Conjunctival lesions in children are nearly always benign. The most common are conjunctival nevi. The rare malignant conjunctival tumors in children are usually larger and appear at an older age. Children with xeroderma pigmentosum are a unique group in whom malignant conjunctival tumors can occur at an early age. In this review, we describe common and rare benign and malignant conjunctival lesions in children, grouped by tissue of origin.

PURPOSE:Trilateral retinoblastoma (TRB), intracranial neoplasm in heritable retinoblastoma patients, is a very rare fatal disease. Many ocular oncology centers conduct routine screening of retinoblastoma patients by brain imaging. Nevertheless, there is a debate regarding its ability to prolong TRB patients' survival and the number-needed-to-treat. We recommend baseline screening brain imaging in bilateral retinoblastoma patients, followed by imaging according to clinical need. We aim to see if this screening schedule has an impact on patients' survival. METHODS:In a retrospective observational study, we reviewed the medical records of patients diagnosed with bilateral retinoblastoma at a tertiary medical center ocular oncology unit between 1.7.1986 and 1.2.2020, who had at least 36 months follow-up or retinoblastoma-related death. We collected data on patients' demographics, clinical features, systemic evaluation, treatment, follow-up, and outcome. RESULTS:The analysis included 109 patients, 60 males and 49 females, diagnosed with bilateral retinoblastoma at a median age of 7.0 months (range 0.43-70.5 months). Germline mutation was found in 43 patients (39.4%) and somatic mutation in 15 patients (13.8%). Genetic status was not recorded in 51 patients (46.8%). Fifty-eight patients (53.0%) underwent baseline brain imaging (MRI in 42 patients and CT scan in 16 patients), in all of whom it was within normal limits. During a median follow-up of 138 months (range 19-787 months), 35 children had follow-up brain imaging (MRI in 25 patients and CT in 10 patients). One patient developed symptomatic TRB during follow-up, and is alive and disease-free (0.9%, Cl:0.02%-5.6%). Looking at survival, six patients (5.5%) developed metastatic disease, and eight patients (7.3%) expired, in all of whom death was retinoblastoma-related. CONCLUSIONS:Due to TRB rarity, routine screening by baseline brain MRI may be sufficient, avoiding anesthesia, expenses, distress, and unnecessary interventions, without a significant impact on patients' survival. Nevertheless, due to TRB fatality and treatment morbidity, periodic brain MRI until age 3 is a legitimate option.

To evaluate the clinical presentation, pathological features and outcomes of retinoblastoma based on the race of origin in a global cohort of patients. Retrospective collaborative study of 1426 patients who underwent primary enucleation for retinoblastoma. Patients were grouped into Caucasians ( n  = 231, 16%), Asians ( n  = 841, 59%), Hispanics ( n  = 226, 16%), Arabs ( n  = 96, 7%) and Others (Africans, African Americans, Indigenous Australians; n  = 32, 2%) cohorts. On histopathology, massive choroidal invasion was higher in Asians (30%) and Hispanics (26%) than Caucasians (15%, p  < 0.001). Post-laminar optic nerve invasion was higher in Asians (28%), Hispanics (20%) and Others (9%) than Caucasians (11%, p  < 0.001). At a mean follow-up of 41 months (median, 35 months; range, < 1–149 months), tumour recurrence and metastasis-related death was higher in Hispanics (9% and 12%, respectively), Asians (4% and 13%, respectively) and Others (6% and 6%, respectively). Multivariate Cox proportional hazards analysis of outcomes based on race with 8th edition AJCC pT stage and adjuvant therapy as covariates revealed 6.8 times greater risk for orbital tumour recurrence in Hispanics compared to Caucasians ( p  = 0.010) and 3.2 times risk hazards for metastasis-related death in Hispanics and Asians compared to Caucasians ( p  = 0.028 and p  = 0.038, respectively). The histopathological features in primarily enucleated eyes with retinoblastoma vary with race. Despite adjusting for tumour staging and adjuvant treatment, race remains an independent predictor of outcomes, including orbital tumour recurrence and metastasis-related death. A stringent follow-up and a more aggressive treatment approach is recommended in Asians and Hispanics who manifest high-risk histopathological features.

Purpose:To assess histopathology and outcomes after primary enucleation of eyes with retinoblastoma presenting with neovascular glaucoma (NVG). Methods:This was an international multicenter case series study across five continents. A retrospective review of patient charts was performed for all patients undergoing primary enucleation for retinoblastoma (n = 1,420) using a standardized data-collection spreadsheet. Clinical features, pathologic grade, and outcomes were compared between NVG patients and those with an American Joint Commission on Cancer eighth edition clinical stage of cT2. High-risk histopathology was defined as American Joint Commission on Cancer eighth edition pathologic stage >= pT2b. Results:Neovascular glaucoma was seen in 224/1,420 (16%) patients. The mean age at presentation of those with NVG was 30 months (median 25, range 0-120 months), and 131 (58%) patients had high-risk histopathology. The univariate logistic regression odds ratio for NVG predicting high-risk histopathology was 1.73 (95% confidence interval: 1.3-2.31) and from multivariate logistic regression was 1.77 (95% confidence interval: 1.23-2.56). Patients with a longer duration of symptoms (P = 0.03), buphthalmos (P = 0.02), and ectropion uveae (P < 0.01) were more likely to have high-risk histopathology. Patients with NVG were more likely to develop metastasis than cT2 patients (P = 0.04). Conclusion:There is a significant association between NVG at presentation, high-risk histopathology, and metastatic risk.

Objective Treatment of palpebral conjunctival lesions is problematic due to late diagnosis, difficult surgical approach, and the need to preserve eyelid integrity. We describe our treatment experience using plaque brachytherapy in the "sandwich technique.” Design A retrospective study. Participants We reviewed the medical records of patients treated by plaque brachytherapy for conjunctival lesions at the Hadassah Medical Center between January 1, 2013, and January 1, 2024, and included in the analysis patients treated for palpebral conjunctival lesions. Methods Ruthenium plaque was sutured to the palpebral conjunctiva. The matching nonradioactive “dummy” plaque was sutured to the external eyelid to flip the tarsal's curvature. Results The study cohort included 5 patients, 2 men (40%) and 3 women (60%) at a median age of 68.11 years (range: 47-79.7 years). Three patients had conjunctival melanoma (60%), 1 had sebaceous carcinoma (20%), and 1 had extensive carcinoma in situ (20%). All lesions were in the left upper eyelid. Median follow-up was 37.6 months (range: 18.7-110.6 months). Four patients demonstrated a complete response (80%), while one had a partial response (20%). There was local recurrence in 1 patient (20%), and 1 patient had new foci elsewhere (20%). All patients had full local control after adding local treatments. One patient developed metastatic disease and died (20%). All patients had manageable madarosis and conjunctival scars. Conclusions Treatment of palpebral conjunctival lesions using “sandwich” plaque brachytherapy is safe and effective. To the best of our knowledge, this treatment was never described before, and we believe it should be added to our armamentarium.

center dot PURPOSE: To compare the clinical outcomes of children with unilateral retinoblastoma (Rb) and high-risk histopathology features (HRHF) following upfront enucleation with/without adjuvant chemotherapy, and investigate cases locally considered non-HRHF but converted to a standardized HRHF definition. center dot DESIGN: Retrospective multinational clinical cohort study. center dot METHODS: Children with Rb who presented to 21 centers from 12 countries between 2011-2020, and underwent primary enucleation were recruited. Centers retrieved clinical data and were asked to report detailed histopathology findings, as well as indicate cases defined locally as high-risk. For analysis, only unilateral cases with standardized HRHF, defined as retrolaminar optic nerve invasion, massive choroidal invasion, scleral invasion, anterior-segment involvement, and/or combined nonmassive choroidal and prelaminar/laminar optic nerve invasion, were included. Main outcome measures included orbital tumor recurrence, systemic metastasis, survival and number, and outcome of cases converted to standardized HRHF. center dot RESULTS: A total of 600 children presenting to 14 centers in 9 countries were included. Of these, 505 (84.2%) were considered locally as HRHF and received adjuvant chemotherapy. After a median follow-up period of 39.2 +/- 1.6 months (range: 0.8-60.0 months), 36 (6.0%) had orbital tumor recurrence, 49 (8.2%) metastasis, and 72 (12.0%) children died. Children not receiving adjuvant chemotherapy were at significantly increased risk of orbital tumor recurrence, metastasis, and death ( P <= .002). Of the study children, 63/600 (10.5%) were considered locally non-HRHF, but converted to standardized HRHF and included in the analysis. Of these, 6/63 (9.5%) had orbital tumor recurrence, 5/63 (7.9%) metastasis, and 6/63 (9.5%) children died. Isolated minor choroidal invasion with prelaminar/laminar optic nerve invasion was reported in 114 (19.0%) children, but considered locally as HRHF only in 68/114 (59.6%). Of these, 6/114 (5.3%) children developed metastasis and subsequently died, yielding a number needed to treat of 15. center dot CONCLUSION: Based on this multinational cohort of children with Rb, we recommend the use of adjuvant chemotherapy following upfront enucleation and diagnosis of HRHF. Variation exists worldwide among centers when defining HRHF, resulting in adverse patient outcomes, warranting standardization. (Am J Ophthalmol 2024;268: 399-408. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: To evaluate high-risk histopathological features following primary enucleation of eyes with retinoblastoma and assess the patient outcomes across continents. Methods: A retrospective study of 1,426 primarily enucleated retinoblastoma eyes from five continents. Results: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathological features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, P = 0.001), postlaminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, P = 0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, P = 0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, P = 0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given to 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% versus 2% versus 0% versus 0% versus 12% (P < 0.001), systemic metastasis was reported in 8% versus 5% versus 2% versus 0% versus 13% (P = 0.001), and death in 10% versus 3% versus 2% versus 0% versus 11% (P < 0.001) patients. Conclusion: There is a wide variation in the infiltrative histopathological features of retinoblastoma across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

Purpose To describe the clinical presentation and treatment outcomes of children diagnosed with retinoblastoma (RB) in the year 2017, throughout Asia. Design Multi-national prospective study including treatment-naïve patients diagnosed with retinoblastoma in Asia during 2017 and followed up thereafter. Participants A total of 2112 patients (2797 eyes) from 96 RB treatment centers in 33 Asian countries. Intervention Chemotherapy, radiotherapy, enucleation, orbital exenteration Main Outcome Measures Enucleation and death Results Within the cohort, 1021 (48%) patients were from South Asia (SA), 503 (24%) from East Asia (EA), 310 (15%) from South-East Asia (SEA), 218 (10%) from West Asia (WA) and 60 (3%) from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, <1 to 261 months). There were 1195 (57%) males and 917 (43%) females. The most common presenting complaints were leukocoria (72%) and strabismus (13%). Based on 8th edition American Joint Committee for Cancer, 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. RB was treated with intravenous chemotherapy in 1450 (52%) eyes and 857 (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, 20% and 11% for WA (p<0.0001 and p<0.0001), respectively. Conclusion At the conclusion of this study, there was a significant heterogeneity in treatment outcomes of RB between the regions of Asian continent. East Asia displayed better outcomes with higher rates of globe and life salvage, while South-East Asia had poorer outcomes compared to the rest of Asia.