The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

BACKGROUND/OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.

Reply to Comment on Roelofs, K.A.; et al. "Detecting Progression of Melanocytic Choroidal Tumours by Sequential Imaging: Is Ultrasonography Necessary?" Cancers 2020, 12, 1856.

We thank Capasso et al [...].

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.

The MOLES System for Planning Management of Melanocytic Choroidal Tumors: Is It Safe?

PURPOSE: To evaluate the MOLES system for identifying malignancy in melanocytic choroidal tumors in patients treated for choroidal melanoma. METHODS: Records of 615 patients treated for choroidal melanoma between January 2017 and December 2019 were reviewed. Patients were excluded if iris and/or ciliary body involvement (106 patients), inadequate fundus photography (26 patients), no images available for review (21 patients) and/or treatment was not primary (11 patients). Demographic data and AJCC TNM Stage were collected. Color fundus and autofluorescence photographs (FAF), optical coherence tomography (OCT) and B-scan ultrasounds were prospectively reviewed. MOLES scores were assigned according to five criteria: mushroom shape, orange pigment, large size, enlarging tumor and subretinal fluid. RESULTS: A total of 451 patients (mean age, 63.9 ± 13.9 years) were included. At treatment, mean largest basal tumor diameter (LBD) and thickness were10.3 ± 2.8 mm (range, 3.0-23.0) and 4.3 mm (range, 1.0-17.0). All but one (0.2%) had MOLES scores of ≥3. Eighty-two patients were treated after surveillance lasting a mean of 1.5 years. Initially, most (63/82; 76.8%) had a MOLES score ≥ 3. Importantly, none of the 451 tumors had a score of <2, and as such, the MOLES protocol would have indicated referral to an ocular oncologist for 100% of patients. CONCLUSION: The MOLES scoring system is a sensitive (99.8%) tool for indicating malignancy in melanocytic choroidal tumors (MOLES ≥ 3). If the examining practitioner can recognize the five features suggestive of malignancy, MOLES is a safe tool to optimize referral of melanocytic choroidal tumors for specialist care.

Primary photodynamic therapy with verteporfin for pigmented posterior pole cT1a choroidal melanoma: a 3-year retrospective analysis.

AIMS: To investigate the outcomes of primary photodynamic therapy (PDT) for pigmented posterior pole cT1a choroidal melanoma. METHODS: Retrospective interventional consecutive case series of 26 patients (26 eyes) with pigmented posterior pole cT1a choroidal melanoma, who were treated with 3 sessions of PDT and followed-up thereafter. RESULTS: Included were 11 males and 15 females that presented at a median age of 66 years (mean: 64) with transformed naevi (n=11) or suspicious lesions (n=15) with ≥3 risk factors for growth, with lipofuscin in all. In all cases, diagnosis was clinically based (no tissue biopsy). Tumour control was achieved in 16 (62%) patients in a median follow-up time of 29 months (mean: 27). Ten patients failed treatment by form of radial expansion, diagnosed in a median time of 13 months (mean: 12) from last treatment. By Kaplan-Meier analysis, success rate after 1, 2 and 3 years was 85%, 59% and 51%, respectively. On statistical analysis, number of suspicious features was found to be the only risk factor predicting failure (P=0.046). One patient developed macula-sparing branch retinal artery occlusion after treatment. Following PDT, subretinal fluid resolved in all cases and visual acuity significantly improved in all treatment-success cases (P=0.043). There were no cases of metastatic spread. CONCLUSION: Primary PDT resulted in tumour regression of small, pigmented choroidal melanoma in 62% after a mean of 27 months. Treatment was more effective in tumours with three or less risk factors for growth, and resulted with fluid elimination and significant improvement in vision in treatment-success cases.