Evolving criteria for group E retinoblastoma: impact on outcomes.

OBJECTIVE: To assess the impact of evolving criteria for group E retinoblastoma on ocular survival outcomes. DESIGN: A retrospective observational study. METHODS: Single-institution consecutive case series of patients with advanced intraocular retinoblastoma (groups D and E) were classified based on International Intraocular Retinoblastoma Classification (IIRC) and International Classification of Retinoblastoma (ICRB) criteria. The main outcomes measured were ocular survival, frequency of histopathologic risk factors (HRF), and the need for adjuvant therapy. RESULTS: A total of 332 eyes of 298 patients were classified into group D (150, 45%) and E eyes (182, 55%) based on IIRC criteria. ICRB classification resulted in upstaging of 57 group D eyes (17%) to group E. Eyes that were upstaged to group E from D in the ICRB classification (E1) differed significantly, with a greater proportion undergoing primary enucleation (17 of 57, 30%) than those that were not (10 of 93, 11%) (p = 0.003). Similar significant differences were observed between group E2 and E3 eyes (p < 0.0001). Ocular survival according to Kaplan-Meier estimates at 12 months of 79%, 59%, 49%, and 1% differed significantly between all groups (ICRB D, E1, E2, and E3, respectively). CONCLUSION: Proposed new subgrouping of group E eyes into E1, E2, and E3 based on clinical criteria is based upon natural history of tumor progression and is predictive of ocular survival. Preservation of the existing lower boundaries for group E by ICRB and IIRC offers the possibility of reanalyzing existing published data.

Aurora Kinase A Is Overexpressed in Human Retinoblastoma and Correlates with Histopathologic High-Risk Factors: Implications for Targeted Therapy.

Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy; however, systemic toxicity and long-term adverse effects remain a significant challenge necessitating the identification of specific molecular targets. Aurora kinase A (AURKA), a critical cell cycle regulator, contributes to cancer pathogenesis, especially in RB1-deficient and MYCN-dysregulated tumors. Our immunohistochemistry study in patient specimens (n = 67) discovered that AURKA is overexpressed in RB, and elevated expression correlates with one or more histopathologic high-risk factors, such as tumor involvement of the optic nerve, choroid, sclera, and/or anterior segment. More specifically, AURKA is ubiquitously expressed in most advanced-stage RB tumors that show a suboptimal response to chemotherapy. shRNA-mediated depletion/pharmacologic inhibition studies in cell lines, patient-derived cells, in vivo xenografts, and enucleated patient specimens confirm that RB cells are highly sensitive to a lack of functional AURKA. In addition, we deciphered that AURKA and MYCN associate with each other to regulate their levels in RB cells. Overall, our results demonstrate a previously unknown up-regulation of AURKA in RB, facilitated by its crosstalk with MYCN, and elevated levels of this kinase may indicate unfavorable prognosis in tumors refractory to chemotherapy. This study provides a rationale and confirms that therapeutic targeting of elevated AURKA in RB could be a potential treatment approach.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Ocular Surface Squamous Neoplasia with Coexistent Pterygia: A Study of 14 Cases and Review of Literature.

PURPOSE: To report the clinical presentation, anterior segment optical coherence tomography features, treatment, and outcomes of ocular surface squamous neoplasia (OSSN) associated with pterygium. METHODS: Retrospective interventional series of 14 cases in a 28-month study period. RESULTS: OSSN was coexistent with pterygium (n = 14) in < 1% of all pterygia (n = 7384). The mean age at the presentation of OSSN with pterygium was 49 years (median, 49 years; range, 36 to 71 years). Referral diagnosis included pterygium sans OSSN (n = 7, 50%), granuloma (n = 1, 7%), actinic keratosis (n = 1, 7%), and conjunctivitis (n = 1, 7%). All OSSNs were unilateral, and six patients (43%) had bilateral pterygia. Tumors arose from the nasal (n = 8, 57%), or temporal (n = 6, 43%) quadrants. The mean tumor diameter was 4 mm (median, 4 mm; range, 2 to 6 mm), and the mean thickness was 2 mm (median, 1 mm; range, 1 to 3 mm). The delineation between OSSN and pterygium could be identified on anterior segment optical coherence tomography (AS-OCT) in all (100%) cases. All patients received 1% topical 5-fluorouracil (5-FU), and complete tumor regression was achieved in 13 (93%) cases with a mean number of 2 cycles (median, two cycles; range, 1 to 4 cycles). There were no significant adverse effects. No tumor recurrence was noted over a mean follow-up period of 11 months (median 12 months; range, 1 to 4 months). CONCLUSION: AS-OCT allows accurate detection and mapping of tumor extent in OSSN with coexistent pterygium, and topical 5-FU yields excellent tumor control.

Ruthenium-106 (106Ru) plaque brachytherapy for treatment of circumscribed choroidal hemangioma.

PURPOSE: To describe the clinical and imaging features of circumscribed choroidal hemangiomas (CCH) and their treatment outcomes with Ruthenium-106 (106Ru) plaque brachytherapy. METHODS: Retrospective study of 24 patients (24 eyes) diagnosed with CCH and treated with 106Ru plaque between 2017 and 2022. Analysis included pre- and post-treatment clinical and imaging features such as tumor regression, reduction in height, subretinal fluid (SRF) resolution, and change in best-corrected visual acuity (BCVA). RESULTS: The mean age at presentation was 36 years (range, 16-57). The most common tumor location was the temporal quadrant (n = 19) with macular involvement (n = 13). Associated features were macular SRF (n = 22) and inferior exudative retinal detachment (n = 10). Nineteen of the 24 patients underwent primary treatment, whereas 5 patients underwent plaque as a salvage treatment. The mean tumor apex dose was 40 Gy. At a median follow-up of 7.5 months (range 3-65 months), 18 eyes showed complete regression, whereas 6 eyes showed partial regression. The mean height decreased from 4.8 (SD 1.28) mm at presentation to 2.5 (SD 1.63) mm. Median BCVA improved from logMAR 1.2 (IQR 0.4-2) at baseline to logMAR 1.05 (IQR 0.1-1.95) (p = 0.4). Complete resolution of the macula and tumor SRF was observed in 15 (68%) and 13 (57%) eyes, respectively. The radiation-related complications observed were radiation maculopathy (4 eyes), retinopathy (1 eye), and vitreous hemorrhage (1 eye). CONCLUSION: Ruthenium-106 plaque brachytherapy is effective for CCH (> 3 mm height) as a primary and salvage treatment for tumors unresponsive to other modalities.

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.

Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

Small extracellular vesicles loaded with carboplatin effectively enhance the cytotoxicity of drug-resistant cells from Y79 cells-in vitro.

Drug resistance (DR) is one of the challenges in treating retinoblastoma (Rb) that warrants novel approaches. With the emerging evidence on the role of small extracellular vesicles (sEVs) as a drug-delivery carrier system, in this study, we derived the drug-resistant (DR) clones of Y79 cells and evaluated the efficacy of sEVs-loaded with carboplatin (sEVs-CPT) to reverse the chemoresistance. Drug-resistant clones of Y79 cells (DR-Y79) were systematically developed through sequential exposure to carboplatin (CPT), showcasing a sixfold increase in inhibitory concentration when compared to parental Y79 cells (IC50: 41.4 µg/mL and 6.2 µg/mL) (P<0.0001). These DR-Y79 cells show higher expression of ABCG2 and higher expression of DR genes than parental Y79 cells (P<0.0001). The sEVs were isolated from the conditioned media of Y79 cells using ultracentrifugation (UC) and characterized. Further, the sEVs were loaded with CPT and achieved higher encapsulation efficiency at one hour, and drug release of sEVs-CPT was highest at ∼80% at pH 5.0. The cytotoxicity of sEVs-CPT on Y79 cells and DR-Y79 was higher when compared to the CPT (IC50: 3.5 µg/mL vs 6.2 µg/mL; 23.1 µg/mL vs 41.2 µg/mL) (p<0.0001). This study demonstrates that sequential exposure to CPT generates DR clones of Y79 cells, which could serve as an appropriate model to evaluate the efficacy of drugs. The sEVs-CPT were highly effective in enhancing cytotoxicity in DR-Y79 cells, and appear to hold promise as a novel complimentary drug delivery system.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

PURPOSE: To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). METHODS: A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). RESULTS: Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). CONCLUSION: Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Generation of an induced pluripotent stem cell line (LVPEIi002-A) with heterozygous RB1 mutation using peri-orbital fat derived mesenchymal cells of a patient with inherited retinoblastoma.

Retinoblastoma is a pediatric intraocular cancer caused by biallelic inactivation of RB1 gene in retinal progenitor cells. Here, we report the generation of a patient-specific induced pluripotent stem cell (iPSC) line (LVPEIi002-A) from a patient diagnosed with retinoblastoma and showing familial inheritance of a nonsense mutation (c.1735C > T) within exon 18 of one of the two alleles. This RB1+/- iPSC line, LVPEIi002-A was generated by reprogramming the peri-orbital fat tissue derived mesenchymal cells and was stably expanded and characterized. It maintains the stemness, pluripotency, normal karyotype, and forms embryoid bodies comprising of all three lineage committed progenitor cells.

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.

SECONDARY SALVAGE INTRAVENOUS CHEMOTHERAPY FOR REFRACTORY/RECURRENT RETINOBLASTOMA: A Study of 41 Eyes.

PURPOSE: To determine the efficacy of secondary salvage intravenous chemotherapy (IVC) for refractory/recurrent retinoblastoma. METHODS: Retrospective, nonrandomized interventional case series of 41 eyes of 33 patients with recurrent retinoblastoma. RESULTS: Of the 33 patients, mean age at the time of commencement of salvage IVC was 5 years (median, 5 years; range, 2-8 years). At presentation, recurrent retinoblastoma in 41 eyes of 33 patients was classified by the International Classification of Retinoblastoma as Group B (n = 7; 17%), Group C (n = 3; 7%), Group D (n = 16; 39%), and Group E (n = 15; 37%). All patients received 6 cycles of IVC as primary treatment. The indication for secondary salvage IVC with focal treatment included recurrent solid tumor (n = 36; 88%), subretinal seeds (n = 22; 54%), or persistent solid tumor (n = 2; 5%). Mean number of cycles of salvage IVC were 8 (median, 6; range, 6-18). Over a mean follow-up period of 43 months (median, 43 months; range, 12-96 months) after completion of salvage IVC, globe salvage was achieved in 22 (54%) eyes, 1 (3%) patient had histopathology-proven bone metastasis, and 1 (3%) patient died because of presumed metastasis. CONCLUSION: Secondary salvage IVC with appropriate focal treatment allows globe salvage in 54% eyes with refractory/recurrent retinoblastoma and thus serves as an alternative to intraarterial chemotherapy or enucleation.

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.

PURPOSE: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration. MAIN OUTCOME MEASURES: Enucleation and death. RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ocular surface pseudoepitheliomatous hyperplasia secondary to allergic eye disease: clinical features and management.

PURPOSE: To study the clinical characteristics and treatment outcomes of ocular surface pseudoepitheliomatous hyperplasia (PEH) associated with chronic vernal keratoconjunctivitis (VKC). METHODS: This retrospective study includes 39 eyes of 32 patients with VKC induced PEH who presented from 2016-2022. A database search was conducted for diagnosis of PEH, and data on clinical features, imaging characteristics, and treatment were analyzed. RESULTS: Of the 32 patients, 11 (34%) were children and adolescents, 21 (66%) were adults. PEH was common in males (72%) and ocular surface squamous neoplasia (OSSN) was the commonest referral diagnosis (43.7%). Mean age at presentation was 26.62 ± 10.18 (range: 6-52) years. While history of VKC was present in 21 patients, 11 were diagnosed with VKC at the time of diagnosis of PEH. The mean base/largest diameter was 5.2 ± 1.67 mm. Anterior segment optical coherence tomography (AS-OCT) showed irregular hyper-reflective epithelium, epithelial dipping, and sub-epithelial hyper-reflective lesion with shadowing in all lesions. Of the 31 eyes that received medical therapy, 21 (67%) and 10 (32%) eyes showed complete and partial resolution respectively with median time to resolution of 3(IQR:2-4) months. Eight eyes that underwent surgical excision showed complete resolution and one developed partial limbal stem cell deficiency. CONCLUSION: Ocular surface PEH is a manifestation of chronic VKC which closely mimics OSSN. Detailed history-taking, examination for signs of allergy, and AS-OCT imaging can distinguish it from OSSN. It responds well to medical therapy and should be considered first-line therapy before planning any surgical intervention.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Serum Metabolomics of Retinoblastoma: Assessing the Differential Serum Metabolic Signatures of Unilateral and Bilateral Patients.

Retinoblastoma (Rb) is the most common pediatric eye cancer. To identify the biomarkers for early diagnosis and monitoring the progression of Rb in patients, mapping of the alterations in their metabolic profiles is essential. The present study aims at exploring the metabolic disparity in serum from Rb patients and controls using NMR-based metabolomics. A total of 72 metabolites, including carbohydrates, amino acids, and organic acids, were quantified in serum samples from 24 Rb patients and 26 controls. Distinct clusters of Rb patients and controls were obtained using the partial least-squares discriminant analysis (PLS-DA) model. Further, univariate and multivariate analyses of unilateral and bilateral Rb patients with respect to their age-matched controls depicted their distinct metabolic fingerprints. Metabolites including 2-phosphoglycerate, 4-aminobutyrate, proline, O-phosphocholine, O-phosphoethanolamine, and Sn-glycero-3-phosphocholine (Sn-GPC) showed significant perturbation in both unilateral and bilateral Rb patients. However, metabolic differences among the bilateral Rb cases were more pronounced than those in unilateral Rb cases with respect to controls. In addition to major discriminatory metabolites for Rb, unilateral and bilateral Rb cases showed specific metabolic changes, which might be the result of their differential genetic/somatic mutational backgrounds. This further suggests that the aberrant metabolic perturbation in bilateral patients signifies the severity of the disease in Rb patients. The present study demonstrated that identified serum metabolites have potential to serve as a noninvasive method for detection of Rb, discriminate bilateral from unilateral Rb patients, and aid in better understanding of the RB tumor biology.

Pediatric ocular melanoma: a collaborative multicenter study and meta-analysis.

PURPOSE: To investigate clinical manifestations and prognoses in pediatric patients (≤12 years old) with ocular melanoma. METHODS: This was a retrospective, multicenter cohort study with individual participant data (IPD) meta-analysis pooling available published cases, and unpublished cases from an international collaboration of seven ocular oncology centers. RESULTS: There were 133 eyes of 133 pediatric patients with choroidal or ciliary body (n = 66 [50%]), iris (n = 33 [25%]), conjunctival (n = 26 [19%]), and eyelid (n = 8 [6%]) melanoma. Overall, the mean patient age at presentation was 7 years (median, 8; range, 1-12 years), with 63 males (49%). The mean age by tumor site was 6.50 ± 3.90, 7.44 ± 3.57, 9.12 ± 2.61, and 5.63 ± 2.38 years, for choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively (P = 0.001). Association with ocular melanocytosis was seen in 15%, 11%, 4%, and 0%, respectively (P = 0.01). Frequency of ocular melanoma family history did not vary by tumor site (7%, 17%, 9% and 12%, resp. [P = 0.26]). After mean follow-up of 74, 85, 50, and 105 months (P = 0.65), metastasis was seen in 12%, 9%, 19%, and 13% of choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively. Death was reported in 5%, 3%, 8%, and 0%, respectively, with survival analysis indicating higher mortality in choroidal/ciliary body and conjunctival melanoma patients. CONCLUSIONS: Ocular melanoma in the pediatric population is rare, with unique clinical features and outcomes. Iris melanoma accounts for about one-third of pediatric uveal melanoma cases.

Anterior segment optical coherence tomography features of ocular surface squamous epithelial hyperplasia: A report of four cases.

Herein, we report the clinico-tomographic and histopathological features of four patients with biopsy-proven ocular surface squamous epithelial hyperplasia (OSSEH), a close mimicker of ocular surface squamous neoplasia (OSSN). The mean age at diagnosis was 58 years (median, 60 years; range, 35-77 years). All lesions were unilateral. Isolated corneal plaque was seen in 50% (n = 2) and nodular lesion at the nasal limbus in 50% (n = 2). Keratinization was seen in 75% (n = 3) of lesions and intrinsic vessels in 75% (n = 3). A clinical diagnosis of OSSN was made in all cases. Anterior segment optical coherence tomography (ASOCT) revealed mild epithelial hyperreflectivity in 100% (n = 4). The epithelium was normal in thickness in 75% (n = 3) and showed mild thickening in 25% (n = 1). Only 25% (n = 1) showed abrupt transition in epithelial thickness from the contiguous corneal epithelium. Histopathological examination revealed hyperplastic squamous epithelium and no cellular atypia in all cases. Stable ocular surface and no recurrences were noted at a mean follow-up of 17 months (median, 11 months; range, 2-43 months). Although OSSEH can mimic OSSN clinically, the presence of mild epithelial hyperreflectivity, lack of epithelial thickening, absence of abrupt transition from normal epithelium, and presence of subepithelial hyperreflectivity on ASOCT favor the diagnosis of OSSEH.