Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis.

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.

Retinoblastoma and mosaic 13q deletion: a case report.

BACKGROUND: Patients with 13q-syndrome are at risk of retinoblastoma when the RB1 gene, located in the chromosomal band 13q14.2, is deleted. This syndrome is frequently associated with congenital malformations and developmental delay, although these signs could be mild. Mosaic 13q-deletion patients have been previously reported in the literature; their phenotype is variable, and they may not be recognized. CASE PRESENTATION: Retinoblastoma diagnosed in a child with 13q-mosaicism confirmed in blood, oral mucosa, healthy retina and retinoblastoma. A second RB1 hit is present exclusively in the retinoblastoma sample (RB1 c.958C>T p.Arg320Ter). Other detected molecular events in retinoblastoma are 6p12.3pter gain and 6q25.3qter loss. Clinical examination is unremarkable except for clinodactyly of the right fifth finger. DISCUSSION AND CONCLUSIONS: We describe a case of mosaic 13q deletion syndrome affected by retinoblastoma. Molecular data obtained from the tumor analysis are similar to previous data available about this malignancy. High clinical suspicion is essential for an adequate diagnosis of mosaic cases.

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.

Intravitreal melphalan therapy for vitreous seeds in retinoblastoma: Implementation and outcomes of a new chemotherapy protocol.

Retinoblastoma is the most common paediatric ocular tumour, which appears in the retina. Without treatment, retinoblastoma grows and destroys the internal ocular globe architecture, even leading to metastasis. When treated, overall survival is close to 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localised treatment. The aim of this study is to describe the implementation of a new intravitreal chemotherapy retinoblastoma treatment protocol for children implanting vitreous seeds through intravitreal melphalan injections and to evaluate the patients' health outcomes treated with it. Between December 2014 and July 2018, seven patients were treated with this protocol. They received a mean of 3.3 cycles of intravitreal melphalan with standard doses of 30 mcg per cycle. In the seven eyes treated in our hospital, the response was as expected; three eyes with vitreous seedings (43%) were successfully treated. The main adverse effects presented by all patients were scars at cryogenisation points. In two patients, the appearance of 'salt and pepper' retinopathy was reported. Oncology pharmacists, as part of the treatment team, can provide information about recommended doses, expected adverse effects, stability of preparations, most appropriate method of processing, packaging, and methods of drug administration, to ensure efficacy and especially safety in the administration of these drugs.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.