Despite the increased risk of subsequent primary tumors (SPTs) external beam radiation (EBRT) may be the only therapeutic option to preserve a retinoblastoma eye. Due to their physical properties, proton beam therapy (PBT) offers the possibility to use the effectiveness of EBRT in tumor treatment and to decisively reduce the treatment-related morbidity. We report our experiences of PBT as rescue therapy in a retrospectively studied cohort of 15 advanced retinoblastoma eyes as final option for eye-preserving therapy. The average age at the initiation of PBT was 35 (14–97) months, mean follow-up was 22 (2–46) months. Prior to PBT, all eyes were treated with systemic chemotherapy and a mean number of 7.1 additional treatments. Indication for PBT was non-feasibility of intra-arterial chemotherapy (IAC) in 10 eyes, tumor recurrence after IAC in another 3 eyes and diffuse infiltrating retinoblastoma in 2 eyes. Six eyes (40%) were enucleated after a mean time interval of 4.8 (1–8) months. Cataract formation was the most common complication affecting 44.4% of the preserved eyes, yet 77.8% achieved a visual acuity of >20/200. Two of the 15 children treated developed metastatic disease during follow-up, resulting in a 13.3% metastasis rate. PBT is a useful treatment modality as a rescue therapy in retinoblastoma eyes with an eye-preserving rate of 60%. As patients are at lifetime risk of SPTs consistent monitoring is mandatory.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013–2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.

A disintegrin and metalloproteinase (ADAM) family proteins, acting as sheddases, are important factors in a number of pathologies, including cancer, and have been suggested as promising therapeutic targets. The study presented focuses on the involvement of ADAM10 and ADAM17 in retinoblastoma (RB), the most common malignant intraocular childhood tumor. A significant correlation between ADAM17 expression levels and RB laterality and RB staging was observed. Levels of ADAM10 or ADAM17 regulating miRNAs miR-145, -152, and -365 were significantly downregulated in RB cell lines, and reduced miR levels with simultaneously upregulated ADAM10 and ADAM17 expression were found in RB patients. The involvement of both ADAMs analyzed in ectodomain shedding of the neuronal cell adhesion molecule L1 (L1CAM), shown to induce pro-tumorigenic effects in RB, was confirmed. Lentiviral ADAM10 and ADAM17 single or ADAM10/17 double knockdown (KD) induced caspase-dependent apoptosis and reduced cell viability, proliferation, growth, and colony formation capacity of RB cells. Moreover, differential phosphorylation of the serine/threonine kinase AKT was observed following ADAM17 KD in RB cells. Chicken chorioallantoic membrane (CAM) assays revealed that ADAM17 and ADAM10/17 depletion decreases the tumorigenic and migration potential of RB cells in vivo. Thus, ADAMs are potential novel targets for future therapeutic RB approaches.

Background/Objectives: Different surgical techniques are available in cases of missing or insufficient capsular bag support. Next to the anterior chamber or iris-fixated intraocular lenses (IOL), the implantation of the Carlevale IOL provides a sutureless and scleral fixated treatment method. Methods: In a retrospective single-center study, the perioperative data of 100 patients who consecutively received a scleral fixated Carlevale IOL combined with a 25 gauge (G) pars plana vitrectomy between September 2021 and June 2024 were investigated. The intraoperative and postoperative results were analyzed in terms of complication rates and refractive outcomes. Results: IOL dislocation was the most common surgical indication (50%) for sutureless Carlevale IOL implantation, followed by postoperative aphakia in 35 patients (35%). Nearly every fourth patient (24%) had a preoperative traumatic event, and 21% had pseudoexfoliation (PEX) syndrome. The average surgery time was 60.2 (±20.1) min. Intraoperative intraocular hemorrhage occurred in seven cases, and IOL haptic breakage in two patients. Temporary intraocular pressure fluctuations represented the most common postoperative complications (28%). Severe complications such as endophthalmitis or retinal detachment were not observed in our cohort. The mean refractive prediction error was determined in 67 patients and amounted to an average of −0.7 ± 2.0 diopters. The best corrected visual acuity (BCVA) at the last postoperative follow-up showed an improvement of 0.2 ± 0.5 logMAR (n = 76) compared to the preoperative BCVA (p = 0.0002). The postoperative examination was performed in 72% of the patients, and the mean follow-up period amounted to 7.2 ± 6.4 months. Conclusions: Overall, sutureless and scleral fixated implantation of the Carlevale IOL represents a valuable therapeutic option in the treatment of aphakia and lens as well as IOL dislocation in the absence of capsular bag support with minor postoperative complications and positive refractive outcomes.

Differentiation between choroidal melanoma (CM) and choroidal nevus (CN) is primarily made clinically with the aid of multimodal imaging. Both entities can be distinguished by their vascular architecture in histopathology. OCT angiography (OCT-A) is a noninvasive method to visualize retinal and choroidal vasculature and has rarely been used to differentiate CM and CN, and if so, exclusively descriptively. The purpose of this study was to differentiate both entities via OCT-A using an open-source vascular analysis software (OCTAVA), using quantitative choroidal vasculature analysis. Retrospective case-control study. Treatment-naïve patients with CM and CN who obtained OCT-A of the tumor at the University Hospital Essen between November 2022 and December 2024. Choroidal OCT-A sections were analyzed using an ImageJ-based open-source software (OCTAVA). To assess the comparison between CM and CN using vessel area density, vessel length density, total vessel length, mean vessel diameter, and tortuosity index. Thirty patients with CM and 30 patients with CN could be included in the study. Choroidal melanoma showed significantly reduced vessel area density (30.46% vs. 37.10%; P < 0.001), vessel length density (1.83% vs. 2.40%; P < 0.001), total vessel length (11.8 vs. 19.7 mm; P < 0.001), and tortuosity index (0.140 vs. 0.155; P = 0.008) compared with CN, whereas vessel diameter showed no significant difference. Receiver operating curve analysis demonstrated good diagnostic performance for vessel area density, vessel length density, and total vessel length (area under the curve: 0.81–0.86). OCT angiography using open-source software quantitative choroidal vasculature analysis may play a future role in objective differentiation between CM and CN. Future role of OCT-A in multimodal imaging for melanocytic choroidal tumors must, however, be further validated in larger, prospective trials and across different, preferably commercially available OCT platforms. The authors have no proprietary or commercial interest in any materials discussed in this article.

Background Adequate management of retinoblastoma requires a multidisciplinary and individual approach to treatment. Intraarterial chemotherapy (IAC) is one of the most commonly used treatment modalities, and enables supraselective application of chemotherapy via the ophthalmic artery and is now established in almost all treatment centres. However, published treatment success rates are heterogeneous. There are some unanswered issues regarding sight-threatening ocular complications and the long-term occurrence of secondary malignancies and metastatic disease. The objective of the present study is to analyse the results of a German national reference centre. Methods Retrospective analysis of all children with an indication for at least one IAC from April 2010 to April 2020. IAC was used either as primary or recurrence therapy. Obligatory follow-up was at least 6 months. Results 137 eyes of 127 children with an indication for IAC could be included. 12 eyes with a follow-up of less than 6 months and 37 eyes in which IAC was technically not feasible were excluded. In summary, 88 eyes of 79 children were finally analysed. Mean follow-up was 38 months, ranging from 7 to 117 months. In total, 195 procedures were completed. In 30 eyes (34.1%) IAC was conducted as primary and in 58 (65.9%) as secondary therapy. There was an initial IAC treatment response in 75 eyes (85.2%) with a recurrence-free rate of 61.3%. Eye salvage rate was 68.1% with 28 enucleated eyes in total. Ocular complications were observed in 36 eyes (40.9%), with 19 eyes (21.6%) showing severe sight-threatening and 11 eyes (12.5%) presenting minor non-sight-threatening toxic reactions. During follow-up, 1 child developed a secondary malignancy, 1 child developed metastasis and 1 child died as a consequence of trilateral retinoblastoma. Conclusion In summary, IAC is a potent modality for retinoblastoma treatment and has been very successful, even in advanced disease and heavily pretreated eyes. However, ocular complications should be taken in consideration, especially when the only seeing eye is treated. Long term incidences of secondary malignancies and metastatic diseases should be further investigated in prospective studies.