To evaluate visual outcomes following stereotactic radiosurgery (SRS) in patients with symptomatic circumscribed choroidal hemangioma (cCH). This retrospective study included 30 patients with symptomatic cCH treated with SRS between 2014 and 2025. SRS was performed using either the CyberKnife or ZAP-X platform depending on the treatment period. Visual outcomes were assessed by changes in best-corrected visual acuity (BCVA). A lower score on the logarithm of the minimum angle of resolution (logMAR) scale indicates better vision. The median patient age was 46 years. Ten patients (33.3

Background Metastatic uveal melanoma (MUM) is a rare malignancy with historically poor prognosis and limited systemic treatment options. This study evaluates treatment responses and survival outcomes in patients with MUM managed at a tertiary reference center along with assessment of long term survivors. Method 91 patients with MUM treated between 2012 and 2025 were evaluated. Demographic, clinical, laboratory, and treatment data were collected. Survival was analyzed using Kaplan–Meier and Cox regression models. Results Among 91 patients, 46 (50.5%) were male, with a median age of 61 years. Most of the patients had metachronous metastatic disease (91%) and median disease-free interval (DFI) was 32 months. Liver metastases were identified in 95% of patients. Tebentafusp was not used in any patients as it was not registered in our country. Immunotherapy (IO) was used in 65 (71%) patients, including 14 patients in the first-line setting. In first-line treatment, IO achieved an objective response rate of 7% and a disease control rate of 64%. Locoregional therapies (LT) were administered in 56%. Median overall survival (OS) for the entire cohort was 16.6 months (95% CI, 13.1–20.1). On multivariate Cox regression analysis, female sex, longer DFI, lower baseline AST levels, and receipt of LT were independently associated with improved OS. Patients who received combined IO (anti-PD1 plus anti-CTLA4; n = 21) had a trend towards longer OS compared to those who received single agent IO (anti-PD1 alone or anti-CTLA4 alone; n = 46) as initial IO regimen (p = 0.12). 30 patients (33%) survived more than 24 months following the diagnosis of metastatic disease. 97% of these patients had metachronous metastases, 83% had DFI > 24 months, 60% had liver directed LT, 67% were females and 70% had enucleation as the primary treatment modality. Conclusion This real-world study showed modest efficacy of IO in the treatment of MUM. Liver directed LT appeared to provide the greatest benefit. Combination IO demonstrated a trend toward improved OS compared to mono-IO. Longer DFI in patients with metachronous metastatic disease, female sex, and normal transaminase levels are other prognostic factors associated with improved OS.

e21509 Background: Metastatic uveal melanoma (MUM) is a rare malignancy with poor prognosis and limited systemic treatment options. This study evaluates prognostic factors and treatment outcomes in patients with MUM managed at a tertiary reference center. Methods: 91 patients with MUM treated between 2012 and 2025 were evaluated. Demographic, and clinical data were collected. Survival was analyzed using Kaplan–Meier and Cox regression models. Results: Among 91 patients, 46 (50.5%) were male, with a median age of 61 years. Most of the patients had metachronous metastases (91%) and median disease-free interval (DFI) was 32 months. Liver metastases were identified in 95%. Immunotherapy (IO) was used in 67 (74%) patients, including 14 patients in the first-line setting. IO achieved an ORR of 7% and a disease control rate of 64%. Tebentafusp was not available in our country. Locoregional therapies (LT) were administered in 56%. Median overall survival (OS) for the entire cohort was 16.6 months (95% CI, 13.1–20.1). On multivariate Cox regression analysis, female sex, longer DFI (>36 months), lower baseline AST levels, and receipt of LT were independently associated with improved OS. Patients who received combined IO (anti-PD1 plus anti-CTLA4; n=21) had a trend towards longer OS compared to those who received single agent IO (anti-PD1 alone or anti-CTLA4 alone; n=46) as initial IO regimen (HR 0.51; 95%CI 0.26-0.99, p=0.049). 30 patients (33%) survived more than 24 months following the diagnosis of metastatic disease. 97% of these patients had metachronous metastases, 67% had DFI >36 months, 60% had liver directed LT, 67% were females and 70% had undergone enucleation as the primary treatment. Conclusions: This real-world study showed modest efficacy of IO in the treatment of MUM. Combination IO demonstrated a trend toward improved OS compared to mono-IO. Liver directed LT appeared to provide the greatest benefit. Long DFI in patients with metachronous metastatic disease, female sex, and normal transaminase levels are other prognostic factors associated with improved OS. Univariate and multivariate Cox regression analysis for overall survival. Variables Univariate HR (95% CI) Univariate p value Multivariate HR (95% CI) Multivariate p value Female (ref: male) 0.47 (0.29–0.77) 0.003 0.43 (0.24–0.79) 0.007 DFI ≤ 36 mo (ref: >36 mo) 2.28 (1.40–3.70) <0.001 2.30 (1.21–4.35) 0.011 Locoregional therapy: Yes (ref: No) 0.35 (0.22–0.58) <0.001 0.32 (0.17–0.57) <0.001 AST >ULN (ref: ≤ULN) 2.85 (1.56–5.21) <0.001 2.78 (1.27–6.09) 0.01 ALP >ULN (ref: ≤ULN) 2.30 (1.27–4.15) 0.006 1.44 (0.57–3.63) 0.43 LDH >ULN (ref: ≤ULN) 2.08 (1.24–3.50) 0.005 1.49 (0.83–2.65) 0.17 Any-line immunotherapy: Yes (ref: No) 0.56 (0.34–0.93) 0.026 1.04 (0.43–2.55) 0.92 ALP: Alkaline phosphatase, AST: Aspartate aminotransferase, DFI: Disease-free interval, HR: Hazard ratio, LDH: Lactate dehydrogenase, ref: Reference, ULN: Upper limit normal.

Chordoid meningioma is a rare histological variant of meningioma classified as World Health Organization Grade II because of its aggressive clinical behavior and high recurrence potential. Orbital involvement is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. We report a long-term clinical course of a patient with orbital chordoid meningioma who initially presented with progressive proptosis and visual impairment. Despite multiple biopsies, radiotherapy, and long-term follow-up, the tumor demonstrated locally aggressive behavior with repeated progression, ultimately requiring orbital exenteration. Histopathological examination confirmed chordoid meningioma with a positive reactivity against SSTR2, and progressively increasing Ki-67 proliferation index, supporting its aggressive nature. This case highlights the diagnostic difficulties, limited response to conventional treatment modalities, and the importance of long-term surveillance in orbital chordoid meningioma.

CLINICAL RELEVANCE:Radiation retinopathy is a common cause of visual impairment following ocular radiotherapy, and systemic inflammatory activity may contribute to retinal vascular damage. Understanding inflammatory mechanisms may support earlier identification of patients at risk and improve clinical monitoring strategies. BACKGROUND:Radiation retinopathy is a vision-threatening complication of radiotherapy for uveal melanoma and has traditionally been considered a localised microvascular disorder. However, the potential contribution of systemic inflammation to its development remains unclear. METHODS:A retrospective review was undertaken of hospital records of patients diagnosed with radiation retinopathy after stereotactic photon radiotherapy for uveal melanoma. Demographic characteristics, tumour features, and systemic inflammatory blood parameters were evaluated before and after the onset of retinopathy. RESULTS:A total of 97 patients were included, with 52.6% female participants. Most tumours were classified as T1 or T2. The median time to retinopathy diagnosis was 24 months. All systemic inflammatory blood parameters showed significant increases after the development of radiation retinopathy (all p < 0.05). CONCLUSION:It is concluded that radiation retinopathy is associated with systemic inflammatory activation, suggesting that inflammatory processes may extend beyond localised retinal injury, and therefore may serve as accessible biomarkers for disease monitoring.

PURPOSE:Intravitreal bevacizumab has been utilized to mitigate radiation retinopathy, yet the potential role of intravitreal melatonin for its prevention remains unexplored. This study aims to evaluate and compare the efficacy of intravitreal melatonin and bevacizumab in preventing radiation retinopathy in an experimental animal model. MATERIALS AND METHODS:Twelve healthy male New Zealand white rabbits (n = 24 eyes) received a single 3000 cGy irradiation dose in both eyes. Intravitreal melatonin (100 mcg/kg = 300 mcg/0.05 mL) was administered to the left eyes of six rabbits, and bevacizumab (1.25 mg/0.05 mL) to the left eyes of the remaining six, with sham injections given to the right eyes as controls. Six weeks after irradiation, bilateral enucleation was performed for biochemical and histopathological evaluation. RESULTS:Oxidative stress markers did not differ significantly between the groups (p = .827). Both melatonin and bevacizumab treatments markedly reduced axonal damage compared to the sham control group (p < .001). Melatonin also demonstrated a trend toward superior neuroprotective effects relative to bevacizumab, though this difference was not statistically significant (p = .07). CONCLUSIONS:Intravitreal melatonin demonstrated efficacy comparable to bevacizumab in reducing radiation-induced retinopathy, with an encouraging trend toward enhanced neuroprotection. These findings position melatonin as a potential novel therapeutic for radiation retinopathy prophylaxis. Further research with larger, long-term studies is warranted to validate these results and investigate melatonin's broader applications in retinal protection.

Orbital neurofibromas are benign tumors originating from the peripheral nerve sheath, often linked to neurofibromatosis type 1 (NF1) [1], although they account for less than 1% of all orbital tumors [2, 3]. These tumors can cause symptoms such as proptosis, vision impairment, and ocular misalignment [4]. While typically linked to NF1, multiple isolated orbital neurofibromas in the absence of a definitive NF1 diagnosis remain exceedingly rare, warranting clinical attention. A 56-year-old female presented with ptosis and dystopia on the right side. MRI revealed multiple intraorbital and extraconal masses, with the largest being excised via anterior orbitotomy. Histopathological analysis confirmed the diagnosis of neurofibroma. The patient had no cutaneous or systemic signs suggestive of NF1. In adults, multiple orbital tumors should prompt suspicion for neurofibromas, even when NF1 is not confirmed. Furthermore, recurrence is possible, emphasizing the importance of long-term follow-up. This case highlights the diagnostic challenge posed by orbital neurofibromas without NF1 and the need for comprehensive systemic evaluation in such presentations.

BACKGROUND:It has been reported that the risk of second malignant neoplasms (SMNs) in long-term follow-up patients with heritable retinoblastoma (Rb) is significantly increased compared with patients with non-heritable Rb and the general population. In this study, we investigated the types, frequencies, clinical and pathologic features, potential risk factors, and outcomes of SMNs occurring in a large group of retinoblastoma patients that were diagnosed, treated, and followed up for a long time in our Pediatric Oncology unit. METHODS:Our study comprehensively analyzed records of Rb patients followed up at Hacettepe University Pediatric Oncology Department over a 51-year period from January 1972 to January 2023. We determined the number, rate, and time of diagnosis of various SMN types and investigated potential risk factors that could lead to the development of SMNs. RESULTS:A total of 491 patients were included in this study. Median age at the time of retinoblastoma diagnosis was 1.25 (range, 0.02 to 12.08) years. Of these cases, 313 (63.7%) were unilateral, 174 (35.4%) were bilateral, and 4 (0.9%) were trilateral Rb. Enucleation was performed in 348 (70.9%) cases. A total of 334 cases received systemic chemotherapy with different protocols. Intra-arterial chemotherapy (IAC) was administered in 101 (20.6%) patients. Radiotherapy was administered in 76 (15.5%) patients. After enucleation, 56 (11.4%) patients were followed up without further treatment. SMNs occurred in 13 (2.6%) of 491 patients. Among these, 9 (69.2%) patients were considered as having heritable Rb. Enucleation was performed in 10 cases. Only 1 patient received radiotherapy and 12 patients received systemic chemotherapy. Most common subtype of SMNs was osteosarcoma (n=7; 53.8%), followed by acute myeloid leukemia (AML) (n=3; 23.1%), acute lymphoblastic leukemia (ALL) (n=1; 7.7%), Wilms tumor (n=1; 7.7%), and colon adenocarcinoma (n=1; 7.7%). The median time from the diagnosis of Rb to the onset of SMN was 136 (range, 24 to 250) months. Among the patients that underwent IAC, no patient developed SMN. Of the 491 patients, 41 (8.3%) died and 450 are still alive. Of the 13 patients with SMN, 8 (61.5%) died and 5 are still alive. Five-year OS of our study group was 91% and it was significantly lower in patients with SMNs compared with those without SMNs ( P =0.001). CONCLUSION:In this study, overall survival (OS) was lower in patients with bilateral retinoblastoma compared with unilateral cases, and similarly reduced in patients who received radiotherapy compared with those who did not. In addition, the development of second malignant neoplasms (SMNs) was significantly higher in hereditary retinoblastoma patients than in non-hereditary cases. These findings highlight the importance of careful long-term monitoring and tailored follow-up strategies in patients at increased risk.

The precise mechanisms underlying radiation-induced cataractogenesis remain incompletely understood. Increased oxidative stress is known to play a central role in cataract pathogenesis. The vitreous humor contributes to maintaining the hypoxic environment of the lens by regulating oxygen pressure and containing antioxidants. This study aims to explore the effect of radiation-induced changes in the vitreous humor on lens health, with a particular focus on its cataractogenic potential. In this experimental study, 12 New Zealand rabbits were utilized. A single 20-Gy dose of radiation was administered to the left eye’s vitreous humor with a lens-sparing technique, while the right eye served as a control. Monthly ophthalmological evaluations were conducted over a 3-month period. At the end of the follow-up, orbital magnetic resonance imaging (MRI) was performed. Vitreous humor samples were analyzed using spectrophotometric methods to determine total oxidant and antioxidant levels. Cataract formation was observed in two of the eight irradiated eyes (25

The aim of this study was to evaluate histopathologically the conjunctival pigmentations occurring in post-enucleation anophthalmic sockets and to identify the common causes. Retrospective cohort study. This was a retrospective chart review of patients who presented with conjunctival pigmentation in the anophthalmic socket at a single tertiary care center and who underwent incisional conjunctival biopsy between 2018 and 2022. Demographic and clinicopathological data, and treatment outcomes were retrieved. A total of 14 consecutive patients aged between 17 and 70 years were enrolled. Indications for primary enucleations were: retinoblastoma in 5 (35.7

Aim: BAP1-tumor predisposition syndrome (BAP1-TPDS) is a rare autosomal dominant condition predisposing to multiple malignancies, most notably uveal melanoma and mesothelioma. The full phenotypic and genotypic spectrum remains incompletely defined, particularly in underrepresented populations. Methods: Six unrelated Turkish probands carrying germline pathogenic or likely pathogenic BAP1 variants were identified through multigene hereditary cancer panel testing. Clinical data, family histories, and segregation analyses were evaluated, and variant classification followed American College of Medical Genetics and Genomics guidelines. Results: All six affected individuals were female, with cancer onset between 38 and 57 years of age. Breast carcinoma was the most common diagnosis (n=4), followed by uveal melanoma (n=2). Three novel BAP1 variants were identified, expanding the mutational landscape of BAP1-TPDS. Pedigree analysis revealed extensive familial clustering of malignancies, including uveal melanoma, colon carcinoma, hepatocellular carcinoma, and mesothelioma. None of the breast cancer patients carried additional pathogenic variants in known susceptibility genes. Conclusion: This study describes the first Turkish cohort of germline BAP1 carriers and broadens the clinical and genetic spectrum of BAP1-TPDS. The predominance of breast carcinoma highlights the need to consider BAP1 testing in patients with early-onset or familial breast cancer. Integrating BAP1 analysis into hereditary cancer panels will enhance recognition, risk stratification, and surveillance across diverse populations.

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect multiple organs, yet neurological involvement has been considered rare and remains under-characterized. We retrospectively analyzed 77 adult patients with IgG4-RD registered in our database between 2014 and 2023. Clinical, laboratory, imaging, histopathological, and therapeutic data were reviewed, with particular focus on neurological manifestations. Neurological involvement was identified in 17 patients (22

To perform a comprehensive dosimetric comparison between the ZAP-X gyroscopic radiosurgery system and the CyberKnife (CK) robotic platform for the treatment of uveal melanoma (UM), with a focus on target coverage, organ at risk (OAR) sparing, plan quality metrics and treatment delivery efficiency. A total of 45 uveal melanoma patients previously treated with the CK system were retrospectively analyzed. For each patient, treatment plans were generated for both the ZAP-X and CK platforms using identical contouring datasets, shell structures, optimization parameters and dose calculation algorithms. Dosimetric parameters related to target coverage and OARs were compared, along with conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient indices (GI50% and GI25%), monitor units (MU) and estimated treatment times. Both systems achieved adequate target coverage with no significant difference in PTV D98% values. ZAP-X demonstrated significantly higher Dmax, lower CI and nCI, and steeper dose gradients (GI50%, GI25%) compared to CK (p < 0.001 for all), indicating better conformity and dose fall-off. ZAP-X also delivered significantly lower doses to several OARs (p < 0.05 for all), including the optic nerves, contralateral eye, lenses, vitreous humor, lacrimal gland and brain. Although ZAP-X required more MUs per fraction, it achieved shorter treatment times. ZAP-X offers superior dose conformity, sharper dose gradients, and improved OAR sparing for uveal melanoma treatment without increasing treatment duration. While further clinical validation is required, these results support the potential of ZAP-X as a promising stereotactic radiosurgery platform for ocular tumors.

PURPOSE:Despite its slow growth pattern, adenoid cystic carcinoma of the lacrimal gland poses challenges due to its high recurrence rate. The rarity of this entity hinders the establishment of prospective studies and a consensus on optimal treatment strategies. Herein, we aim to report the results of patients with adenoid cystic carcinoma of the lacrimal gland treated with hypofractionated stereotactic body radiations or conventionally-fractionated radiations. MATERIALS AND METHODS:This study included patients with non-metastatic adenoid cystic carcinoma of the lacrimal gland treated with a curative-intent from 2006 to 2019. Patient data, tumour characteristics, treatment details, and follow-up information were collected. Recurrence patterns, oncologic outcomes, and toxicity were assessed. RESULTS:We evaluated the data of 12 patients with a median 29years of age who received stereotactic body radiotherapy (n=5) or conventionally-fractionated radiotherapy (n=7). After a median follow-up of 98months, the overall local control rate was 50 %, with recurrences mostly marginal to the radiotherapy field. Although the 10-year overall survival rate was a promising 92 %, the respective rate for local recurrence-free survival was 37 %, which was significantly lower in patients who received stereotactic body radiotherapy (20 %) compared to patients who had with conventionally-fractionated radiotherapy (72 %). Although not statistically significant, patients in the stereotactic body radiotherapy arm encountered a higher rate of severe late toxicity (80 % versus 17 % in the conventionally-fractionated radiotherapy arm, P=0.07). The overall eye preservation rate was 64 %, all eye-losses due to local recurrence. CONCLUSION:Our findings raise concerns about using stereotactic body radiotherapy for adenoid cystic carcinoma of the lacrimal gland based on increased rates of severe late toxicity and local recurrence. Conventional radiotherapy techniques should be applied to these patients to successfully control the local tumour with less toxicity.

BACKGROUND:Jeune syndrome is an autosomal recessive chondrodysplasia characterized by skeletal deformities and extra-skeletal organ involvement. Retinal astrocytic hamartomas (astrocytomas) are benign glial cell 10 15 Q1 tumors that are generally asymptomatic and diagnosed incidentally. The IFT74 gene is responsible for the formation of IFT proteins, which play a major role in ciliogenesis. CASE PRESENTATION:In this retrospective clinical laboratory observational study, an 18-year-old male with Jeune syndrome and night vision loss is presented. Fundus examination revealed bilateral optic discs with minimally blurred margins and bilateral retinal pigment epithelium changes in salt-pepper pattern in the peripheral retina. Additionally, a yellowish retinal astrocytoma was observed inferior to the optic disc in the left eye. Genetic analysis of the patient revealed a homozygous deletion in exon 2 of the IFT74 gene. CONCLUSIONS:Our observations on this patient and some relationships between hamartoma and ciliopathies other than eye may potentially suggest a possible association between Jeune syndrome and retinal astrocytoma in the context of IFT74-related ciliopathies.

To review long-term outcomes of circumscribed choroidal hemangioma (CCH). Hospital charts of all CCH cases diagnosed from 2008 to 2019 were retrospectively reviewed. All 172 patients were managed with either observation, transpupillary thermotherapy, argon laser photocoagulation, photodynamic therapy, plaque brachytherapy or stereotactic radiosurgery. The most common 3 modes of management were clinical observation (30.2

Purpose:To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods:Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results:The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions:We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

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.