Orbital Sarcoma with BCOR Genetic Alterations in the Pediatric Age Group.

Introduction: Pediatric orbital tumors encompass a wide spectrum of neoplasms, many of which are malignant small round cell tumors with overlapping histology. Sarcomas with BCOR genetic alterations are undifferentiated round cell sarcomas (URCS) characterized by BCOR rearrangements or internal tandem duplications, having distinct clinical features. Being previously unrecognized in the orbit, they have potential for misdiagnosis. Patients: We describe two cases of orbital sarcomas with BCOR genetic alterations. Results: Both girls, 8 and 16 months of age, respectively, presented with progressive proptosis. Both tumors showed sheets of round to ovoid cells with monomorphic nuclei and frequent mitoses. Delicate branching capillaries and myxoid stroma were absent. Diffuse BCOR, cyclin D1, and SATB2 immunopositivity was present. Conclusion: Orbital sarcomas with BCOR genetic alterations are extremely rare. Pathologists should have high index of suspicion for novel genetically defined entities in the differential diagnosis of pediatric orbital URCS and perform appropriate ancillary tests for accurate diagnosis.

Neoadjuvant Chemotherapy in Non-Metastatic Eyelid Sebaceous Gland Carcinoma: A Report in 10 Cases.

Introduction: Eyelid sebaceous gland carcinoma (SGC) is an aggressive malignancy. Surgical excision is the standard treatment for non-metastatic eyelid SGC. This study aimed to evaluate treatment outcomes with use of neoadjuvant chemotherapy (NACT) and any change in ease/difficulty of surgical treatment in such cases. Methods: This was a prospective interventional study conducted over 24-month period. Histopathologically, confirmed cases without any systemic metastasis were included. Clinico-demographic details were collected for 30 patients. 10 patients received NACT using cisplatin and 5-FU. Tumour response was evaluated using RECIST criteria. An ease of surgery questionnaire was used to assess difficulty of surgical treatment before and after NACT. Results: Of the 30 patients evaluated for recruitment, 37% had recurrent SGC and 72% had advanced tumour stage. Ten patients were recruited for NACT. There was partial response in 80% and complete response in 10% cases. Tumour T category downstaging was seen in 50% of cases. While tumour dimensions/volume reduced substantially, surgical ease improved in only 40% cases. Conclusion: A significant proportion of SGC patients evaluated in our study presented with recurrent and/or advanced disease. NACT caused tumour regression in 90% of cases. However, surgical ease improvement was limited, pointing to a need for surgical modification in such cases. Corneal ulceration was noted in 2 cases with large tumours causing a complete mechanical ptosis. Overall, the study introduced an ease of surgery questionnaire and provided insights into benefits and challenges of using NACT for eyelid SGC management.

Clinicopathological presentations of eyelid malignancy in COVID era versus pre-COVID era.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic led to overall interrupted medical care, resulting in disease progression and morbidity. The study aimed to evaluate clinicopathological presentations and severity of eyelid malignancy during the COVID era, comparing the results with patients presented during pre-COVID era and evaluating the reasons for delayed presentation in patients with advanced eyelid malignancy in the COVID-era. METHODS: This was a comparative, ambispective observational study. Data regarding demographic, clinical, histopathology, and treatment modalities of confirmed cases of eyelid malignancy admitted during the period from March 2020 to September 2022 (defined as COVID era group) were collected and compared with retrospectively collected data from March 2017 to March 2020 (defined as pre-COVID era group). COVID era patients were further categorized as localized and advanced disease. Patients with advanced eyelid malignancy during COVID era were further subjected to a questionnaire to evaluate the reasons for delayed presentation. RESULTS: In total, 115 patients of eyelid malignancy were studied [COVID era group 40 (35%) and pre-COVID era group 75 (65%)]. A statistically significant increase in the duration of disease (P = 0.0001) and advanced tumor T-stage (P = 0.03) was noticed in the COVID era group. Demographic, histopathology, and ocular morbidity details were similar in both groups. The common reasons that led to delay in presentation and treatment in advanced T-stage patients during the COVID era were fear of acquiring COVID, lockdown, and lack of medical facilities. CONCLUSION: During the COVID-19 pandemic, both hospital- and patient-related factors contributed to delay in presentation, leading to advanced-stage disease indicating need of triaging of eyelid malignancy in the event of such pandemics in future.

Wnt/ß-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment.

The evolutionarily conserved Wnt signaling has a significant and diverse role in maintaining cell homeostasis and tissue maintenance. It is necessary in the regulation of crucial biological functions such as embryonal development, proliferation, differentiation, cell fate, and stem cell pluripotency. The deregulation of Wnt/ß-catenin signaling often leads to various diseases, including cancer and non-cancer diseases. The role of Wnt/ß-catenin signaling in adult tumors has been extensively studied in literature. Although the Wnt signaling pathway has been well explored and recognized to play a role in the initiation and progression of cancer, there is still a lack of understanding on how it affects pediatric tumors. This review discusses the recent developments of this signaling pathway in pediatric tumors. We also focus on understanding how different types of variations in Wnt signaling pathway contribute to cancer development and provide an insight of tissue specific mutations that lead to clinical progression of these tumors.

Clinicodemographic profile of orbital exenteration in a tertiary eye care center - A 20-year experience.

PURPOSE: This study aimed to determine the clinical indications for orbital exenteration, demographic profile of these patients, and clinicopathologic correlations in the current times and to compare these results with previous published data. METHODS: It was a retrospective study. All exenterations performed at a tertiary eye care center over a period of 20 years (from January 2001 to June 2020) were retrospectively evaluated. Patient records were reviewed to obtain demographic data, presenting symptoms and their duration, laterality, and clinical and histopathologic diagnosis. RESULTS: A total of 352 cases (males:females = 222:130) who underwent exenteration were identified. Patients age ranged from 11 months to 87 years (mean: 43.86 years, median: 50 years). The most common indication for exenteration was found to be eyelid malignancy in 54.36%, followed by retinoblastoma in 18.75% and primary orbital tumors in 14.49%. Out of 156 cases of eyelid malignancies requiring exenteration, squamous cell carcinoma (SCC) was the most common histologic subtype ( n = 94, 60.26%), followed by sebaceous gland carcinoma ( n = 40, 25.64%) and basal cell carcinoma ( n = 20, 12.82%). The most common primary orbital tumors requiring exenteration were adenocystic carcinoma of the lacrimal gland in adults and rhabdomyosarcoma in the pediatric age group. Benign conditions requiring exenteration included fulminant fungal orbital infections and lymphangioma among others. CONCLUSION: The number of exenterations performed have significantly increased in terms of absolute numbers. However, the ratio of exenteration to other tumor-related surgeries, mainly excision biopsy, has reduced compared to that reported from a previous study. The most common indication in our study remains eyelid malignancy followed by intraocular malignancy. However, SCC has emerged as the most common tumor histologic subtype requiring exenterations.

Tumor DNA sampling from aqueous humor in retinoblastoma - A report from South Asia.

PURPOSE: Retinoblastoma (RB) is the most common intraocular tumor in pediatric age group. The role of genetics has been explored in predicting survival prognosis, but its role in predicting globe salvage remains largely unexplored. We hereby aim to isolate cell-free DNA (cfDNA) from aqueous humor (AH) in RB eyes and validate its use for genetic studies. METHODS: AH was obtained from 26 eyes undergoing enucleation (arm A) or intravitreal chemotherapy (arm B). Isolation of cfDNA was done using QIAamp ® Circulating Nucleic Acid kit, and the cfDNA was utilized for targeted sequencing of RB1 gene. RESULTS: We could isolate cfDNA in all eyes (72% unilateral and 28% bilateral) with a distribution peak between 140 and 160 bp and a mean concentration of 27.75 ng/µl for arm A and 14 ng/µl for arm B. Targeted sequencing done on four samples showed RB1 gene mutations, namely, inframe deletion (c. 78-80del, p.Pro29del), start-loss mutation (c.1A>T, p.Met1?), nonsense mutations (c.2236G>T, p.Glu746Ter), (c.1659T>A, p.Cys553Ter), and (c.2065C>T, p.Gln689Ter), and novel missense mutations (c.672C>A, p.Asp224Glu) and c.692C>T (p.Pro231Leu). Genetic profile of cfDNA extracted from AH and genomic DNA from the tumor tissue was comparable. CONCLUSION: Our study supports the previous reports that AH may be used as a source of tumor-derived cfDNA. This is the first report from South Asia on isolation and genetic analysis of cfDNA from AH of RB eyes and, therefore, a big step forward in paving the role of tumor genetics in RB. Further studies are required to elucidate concordance between the tumor and AH genetic profile.

Comparison of HASTE versus EPI-Based DWI for Retinoblastoma and Correlation with Prognostic Histopathologic Parameters.

BACKGROUND AND PURPOSE: Non-EPI-based DWI has shown better performance in head and neck pathologies owing to lesser susceptibility artifacts compared with EPI-DWI. However, only sporadic studies have investigated the feasibility of non-EPI-based DWI in retinoblastoma (RB). We qualitatively and quantitively compared EPI-DWI and HASTE-DWI in RB and correlated the tumor ADC values obtained from these 2 techniques with histopathologic markers. MATERIALS AND METHODS: Twenty-one treatment-naive patients with RB underwent 1.5T orbital MR imaging. EPI-DWI and HASTE-DWI were acquired at 3 b-values (0, 500, and 1000 s/mm2). All patients subsequently underwent surgical enucleation. For qualitative image assessment, scoring of overall image quality, artifacts, tumor sharpness, and tumor conspicuity was done by using a 5-point Likert scale. Quantitative assessment included calculations of SNR, contrast-to-noise ratio (CNR), geometric distortion, and ADC. Qualitative scores were compared by using the Wilcoxon signed-rank test, and quantitative parameters were analyzed with a t test. RESULTS: All 21 patients had unilateral RB; 15 were male and 6 were female with a median age of 36 months (range, 9-72 months). On histopathology, patients had either poorly differentiated (n = 13/21) or moderately differentiated (n = 8/21) RB. Other poor prognostic markers evaluated were optic nerve invasion (n = 10/21), choroidal invasion (n = 12/21), and anterior eye segment enhancement on MRI (n = 6/21). HASTE-DWI demonstrated higher image quality scores than EPI-DWI (P < .01), except for tumor conspicuity score, which was higher for EPI-DWI (P < .001). HASTE-DWI showed lower SNR, CNR, and geometric distortion than EPI-DWI (P < .001). The average acquisition times of EPI-DWI and HASTE-DWI were ∼1 and 14 minutes, respectively. The mean tumor ADC value on EPI-DWI was 0.62 ± 0.14 × 10-3 mm2/s and on HASTE-DWI was 0.83 ± 0.17 × 10-3 mm2/s. A significant correlation between EPI-DWI and HASTE-DWI ADC values (r = 0.8; P = .01) was found. Lower ADC values were found in tumors with poor prognostic markers, but none reached a statistically significant difference. CONCLUSIONS: HASTE-DWI shows improved overall image quality; however, it lacks in terms of tumor conspicuity, SNR, CNR, and longer acquisition time compared with EPI-DWI. ADC values derived from HASTE-DWI show no advantage over EPI-DWI in correlation with histopathologic prognostic markers.

Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target.

Receptor tyrosine kinases (RTKs) serve as molecular targets for the development of novel personalized therapies in many malignancies. In the present study, expression pattern of receptor tyrosine kinases and its clinical significance in orbital RMS has been explored. Eighteen patients with histopathologically confirmed orbital RMS formed part of this study. Comprehensive q-PCR gene expression profiles of 19 RTKs were generated in the cases and controls. The patients were followed up for 59.53 ± 20.93 years. Clustering and statistical analysis tools were applied to identify the significant combination of RTKs associated with orbital rhabdomyosarcoma patients. mRNA overexpression of RTKs which included MET, AXL, EGFR was seen in 60-80% of cases; EGFR3, IGFR2, FGFR1, RET, PDGFR1, VEGFR2, PDGFR2 in 30-60% of cases; and EGFR4, FGFR3,VEGFR3 and ROS,IGFR1, EGFR1, FGFR2, VEGFR1 in 10-30% of cases. Immunoexpression of MET was seen in 89% of cases. A significant association was seen between MET mRNA and its protein expression. In all the cases MET gene expression was associated with worst overall survival (P = 0.03).There was a significant correlation of MET mRNA expression with RET, ROS, AXL, FGFR1, FGFR3, PDGFR1, IGFR1, VEGFR2, and EGFR3 genes. Association between MET gene and collective expression of RTKs was further evaluated by semi-supervised gene cluster analysis and Principal component analysis, which showed well-separated tumor clusters. MET gene overexpression could be a useful biomarker for identifying high risk orbital rhabdomyosarcoma patients. Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored.

Baseline and Post-NACT Imaging in Retinoblastoma With Optic Nerve Involvement: Can MRI Predict Prognosis?

PURPOSE: To describe a staging system for optic nerve invasion using magnetic resonance imaging (MRI) and report any correlation with survival outcome. METHODS: This was a ambispective study. Twenty-one patients with retinoblastoma who had optic nerve involvement on MRI were staged at baseline based on contrast enhancement and/or thickening and length of involvement. Response to neoadjuvant chemotherapy (NACT) was noted according to proposed response evaluation criteria and results were correlated with survival outcome. RESULTS: Baseline MRI staging was able to predict event-free survival (EFS) (P = .0015) using the log-rank test for trends. Patients with optic nerve enhancement alone showed 100% survival prognosis. Optic nerve thickening cases with complete or partial response to NACT showed better EFS (P > .90) than those with stable disease according to response evaluation criteria. CONCLUSIONS: The modified staging system for optic nerve invasion used in the current study significantly predicted EFS. The study also showed that response to NACT may be affected by baseline staging. The authors recommend that cases with optic nerve enhancement only, irrespective of the length of involvement (stage 0), may be treated with upfront enucleation. Cases with optic nerve thickening may be staged to evaluate the correlation with survival outcome in a larger cohort in future studies. [J Pediatr Ophthalmol Strabismus. 2024;61(2):98-105.].

Can Enhancement Pattern in Normal-Sized Optic Nerves on Magnetic Resonance Imaging Better Predict Tumor Invasion in Retinoblastoma Eyes?

Introduction: Optic nerve (ON) enhancement alone without ON thickening on contrast-enhanced magnetic resonance imaging (CE-MRI) can be associated with post-laminar optic nerve invasion (PLONI) in eyes with group E retinoblastoma. A few case reports and retrospective studies in the literature show a poor correlation between ON enhancement on MRI and ON invasion on histopathological examination (HPE). There is no universal consensus on the management of such cases. It is desirable that the presence and extent of a true ON invasion be reliably picked up before planning upfront enucleation in order to avoid stage II disease. Methods: In a prospective study conducted at a tertiary eye care center in North India, all retinoblastoma patients presenting with ON enhancement on imaging were evaluated. Demographic and imaging details, histopathological findings, and treatment details were recorded. The length and pattern of enhancement noted on MRI were correlated with histopathology. Follow-up was done till the end of the study period. Results: Six group E retinoblastoma eyes were evaluated. 3 eyes (50%) showed solid enhancement, 2 eyes (33.33%) had tram track pattern and 1 eye (16.66%) showed punctate enhancement pattern on CE-MRI. On histopathology, 5 (83.33%) cases showed PLONI and all 6 (100%) had ON head infiltration. The cut end of the ON was free in all cases. On correlating MRI and HPE, all eyes with solid enhancement pattern showed PLONI, of which 2/3 (66.6%) had diffuse ON infiltration. Only 50% of eyes with tram track patterns showed PLONI. The case which showed a punctate enhancement pattern showed focal infiltration by tumor cells with vacuolated cytoplasm on HPE. At the last follow-up, all patients were alive and free of disease. Conclusion: ON enhancement patterns may make it more predictive for PLONI on HPE. Solid enhancement pattern appears to correlate better with the extent of ON invasion on HPE, and longer lengths of solid ON enhancement may be considered for neoadjuvant chemotherapy rather than upfront enucleation.

HPV-Associated Squamous Cell Carcinoma of the Eyelid: Diagnostic Utility of p16 Immunohistochemistry and mRNA In Situ Hybridization.

BACKGROUND: High-risk (HR) Human papillomavirus (HPV) has been implicated in pathogenesis of squamous cell carcinomas (SCC) at several sites with mucocutaneous junctions, including the head and neck. SCC is the second most common eyelid malignancy. However, its association with transcriptionally active HR-HPV has not been adequately studied. METHODS: Two index cases of eyelid HPV-associated SCC are described in detail. A retrospective cohort of eyelid SCC was examined for p16 immunoexpression. Cases demonstrating p16 positivity or equivocal staining were subjected to high-risk HPV mRNA in situ hybridization (ISH). Quantitative real-time PCR (qPCR) was performed in mRNA ISH-positive cases for HPV genotyping. RESULTS: The two index patients were older adult females, with upper eyelid tumours. On histology, both tumours were non-keratinizing SCC with trabecular and nested architecture reminiscent of oropharyngeal HPV-associated non-keratinizing SCC, prompting p16 immunohistochemistry, which was positive. HR-HPV mRNA ISH was positive, and qPCR detected HPV16 in both cases. Three of 20 (15%) archival cases showed p16 immunopositivity and two (10%) showed equivocal staining. However, mRNA ISH was negative. All cases showing p16 immunostaining and lacking HR-HPV were keratinizing SCCs. Thus, 9% of all eyelid SCC examined demonstrated HR-HPV. CONCLUSION: The prevalence of HR-HPV in eyelid SCC is low in Indian patients. HPV-associated SCC may mimic commoner eyelid carcinomas as it lacks overt keratinization. In basaloid-appearing eyelid carcinomas, p16 immunopositivity should be followed by reflex HR-HPV mRNA ISH, as p16 immunohistochemistry alone has low specificity. The prognostic role, if any, of HPV association needs further evaluation.

Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma.

BACKGROUND: Pigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM. METHODS: Transmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers. RESULTS: Premelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression. CONCLUSION: Our results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.

Comparative evaluation of isoflurane and desflurane for postoperative cognitive decline in elderly patients: A prospective observational pilot study.

BACKGROUND: Approximately 16%-62% of patients undergoing non cardiac surgeries develop postoperative cognitive dysfunction. We compared the incidence of postoperative cognitive dysfunction in older adults aged 60-80 years who underwent open abdominal surgeries under general anaesthesia using isoflurane or desflurane and correlated it with the serum concentration of interleukin 1, interleukin 6, tumour necrosis factor alpha, amyloid ß and S100 on postoperative day 3. METHOD: Forty American Association of Anesthesiologists Physical Classification I or II patients were included after acquiring institutional ethics committee approval, registering in the Clinical Trials Registry - India, and informed written consent. They underwent open abdominal surgery under general anaesthesia and epidurals between 2017 and 2019. Patients with substance abuse or any disorder affecting cognition were excluded. Postoperative cognitive dysfunction was assessed by Stroop test, Wisconsin Card Sorting Test, Trail making test - B, Porteus Maze test, PGI memory scale, mini-mental state examination, and Bender Gestalt test the day before surgery and on the third postoperative day along with blood samples. RESULTS: Thirty-seven percent of the patients developed postoperative cognitive dysfunction. The risk was similar to isoflurane in comparison with desflurane (risk ratio: 0.65, 95% confidence interval: 0.30, 1.40). A significant percentage increase in reaction time for Porteus Maze test and Trail making test - B was noted with isoflurane (6.69 (4.20-8.94) and 8.01 (2.08-12.5), respectively) in comparison with desflurane group (13.01 (9.09-17.33), p = 0.003 and 11.62 (7.5-17.5), p = 0.017, respectively). CONCLUSION: Isoflurane and desflurane had a similar impact on the elderly for developing postoperative cognitive dysfunction and no correlation with any of the biomarkers used in the study on postoperative day 3.

Rare case of corneal keloid following radial keratotomy for myopia.

An adult male in his 50s presented with complaints of glare and gradual, painless, progressive diminution of vision in the right eye (RE). Visual acuity in RE was noted to be 2/60, and slit lamp biomicroscopy revealed a pearly grey-white elevated corneal opacity measuring 4 mm × 3 mm, obscuring the visual axis. There was no history of ocular trauma or infection. The patient had undergone bilateral radial keratotomy for myopia correction 25 years ago. Anterior segment optical coherence tomography imaging demonstrated increased corneal thickness of 1080 µm at the site of lesion and the height of the epicorneal mass was noted to be 493 µm. The patient underwent fibrin glue-aided anterior lamellar keratoplasty. Histopathological examination of the excised host tissue confirmed the diagnosis of corneal keloid.

Transconjunctival excision of external angular dermoid cyst: A novel approach.

PURPOSE: To excise external angular dermoid cyst (EADC) by transconjunctival approach and compare the surgical outcomes with the standard transcutaneous approach. DESIGN: This was a prospective, pilot, interventional, comparative study. METHODS: Patients with EADC with no or minimal fixity to the underlying bone on palpation and limited to eyelid were recruited. Patients were randomized into 2 groups; group 1 included patients with transcutaneous approach, and group 2 included patients with transconjunctival approach. The parameters assessed were intraoperative complications, duration and ease of surgery, postoperative complications, and overall satisfaction. RESULTS: Six children with a painless, round lesion in outer aspect of eyelid were recruited in each group. None of the patients had any intraoperative or postoperative complications, including dysfunction of eyelid contour and fold, persistence or late occurrence of lateral eyelid droop, excessive or recurrence of swelling, and ocular surface problems, especially in group 2, but a skin scar though hidden was inevitable in group 1. The duration of surgery was comparable with better ease of surgery in group 1 and a gradual learning curve in group 2. The overall satisfaction scores were significantly better in group 2 (p < 0.0001). In group 1, parents of 5 of 6 patients had to be reassured that the skin scar will fade with time. CONCLUSION: Transconjunctival excision of EADC is a viable and novel approach in patients with mobile cyst that is limited to the eyelid with no obvious bony fossa. Main limitations of the approach are that it requires surgical expertize, provides less surgical space, and has a gradual learning curve.

Implications of LAG3 and CTLA4 immune checkpoints beyond PD-1/PD-L1 as a potential target in determining the prognosis of uveal melanoma patients.

BackgroundResponse rate of PD-1/PD-L1 immunotherapeutic blockade agents in uveal melanoma (UM) is poor. Lymphocyte activation gene 3 (LAG3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are the two promising immune checkpoint targets. Therefore, our aim was to explore at how these proteins were expressed in tumour tissue and serum, as well as their prognostic implications in UM. METHODS: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was determined by immunohistochemistry in 54 enucleated UM tissue samples. mRNA expression level of LAG3 and CTLA-4 was determined by quantitative real-time PCR and corroborated by western blotting. Furthermore, soluble form of LAG3, CTLA-4 and CCR8 expression in serum was measured in 40 UM patients using ELISA. RESULT: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was observed in 30%, 33%, 41%, 35%, 50% and 39% of the cases, respectively. Loss of nBAP1 expression was significantly correlated with CD8+expression (p=0.012) but not with tumour infiltrating lymphocytes. LAG3 and CTLA-4 mRNA levels were higher in UM compared with normal uveal tissues. Higher LAG3 expression with CD8+expression was associated with lower metastasis-free survival (MFS) (p=0.049), but not with CTLA-4 in UM patients. MFS rate was reduced in patients having lower levels of CCR8 protein (p=0.050) and increased level of LAG3 protein (p=0.001). CONCLUSION: Our findings suggest that higher levels of LAG3 in UM with histopathologically high-risk parameters predict high metastatic potential and that it could be used as a targeted immunotherapy alone or in combination with PD-1/PD-L1 blockade agents.

Intra-ocular hydatid cyst in a child: A rare presentation.

Intra-ocular cystic lesion in a young child can be parasitic lesion, old retinal detachment with cysts or simply a vitreous cyst. Intra-ocular localization of hydatid cysts is extremely rare accounting for less than one percent of all cases. This case describes a young child with left eye pain, redness and progressive diminution of vision with progressively enlarging intra- ocular cyst. Diagnosed as intra-ocular hydatid cyst, the radiological, intraoperative and microbiological features of same are described. Also, the management required in such a case is discussed.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. RESULTS: Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. CONCLUSION: Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome.

PURPOSE: Molecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance. METHODS: In this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes. RESULTS: MMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050). CONCLUSION: Our findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.