Role of MYCN in retinoblastoma: A review of current literature.

Chromosomal abnormalities that involve the MYCN gene are rare; however, it is one of the most commonly mutated genes in retinoblastoma (RB) after the RB1 gene. MYCN is amplified in approximately 1-9 % of all RB tumors. It plays a role in RB oncogenesis via many mechanisms, including synergism with RB1 deletion, positive feedback with MDM2, upregulation of cell cycle regulating genes, upregulation of miRNA, and upregulation of glucose metabolism. MYCN amplifications are not mutually exclusive and can occur even in the presence of RB1 gene mutations. Clinically, RB1+/+MYCNA tumors present as sporadic, unilateral, advanced tumors in very young children and tend to follow an aggressive course. Magnetic resonance imaging features include peripheral tumor location, placoid configuration, retinal folding, tumor-associated hemorrhage, and anterior chamber enhancement. Genetic testing for MYCNA is especially recommended in patients with unilateral RB where genetic blood testing and tumor tissue show a lack of RB1 mutation. MYCN-targeted therapies are evolving and hold promise for the future.

Melanocytic Nevus of the Superior Conjunctival Fornix: A Case Report.

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

Global retinoblastoma studies: A review.

In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in underdeveloped nations. The understanding of similarities and disparities between various nations across the world aids in achieving comparable outcomes. With dissolving geographic barriers and evolving collaboration, global collaborative studies on RB are becoming increasingly common. They provide real-world, robust evidence on several aspects of RB. This review discusses insights gained from global RB studies regarding the demographics, certain aspects of etiopathogenesis and epidemiology, international travel burden, disparities in clinical presentations based on national income levels, management protocols, pathology, treatment outcomes, and the effect of COVID-19 on RB care across the world. These insights are likely to impact individual practice as well as inform policy reforms.

Spheno-Orbital Meningioma - Treatment Outcomes and Factors Influencing Recurrence.

PURPOSE: To determine treatment outcomes, recurrence rates, and predictors of recurrence, to inform future therapeutic approaches for spheno-orbital meningiomas (SOM). METHODS: A retrospective single-center study of SOM treated from 1990 to 2021 was conducted with comprehensive neuro-ophthalmologic follow-up at Columbia University Medical Center (CUMC). Recurrence requiring reintervention was defined clinically as worsening of visual acuity, visual field defect, or ocular motility after an initial period of stabilization or 6 months of improvement following treatment, or radiologically as either a regrowth with an increase in tumor size by 20% at the site of previous growth or a new region of tumor growth. RESULTS: In total 46 patients met the inclusion criteria. The mean follow-up was 106 months (range 1-303). Dictated by the phenotype of the disease, patients underwent either gross- (50%), near- (17%), or subtotal resection (26%). Removal of the anterior clinoid process (ACP) was performed in 52% of patients. Nine patients (20%) required an enucleation or exenteration. Radiotherapy was employed at some point of treatment in 50% of cases. Inherited cases (24%) were referred to CUMC for treatment following 1 or more recurrences. The total recurrence rate, including inherited cases, was 54%, occurring at a mean interval of 43 months. The recurrence rate of patients treated solely at CUMC was 40%, occurring at a mean interval of 41 months. A subset of patients (32%) had 2 or more recurrences. Histopathology at the first surgery was WHO grade I (87%) and II (13%) and at the final surgery was WHO grade I (74%), II (21%), and III (4%). A subset of grade I tumors that received radiotherapy (35%) evolved to a higher grade or developed multiple recurrences without a change in histologic grade I. Grade II tumors and treatment with radiotherapy increased the odds of recurrence. Removal of the ACP and gross total resection decreased the odds of recurrence. CONCLUSION: Due to the routinely long interval to tumor recurrence, lifelong surveillance of patients with SOM is prudent. ACP resection and gross total resection, where possible, reduce tumor recurrence and the need for further treatment. Radiotherapy should be reserved for higher-grade meningiomas and select grade I tumors.

Orbital tuberculosis: a case report and update on the role of imaging in treatment.

Orbital tuberculosis is a manifestation of extra-pulmonary tuberculosis that is challenging to diagnose and treat. Here, we describe the pivotal role of serial imaging in the diagnosis and treatment of orbital tuberculosis. A 28-year-old male presented with recurrent right upper eyelid swelling and a supraduction deficit associated with a firm painless orbital mass, seen on initial computed tomography to be an extensive superomedial lesion producing mass effect. Biopsy revealed a tuberculosis-like granulomatous inflammation, which, coupled with a positive QuantiFERON gold test, led to empiric anti-tuberculin treatment. Serial radiologic imaging following initiation of treatment showed progressive reduction in mass size, supporting the diagnosis and determining the length of treatment. This rare case demonstrates the utility of serial radiologic exams in the diagnosis and treatment of orbital tuberculosis.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

Anterior segment optical coherence tomography features of pseudoepitheliomatous hyperplasia of the ocular surface: a study of 9 lesions.

PURPOSE: To describe anterior segment optical coherence tomography (AS-OCT) features of pseudoepitheliomatous hyperplasia (PEH) of the ocular surface. METHODS: This is a retrospective study of 9 lesions of 8 patients with histopathologically proven PEH RESULTS: Mean age at diagnosis of PEH was 31 years (median 31 years; range 12 to 62 years). The lesion was unilateral in 7 (88%) patients and bilateral in one (12%). Two patients (25%) had xeroderma pigmentosum, who also had a history of prior surgical intervention in the same eye for conjunctival tumor excision. Referral diagnosis was ocular surface squamous neoplasia (OSSN) in all cases. Ocular surface mass (n = 4, 44%) was the most common presenting complaint. The mean duration of symptoms was 18 months (median 3 months; range < 1 to 84 months). All lesions were perilimbal, and the mean basal diameter of the tumor was 7 mm (median 6 mm; range 4 to 12 mm). Clinical diagnosis included OSSN (n = 5; 56%), PEH (n = 3; 33%), or leiomyosarcoma (n = 1; 11%). AS-OCT features included irregular hyperreflective epithelium, epithelial dipping, and subepithelial hyperreflective lesion with posterior shadowing in all cases. Histopathology confirmed the diagnosis of PEH in all cases. The underlying cause of PEH in these cases included vernal keratoconjunctivitis (n = 4; 44%), idiopathic severe blepharitis (n = 2; 22%), or prior surgical intervention (n = 2; 22%). No apparent cause could be determined in one eye (11%). CONCLUSION: Ocular surface PEH is a close mimicker of OSSN. Careful history-taking, clinical examination, and characteristic AS-OCT features aid in accurate diagnosis.

Post-Brachytherapy Pigment Dispersion in Uveal Melanoma.

We report delayed intravitreal pigment dispersion following Iodine-125 plaque brachytherapy, without evidence of tumor recurrence, in 4 patients treated for choroidal melanoma. These patients were treated with Iodine-125 plaque brachytherapy, with or without transpupillary thermotherapy, and were followed clinically and using ancillary investigations for signs of tumor recurrence. All 4 patients were noted to develop pigment dispersion - it was detected on the surface of the retina (2 patients), diffusely in the vitreous (1 patient), or both (1 patient). Follow-up ranged from 70 to 343 months (mean 165 months; median 124 months) post-treatment with plaque brachytherapy, throughout which the location and amount of pigment remained grossly unchanged. None of the patients developed tumor recurrence or metastasis. We conclude that post-brachytherapy pigment dispersion is an unusual but known complication in the treatment of uveal melanoma. Close surveillance to rule out tumor recurrence and metastasis may be a reasonable line of management.

Cataract surgery in treated retinoblastoma eyes: A study of 29 eyes.

PURPOSE: To study the outcomes of cataract surgery in treated retinoblastoma (RB) eyes. METHODS: Retrospective study of 29 eyes of 27 patients. RESULTS: Based on International Classification of Intraocular Retinoblastoma, tumors belonged to group B (n = 3, 10%), C (n = 1, 4%), D (n = 10, 34%), and E (n = 3, 10%). The remaining 12 eyes (41%) had regressed tumors on presentation due to prior treatment. The RB treatment details included intravenous chemotherapy (n = 24, 83%), external beam radiotherapy (n = 14, 48%), and others. The mean time interval between tumor regression and cataract surgery was 51 months (median, 26 months; range, 6-245 months). The post-operative visual acuity was 20/200 or better in 12 (41%) eyes. Overall, 16 (55%) eyes displayed improvement of vision post-cataract surgery, while 13 (45%) eyes had no improvement in vision. The complications of cataract surgery included visual axis opacification (n = 15, 52%), pupillary membrane (n = 4, 14%), hyphema (n = 1, 3%), and extraocular tumor extension (n = 1, 3%). Clearer fundus view post-surgery revealed underlying tumor edge recurrence in 1 (3%) eye, and two (7%) patients had tumor recurrence at a mean interval of 8 months (median, 8 months; range, 7-8 months) following cataract extraction. Globe salvage was achieved in 26 (90%) eyes over a mean follow-up period of 103 months (median, 91 months; range, 19-267 months). CONCLUSION: Cataract surgery in treated RB is safe with vision salvage in 55% eyes and globe salvage in 90% eyes. Though there is a risk of extraocular tumor extension, its occurrence is rare (3%).

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.

Clinical presentation and outcome of retinoblastoma based on age at presentation: a review of 1450 children.

PURPOSE: To compare the clinical presentation and outcomes of retinoblastoma (RB) based on age at presentation. METHODS: Retrospective comparative study of 1940 eyes of 1450 children with RB. RESULTS: Presentation of RB with enlarged eyeball and eyelid swelling (2% and < 1% in ≤ 1 year, 4% and 2% in > 1-2 years, 7% and 2% in > 2-3 years, and 12% and 4% in > 3 years; p < 0.0001 and p = 0.05, respectively) is more common with increasing age. Based on the 8th edition of American Joint Committee Classification, T1 is more common in children younger than 1 year (27%), while T4 is more common in children > 3 years of age (20%) (p < 0.0001). Kaplan-Meier (KM) estimate at 1 and 5 years for globe salvage was 64% and 58% in children ≤ 1 year of age versus 30% and 20% in children > 3 years, respectively [Hazard ratio (HR) = 2.48; p < 0.0001], and KM estimate at 1 and 5 years for life salvage was 99% and 97% in children ≤ 1 year of age versus 89% and 78% in children older than 3 years, respectively (HR = 7.65; p < 0.0001). CONCLUSION: Uncommon clinical features of RB including enlarged eyeball and eyelid swelling are more common with increasing age. Younger age at presentation with RB is associated with better prognosis including higher chances of life and globe salvage.

Congenital choroidal melanocytoma in a child with ocular melanocytosis.

A 1-day-old child was brought to the clinic for evaluation of enlarged right eye (OD). On examination, OD showed buphthalmos with diffuse scleral melanocytosis, fleshy blackish-brown extrascleral mass with corneal extension, and secondary glaucoma. Anterior segment evaluation revealed darkly pigmented iris and fundus evaluation OD revealed a darkly pigmented choroidal lesion. The left eye was within normal limits. A clinical diagnosis of choroidal melanocytoma with ocular melanocytosis was made. Enucleation OD followed by orbital implant was performed. Histopathology showed features of diffuse ocular melanocytosis involving limbus, iris, ciliary body, choroid, sclera, optic nerve head, optic nerve sheath, along with choroidal melanocytoma with extrascleral tumour extension. We presume that choroidal melanocytoma may have arisen from ocular melanocytosis.

Ocular and Periocular Tumors in Xeroderma Pigmentosum: A Study of 120 Asian Indian Patients.

PURPOSE: We studied the incidence, treatment, and outcome of ocular and periocular tumors in patients with xeroderma pigmentosum (XP). DESIGN: Retrospective case series. METHODS: This single-institution study included 120 patients with XP who underwent intervention with excisional biopsy, enucleation, or orbital exenteration. The primary outcome measures were the occurrence of eyelid or ocular surface tumor, globe salvage, locoregional and systemic metastasis, and death. RESULTS: The mean age at presentation was 19 years. A family history of XP was present in 32 (27%) patients. Over a mean follow-up of 61 months, 34 (28%) patients developed no ocular/adnexal tumor, 86 (72%) developed ocular surface malignancy, 15 (13%) developed eyelid malignancy, and 22 (18%) developed other head and neck malignancies. Of the 86 patients with ocular surface malignancy, 48 (56%) had unilateral tumor and 38 (44%) had bilateral tumors. Invasive squamous cell carcinoma (n = 51, 41%) was the most common ocular surface tumor. Of the 15 patients with eyelid tumors, 14 (93%) had unilateral tumor and 1 (7%) had bilateral involvement. Basal cell carcinoma (n = 8, 50%) was the most common eyelid tumor. There were events of ocular surface tumor recurrence (n = 55 eyes, 44%), eyelid tumor recurrence (n = 5 eyes, 31%), locoregional lymph node metastasis (n = 3, 2%), systemic metastasis (n = 1, 1%), and death (n = 1, 1%). Overall, globe salvage was achieved in 119 (99%) patients (both eyes were salvaged in 92 [76%] patients and at least 1 eye was salvaged in 27 [23%] patients). CONCLUSION: XP is frequently associated with ocular surface, eyelid, and other head and neck malignancies. Lifelong follow-up is mandatory in these patients.