Aqueous humor cytokines and cellular profiles in pediatric ocular granulomas caused by theTrematode Fluke Procerovum sp.

BACKGROUND: Children from coastal areas of South India develop granulomatous eye disease after swimming in their village ponds, the causative organism being trematode Procerovum. AIM: To understand the pathogenesis by analyzing the cellular profile, cytokines, and chemokines of aqueous fluid. METHODS: This was a prospective study over 1 year on pediatric patients with ocular granuloma caused by a Trematode Fluke Procerovum sp. Granuloma was aspirated along with 100 µl volume of aqueous humor. Immunohistochemical analysis of granuloma was performed. Bio-Plex Pro™ Human Cytokine 17-plex Assay (M5000031YV) was used to measure cytokine and chemokines. RESULTS: The immunohistochemistry revealed predominantly eosinophils, followed by macrophages (CD68+) and T - lymphocytes (CD4+). Both T-helper (Th) 1 and 2 mediated cytokines and chemokine levels were significantly high. As the disease duration increased, direct Th1 response reduced and was replaced by IL-12 and IL-17 mediated secondary Th1 response. CONCLUSION: Procerovum associated granulomatous disease is immunologically characterized by Th1 and Th2 cell-mediated responses. A balance between both arms maintains the eyes between granulomatous inflammation and healing by fibrosis.

Keratitis occurring in patients treated with miltefosine for post-kala-azar dermal leishmaniasis.

AIM: To describe the characteristic clinical features and management of keratitis in the patients receiving miltefosine for post-kala-azar dermal leishmaniasis (PKDL). METHODS: The medical records of five patients with PKDL who presented with keratitis were reviewed retrospectively from April 2018 to December 2019. The evaluation included a thorough medical history including details on drugs used, particularly miltefosine. The drug causality assessment was also performed. The clinical and microbiological characteristics of keratitis were noted. RESULTS: The ocular symptoms included pain, redness, watering, photophobia and diminution of vision. Slit-lamp biomicroscopy revealed peripheral, paralimbal, ring-shaped, full-thickness stromal infiltration resulting in ulcerative keratitis in all cases. Two patients had unilateral keratitis, while three had bilateral keratitis. All five patients received miltefosine for an average period of 48 days before the onset of keratitis. The corrected distance visual acuity at presentation ranged from hand movement to 20/125. The causality assessment revealed a 'probable' association between the adverse drug reaction and miltefosine in all patients. Discontinuation of miltefosine and initiation of corticosteroid therapy resulted in resolution of keratitis in all cases. The unilateral keratitis treated with topical corticosteroids had improved outcomes, but poor outcomes were found in the bilateral keratitis. CONCLUSION: These observations indicate that prolonged use of miltefosine might cause keratitis that resembles infectious keratitis. Early diagnosis with discontinuation of the drug and initiation of corticosteroid therapy are the key to successful management.

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.

Molecular diagnosis and ocular imaging of West Nile virus retinitis and neuroretinitis.

PURPOSE: To describe the ocular features of West Nile virus (WNV) infection proven by serology and molecular diagnostic techniques. DESIGN: Prospective case series. PARTICIPANTS: Fifty-two patients who presented to the uveitis clinic with ocular inflammatory signs and history of fever preceding ocular symptoms between January 2010 and January 2012 were enrolled for laboratory diagnosis. Serum samples were collected from 30 healthy controls from the same geographic area. METHODS: Patients were tested for all endemic infectious diseases that can cause ocular inflammation by serology or molecular diagnostics. When patients had positive antibodies for WNV, serum/plasma samples were tested by real-time reverse transcription (RT) polymerase chain reaction (PCR) and RT loop-mediated isothermal gene amplification assays. The PCR product was subjected to nucleotide sequencing. Fundus fluorescence angiography (FFA), optical coherence tomography (OCT), and indocyanine green angiography were performed. Visual prognosis was analyzed. MAIN OUTCOME MEASURES: Clinical signs (retinitis, neuroretinitis, and choroiditis) and ocular complications (decrease in vision). RESULTS: A total of 37 of 52 patients (71%) showed positive results for at least 2 laboratory tests for WNV. Fundus examination revealed discrete, superficial, white retinitis; arteritis; phlebitis; and retinal hemorrhages with or without macular star. The FFA revealed areas of retinal inflammation with indistinct borders, vascular and optic disc leakage, vessel wall staining, or capillary nonperfusion. Indocyanine green angiography confirmed choroidal inflammation in 1 of the patients who was diabetic. The OCT scan of the macula revealed inner retinal layer edema in active inflammation and retinal atrophy in late stage. At the final visit, 43% of patients had visual acuity better than 6/12. CONCLUSIONS: In addition to previously reported clinical signs, retinitis, neuroretinitis, and retinal vasculitis were seen in this population. Atrophy of the inner retinal layer was seen on OCT after resolution of inflammation. Visual prognosis was good in patients with focal retinitis and poor in patients with occlusive vasculitis. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Analysis of the SALL4 gene in patients with Duane retraction syndrome in a South Indian population.

Duane retraction syndrome (DRS) is a congenital eye movement disorder characterized most typically by partial or complete failure of abduction and narrowing of palpebral fissure with globe retraction on adduction. Recently mutations of the SALL4 gene on chromosome 20 have been linked to DRS associated with radial forearm malformations (Okihiro syndrome). In this prospective, non-interventional study we screened for SALL4 mutations in 72 patients clinically diagnosed as having isolated DRS or DRS associated syndromes. All four exonic and the neighboring intronic regions of SALL4 gene were amplified by sixteen sets of primers using polymerase chain reaction and were subjected to bi-directional sequencing and BLAST analysis. No genetic variations were detected in the coding region and in the neighboring intronic regions of the SALL4 gene suggesting an alternative mechanism in the pathogenesis of these disorders in the South Indian population.