Histopathological spectrum of ocular surface squamous neoplasia: A retrospective study of 776 lesions.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) comprises neoplasm arising from the ocular surface, which includes conjunctiva, cornea, and limbus and ranges from mild dysplasia to invasive squamous cell carcinoma. PURPOSE: The aim of this work was to study the spectrum of OSSN based on histopathological analysis. Materials and. METHODS: This was a retrospective cross-sectional study comprising 776 histopathologically diagnosed cases of OSSN from January 2004 to December 2014. RESULTS: The mean age of presentation of OSSN was 45 years (median, 45 years; 2 to 87 years) with male preponderance (74%). The most common age group of presentation was 41-60 years (n = 299; 39%). The most common type of OSSN was invasive squamous cell carcinoma seen in 50% (n = 383) eyes followed by severe dysplasia/carcinoma in situ in 31% (n = 250) eyes. Tumor infiltration at base was seen in 16% (n = 124), positive margins in 32% (n = 248), scleral infiltration in 14% (n = 109), intraocular extension in 3% (n = 23), and orbital extension in 4% (n = 26) eyes. OSSN was associated with actinic keratosis in 21% (n = 165) cases. CONCLUSION: Based on histopathology, invasive squamous cell carcinoma is the most common form of OSSN in the Asian Indian population.

Primary orbital polymethylmethacrylate implant following primary enucleation for retinoblastoma: a study of 321 cases.

Purpose: To evaluate the outcome of primary orbital polymethylmethacrylate (PMMA) implant following the primary enucleation for retinoblastoma. Methods: Retrospective study of 321 retinoblastoma patients who underwent unilateral enucleation and PMMA implant for retinoblastoma by myoconjunctival technique. Outcome measures included implant centration and extrusion. Results: The mean age at the time of enucleation of patients with retinoblastoma was 35 months (median, 30 months; range, <1 to 449 months). After primary enucleation, primary orbital PMMA implant was used in all cases. The mean diameter of implant was 18 mm (median, 18 mm; range, 12-20 mm) and the mean horizontal diameter of the socket conformer was 24 mm (median, 24 mm; range, 18 mm-26 mm). Post-enucleation and implant, seven (2%) patients underwent orbital external beam radiotherapy owing to microscopic extrascleral tumor extension or tumor infiltration of optic nerve transection. Over a mean follow-up period of 40 months (median, 34 months; range, 4-129 months), implant migration was noted in 28 (9%) patients, implant extrusion in 9 (3%), and implant exposure in 5 (2%), and contracted socket in 5 (2%) patients including grade 1 contraction in 3 (1%), grade 2 in 1 (<1%), and grade 4 in 1 (<1%) patient. Implant exchange for an improved prosthesis fit was performed in 4 (1%) cases. Stable customized ocular prosthesis was achieved in all but one patient. Conclusion: Primary orbital PMMA implant following primary enucleation for retinoblastoma is associated with minimal complications and provides acceptable cosmetic outcomes.

Ocular surface squamous neoplasia with intraocular tumour extension: a study of 23 patients.

PURPOSE: To describe the clinical features, histopathology and treatment of ocular surface squamous neoplasia (OSSN) with intraocular tumour extension. METHODS: Retrospective study of 23 patients. RESULTS: The mean age at presentation of OSSN with intraocular tumour extension was 48 years. Mass (52%) and pain with redness (30%) were the most common presenting complaints. The mean duration of symptoms was 9 months. History of human immunodeficiency virus (HIV) infection was present in eight (35%) patients and one (4%) had xeroderma pigmentosum. History of prior tumour excision was noted in 16 (70%) patients. The mean basal diameter was 17 mm and the mean tumour thickness was 4 mm. Fifteen (65%) tumours had a nodulo-ulcerative tumour pattern at the time of detection of intraocular extension of OSSN. Anterior chamber cells and flare was noted in five (24%) cases and two (9%) patients had secondary glaucoma. Ultrasound biomicroscopy (UBM) (n = 11) revealed blunting of anterior chamber in three (27%) cases and uveal thickening in seven (67%) cases. Over the course of follow-up, extended enucleation (n = 6; 26%) or orbital exenteration (n = 17; 74%) was required for tumour control. At a mean follow-up period of 18 months, locoregional lymph node metastasis was seen in two (9%) patients, and one patient died with systemic metastasis. On histopathology, ciliary body was involved in all (100%) cases. CONCLUSION: Multiple tumour recurrences with history of prior tumour excision and nodulo-ulcerative tumour pattern are commonly associated with intraocular tumour extension of OSSN. UBM is a useful tool to detect intraocular extension of OSSN.

INADVERTENT INTRAOCULAR SURGERY IN CHILDREN WITH UNSUSPECTED RETINOBLASTOMA: A Study of 14 Cases.

PURPOSE: To study the clinical presentation and treatment outcome of patients who underwent inadvertent intraocular surgery before the diagnosis of retinoblastoma. DESIGN: Retrospective study of 14 patients who had undergone an inadvertent intraocular surgery before the diagnosis of retinoblastoma. RESULTS: The mean age at presentation to the ocular oncology clinic was 69 months. The most common initial misdiagnosis was endophthalmitis (n = 4). The most common inadvertent intraocular surgeries were pars plana vitrectomy (n = 6) with/without lensectomy and evisceration with/without previous pars plana vitrectomy (n = 5). The mean interval between intraocular procedure and initiation of treatment for retinoblastoma was 7 months. At presentation in the oncology clinic, the tumor was intraocular (n = 3), with extrascleral tumor extension (n = 11), and/or optic nerve tumor extension (n = 5). All patients were started on multimodal treatment including 12 cycles of high-dose systemic chemotherapy, enucleation or orbital exenteration, and orbital external beam radiotherapy. Over a mean follow-up period of 27 months, 8 (57%) patients died because of progressive disease despite initiation of treatment. CONCLUSION: Misdiagnosis and inadvertent surgical intervention in cases of retinoblastoma in combination with delayed initiation of appropriate treatment is associated with poor prognosis. High index of suspicion for retinoblastoma is needed to avoid misdiagnosis and mismanagement.

Conjunctival Retention Cysts: Outcomes of Aspiration and Sclerotherapy With Sodium Tetradecyl Sulfate.

PURPOSE: To assess the outcome of aspiration and sclerotherapy with sodium tetradecyl sulfate in the management of conjunctival inclusion cysts. METHODS: Retrospective interventional case series of 6 patients with clinical diagnosis of conjunctival inclusion cysts treated with cyst aspiration and foam sclerotherapy with 3% sodium tetradecyl sulfate. The volume of the sclerosant was 20% of the aspirated cyst volume. RESULTS: Four patients had an inclusion cyst in anophthalmic sockets and 2 patients in sighted eyes. Average time lag between primary surgery and cyst formation was 14.6 months (range 2-30 months). Average amount of fluid aspirated from cyst was 3.07 ml (range 1-9 ml). Average volume of sclerosant injected was (20% of the aspirated volume) 0.55 ml (range 0.2-1.1 ml). All 6 patients showed complete resolution of cyst at a mean follow-up period of 15.6 months (range 9-24 months). All but one showed complete resolution of cyst with single injection sclerosant. Only 1 patient required a second sclerosant injection. There was no ocular surface or implant-related complications in this cohort. CONCLUSIONS: Cyst aspiration and sodium tetradecyl sulfate foam sclerotherapy is a minimally invasive procedure for the management of conjunctival inclusion cysts in anophthalmic sockets and sighted eyes. The injection of sodium tetradecyl sulfate in a dose of 20% of the aspirate is effective in the management of conjunctival inclusion cysts over a follow-up period of 13 months. The procedure is safe, with insignificant inflammation and without ocular surface or implant complications.

Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF.

BACKGROUND: Hepatitis E is endemic to resource-poor regions, where it manifests as sporadic cases and large waterborne outbreaks. The disease severity ranges from acute self-limited hepatitis with low mortality to fulminant hepatic failure with high mortality. It is believed that the host response plays an important role in determining the progression and outcome of this disease. We profiled the plasma peptidome from hepatitis E patients to discover suitable biomarkers and understand disease pathogenesis. RESULTS: The peptidome (< 10 kDa) fraction of plasma was enriched and analyzed by mass spectrometry. A comparative analysis of the peptide pattern of hepatitis E patients versus healthy controls was performed using ClinPro Tools. We generated a peptide profile that could be used for selective identification of hepatitis E cases. We have identified five potential biomarker peaks with m/z values of 9288.6, 7763.6, 4961.5, 1060.572 and 2365.139 that can be used to reliably differentiate between hepatitis E patients and controls with areas under the receiver operating characteristic curve (AUROC) values of 1.00, 0.954, 0.989, 0.960 and 0.829 respectively. A number of proteins involved in innate immunity were identified to be differentially present in the plasma of patients compared to healthy controls. CONCLUSIONS: Besides the utility of this approach for biomarker discovery, identification of changes in endogenous peptides in hepatitis E patient plasma has increased our understanding of disease pathogenesis. We have identified peptides in plasma that can reliably distinguish hepatitis E patients from healthy controls. Results from this and an earlier proteomics study are discussed.

Plasma and urine biomarkers in acute viral hepatitis E.

BACKGROUND: Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatitis E. RESULTS: We analyzed proteins in the plasma and urine of hepatitis E patients and healthy controls by two-dimensional Differential Imaging Gel Electrophoresis (DIGE) and mass spectrometry, and identified over 30 proteins to be differentially expressed during acute hepatitis E. The levels of one plasma protein, transthyretin, and one urine protein, alpha-1-microglobulin (alpha1m), were then quantitated by enzyme immunoassay (EIA) in clinical samples from a larger group of patients and controls. The results showed decreased plasma transthyretin levels (p < 0.005) and increased urine alpha1m levels (p < 0.001) in acute hepatitis E patients, compared to healthy controls. Preliminary results also showed lower urine zinc alpha glycoprotein levels in fulminant hepatitis E compared to acute disease; this remains to be confirmed with more fulminant cases. CONCLUSION: Our results demonstrate the utility of characterizing plasma and urine proteomes for signatures of the host response to HEV infection. We predict that plasma transthyretin and urine alpha1m could be reliable biomarkers of acute hepatitis E. Besides the utility of this approach to biomarker discovery, proteome-level changes in human biofluids would also guide towards a better understanding of host-virus interaction and disease.

Molecular biology and pathogenesis of hepatitis E virus.

The hepatitis E virus (HEV) is a small RNA virus and the etiological agent for hepatitis E, a form of acute viral hepatitis. The virus has a feco-oral transmission cycle and is transmitted through environmental contamination, mainly through drinking water. Recent studies on the isolation of HEV-like viruses from animal species also suggest zoonotic transfer of the virus. The absence of small animal models of infection and efficient cell culture systems has precluded virological studies on the replication cycle and pathogenesis of HEV. A vaccine against HEV has undergone successful clinical testing and diagnostic tests are available. This review describes HEV epidemiology, clinical presentation, pathogenesis, molecular virology and the host response to HEV infection. The focus is on published literature in the past decade.