Comparison between effects of instrument-assisted soft tissue mobilization and manual myofascial release on pain, range of motion and function in myofascial pain syndrome of upper trapezius - A randomized controlled trial.

Background: Myofascial pain syndrome (MPS) is a muscle pain disorder characterized by the presence of Myofascial Trigger Point (MTrP) within a taut band, local tenderness, referral of pain to a distant site, restricted range of motion, and autonomic phenomena. The upper trapezius is the muscle most often affected by MTrPs. Manual myofascial release (MFR) and Instrument-Assisted Soft Tissue Mobilization (IASTM) are techniques of soft tissue release that are used to resolve MPS. Fifty six percent of physiotherapists complain of pain in multiple areas due to the massage and manual therapy that they have to perform. Objective: The objective of this study is to find whether IASTM is better than manual MFR in treating patients with MPS in upper trapezius. Methods: This study was a single-blinded randomized controlled trial that included 31 participants, both males and females between the age groups of 18-50 years. Participants were randomly divided into two groups. Three sessions were given over a period of one week for both groups. Group A received IASTM along with conventional treatment and Group B received Manual MFR along with the conventional treatment. The outcome measures evaluated were pain, cervical range of motion, pain pressure threshold (PPT) of trigger points, and the neck disability index. Pre- and post-measurements were taken and the analysis was done. Results: Both the treatment methods significantly reduced pain, improved PPT, range of motion, and function. The effects between the groups showed that IASTM was significantly better than manual MFR to reduce pain. The improvement in PPT, range of motion and function were equal in both the groups. Conclusion: IASTM and manual MFR both are effective individually as treatment procedures for pain, PPT, range of motion, and function. Neither of the treatment options can be considered better that the other. The clinician can decide based on the availability of the instrument, training, patient's preference, and his/her comfort whether which of the two treatment methods should be used.

Central Giant Cell Granuloma: Negotiating the Diagnostic and Management Dilemmas.

Introduction: Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs. Background: We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma. Conclusion: Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.

Unique cytokine signature in ocular Stevens-Johnson syndrome non-responders.

PURPOSE: To clinically define a subset of patients with chronic ocular Stevens-Johnson syndrome non-responders (SJS-NR) and analyze their cytokine profile compared to clinical responders (SJS-CR). METHODS: A total of 32 SJS cases (n = 32, 64 eyes) managed over a period of three years were segregated into clinical responders (n = 24, 48 eyes) and non-responders (n = 8, 16 eyes). Cases were determined as non-responders based on persistent, refractory, and non-mechanical inflammation of the conjunctiva. Age- and sex-matched healthy controls (n = 25, 50 eyes) were recruited. Tear specimens collected using Schirmer's strip were profiled for 27 cytokines using an immunoassay-based 27-bioplex array. RESULTS: Tear cytokine profiling revealed 18 cytokines to be differentially expressed in SJS-NR compared to SJS-CR. While PDGF-BB, IL-4, IL-1ß, VEGF, IL-12p70, IFN-γ, IL-9, and IL-1RA were upregulated, GM-CSF, eotaxin, IP-10, IL-10, MCP-1, G-CSF, IL-6, IL-13, and bFGF were downregulated in SJS-NR compared to SJS-CR. The cytokines IL-13, IL-10, and IP-10 were decreased in both SJS-NR and SJS-CR compared to controls. CONCLUSION: The inflammation in SJS-NR continues to worsen despite the correction of mechanical causes, resulting in progressive deterioration of the cornea. The cytokine profile of SJS-NR was remarkably different from that of SJS-CR, indicating a T helper 2-type protective proliferative response and an impaired migratory potential of the conjunctival epithelium. These factors could possibly lead to poor healing of the corneal epithelium in a markedly pro-inflammatory and pro-angiogenic milieu. The top four differentially expressed cytokines, PDGF-BB, IL-4, IL-10, and IL-6, are proposed as potential biomarkers of SJS-NR.

Predicting nodal metastases in squamous cell carcinoma of the oral tongue using artificial intelligence.

OBJECTIVE: The presence of occult nodal metastases in patients with squamous cell carcinoma (SCC) of the oral tongue has implications for treatment. Upwards of 30% of patients will have occult nodal metastases, yet a significant number of patients undergo unnecessary neck dissection to confirm nodal status. This study sought to predict the presence of nodal metastases in patients with SCC of the oral tongue using a convolutional neural network (CNN) that analyzed visual histopathology from the primary tumor alone. METHODS: Cases of SCC of the oral tongue were identified from the records of a single institution. Only patients with complete pathology data were included in the study. The primary tumors were randomized into 2 groups for training and testing, which was performed at 2 different levels of supervision. Board-certified pathologists annotated each slide. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic (ROC) curves and the Youden J statistic were used for primary analysis. RESULTS: Eighty-nine cases of SCC of the oral tongue were included in the study. The best performing algorithm had a high level of supervision and a sensitivity of 65% and specificity of 86% when identifying nodal metastases. The area under the curve (AUC) of the ROC curve for this algorithm was 0.729. CONCLUSION: A CNN can produce an algorithm that is able to predict nodal metastases in patients with squamous cell carcinoma of the oral tongue by analyzing the visual histopathology of the primary tumor alone.

Depth, size of infiltrate, and the microbe - The trio that prognosticates the outcome of infective keratitis.

PURPOSE: To analyze the influence of infiltrate size, depth, and organism on the outcome of microbial keratitis. DESIGN: Retrospective comparative study. METHODS: Medical records of patients with infective keratitis, who reported from January 2015 to December 2019 to a tertiary eye care center, were analyzed. Size and depth of ulcer at presentation were the factors used to group patients, and the influence on the outcome of the organism causing it was analyzed. Grouping was as follows: group A: ulcer size <6 mm/anterior to midstromal infiltrate, group B: ulcer < 6 mm/full-thickness infiltrate, group C: ulcer >6 mm/anterior to midstromal infiltrate, group D: ulcer > 6 mm/full-thickness infiltrate. Patients with viral keratitis or unidentified organism were excluded. Response to treatment and best-corrected visual acuity (BCVA) at the final follow-up were the outcome measures. RESULTS: In the study, 1117/6276 patients were included, with 60.8% patients in group A. A significant improvement in visual acuity was noted in groups A/B compared to groups C/D. Group A had the best response to medical management, irrespective of the organism. Higher risk for surgery was noted in group C compared to group B, with group A as the reference. Overall resolution with medical treatment was noted in 70% miscellaneous keratitis, 64.8% bacterial keratitis, 64.3% mixed keratitis, 62.5% acanthamoeba keratitis, 52.6% fungal keratitis, and 12.1% Pythium keratitis. Bacteria and acanthamoeba responded better to medical management than fungal keratitis, whereas Pythium had the highest risk for surgery. CONCLUSION: An interplay between virulence of the organism along with depth and size of the infiltrate determines the outcome of microbial keratitis.

Salivary Duct Carcinoma Arising in a Warthin Tumor of the Parotid Gland: A Rare Case Report with Review of Literature and PD-L1 Expression.

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary duct carcinoma. He subsequently underwent left parotidectomy along with left level II-IV lymph node dissection. Histology revealed both in situ as well as invasive salivary duct carcinoma arising from Warthin tumor. Immunohistochemistry showed tumor cells positive for CK7, AR, and GATA3, while p63 highlighted the myoepithelial cell layer in the in situ component. Her2 was 2+ by immunohistochemistry. In addition, PD-L1 IHC revealed positive expression with a combined positive score of 20%.

Necrotizing Scleritis: A Review.

Necrotizing scleritis is the most destructive and vision-threatening form of scleritis. Necrotizing scleritis can occur in systemic autoimmune disorders and systemic vasculitis, as well as following microbial infection. Rheumatoid arthritis and granulomatosis with polyangiitis remain the commonest identifiable systemic diseases associated with necrotising scleritis. Pseudomonas species is the most common organism causing infectious necrotizing scleritis, with surgery the most common risk factor. Necrotizing scleritis has the highest rates of complications and is more prone to secondary glaucoma and cataract than other phenotypes of scleritis. The differentiation between non-infectious and infectious necrotizing scleritis is not always easy but is critical in the management of necrotizing scleritis. Non-infectious necrotizing scleritis requires aggressive treatment with combination immunosuppressive therapy. Infectious scleritis is often recalcitrant and difficult to control, requiring long-term antimicrobial therapy and surgical debridement with drainage and patch grafting due to deep-seated infection and the avascularity of the sclera.

Essential oil and nanocarrier-based formulations approaches for vaginal candidiasis.

An exclusive site for local drug delivery is the vagina, especially for vaginal infections. The fungus Candida albicans causes vaginal infection known as vulvovaginal candidiasis, a highly prevalent and recurrent gynaecological disease among women. Vaginal candidiasis affects over 75% of women at a certain point in their life and has a recurrence rate of 40-50%. Medicinal plants provide some very effective phytoconstituents which when delivered as nanosystems have enhanced therapeutic action and efficacy by alteration in their characteristics. Antifungal drugs are used to treat these conditions, alternative medicine is required for prophylaxis and improved prognosis. The current review focuses on the research carried out on various nanocarrier-based approaches and essential oil-based formulations for vaginal candidiasis.

The vagina is a part of a woman's body that can sometimes get sick from a fungus called Candida albicans. This sickness is called thrush, and it's very common. More than 75% of women will get it at some point, and it might come back again after it's gone. There are medicines that can help, but some plants can also be used to make powerful medicine that can heal the sickness from tiny particles called 'nanosized carriers'. Scientists are studying different ways to give the medicine to the sick area from these plants.

Atypical Squamous Verrucous Lesions of the Oral Cavity: Challenges in Interpretation of Small Incisional Biopsies.

BACKGROUND: Squamous verrucous proliferative lesions of oral cavity can pose a diagnostic challenge for the general pathologist, especially on small biopsies. The superficial nature of incisional biopsies and inconsistent histologic terminologies used for these lesions contribute to often-discrepant clinical diagnosis, resulting in delayed treatment. This study aims to explore the proliferative squamous lesions of oral cavity, correlate biopsy & resection diagnoses, and evaluate possible reasons for discrepant diagnosis (if any). DESIGN: A retrospective review of oral verrucous squamous lesions was undertaken. Pathology database was searched for oral cavity biopsies from January2018 through August2022 with the keywords: atypical, verrucous, squamous, and proliferative. Cases with follow-up were included in this study. A blinded review of the biopsy slides was performed and documented by a single head and neck pathologist. Demographic data, biopsy and final diagnosis were recorded. RESULTS: Twenty-three cases met criteria for inclusion. The mean patient age was 61.1 years with a male: female ratio of 1.09. Most frequent site was lateral border of tongue (36%) followed by buccal mucosa and retromolar trigone. The most common biopsy diagnosis was "Atypical squamoproliferative lesion, excision recommended" (n = 16/23, 69%) with 13/16 showing conventional squamous cell carcinoma (SCC) on follow-up resection. 2/16 atypical cases underwent repeat biopsy for confirmation of diagnosis. Overall, conventional SCC was the most prevalent final diagnosis (73%, n = 17), followed by verrucous carcinoma (17%, n = 4). On slide review, six initial biopsies were reclassified as SCC, while one final diagnosis was reclassified as a hybrid carcinoma (on resection specimen). Diagnostic concordance (biopsy and resection) was observed in three cases, all three were recurrences. The primary reasons for discrepant diagnosis on initial biopsies were found to be 1. Obscuring inflammation, 2. Superficial biopsies, and 3. Under recognition of morphologic features (e.g., tear shaped rete, loss of polarity, dyskeratotic cells, paradoxical maturation) that help differentiate dysplasia from reactive atypia. CONCLUSION: This study highlights the rampant interobserver variability in diagnosis of oral cavity squamous lesions and emphasizes importance of identifying morphologic clues that can aid in correct diagnosis, thereby helping in adequate clinical management.

Keratoprosthesis in dry eye disease.

Bilateral corneal blindness with severe dry eye disease (DED), total limbal stem cell deficiency with underlying corneal stromal scarring and vascularization, combined with adnexal complications secondary to chronic cicatrizing conjunctivitis is a highly complex situation to treat. In such eyes, procedures such as penetrating keratoplasty alone or combined with limbal stem cell transplantation are doomed to fail. In these eyes, keratoprosthesis (Kpro) or an artificial cornea is the most viable option, eliminating corneal blindness even in eyes with autoimmune disorders such as Stevens-Johnson syndrome, ocular mucous membrane pemphigoid, Sjogren's syndrome, and nonautoimmune disorders such as chemical/thermal ocular burns, all of which are complex pathologies. Performing a Kpro in these eyes also eliminates the need for systemic immunosuppression and may provide relatively early visual recovery. In such eyes, the donor cornea around the central cylinder of the Kpro needs to be covered with a second layer of protection to avoid desiccation and progressive stromal melt of the underlying cornea, which is a common complication in eyes with severe DED. In this review, we will focus on Kpro designs that have been developed to survive in eyes with the hostile environment of severe DED. Their outcomes in such eyes will be discussed.

E-PIX: An enhanced grading for acute ocular burns.

An enhanced online and manual grading system, based on the I's and E's, for acute ocular chemical injuries is being proposed. E-PIX is designed to be an online/manual grading system that includes all the parameters that adversely affect the outcome of acute chemical injuries. The importance of addressing the I's and E's in chemical burns cannot be underestimated. These include the need for the documentation and management of epithelial defect (E), intraocular pressure (P) (IOP), ischemia (scleral) (I), and exposure (X) (acronym - E-PIX). Epithelial defect includes that involving the limbus (L), along with conjunctival (C), corneal (K), and tarsal (T). These additional parameters are graded and represented as an annotation along with the limbal grade providing a comprehensive grading for the injury. A manual entry sheet and a freely accessible online grade generator are a part of the system. The proposed enhanced grading offers a final annotation that provides a clear understanding of all factors that can lead to vision-threatening complications ensuring their assessment and hence subsequently their addressal to improve outcomes, if abnormal. The prognostication continues to be based on the grade of limbal involvement. The additional annotations impact prognosis and outcome if not addressed. Including the laterality of injury provides, in addition, a futuristic understanding of available options. The grade generator retains the flexibility to be dynamic with changes reflecting upon the healing process in the acute stage. The proposed system aims to provide primary and tertiary caregivers alike with a uniform grading system.

Dry eye module - An application intelligence platform for diagnosing and monitoring dry eye disease.

Dry Eye Module (DEM), a software application, was developed to facilitate the streamlining of dry eye evaluation and documentation, to unify diagnostic jargon, and to analyze data input to generate a dry eye diagnostic report. This diagnostic report generated is based on the current understanding of dry eye diagnostic algorithms (Dry Eye Workshop 2 [DEWS2]/Asia Dry Eye Society [ADES]). Apart from its plausible role in aiding unprecedented multicentric dry eye demographic data collection, the application software can generate a customized referral letter to the rheumatologist, highlighting the salient ophthalmic features to be shared. DEM uses schematic illustrations to depict eyelid, conjunctival, and corneal parameters that impact the ocular surface in dry eyes that can be captured and compared during serial visits. Furthermore, DEM displays a symptom sign trend chart that graphically represents improvement/stability or worsening of the subjective and objective dry eye status. DEM can generate a curated prescription using preloaded advice templates. DEM includes facility for state-of-the-art advanced dry eye diagnostic reporting for super specialty use. The addition of DEM to the dry eye diagnostic armamentarium would help bridge the current unmet needs of dry eye evaluation. These are lack of uniform reporting, lack of multicentric data on a unified platform, the inability to ensure complete evaluation, inability to avoid lacunae during follow-up visits, and the lack of a simple patient-ophthalmologist and an ophthalmologist-rheumatologist interface.

Aqueous deficiency dry eye in post conjunctivitis cicatrization - Effect of deep thermal punctal cautery.

Purpose: To evaluate the effect of deep thermal punctal cautery in eyes with post-conjunctivitis cicatrization. Methods: This retrospective study consisted of patients who underwent deep thermal punctal cautery for post-conjunctivitis dry eye (PCDE). The diagnosis was based on a history suggestive of viral conjunctivitis in past followed by the onset of present clinical features of aqueous deficiency dry eye (ATD). All patients underwent a rheumatological evaluation to rule out underlying systemic collagen vascular disease as a cause for dry eye. The extent of cicatricial changes was noted. Best-corrected visual acuity (BCVA), Schirmer's test, and fluorescein staining score (FSS; total score of 9) were analyzed pre- and post-cautery. Results: Out of 65 patients (117 eyes), 42 were males. The mean age at presentation was 25.769 ± 12.03 years. Thirteen patients presented with unilateral dry eye. Pre-cautery BCVA (logarithm of the minimum angle of resolution [logMAR]) and Schirmer's test (mm) improved from 0.5251 ± 0.662 to 0.372 ± 0.595 (P value = 0.000, 95% confidence interval [CI]: 0.09-0.22), and 1.952 ± 2.763 to 4.929 ± 4.338 (P value = 0.000, 95% CI: -3.79--2.17); post-cautery, respectively. The pre-cautery FSS of 5.9 ± 2.82 reduced to 1.58 ± 2.38 (P value = 0.000, 95% CI: 3.46-5.17) post-cautery. The mean follow-up was 11.22 ± 13.32 months. No progression in cicatricial changes was noted in any eye during the follow-up. Re-canalization rate was 10.64%, and repeat cautery was performed with successful closure of puncta. Conclusion: Symptoms and clinical signs of ATD in PCDE patients improve with punctal cautery.

Lymph Node Metastases in Papillary Thyroid Carcinoma can be Predicted by a Convolutional Neural Network: a Multi-Institution Study.

OBJECTIVES: The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. METHODS: Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated "positive" if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution's data and tested independently on the other institution's data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. RESULTS: There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution's data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. CONCLUSION: A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data.

Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications.

Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid. Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings.

Role of polymerase chain reaction-based viral detection in pterygia.

Purpose: Pterygium is a fibrovascular disease that originates in the conjunctiva and commonly spreads to the corneal surface, thereby posing a threat to eyesight. Despite intensive research, the pathophysiology of this disease remains unclear. Recent research suggests that oncogenic viruses, such as human papillomavirus (HPV), cytomegalovirus, and Epstein-Barr virus (EBV), may play a role in pterygia development. Although there are questions concerning the function of oncogenic viruses in pterygium pathogenesis, existing research shows a lack of consensus on the subject, demonstrating the heterogeneity of pterygium pathophysiology. Therefore, we aimed to simultaneously detect the three common viral pathogens that have been reported in pterygium tissue obtained after excision. Methods: Thirty-five tissue specimens of pterygium from patients undergoing pterygium surgery (as cases) were analyzed for evidence of viral infection with multiplex polymerase chain reaction (PCR), and virus-specific real-time quantitative PCR was used for the samples that were detected positive by multiplex PCR. Results: Of the 35 patients, one sample was positive for EBV and two samples were positive for HPV. Further PCR-based DNA sequencing of the HPV PCR-positive product showed identity with HPV-16. Real-time quantitative PCR on samples that showed EBV or HPV positivity did not yield any detectable copy number. Conclusion: Our study results confirmed that PCR positivity could be due to transient flora, but it was not quantitatively significant to conclude as the causative factor of pterygium pathogenesis. However, additional studies with larger sample populations are warranted to fully determine the role of the virus in pterygium.

Possible Synergistic Role of Cryo-Alcohol Therapy in Infectious Scleritis-Scope and Rationale for Expanding Indications and Review of the Literature.

PURPOSE: The purpose of this study was to highlight the use of topical ethanol as an adjunct to cryotherapy, termed cryo-alcohol therapy, in the management of fungal/acanthamoeba scleritis along with a review of the literature. METHOD: Retrospective interventional case reports of fungal and acanthamoeba scleritis along with a review of the literature. RESULTS: The patient with circumferential necrotic fungal scleritis resolved in 6 weeks achieving a best-corrected visual acuity (BCVA) of 20/20, and the patient with acanthamoeba scleritis is awaiting optical keratoplasty after complete resolution in 8 weeks. The literature review from January 1990 to December 2020 revealed BCVA >20/200 in 50% of the eyes with a mean time to resolution being 4.16 ± 2.13 months in fungal scleritis, with 27.02% and 75% of the eyes requiring evisceration in fungal and acanthamoeba scleritis, respectively. CONCLUSIONS: Cryotherapy is a useful adjunct in managing refractory infectious scleritis, and its efficacy can be enhanced by combining the use of topical ethanol to aid in faster recovery and reduce visual morbidity.

Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis.

BACKGROUND: The etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease. METHODS: Active VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells. RESULTS: Significantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (p<0.001) and S1P(d17:1) (p<0.01) specifically in severe/very severe VKC compared with both mild/moderate VKC and control. Cer(d18:/17:0) (p<0.001), ceramide-1-phosphate (C1P)(d18:1/8:0) (p<0.01) and C1P(d18:1/2.0 (p<0.05) were lowered in severe/very severe VKC compared with mild/moderate VKC. Cultured mast cells treated with IgE revealed significantly increased gene expression of S1P1 and 3 receptors and the protein expression of histone deacetylases (1, 6). CONCLUSION: Altered sphingolipid metabolism in the ocular surface results in low tear ceramide and sphingosine levels in severe/very severe VKC compared with the mild/moderate cases. The novel finding opens up fresh targets for intervention in these refractory cases.