Background: Radiation‐induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series.Methods: All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post‐treatment follow‐up was recorded. A 1:2 propensity score matched case–control study was performed for the evaluation of the prognostic value of different tumour‐ and treatment‐associated parameters.Results: RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26–226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case–control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour‐ and treatment‐associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014).Conclusions: Our study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established.

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1-secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC-therapy-responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients’ blood serum displayed low-to-undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared with blood serum, AH represents the more reliable source of TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimally invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.

The main objective of this prospective observational study was the characterization of the feasibility and early outcome of image-guided (IG) volumetric modulated arc (VMAT) radiosurgery (SRS) followed by resection for patients with large intraocular melanoma. Our study included consecutive patients with unfavorable-risk melanoma, enrolled in an ophthalmic oncology center. IG-VMAT-SRS was applied by high-resolution 4D image guidance and monitoring. Current stereotactic technique parameters were evaluated for comparison. Side effects and eye function, based on a 5-point CTC assessment score, were quantified. In patients with tumors located more than 0.7–1 mm apart from the optic nerve, partial to complete volume-sparing of the optic nerve head could be achieved. In 95.5% of this subgroup, the vitality of the optic nerve and vision could be preserved by the multimodality-treatment approach (mean follow-up: 18 months (7.5–36 months)). The advanced technology of stereotactic radiotherapy demonstrated the achievability of steep dose gradients around the high-dose volume, with 4D-IG-VMAT dose application. These results enforce IG-VMAT-SRS followed by resection as one of the major therapeutic options for patients with large intraocular melanoma. The combination of 4D-IG high-precision SRS and resection provides an effective treatment for large intraocular melanoma, with few side effects, and enables an eye bulb and even vision preserving modus operandi.

Dose-response relationships for optic neuropathy and optic nerve atrophy after brachytherapy for posterior uveal melanoma were poorly defined from previous studies. Here, the outcome differences were analyzed in dependence on dosimetric factors, the applicator type, and tumor dependent variables. Primary objective was to evaluate the association of applied dose and on-set of optic nerve atrophy after brachytherapy for posterior uveal melanoma in order to allow risk estimation for new patients. This retrospective study was performed at a single high volume centre for ocular oncology. Patients receiving brachytherapy with Ruthenium-106 applicators for posterior uveal melanoma with a maximum distance between optic nerve and the nearest tumor margin of 4 optical disc diameters and follow-up with fundus photographs were included. The dose distribution at the optic nerve was reconstructed from the fundus photographs at latest follow-up and the dose-distribution of the applicator using a dedicated software. A first mask with important structural elements such as optic nerve, macula, tumor and vessels was first superimposed on the fundus photograph and adapted to the real contours. In a second step, an applicator contour mask was adapted to the radiation scar in order to calculate the dose distribution in all structures. Dose-response relations were obtained by weighted logistic regression. The maximum dose at the optic disc (OD_max) in this group of 109 patients ranged from 5.8 Gy - 242.2 Gy, median 48.7 Gy. Optic nerve atrophy was observed in 29patients. Median time to radiation induced optic nerve atrophy was 18months. Using weighted logistic regression, the dependence of optic nerve atrophy on OD_max was significant (p = 0.0001, chi²-test). There was a considerable interobserver variability in OD_max values (p < 0.02, signed rank test). An additional factor influencing the dose-response was the applicator type (p = 0.0315, chi²-test). The OD_max for a probability of optic nerve atrophy of 50 % (ED50) were 77.6 Gy ± 7.0 Gy for patients treated with notched COB applicators and 53.2 Gy ± 8.2 Gy for patients with other applicators. Including the applicator type, the area under ROC curve reached a value of 0.857 (95 %-CI: 0.793-0.921) for the logistic model with OD_max. The ED50 for optic nerve neuropathy, classified as grade ≥ 1 toxicity, was estimated to be 46.9 Gy ± 4.1 Gy for the maximum dose at the optic disc. Significant dose-response curves were found for optic nerve atrophy at low dose rate brachytherapy. A standard position of COB applicators was identified that allows estimation of the dose-response relation from the scleral dose of the applicator for risk estimation without fundus photographs. This larger data set enhances the knowledge of dose-response relationships for irradiation near the optic nerve.

Purpose: Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery. Methods: All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included. Achievement of the tectonic stability and evaluation of incidence and the risk factors for a repetitive patch surgery (RPS) were the main endpoints. Results: The final analysis included 57 patients (mean age: 58.7 years; 63.2% female patients), where 55 individuals underwent a patch grafting, and 2 cases were treated with conjunctival reconstructive surgery. The mean follow-up time after grafting was 38.5 months (0.03–221.1 months). Tectonic stability was achieved in 56 (98.3%) patients. Scleral graft (38/55, 69.1%) was the most frequent patching material, followed by Tutopatch (7/55, 12.7%), corneal graft (7/55, 12.7%), dura graft (2/55, 3.6%), and fascia lata (FL) graft (1/55, 1.8%). Eleven patients (20%) underwent RPS after the mean time of 12.9 months (0.3–50.3 months). In the final multivariate Cox regression analysis, the use of Tutopatch (5/7; 71.4%, adjusted hazard ratio = 4.66, P = 0.044) and RISN progression after patch grafting (9/11; 81.8%, adjusted hazard ratio = 9.67, P = 0.008) were independent risk factors for RPS. Conclusions: RISN surgery maintains long-term tectonic stability in most of the cases underwent surgical repair for RISN after brachytherapy for UM. Depending on graft material and, particularly, further RISN progression, an RPS might be necessary in certain cases.