Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

A Novel Method for Transillumination.

PURPOSE: To introduce a cost-efficient device for transillumination in the management of uveal melanoma. METHODS: Todorich Illuminated Depressor is a ball-point depressor, designed to work with the 23-, 25- and 27-gauge Alcon Constellation endoillumination. It was invented to allow indentation and peripheral vitreous visualization for vitrectomy. RESULTS: Todorich depressor combined with endoillumination can also work as a device for transillumination for tumor localization. We started using this method of transillumination for the management of uveal melanomas since September 2020 and have successfully performed Ru-106 plaque brachytherapy for 10 cases of uveal melanoma. Three were large choroidal melanoma cases, and en bloc tumor resection by partial lamellar sclerouvectomy was successfully performed after precise localization of tumors using this method. CONCLUSION: Alcon Constellation endoillumination capped with Todorich Illuminated Depressor is an affordable and viable alternative for transillumination of intraocular tumors.

An empirical approach to the definition of the target margins in eye radiosurgery.

INTRODUCTION: A system for stabilizing and monitoring eye movements during LINAC-based photon beam one single fraction stereotactic radiotherapy was developed at our Institution. This study aimed to describe the feasibility and the efficacy of our noninvasive optical localization system that was developed, tested, and applied in 20 patients treated for uveal melanoma. METHODS: Our system consisted of a customized thermoplastic mask to immobilize the head, a gaze fixation LED, and a digital micro-camera. The localization procedure, which required the active collaboration of the patient, served to monitor the eye movements during all phases of the treatment, starting from the planning computed tomography up to the administration of radiotherapy, and allowed the operators to suspend the procedure and to interact with the patient in case of large movements of the pupil. RESULTS: Twenty patients were treated with stereotactic radiosurgery (27 Gy in one fraction) for primary uveal melanoma. All patients showed a good tolerance to the treatment; until now, all patients were in local control during the follow up and one died for distant progression 6 months after radiosurgery. CONCLUSIONS: This study showed that this noninvasive technique, based on eye position control, is appropriate and can contribute to the success of LINAC-based stereotactic radiotherapy. A millimetric safety margin to the clinical target volume was adequate to take account for the organ movement. All patients treated till now showed a good local control; failures in the disease control were due to metastatic spread.

Stereotactic radiosurgery for medium and large uveal melanoma with a non-invasive eye immobilization device, a single institutional case series.

PURPOSE: To investigate the treatment outcome, visual outcome, and adverse effects of five-fraction stereotactic radiosurgery (SRS) to medium- and large-sized uveal melanoma with a non-invasive eye immobilization device. METHODS: Medical records of 14 patients with uveal melanoma receiving SRS with a total dose of 50 Gy in five fractions from 2008 to 2017 were retrospectively reviewed. A non-invasive eye fixation device was used to achieve and monitor eye immobilization. RESULTS: Local tumor control rates were 85.7% and 75.0% at 2 and 5 years, respectively. The average tumor diameter decreased significantly from 10.0 ± 3.21 mm to 8.36 ± 3.71 mm (p = 0.038) 15 months after SRS, while the average tumor thickness decreased significantly from 5.45 ± 2.21 mm to 4.34 ± 2.29 (p = 0.036) 21 months after SRS. The 5-year metastasis-free survival was 87.5%. The mean best-corrected visual acuity (BCVA) deteriorated from logMAR 0.296 at baseline to logMAR 1.112 at the last individual follow-up visits (p < 0.001). Adverse effects of SRS were comparable to those reported with proton-beam radiotherapy or Gamma knife therapy. CONCLUSION: SRS combined with a non-invasive eye immobilization device is an effective and safe alternative eye-preserving treatment for medium- to large-sized uveal melanoma. BCVA at 3 months may be a predictor for BCVA at 1 year.

Tumor Growth Rate as a Predictive Marker for Recurrence and Survival After Liver Resection in Patients with Liver Metastases of Uveal Melanoma.

BACKGROUND: Surgical management of liver metastases of uveal melanoma (LMUM) is associated with the best survival rates, especially for patients with a low tumor burden in the liver. The aim was to determine whether the tumor growth rate (TGR0) before liver resection helps predict survival in patients with resectable LMUM. METHODS: This retrospective study included 99 patients with LMUM treated with liver resection between November 2007 and November 2020. TGR0 was expressed as the percentage change in tumor volume over 1 month according to two pretreatment imaging scans. Multivariate Cox analyses identified independent predictors of disease-free survival (DFS) and overall survival (OS). RESULTS: DFS and OS had a statistically significant positive linear relationship (Spearman correlation r = 0.68, p < 0.001). A disease-free interval (DFI) > 24 months and a TGR0 ≤ 50%/month were independent factors associated with better DFS and OS. The 2-component model including TGR0 and DFI had a mean time-dependent area under the curve (AUC) of 0.81 (95% CI, 0.75-0.86) and 0.77 (95% CI, 0.67-0.87), respectively, for predicting DFS and OS. DFI with TGR0 defined three kinetic risk groups that had distinct DFS and OS outcomes (p < 0.001). Cytogenetic alterations at baseline were partially predictive factors of the kinetic risk score based on TGR0 and DFI. DISCUSSION: The assessment of TGR0 improves prognostic stratification by identifying patients at high risk of recurrence and poor survival after liver resection. TGR0 and DFI, reflecting tumor aggressivity, have the potential to be important markers for systemic adjuvant decisions.

Outcomes of fractionated CyberKnife radiosurgery in patients with choroidal malignant melanoma.

OBJECTIVE: The aim of this study was to evaluate local tumor control and complication development rates of fractionated CyberKnife radiosurgery (CRS) in patients with choroidal melanoma. METHODS: A total of 29 patients with choroidal melanoma were treated with fractionated CRS at Ankara Oncology Research and Training Hospital, Department of Radiotherapy between May 2009 and December 2013. Patients were treated with CRS if the initial height of the choroidal melanoma was ≥ 6 mm, or juxtapapillary and/or juxtamacular tumors with a height of >2.5 mm. Ophthalmic examinations were performed at baseline and at months 3, 6, 9 and 15 after radiotherapy. Assessment of visual acuity and measurement of tumor base dimension and height using A-scan and B-scan echography were done at each visit. RESULTS: The mean age was 56 (27-75) years. Tumor was located on choroid in 23 and on ciliochoroid in 6 patients. 86.2% of all melanomas were classified as medium sized and 23.8% as large sized. A median total dose of 5000 cGy was applied. Median tumor height decreased from 7.5 mm at baseline to 4.4 mm at the last follow-up visit (p < 0.001). Median visual acuity decreased from 0.4 at baseline to hand motion (p < 0.001). One patient had been lost to the metastatic disease and one patient had been treated with enucleation due to recurrent tumor growth. CONCLUSION: CRS is an effective and reliable local treatment modality in uveal melanoma.

Surgical Technique, Indications, and Outcomes of BIOM-Assisted Transvitreal Biopsy for Uveal Melanoma.

PURPOSE: Controversy exists regarding the best method for biopsy of uveal melanoma. We describe our transvitreal technique and evaluate the safety of this technique as well as the efficacy for obtaining sample for prognostic genetic profiling. METHODS: Description of surgical technique and retrospective case series. Medical records for uveal melanoma patients who underwent transvitreal biopsy using our described technique were analyzed for tumor size, location, primary treatment, method of biopsy, and any complications thereof. Characteristics of tumors that underwent transvitreal biopsy were noted including tumor size, location, or presence of subretinal fluid, to see whether these affected surgeon preference for biopsy modality. A cohort of contemporaneous uveal melanoma patients who underwent biopsy through a transscleral technique served as a comparator group for these patient, tumor, and complication factors. RESULTS: A total of 27 patients aged 27.2 to 88.6 years (mean 64.8) underwent transvitreal biopsy using our described technique between 2013 and 2016. There were 15 small, 10 medium, and 2 large tumors at diagnosis with the majority (n = 17) posterior to the equator. Intraoperative complications included a clot or small trickle of blood at the biopsy site in 20 (74.1%) of patients, small localized subretinal hemorrhage in 8 (29.6%), small vitreous hemorrhage in 4 (14.8%), and small transient choroidal detachments in 1 patient (3.6%). When subretinal hemorrhage occurred, it was almost always into a pre-existing pocket of subretinal fluid ( P = 0.0093). However, the presence of subretinal fluid was not associated with the decision to proceed with any biopsy ( P = 0.36) or transvitreal biopsy specifically ( P = 1.00). By 3 months, subretinal and/or vitreous hemorrhage resolved in essentially all cases. There were no cases of iatrogenic retinal detachment or extraocular tumor spread over a mean follow-up of 41.7 (range: 20-62.1) months. Adequate tissue for gene expression profiling was obtained from each biopsy. The comparator group of patients undergoing transscleral biopsy including 21 uveal melanomas in 20 patients (one eye had two melanomas). Transvitreal biopsies were more common in patients with small (n = 15; P < 0.0001), posterior (n = 17; P < 0.0001) tumors, compared with patients who underwent transscleral biopsy during the same period. CONCLUSION: This technique can be used for small or posterior tumors or for small anterior tumors where a transscleral approach would risk tumor perforation. Complications were minor, transient, and self-limited. Biopsy yields for molecular prognosis were adequate in all cases. The presence of subretinal fluid may be considered a relative contraindication because it may lead to subretinal hemorrhage in the fluid pocket but did not dissuade us from using this transvitreal technique for patients who would benefit from it.

Retrospective analysis of secondary enucleation for uveal melanoma after plaque radiotherapy.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Plaque brachytherapy (PRT) is widely accepted as an effective globe-conserving treatment modality for UM. However, local treatment failure and complications lead to the enucleation of irradiated eyes. We conducted this study to explore the causes and long-term prognosis for UM patients who accepted secondary enucleation after plaque radiotherapy. METHODS: This was a retrospective cohort study. Data of patients who underwent secondary enucleation for UM after plaque radiotherapy, from July 2007 to July 2019, at Beijing Tongren Hospital were analyzed. Kaplan-Meier analysis was performed to assess the probability of indications, metastasis, and metastasis-related death. Cox regression analysis was used to analyze associations of the prognostic factors. RESULTS: Eight hundred and eighty patients were clinically diagnosed with uveal melanoma and initially treated by iodine-125 plaque radiotherapy, 132 of whom underwent secondary enucleation and pathological examination in the same hospital. Fifty-two (39.4%) eyes were enucleated simply because of uncontrollable neovascular glaucoma (NVG). Forty-four (33.3%) patients suffered from tumor recurrence. Tumor non-response occurred in 18 (13.6%) cases. Ten (7.6%) eyes received enucleation entirely due to other types of glaucoma. Failure to preserve the eyes for other reasons occurred in eight (6.1%) patients. At a median follow-up of 58.1 [IQR: 40.9-90.5] months, the systemic spread was detected in 45 (34.1%) patients, and 38 of them died. On multivariate analysis, tumor largest basal diameter (HR 1.15 [95% CI: 1.01, 1.31]), tumor non-response (HR 7.22 [95% CI: 2.63, 19.82]), and recurrence (HR 3.29 [95% CI: 1.54, 7.07]) were risk factors for metastasis. Increased age (HR 1.54 [95% CI: 1.07, 2.23]), tumor non-response (HR 7.91 [95% CI: 2.79, 22.48]), and recurrence (HR 3.08 [95% CI: 1.13, 7.23]) were risk factors for metastasis-related death. CONCLUSIONS: NVG was the major reason for secondary enucleation for Chinese UM patients after PRT. Tumor non-response and recurrence were associated with a significantly higher risk of long-term metastasis and metastasis-related death.

Integrated differential DNA methylation and gene expression of formalin-fixed paraffin-embedded uveal melanoma specimens identifies genes associated with early metastasis and poor prognosis.

PURPOSE: Uveal melanoma (UM) is an aggressive malignancy, in which nearly 50% of the patients die from metastatic disease. Aberrant DNA methylation is recognized as an important epigenomic event in carcinogenesis. Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable source of tumor tissue, and recent technology has enabled the use of these samples in genome-wide DNA methylation analyses. Our aim was to investigate differential DNA methylation in relation to histopathological classification and survival data. In addition we sought to identify aberrant DNA methylation of genes that could be associated with metastatic disease and poor survival. METHODS: FFPE samples from UM patients (n = 23) who underwent enucleation of the eye in the period 1976-1989 were included. DNA methylation was assessed using the Illumina Infinium HumanMethylation450 array and coupled to histopathological data, Cancer Registry of Norway- (registered UM metastasis) and Norwegian Cause of Death Registry- (time and cause of death) data. Differential DNA methylation patterns contrasting histological classification, survival data and clustering properties were investigated. Survival groups were defined as "Early metastasis" (metastases and death within 2-5 years after enucleation, n = 8), "Late metastasis" (metastases and death within 9-21 years after enucleation, n = 7) and "No metastasis" (no detected metastases ≥18 years after enucleation, n = 8). A subset of samples were selected based on preliminary multi-dimensional scaling (MDS) plots, histopathological classification, chromosome 3 status, survival status and clustering properties; "Subset Early metastasis" (n = 4) vs "Subset No metastasis" (n = 4). Bioinformatics analyses were conducted in the R statistical software. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in various comparisons were assessed. Gene expression of relevant subgroups was determined by microarray analysis and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: DNA methylation analyses identified 2 clusters that separated the samples according to chromosome 3 status. Cluster 1 consisted of samples (n = 5) with chromosome 3 disomy (D3), while Cluster 2 was comprised of samples (n = 15) with chromosome 3 monosomy (M3). 1212 DMRs and 9386 DMPs were identified in M3 vs D3. No clear clusters were formed based on our predefined survival groups ("Early", "Late", "No") nor histopathological classification (Epithelioid, Mixed, Spindle). We identified significant changes in DNA methylation (beta FC ≥ 0.2, adjusted p < 0.05) between two sample subsets (n = 8). "Subset Early metastasis" (n = 4) vs "Subset No metastasis" (n = 4) identified 348 DMPs and 36 DMRs, and their differential gene expression by microarray showed that 14 DMPs and 2 DMRs corresponded to changes in gene expression (FC ≥ 1.5, p < 0.05). RNF13, ZNF217 and HYAL1 were hypermethylated and downregulated in "Subset Early metastasis" vs "Subset No metastasis" and could be potential tumor suppressors. TMEM200C, RGS10, ADAM12 and PAM were hypomethylated and upregulated in "Subset Early metastasis vs "Subset No metastasis" and could be potential oncogenes and thus markers of early metastasis and poor prognosis in UM. CONCLUSIONS: DNA methylation profiling showed differential clustering of samples according to chromosome 3 status: Cluster 1 (D3) and Cluster 2 (M3). Integrated differential DNA methylation and gene expression of two subsets of samples identified genes associated with early metastasis and poor prognosis. RNF13, ZNF217 and HYAL1 are hypermethylated and candidate tumor suppressors, while TMEM200C, RGS10, ADAM12 and PAM are hypomethylated and candidate oncogenes linked to early metastasis. UM FFPE samples represent a valuable source for methylome studies and enable long-time follow-up.

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma.

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive.

Vitreoretinal Surgery in the Prevention and Treatment of Toxic Tumour Syndrome in Uveal Melanoma: A Systematic Review.

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated.

Gamma knife radiosurgery for uveal melanomas and metastases: a systematic review and meta-analysis.

BACKGROUND: Gamma knife radiosurgery is regarded as the gold-standard stereotactic radiosurgery modality for the treatment of intracranial tumours, and its use has been expanded for the treatment of intraocular malignancies. The aim of this study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife radiosurgery for uveal melanomas and metastases. METHODS: We did a systematic review and meta-analysis to aggregate the clinical outcomes of patients with uveal melanomas or intraocular metastases treated primarily with gamma knife radiosurgery. We searched MEDLINE and Embase for studies published between Sept 1, 1960, and Feb 1, 2020, reporting the use of gamma knife radiosurgery as primary treatment for uveal melanoma or uveal metastases. The search was restricted to clinical studies and relevant grey literature published in English. Studies reporting treatment of benign tumours, extraocular tumours, or other forms of stereotactic radiosurgery were excluded to reduce heterogeneity. No restrictions were placed on participant criteria. Local tumour control and tumour regression were extracted as the primary outcomes and analysed via a random-effects meta-analysis of proportions using the DerSimonian and Laird method with a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42019148165. FINDINGS: Our search returned 454 studies, of which 109 were assessed for full-text eligibility. 52 studies, reporting on 1010 patients with uveal melanoma and 34 intraocular metastases, were eligible for systematic review. 28 studies were included in the meta-analysis. 840 of 898 patients (0·96, 95% CI 0·94-0·97; I2=16%) from 19 studies had local control, and 378 of 478 patients (0·81, 0·70-0·90; I2=83%) from 16 studies experienced tumour regression. INTERPRETATION: Gamma knife radiosurgery is an efficacious primary method of treating uveal melanomas and intraocular metastases, with reliable tumour control rates. Randomised controlled trials should further evaluate the safety and efficacy of gamma knife radiosurgery in this setting. FUNDING: The Rhodes Trust and the Howard Brain Sciences Foundation.

BRAF Wild-type, PTEN Mutant Malignant Uveal Melanoma Arising Within a Mature Ovarian Teratoma: A Case Report and Review of the Literature.

Mature cystic teratomas are common in women of all ages; however, malignant transformation within them is rare and difficult to diagnosis preoperatively. Primary melanoma of the ovary is exceptionally rare and only occurs in relation to a teratoma where it can originate from sporadic somatic mutagenesis within epidermal junctional melanocytes, through malignant transformation of a benign nevus formed within the mature cystic teratoma or from other well differentiated pigment-containing structures such as the uvea. We present a case of primary malignant melanoma arising within a mature cystic teratoma in a young patient, who ultimately developed widespread metastasis necessitating systemic therapy. Our case highlights the role of molecular medicine not only in forming an understanding the origin of the melanoma, but also guiding targeted systemic therapies. Alongside the case we present a review of the literature describing the incidence of molecular aberrations within melanoma as well as the established and emerging techniques and cytotoxic agents for malignant melanoma.

Uveal amelanotic melanoma in a ragdoll cat.

A 13-year-old castrated male ragdoll cat's left eye was evaluated for dyscoria, iridal thickening and color change of 2 years duration, as well as elevated intraocular pressure. The primary lesion seen on ophthalmic examination was a pale pink-white mass observed in the dorsomedial aspect of a diffusely thickened iris. Metastatic workup revealed hepatic and splenic nodules, but cytology was inconclusive. The left eye was enucleated, and histopathology was consistent with uveal amelanotic melanoma.

Mélanome uvéal amélanotique chez un chat ragdoll. L'oeil gauche d'un chat mâle ragdoll castré âgé de 13 ans fut évalué pour dyscorie, épaississement iridien et changement de couleur présent depuis deux ans, de même que pour une pression intra-oculaire élevée. La lésion primaire vue lors de l'examen ophtalmique était une masse blanc-rosée pâle observée à l'aspect dorso-médial d'un iris épaissi de manière diffuse. Une vérification pour métastases révéla des nodules hépatiques et spléniques, mais la cytologie était non-concluante. L'oeil gauche fut énucléé et l'histopathologie était compatible avec un mélanome uvéal amélanotique.(Traduit par Dr Serge Messier).

Endoresection utilizing pars plana vitrectomy for benign and malignant intraocular tumors.

PURPOSE OF REVIEW: Endoresection of intraocular tumors is a complicated procedure utilizing pars plana vitrectomy techniques. Though it has potential downsides and complications, there is potential for this technique in the treatment of malignant and benign intraocular tumors. RECENT FINDINGS: Endoresection has been utilized in some form for the last three decades, but recent advances in vitreoretinal surgery have improved the technique. Endoresection is used most commonly to treat posterior uveal melanoma, but success in treating benign tumors, such as astrocytoma or retinal capillary hemangioblastoma has emboldened surgeons to expand its indications. It appears that removal of a malignant tumor, such as uveal melanoma may spare the eye some damaging effects of radiation retinopathy and radiation optic neuropathy. These benefits may occur even when the tumor is treated concurrently with plaque brachytherapy, proton beam irradiation, or stereotactic radiotherapy. The benefits of the technique are tempered, however, by the inherent difficulties associated with performing the surgery. These include potentially severe intraoperative bleeding, recurrent rhegmatogenous retinal detachment with proliferative vitreoretinopathy, air embolism, and recurrence of the tumor at the edge of the resection. Nonetheless, endoresection has recently been used for retinoblastoma in refractory cases in order to spare the globe. SUMMARY: Endoresection is an advanced vitreoretinal surgical technique that has potential advantages in the treatment of malignant and benign intraocular tumors.

Locoregional ablative treatment of melanoma metastases.

Standard treatment of melanoma has been evolving rapidly over the last decade, with novel treatment approaches improving therapeutic outcome not only in early-stage disease but also in advanced stage metastatic patients. Despite the improvement of systemic therapy outcomes, the current treatment guidelines reflect the fact that locoregional treatment approaches can be beneficial in patients suffering from oligometastatic disease. Minimally invasive ablation techniques have been established as a therapeutic cornerstone in the management of liver tumors, representing a local curative, relatively low-risk procedure. Depending on the size and location of metastatic disease, and on the applied ablation and guidance technique, ablative treatment approaches are effective to treat metastases in solid organs such as the liver or lungs, effectively covering the entire tumor with the ablation zone including a safety margin (A0 ablation in analogy to R0 resection). However, only retrospective data and case reports on locoregional treatment of melanoma metastases are available up to now, and prospective evaluation of this therapeutic approach is warranted to evaluate the beneficial role in the treatment of metastatic melanoma patients.

Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors.

PURPOSE: Uveal melanoma (UM) is an intraocular malignancy commonly arising from choroid which can cause visual loss or metastasis. Ataxia-telangiectasia mutated (ATM) protein is an activator of DNA damage response and its role in uveal melanoma (UM) is still unexplored. Therefore, the study aims to detect the expression and localization of ATM protein and its association with clinicopathological parameters METHODS: Expression of nuclear ATM (nATM) was investigated on 69 formalin fixed paraffin embedded choroidal melanoma samples by immunohistochemistry and validated by western blotting. Results were then correlated with clinical and histopathological parameters. Prognostic significance was determined by the Kaplan-Meier analysis and the multivariate analysis by Cox's hazard proportional method. RESULTS: Loss of nATM was observed in 65% of cases, which was statistically significant with the reduced disease-free survival (p = 0.042). This loss was more frequently found in cases with high-risk histopathological factors like epithelioid cell type, tumor infiltrating lymphocytes and high pigmentation which might help in the progression of melanoma. On multivariate analysis, extraocular spread and loss of nATM were found to be independent prognostic factors (p < 0.05). CONCLUSION: Our data suggest that loss of nATM protein might serve as a poor prognostic marker in the pathogenesis of uveal melanoma which may lead to increased risk of metastasis.

Secondary glaucoma in small versus large uveal melanoma patients treated with stereotactic radiosurgery on linear accelerator.

AIM: Secondary radiation-related side effects like secondary glaucoma (SG) of different modalities of treatment in uveal melanoma patients can appear in certain interval after therapy. This study describes the incidence of SG in patients after stereotactic radiosurgery (SRS). METHOD: The data of 230 patients treated by SRS were reviewed for SG. Group of 83 patients who were observed 5 years after treatment in one center with follow-up regularly at least 4 times per year were analyzed. RESULTS: In group of 83 patients with the median age 59 years, the median tumor volume at baseline was 0.41 cm3. The survival without SG after single dose SRS was 94 % in 1.5 year, 77 % in 2 years, 57 % in 3 years, 43 % in 3.5 years, and 18 % in 4.5 year after irradiation. In 6 patients (7.2 %) secondary enucleation was necessary due to SG. Both predictors (tumor volume and age of patient) at the time of SRS were not statistically significant by Cox proportional-hazards regression. CONCLUSIONS: Complications like SG in 5 year interval after irradiation can lead to secondary enucleation of the eye globe (Fig. 3, Ref. 44).

Four cases of iridociliary tumors in domestic rabbits (Oryctolagus Cuniculus).

Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case series presents four cases of rabbits diagnosed with iridociliary tumors, which have not been previously reported in this species. Major pathological findings include epithelial tumors affecting the anterior uvea with variable pigmentation and basement membrane formation. Follow-up information was only available for two cases, but neither showed evidence of metastasis, suggesting that the prognosis for these tumors in rabbits, as in other species, may be very good.