Heuristics and Learning Models for Dubins MinMax Traveling Salesman Problem.

This paper addresses a MinMax variant of the Dubins multiple traveling salesman problem (mTSP). This routing problem arises naturally in mission planning applications involving fixed-wing unmanned vehicles and ground robots. We first formulate the routing problem, referred to as the one-in-a-set Dubins mTSP problem (MD-GmTSP), as a mixed-integer linear program (MILP). We then develop heuristic-based search methods for the MD-GmTSP using tour construction algorithms to generate initial feasible solutions relatively fast and then improve on these solutions using variants of the variable neighborhood search (VNS) metaheuristic. Finally, we also explore a graph neural network to implicitly learn policies for the MD-GmTSP using a learning-based approach; specifically, we employ an S-sample batch reinforcement learning method on a shared graph neural network architecture and distributed policy networks to solve the MD-GMTSP. All the proposed algorithms are implemented on modified TSPLIB instances, and the performance of all the proposed algorithms is corroborated. The results show that learning based approaches work well for smaller sized instances, while the VNS based heuristics find the best solutions for larger instances.

Road Descriptors for Fast Global Localization on Rural Roads Using OpenStreetMap.

Accurate pose estimation is a fundamental ability that all mobile robots must posses in order to navigate a given environment. Much like a human, this ability is dependent on the robot's understanding of a given scene. For autonomous vehicles (AVs), detailed 3D maps created beforehand are widely used to augment the perceptive abilities and estimate pose based on current sensor measurements. This approach, however, is less suited for rural communities that are sparsely connected and cover large areas. Topological maps such as OpenStreetMap have proven to be a useful alternative in these situations. However, vehicle localization using these maps is non-trivial, particularly for the global localization task, where the map spans large areas. To deal with this challenge, we propose road descriptors along with an initialization technique for localization that allows for fast global pose estimation. We test our algorithms on (real world) maps and benchmark them against other map-based localization as well as SLAM algorithms. Our results show that the proposed method can narrow down the pose to within 50 cm of the ground truth significantly faster than the state-of-the-art methods.

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.

Vehicle Detection and Tracking Using Thermal Cameras in Adverse Visibility Conditions.

Level 5 autonomy, as defined by the Society of Automotive Engineers, requires the vehicle to function under all weather and visibility conditions. This sensing problem becomes significantly challenging in weather conditions that include events such as sudden changes in lighting, smoke, fog, snow, and rain. No standalone sensor currently in the market can reliably perceive the environment in all conditions. While regular cameras, lidars, and radars will suffice for typical driving conditions, they may fail in some edge cases. The goal of this paper is to demonstrate that the addition of Long Wave Infrared (LWIR)/thermal cameras to the sensor stack on a self-driving vehicle can help fill this sensory gap during adverse visibility conditions. In this paper, we trained a machine learning-based image detector on thermal image data and used it for vehicle detection. For vehicle tracking, Joint Probabilistic Data association and Multiple Hypothesis Tracking approaches were explored where the thermal camera information was fused with a front-facing radar. The algorithms were implemented using FLIR thermal cameras on a 2017 Lincoln MKZ operating in College Station, TX, USA. The performance of the tracking algorithm has also been validated in simulations using Unreal Engine.

Efficacy and Safety of Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment: Results from the Sirolimus Study Assessing Double-Masked Uveitis Treatment (SAKURA) Program.

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). DESIGN: Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. PARTICIPANTS: 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). METHODS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Cloning, expression & evaluation of potential immunogenic recombinant capsid premembrane protein of West Nile virus.

Background & objectives: West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis. The early confirmatory diagnosis of WNV infections is important for timely clinical management and in areas where multiple flaviviruses are endemic. Diagnosis of WNV infection is primarily based on serodiagnosis, followed by virus isolation and identification. The aim of this study was to develop and evaluate a highly sensitive and specific immunoglobulin M (IgM) ELISA using the recombinant CprM protein (rWNV-CprM) for rapid, early and accurate diagnosis of WNV. Methods: The gene coding for the CprM protein of WNV was cloned and expressed in pET 28a vector followed by purification. An indirect IgM microplate ELISA using purified rWNV-CprM protein was optimized having no cross-reactivity with healthy human serum and serum samples obtained from patients with dengue and Japanese encephalitis viruses infection. Results: The comparative evaluation of this rWNV-CprM protein-specific IgM ELISA with plaque reduction neutralization test using 105 blood samples collected from patients suspected to have acute WNV infection revealed 98 per cent concordance with sensitivity and specificity of 100 and 97 per cent, respectively. Interpretation & conclusions: The recombinant CprM protein-based WNV-specific ELISA reported in this study may be useful for rapid screening of large numbers of blood samples in endemic areas during outbreaks.

Evaluation of real-time reverse-transcription loop-mediated isothermal amplification assay for clinical diagnosis of West Nile virus in patients.

Background & objectives: West Nile virus (WNV) is a mosquito-borne flavivirus. The disease can be diagnosed by isolation followed by fluorescent antibody tests, enzyme-linked immunosorbent assay and polymerase chain reaction (PCR) assay. These diagnostic methods are laborious and time-consuming. The present study was aimed to evaluate the real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, early and accurate diagnosis of WNV. Methods: A one-step single tube accelerated quantitative RT-LAMP assay was evaluated by targeting the Env gene of WNV. The gene amplification was accomplished by incubating the reaction mixture at 63°C for 60 min in both real time turbidimeter as well as routine laboratory water bath/dry heating bath. To rule out contamination issues, proper negative controls, including no template, no primer; and no enzyme, were always kept alongside each run. The RT-LAMP assay was evaluated on 105 clinical samples from individuals having ocular infection. Results: Of the 105 samples tested, 27 were positive for WNV by RT-LAMP assay. The comparative evaluation with conventional RT-PCR revealed 100 per cent accordance with sensitivity and specificity of 100 and 95 per cent, respectively. The specificity of this assay was confirmed with serum samples obtained from patients with dengue and chikungunya. Interpretation & conclusions: The RT-LAMP test seemed to be a sensitive and specific method for rapid detection of WNV infection and would be useful for rapid screening of a large number of clinical samples in endemic areas during outbreaks.

A Two-Stage Approach for Routing Multiple Unmanned Aerial Vehicles with Stochastic Fuel Consumption.

The past decade has seen a substantial increase in the use of small unmanned aerial vehicles (UAVs) in both civil and military applications. This article addresses an important aspect of refueling in the context of routing multiple small UAVs to complete a surveillance or data collection mission. Specifically, this article formulates a multiple-UAV routing problem with the refueling constraint of minimizing the overall fuel consumption for all the vehicles as a two-stage stochastic optimization problem with uncertainty associated with the fuel consumption of each vehicle. The two-stage model allows for the application of sample average approximation (SAA). Although the SAA solution asymptotically converges to the optimal solution for the two-stage model, the SAA run time can be prohibitive for medium- and large-scale test instances. Hence, we develop a tabu search-based heuristic that exploits the model structure while considering the uncertainty in fuel consumption. Extensive computational experiments corroborate the benefits of the two-stage model compared to a deterministic model and the effectiveness of the heuristic for obtaining high-quality solutions.

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.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

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.

Interobserver agreement in clinical grading of vitreous haze using alternative grading scales.

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.

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.

Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

Systemic and Ophthalmic Manifestations of Chikungunya Fever.

PURPOSE: 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. METHOD: A review of literature was conducted using online databases. RESULTS: 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. CONCLUSIONS: 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.

A Cross-Sectional Assessment of Knowledge, Attitude, and Practice Toward Leptospirosis among Rural and Urban Population of a South Indian District.

Back ground: Leptospirosis is one of the common zoonotic diseases, endemic among farmers. Globally, awareness of risk factors is reported to be very low. This study aims to quantitatively analyze the knowledge and attitude related to leptospirosis in Madurai district and to identify misconceptions that result in poor practice.Material & methods: A cross-sectional survey on rural and urban population using a structured, validated questionnaire to assess Knowledge, Attitude and Practice on Leptospirosis.Results: 902 participants from rural and 1074 participants from urban population were enrolled. More than 98% knew seasonal fever to be common during rainy season, of them only 2.8% and 3.6% from rural and urban population mentioned microbes as a cause.Conclusion: Vulnerable populations were found to be less knowledgeable on risk factors and they had poor practice. Education had significant impact on knowledge and attitude of urban population; however, their practice did not improve with education.

Knowledge, Attitude, and Practice Towards Leptospirosis among Undergraduate and Postgraduate Medical Students in India.

Background: Students of medicine in India tend to follow textbooks from western authors for rural pathologies, zoonosis, and this geographical disconnect leads to gaps in familiarity with local diseases.Aim: This study aims to assess knowledge, practices, and attitudes on leptospirosis among undergraduate and postgraduate medical students.Methods: A cross-sectional, self-administered questionnaire study was performed from June 2018 to May 2019 among 778 undergraduate students from six medical colleges of Tamil Nadu and 446 postgraduate students from two postgraduate institutions.Results: The survey of 1224 medical students revealed that the postgraduate medical students' knowledge of leptospirosis was better than undergraduates; however, there were important knowledge gaps in risk factors and management of leptospiral infection.Conclusions: Although the results of the study are encouraging, poor knowledge of risk factors and of diagnosis of leptospirosis can significantly affect the quality of patient care. This calls for multifaceted interventions to improve the medical curriculum.

Molecular Mimicry between Betaine Aldehyde Dehydrogenase of Leptospira and Retinal Dehydrogenase 1 of Human Lens: A Potential Trigger for Cataract Formation in Leptospiral Uveitis Patients.

Purpose: Rapidly progressing cataract is one of the ocular manifestations in leptospiral uveitis patients. We examined whether molecular mimicry between the leptospira antigens and lens proteins exists that could result in cataract in these patients.Methods: Immunoblot analysis using patient sera was done with proteins from normal lens and cataract lens from leptospiral uveitis patients and the cross-reacting lens proteins were identified by mass spectrometry analysis.Results: Retinal dehydrogenase 1 and crystallins (α-B, α-A2, ß-B2), were recognized by the antibodies in the serum of leptospiral uveitis patients. And, retinal dehydrogenase 1 is homologous to the leptospiral protein, betaine aldehyde dehydrogenase.Conclusions: Leptospiral uveitis patient serum contains antibodies that cross-react with multiple lens proteins that have a role in maintaining lens transparency. And, these antibodies could act as a potential trigger for cataractogenesis.

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.

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.

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.