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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Heminasal agenesis is an exceedingly rare congenital anomaly which is frequently associated with disorders of eye, lacrimal drainage system and face. At times, a proboscis may also be noted with this condition. Herein, we present a case of a 13-year-old boy who presented to us with heminasal agenesis with concomitant microphthalmos, leucomatous corneal opacity, blepharoptosis, dacryocystocoele and maxillary hypoplasia. The child underwent a modified transeptal external dacryocystorhinostomy with placement of a lacrimal stent. There was significant improvement of epiphora and discharged following surgery. Heminasal aplasia with dacryocystocoele is surgical challenge; however, a well thought out surgical approach can yield satisfactory outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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A 19-year-old woman presented to the outpatient department with occasional ocular pain and redness and a perilimbal mass, which she noticed 5 months ago in her left eye. She had no systemic complaints. Ultrasound biomicroscopy of the mass showed a hypoechoic lesion with uniform reflectivity. The patient underwent an excision biopsy and a histopathological analysis revealed features suggestive of a granulocytic sarcoma/myeloid sarcoma. Further haematopathological evaluation confirmed concurrent acute myeloid (myelomonocytic) leukaemia French American British classification M4. There was complete remission of the ocular surface lesion and leukaemia with systemic chemotherapy. At the last follow-up of 18 months post-treatment the patient is free of disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Orbital cellulitis is the most common subset of orbital inflammatory disease. We describe a patient with necrotic choroidal melanoma who presented with orbital cellulitis. MRI revealed a mass lesion suggesting intraocular melanoma with no extrascleral extension. There was no metastasis on positron emission tomography-CT scan. Enucleation with orbital implant was performed. Histopathological analysis of the specimen revealed intraocular necrotic melanoma with very few recognisable melanoma cells. The necrotic subtype is more commonly associated with extrascleral extension, distant metastasis and poorer prognosis than other melanoma types. Sterile orbital cellulitis may rarely be a manifestation of ocular tumours in adults, and a high index of suspicion should be maintained to rule out the same., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical evaluation of an early-onset left esotropia in an adolescent revealed a large macular lesion with extensive posterior pole retinochoroidal atrophy from superior arcade to inferior arcade. The lesion also showed pigmentary changes over the base, edges and beyond, along with a popcorn-like calcification just above the inferior arcade. Swept-source optical CT (SS-OCT) confirmed extensive chorioretinal thinning with hyper-reflective foci corresponding to the calcification, and optical CT angiography revealed a disorganised superficial retinal plexus. Likewise, fundus screening of the other eye showed a well-defined fleshy mass lesion along the temporal retina in absence of any calcification. SS-OCT of the left eye lesion showed intraretinal mass with poorly defined retinal layers., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

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A 65-year-old man presented with giant orbital myxofibrosarcoma with no extraorbital extension. Imaging was suggestive of mesenchymal malignancy with significant vascularity. Incisional biopsy was suggestive of low-grade fibromyxoid sarcoma. The clinical and imaging features did not support the pathological diagnosis. Histopathology of the exenterated sample revealed features of high-grade myxofibrosarcoma. To the best of our knowledge, this is the largest reported myxofibrosarcoma of the orbit. Adjuvant radiotherapy was advised. Correlating the case history, imaging and histopathology, this case can best be summarised as a natural history of conversion from a low to high-grade myxoid malignancy. We emphasise that the overlapping features of myxoid malignancy (fibromyxosarcoma vs myxofibrosarcoma) and regional variation in tumour morphology in biopsy specimen may mislead the clinician. Therefore, knowledge about the key differentiating features as well as incisional biopsy of each radiologically different area can increase the possibility of correct diagnosis and management of each case., (2016 BMJ Publishing Group Ltd.)