Influence of intraocular inflammatory cytokine levels on postoperative complications in congenital cataract surgery.

PURPOSE: Posterior capsular opacification (PCO) accounts for the most significant and most challenging complication after successful cataract surgery in children. Our study aimed to investigate the levels of cytokines in the aqueous humor of children afflicted with congenital cataracts and their association with PCO. METHODS: This was an observational study conducted at a tertiary referral center in India. Consecutive children aged less than 5 years with unilateral/bilateral isolated idiopathic congenital cataracts and planned for cataract extraction with intraocular lens implantation were included. During cataract surgery, 100-500 µl of aqueous samples were collected and the levels of inflammatory cytokines were quantified in the aqueous humor. RESULTS: An analysis of 28 samples was done. The mean age of the patients was 16.7 ± 0.4 months (range 3-60 months) with a mean follow-up 14.2 ± 2.3 months. On binary logistic regression, the level of MCP-1 was significantly related to the development of PCO at 1 year (P = 0.0072). Levels of IL-6 and IL-8 were not associated with the development of PCO (P = 0.05 and P = 0.07, respectively). CONCLUSION: Inflammatory markers like IL-6 and IL-8 were raised in children with pediatric cataracts in our study. Chronic high levels of MCP-1-induced fibrosis may be associated with PCO.

Predicting visual outcomes following anti-vascular endothelial growth factor treatment for diabetic macular edema.

PURPOSE: To assess the utility of pre-defined imaging biomarkers on optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy in determining visual and anatomical outcomes. METHODS: In this prospective, non-randomized, and interventional study, 17 patients with treatment-naive DME were included. OCT biomarkers [size/reflectivity of cysts, disorganization of retinal inner layers, integrity of ellipsoid zone or external limiting membrane, subfoveal serous retinal detachment, hyper-reflective foci (HRF)] and OCTA [vascular density (VD), foveal avascular zone (FAZ), and total micro-aneurysms in superficial capillary plexus and deep capillary plexus (DCP)] were analyzed at baseline and after three monthly intravitreal anti-VEGF injections. Response was defined as a decrease of 10% or more in central macular thickness from the baseline after three injections. RESULTS: 13/17 (76.47%) patients were categorized as responders to anti-VEGF therapy. Non-responders had significantly greater hyper-reflectivity of cysts (P = 0.015), larger cystic spaces (P = 0.023), and an increased number of HRF (P = 0.04) at baseline. On OCTA, non-responders showed larger FAZ in DCP (1.35 ± 0.21 versus 1.14 ± 0.28 mm2) (P = 0.042) and lower VD (61.17 ± 0.45 versus 62.73 ± 3.32) in DCP at baseline. At 3 months, the VD increased in responders (63.10 ± 3.42) compared to a decrease in non-responders (60.82 ± 1.13) (P = 0.032). CONCLUSIONS: Non-responders show a higher number of micro-aneurysms, larger FAZ, and lower VD in the DCP on OCTA and higher cyst hyper-reflectivity and HRF and larger cystic spaces on OCT imaging.

CYP1B1 and MYOC variants in neonatal-onset versus infantile-onset primary congenital glaucoma.

OBJECTIVE: To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). METHODS: This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups. RESULTS: Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. CONCLUSIONS: Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.

Correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis.

PURPOSE: To determine the correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis (OTB). METHODS: Vitreous fluid was analysed for cytokines in patients with OTB and non-OTB uveitis using multiplex fluorescent bead-based flow cytometric assay. The clinical phenotypes were recorded and correlated with vitreous biomarkers. RESULTS: Vitreous humour from OTB patients had elevated levels of interleukin-10 (IL-10), IL-17-A, interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α). Angiopoietin (Ang-2) levels were higher in the panuveitis phenotype. OTB posterior uveitis phenotype had relatively higher vascular endothelial growth factor (VEGF) levels and lower fibroblast growth factor (FGF) levels. Additionally, eyes with choroiditis and vasculitis had elevated levels of VEGF and Ang-2 with FGF downregulation. Both IFN-γ and IL-10 were upregulated in the choroiditis phenotype of OTB. CONCLUSION: Angiogenic growth factors and inflammatory cytokines were altered in the vitreous humour of OTB patients. IFN-γ, VEGF, and IL-10 levels are increased in choroiditis and vasculitis phenotypes. Receiver operating characteristic (ROC) curve analysis further emphasized the importance of the IFN-γ assay in the diagnosis of OTB.

Chitosan Hydrogels with Embedded Thermo- and pH-Responsive Microgels as a Potential Carrier for Controlled Release of Drugs.

We report a promising strategy based on chitosan (CS) hydrogels and dual temperature- and pH-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-co-MAA) microgels to facilitate release of a model drug, moxifloxacin (MFX). In this protocol, first, the microgels were prepared using a free radical copolymerization method, and subsequently, these carboxyl-group-rich soft particles were incorporated inside the hydrogel matrix using an EDC-NHS amidation method. Interestingly, the resulting microgel-embedded hydrogel composites (MG-HG) acting as a double barrier system largely reduced the drug release rate and prolonged the delivery time for up to 68 h, which was significantly longer than that obtained using microgels or hydrogels alone (20 h). On account of the dual-responsive features of the embedded microgels and the variation of water-solubility of drug molecules as a function of pH, MFX could be released in a controllable manner by regulating the temperature and pH of the delivery medium. The release kinetics followed a Korsmeyer-Peppas model, and the drug delivery mechanism was described by Fickian diffusion. Both the gel precursors and the hydrogel composites exhibited low cytotoxicity against mammalian cell lines (HeLa and HEK-293) and no deleterious hemolytic activity up to a certain higher concentration, indicating excellent biocompatibility of the materials. Thus, the unprecedented combination of modularity of physical properties caused by soft particle entrapment, unique macromolecular architecture, biocompatibility, and the general utility of the stimuli-responsive polymers offers a great promise to use these composite materials in drug delivery applications.

Axial myopia, a protective factor for diabetic retinopathy-role of vascular endothelial growth factor.

Long axial length is one of the ocular protective factors in development of diabetic retinopathy (DR). In this study we examined the effect of axial length (AL) on aqueous humor vascular endothelial growth factor (VEGF) levels in patients with diabetes mellitus with or without DR. Forty-eight eyes of 48 participants were divided into three groups of 16 each. Group A consisted of non-diabetic patients, Group B had diabetic patients without DR, and Group C had diabetic patients with treatment-naive non-proliferative DR (NPDR). The groups were further subdivided based on axial lengths i.e., AL ≤ 23.30 mm (A1, B1, C1) and AL > 23.30 mm (A2, B2, C2). Undiluted aqueous humor was obtained during cataract surgery to measure the VEGF levels. We observed significant decrease in VEGF concentration in patients with AL ≥ 23.30 mm as compared with AL ≤ 23.30 mm in non-diabetic as well as diabetic patients. As the eye elongates, there is less secretion of VEGF in non-diabetics as well in diabetics with or without DR. Our findings strengthened the concept that an increase in AL leads to less VEGF in diabetic eyes, thus leading to less severe DR changes.

Corneal reconstruction in chemically damaged cornea using temperature responsive surface assisted mesenchymal stem cell transplantation in rabbits.

PURPOSE: Transplantation of autologous stem cells over damaged cornea seems to be a promising approach for corneal reconstruction. Use of a biocompatible carrier is still a challenge in bedside translation of transplantation. We investigated corneal reconstruction and tissue remodelling by transplantation of mesenchymal stem cells (MSCs) using temperature responsive membranes in chemically damaged rabbit cornea model. METHODS: MSCs were cultured from rabbit's bone marrow and transplanted over alkali injured cornea, using either temperature responsive membrane or fibrin glue method. Endogenous levels of MSCs were assessed to decide the optimal time point for transplanting cells. MSC transplanted corneas were harvested at different time points post-transplantation. Corneal repair markers were evaluated using histopathology, immunohistochemistry (IHC) and real time qPCR. The quality of cornea reconstructed was evaluated and compared using corneal opacity scoring and immunohistochemistry (IHC). RESULTS: Use of temperature responsive surface as carrier resulted in uniform and homogenous delivery of MSCs sheet over the damaged corneal surface. Corneal transparency improved day 7 onwards post-MSC transplantation in rabbit chemically injured cornea. Complete re-epithelialization of injured cornea was observed 15 days after MSC transplantation. Restoration of vimentin, α-smooth muscle actin and collagen levels in MSC transplanted cornea was observed post-transplantation. Further, differentiation of MSCs into mature corneal epithelial cells was also observed upon transplantation. CONCLUSIONS: The extent of corneal repair was apparently better using temperature responsive surfaces. The surface provides biocompatible niche for MSCs and can be a method of choice in clinics for cell transplantation over the damaged ocular surfaces.

Tear IL-6 and IL-10 levels in HLA-B27-Associated Uveitis and Its clinical Implications.

Purpose: To evaluate the cytokine levels in tear samples of human leukocyte antigen B27 (HLA-B27)-associated uveitis.Methods: Twenty HLA-B27-associated uveitis patients and 10 non-HLA-B27 uveitis controls were enrolled for the estimation of interleukin-6 (IL-6) and IL-10 levels in the tear samples. The cytokine levels were determined by flow cytometry using a bead-based assay.Results: IL-6, and IL-10 levels and IL-6/IL-10 ratio were found to be higher in the tear samples of HLA-B27-associated uveitis patients as compared to controls. IL-6 levels were also elevated in the active disease as compared to the quiescent group; likewise, IL-6 levels were higher even in the quiescent phase in comparison to non-HLA-B27 disease control. Additionally, levels of IL-6 were significantly correlated with multiple disease episodes. Moreover, IL-6 showed a good area under the curve in receiver operating characteristic analysis.Conclusions: Elevated tear IL-6 levels were associated with active disease and multiple disease episodes and thus could be used as putative markers for disease episodes.

Mycobacterium Tuberculosis Modulates Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Ocular Tuberculosis.

Purpose: To evaluate the role of angiogenic growth factors in the pathogenesis of intraocular tuberculosis.Methods: Retinal Pigment Epithelium (RPE) cells were infected with varying dilution of Mycobacterium tuberculosis (MTB), ranging from several thousand to a few MTB bacilli to replicate paucibacillary conditions. Angiogenesis growth factors were evaluated using multiplex fluorescent bead based flow cytometry in the culture supernatant of RPE cells infected with MTB, vitreous fluids and tear samples of uveitis patients visiting retina clinic.Results: Vascular endothelial growth factor (VEGF) levels were elevated and fibroblast growth factors (FGFs) were down regulated in RPE-infected MTB cells. Similar pattern of VEGF and FGF was observed in the vitreous of IOTB patients. However, no changes were observed in tear samples.Conclusions: MTB exploits the angiogenesis growth factors for pathogenesis by decreasing FGF with concomitant surge of VEGF in MTB infected RPE as well in the vitreous of IOTB patients.

Neonatal-Onset Congenital Ectropion Uveae: A Distinct Phenotype of Newborn Glaucoma.

PURPOSE: To describe neonatal-onset congenital ectropion uveae (N-CEU) as a distinct clinical entity of newborn glaucoma (NG) and to study its significance toward the severity and outcome of NG. DESIGN: Prospective clinical cohort study. METHODS: The study took place at a tertiary care postgraduate teaching institute. It included consecutive patients with NG who presented between July 1, 2016 and September 30, 2017, with a minimum postoperative follow-up of 1 year. Infants with any ocular anomaly apart from CEU were excluded. Patients with N-CEU were compared with those with neonatal-onset primary congenital glaucoma (N-PCG). All infants underwent goniotomy or trabeculotomy, with trabeculectomy depending on corneal clarity. Clinical features at presentation and outcome 1 year after surgery were defined as good or satisfactory if intraocular pressure was ≤16.0 mm Hg under anesthesia without or with topical medications, respectively, and poor if the infant required additional surgery. RESULTS: Twenty eyes of 10 patients with N-CEU were compared with 16 eyes of 9 patients with N-PCG. Infants with N-CEU had significantly worse corneal clarity (mean grade 2.0 ± 0.7 vs 1.4 ± 0.8; P = .026) and poorer outcomes compared with those with N-PCG. Seven of 16 (43.7%) eyes with N-PCG had a cornea clear enough at presentation for a goniotomy compared with only 2 of the 20 (10%) eyes with N-CEU (P = .026). Thirteen of 16 (81.2%) eyes with N-PCG had a good or satisfactory outcome compared with 6 of 20 (30%) eyes with N-CEU (P = .001). CONCLUSIONS: N-CEU appears to be distinct from the unilateral CEU in older patients described in the literature and may be considered a poorer prognosis phenotype of neonatal-onset glaucoma.

Proteomic profile of vitreous in patients with tubercular uveitis.

OBJECTIVE: To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). METHODS: Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software. RESULTS: Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism. CONCLUSION: This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.

Transcriptional signatures of Mycobacterium tuberculosis in mouse model of intraocular tuberculosis.

BACKGROUND: Studies on human intraocular tuberculosis (IOTB) are extremely challenging. For understanding the pathogenesis of IOTB, it is important to investigate the mycobacterial transcriptional changes in ocular environment. METHODS: Mice were challenged intravenously with Mycobacterium tuberculosis H37Rv and at 45 days post-infection, experimental IOTB was confirmed based on bacteriological and molecular assays. M. tuberculosis transcriptome was analyzed in the infected eyes using microarray technology. The identified M. tuberculosis signature genes were further validated and investigated in human IOTB samples using real-time polymerase chain reaction. RESULTS: Following intravenous challenge with M. tuberculosis, 45% (5/12) mice showed bacilli in the eyes with positivity for M. tuberculosis ribonucleic acid in 100% (12/12), thus confirming the paucibacillary nature of IOTB similar to human IOTB. M. tuberculosis transcriptome in these infected eyes showed significant upregulation of 12 M. tuberculosis genes and five of these transcripts (Rv0962c, Rv0984, Rv2612c, Rv0974c and Rv0971c) were also identified in human clinically confirmed cases of IOTB. CONCLUSIONS: Differentially expressed mycobacterial genes identified in an intravenously challenged paucibacillary mouse IOTB model and presence of these transcripts in human IOTB samples highlight the possible role of these genes for survival of M. tuberculosis in the ocular environment, thus contributing to pathogenesis of IOTB.

Long-Term Outcomes of Oral Anti-Tubercular Therapy in Patient with Tubercular Dacryoadenitis: A Case Series.

Purpose: To describe the clinico-radiological features and long-term outcomes in patients with tubercular dacryoadenitis (TbD) Methods: Retrospective, observational study of TbD patients who underwent a thorough clinical examination, orbital imaging study, and tailored ancillary investigations. Polymerase chain reaction (PCR) and microscopy were done in specific cases. A 4-drug anti-tubercular therapy (ATT) was started and clinical response was monitored in all. Patients with a minimum follow-up of 6 months "off-ATT" were included. Results: All patients were women and three presented with pain, blepharoptosis, and bilateral involvement. In all, ESR was raised, Mantoux test was positive and orbital imaging revealed enlarged lacrimal gland/s. Positive PCR and granulomatous inflammation on microscopy were seen in two patients. At a mean follow-up of 17.25 months, all women responded with no relapse or clinical recurrence. Conclusion: Bilateral lacrimal gland enlargement, positive Mantoux & PCR with early response to ATT may provide sufficient evidence for diagnosing TbD.

Longitudinal analysis of serum cytokine profile among patients with tubercular multifocal serpiginoid choroiditis: a pilot study.

PURPOSE: To analyze the serum cytokines profile in patients with tubercular multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy (ATT) and oral corticosteroids. METHODS: In this prospective longitudinal study, patients with active TB MSC were included. Serum levels of interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α were analyzed using bead-based immunoassay. The levels of transforming growth factor (TGF)-ß were measured using cytokine bead array. Serial measurement was performed at baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing paradoxical worsening (PW) of TB MSC were identified and their serum levels of cytokines were compared with those patients who showed healing of lesions. Comparison of cytokine levels with baseline values was also performed. RESULTS: Twelve patients (three females) were included in the study. Four patients showed paradoxical worsening of TB MSC at 3.2 ± 1 weeks after initiation of therapy. Compared to patients who showed healing of lesions, patients with PW showed higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW, levels of IFN-γ peaked at 1 week ((p = 0.01) and levels of TNF-α peaked at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed healing. There was no significant difference in TGF-ß levels at any time point in either group (p > 0.47). CONCLUSIONS: Baseline and serial levels of inflammatory serum cytokines may help in predicting the response to ATT and corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in pro-inflammatory cytokines after initiation of ATT indicating higher bacillary load.

Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis.

Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells. Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples. Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients. Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB.

Choroidal Structural Changes in Tubercular Multifocal Serpiginoid Choroiditis.

PURPOSE: To assess choroidal vascular changes among patients with tubercular multifocal serpiginoid choroiditis (TB MSC) using previously validated techniques. METHODS: Patients with TB MSC (n = 18) and healthy controls (n = 30) underwent enhanced-depth imaging optical coherence tomography (EDI-OCT) imaging. Using previously validated algorithm of image binarization, EDI-OCT scans were segmented to derive total choroidal area, luminal area, stromal area, and choroidal vascularity index (CVI). RESULTS: There was a statistically significant difference in the CVI between controls (66.90 ± 1.77%) and TB MSC patients (65.46 ± 2.53%; p < 0.001). There was significant reduction in CVI at follow-up (3 months) (63.77 ± 3.91%; p = 0.05). The choroidal thickness was higher in TB MSC compared to controls (278.90 ± 57.84 µm versus 329.33 ± 27.69 µm; p = 0.001). CONCLUSIONS: CVI provides insight into structural changes in choroid in TB MSC. During the active disease, there is relative decrease in choroidal vascularity. As the lesions heal, choriocapillaris atrophy occurs with remodeling of choroid.

Clinical Course and Outcomes of Pediatric Tubercular Uveitis in North India.

PURPOSE: To analyze the clinical features, course, management, and outcomes of tubercular (TB) uveitis in the pediatric population and assess the response to anti-tubercular therapy (ATT). METHODS: Hospital records of children (≤16 years) from a large tertiary-care institute between January 2001 and December 2015 were reviewed. RESULTS: A total of 32 children (mean age: 10.7 ± 4.27 years; range 2-16) were diagnosed with TB-associated uveitis. The most common presentation was posterior uveitis (n = 14, 43.75%) and panuveitis (n = 14, 43.75%), followed by intermediate uveitis (n = 2, 6.25%) and anterior uveitis (n = 2, 6.25%); 14 children had probable intraocular tuberculosis (IOTB) (43.75%) and 17 (53.13%) had possible IOTB. Despite ATT and corticosteroids, 29.63% patients showed suboptimal response or worsening of disease requiring additional immunosuppression. CONCLUSIONS: TB is an important cause of pediatric uveitis in endemic countries. The manifestations of the disease resemble adult TB-related uveitis. However, higher inflammatory response in children may require more aggressive therapy with corticosteroids/immunosuppression.

Role of Regulatory T Cells in Tubercular Uveitis.

PURPOSE: To study the role of regulatory T cells (Tregs) in patients with tubercular uveitis. METHODS: Frequencies of peripheral Tregs, Th1, Th17 cells, and intracellular cytokines were determined in 17 tubercular uveitis patients and 18 disease controls. Function of Tregs, Th1, and Th17 cells was assessed in vitro. Simultaneously, ocular levels of IFN-γ, IL-17A, IL-4, and IL-10 were also measured. RESULTS: Frequencies of peripheral Tregs in tubercular uveitis subjects were significantly lower compared with disease controls. Furthermore, expression of TGF-ß and IL-2Rα, but not CTLA4, was reduced in Tregs of the tubercular uveitis group. The tubercular uveitis group demonstrated heightened Th1, Th17 responses following in vitro stimulation with phorbol myristate acetate (PMA)/ionomycin. Interestingly, Treg suppression assay did not show a significant difference between the two groups. Ocular levels of IFN-γ, IL-17A, and IL-10 were also elevated in tubercular uveitis group. CONCLUSIONS: Low Treg frequency and hyporesponsive function contribute to proinflammatory responses manifesting at ocular level in tubercular uveitis.