteria for grading the location of intraocular inflammation had moderate reproducibility (κ range, 0.49 to 0.61). Reproducibility improved (κ range, 0.61 to 0.73) when the newly proposed category of anterior and intermediate uveitis was excluded. The ranges of κ statistics for exact agreement on gradings of AC cells (range, 0.34 to 0.43) demonstrated low to moderate levels of agreement, and gradings of AC flare (range, 0.50 to 0.64), vitreous cells (range, 0.48 to 0.51), and vitreous haze (0.53) were in the moderate agreement range. However, agreement within 1 grade was outstanding for AC cells (κ range, 0.81 to 1.00) and vitreous haze (κ, 0.75). For AC flare, a distribution skewed toward low grades within 1 grade made κ statistics unstable. Conclusions: Proposed methods for grading inflammatory activity have moderate reproducibility for exact agreement in most instances. However, agreement within 1 grade is excellent for grading of AC cells and vitreous haze. The method for grading the site of intraocular inflammation also produces moderate levels of agreement, and in our hands was improved by excluding both anterior and intermediate uveitis. Improved methods for grading AC flare and vitreous cells are needed. [Copyright &y& Elsevier]

Keywords: Masquerade syndrome; iris metastasis; iris tumour; uterine carcinoma Endometrial carcinoma can be pathologically subdivided into type I adenocarcinoma and type II serous carcinoma.[[1]] Uterine endometrial adenocarcinoma is the most common and less aggressive. Masquerade syndrome, iris metastasis, iris tumour, uterine carcinoma. [Extracted from the article]

A preface to the April 2010 issue of the "International Ophthalmology Clinics" is presented.