The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Pediatric ocular melanoma: a collaborative multicenter study and meta-analysis.

PURPOSE: To investigate clinical manifestations and prognoses in pediatric patients (≤12 years old) with ocular melanoma. METHODS: This was a retrospective, multicenter cohort study with individual participant data (IPD) meta-analysis pooling available published cases, and unpublished cases from an international collaboration of seven ocular oncology centers. RESULTS: There were 133 eyes of 133 pediatric patients with choroidal or ciliary body (n = 66 [50%]), iris (n = 33 [25%]), conjunctival (n = 26 [19%]), and eyelid (n = 8 [6%]) melanoma. Overall, the mean patient age at presentation was 7 years (median, 8; range, 1-12 years), with 63 males (49%). The mean age by tumor site was 6.50 ± 3.90, 7.44 ± 3.57, 9.12 ± 2.61, and 5.63 ± 2.38 years, for choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively (P = 0.001). Association with ocular melanocytosis was seen in 15%, 11%, 4%, and 0%, respectively (P = 0.01). Frequency of ocular melanoma family history did not vary by tumor site (7%, 17%, 9% and 12%, resp. [P = 0.26]). After mean follow-up of 74, 85, 50, and 105 months (P = 0.65), metastasis was seen in 12%, 9%, 19%, and 13% of choroid/ciliary body, iris, conjunctiva, and eyelid melanoma, respectively. Death was reported in 5%, 3%, 8%, and 0%, respectively, with survival analysis indicating higher mortality in choroidal/ciliary body and conjunctival melanoma patients. CONCLUSIONS: Ocular melanoma in the pediatric population is rare, with unique clinical features and outcomes. Iris melanoma accounts for about one-third of pediatric uveal melanoma cases.

Lapatinib dysregulates HER2 signaling and impairs the viability of human uveal melanoma cells.

Uveal melanoma (UM) is the principal type of intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease with very poor survival. There are few drugs available to treat the primary or metastatic UM. This study was undertaken to evaluate the anti-cancer effect of lapatinib and corroborate the potential of HER2 inhibition in the treatment of UM. The anti-UM activity of lapatinib was assessed using cell viability, cell death and cell cycle analysis, and its anti-metastatic actions were evaluated using would healing, invasion and colony formation assays. Immunoblotting was used to substantiate the actions of lapatinib on apoptotic and HER2 signaling. The anti-UM activity of lapatinib was further evaluated in a UM xenograft mouse model. Lapatinib decreased the viability of four UM cell lines (IC50: 3.67-6.53 µM). The antiproliferative activity of lapatinib was corroborated in three primary cell lines isolated from UM patient tumors. In UM cell lines, lapatinib promoted apoptosis and cell cycle arrest, and strongly inhibited cell migration, invasion and reproductive cell growth. Lapatinib dysregulated HER2-AKT/ERK/PI3K signalling leading to the altered expression of apoptotic factors and cell cycle mediators in UM cell lines. Importantly, lapatinib suppressed tumourigenesis in mice carrying UM cell xenografts. Together the present findings are consistent with the assertion that HER2 is a viable therapeutic target in UM. Lapatinib is active in primary and metastatic UM as a clinically approved HER2 inhibitor. The activity of lapatinib in UM patients could be evaluated in future clinical trials.

The application of natural compounds in uveal melanoma drug discovery.

OBJECTIVES: Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM. KEY FINDINGS: Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth. SUMMARY: The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM.

Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) as a Screening Marker for Familial Adenomatous Polyposis (FAP): Systematic Literature Review and Screening Recommendations.

Purpose: Familial adenomatous polyposis (FAP) has an almost 100% colorectal cancer risk warranting early detection in gene carriers. This study presents congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a highly specific phenotypical marker for FAP that can be used in screening at-risk individuals. Screening recommendations including morphological subclassification were formulated with supporting literature. Methods: A systematic literature review with a comprehensive search strategy was conducted using online databases. Manual searches of bibliographies and reference lists were also performed. Studies meeting inclusion criteria were graded with respect to their hierarchy of evidence and strength of recommendations according to the National Health and Medical Research Council (NHMRC) guidelines of Australia. Results: Almost 4500 participants were analysed across 28 included studies. The mean specificity of CHRPE as a phenotypical screening marker of FAP was 89% (standard deviation (SD); 14) with a mean sensitivity of 79% (SD; 8). The mean prevalence of CHRPE amongst FAP participants; at-risk participants were found to be 76% (SD; 24) and 37% (SD; 21) respectively. Bilateralism and multiple lesion number ≥3 are features highly specific for FAP. Conclusion: CHRPE was found to be a non-invasive, rapid, early phenotypical screening marker of FAP. Clinical recognition further allows increased gene analysis efficiency. The absence of CHRPE alone cannot exclude FAP. Our screening recommendations provide guidance to clinicians on evidence based CHRPE assessment. We would advocate inclusion of ocular examinations as part of a three-pronged approach, along with endoscopy and genetic testing, for efficient, timely FAP assessment in at-risk individuals.

BAP1 GERMLINE MUTATION WITH IRIDOCILIOCHOROIDAL MELANOMA AND MALIGNANT PERITONEAL MESOTHELIOMA.

PURPOSE: BAP1 germline mutation can promote risk of uveal melanoma and mesothelioma. In this study, we report a patient with BAP1 germline mutation and uveal melanoma who developed a rare form of mesothelioma in the peritoneum. METHOD: Case report. RESULTS: A 55-year-old white man noted blurred vision in the left eye. Examination revealed superotemporal episcleral sentinel vessels and a dark brown iris mass suspicious for melanoma, with angle invasion and involvement of the ciliochoroidal region. The tumor measured 14 mm in diameter and 10.3 mm in thickness. A diagnosis of iridociliochoroidal melanoma was rendered and plaque radiotherapy applied. Genetic testing revealed BAP1 germline mutation. At 3.5-year follow-up, tumor control was achieved, but radiation-related complications led to enucleation. At 5.5-year follow-up, incidental findings by laparoscopy revealed multiple peritoneal tumors, histopathologically proven to be malignant peritoneal mesothelioma. Lung evaluation was normal, and there was no melanoma-related or mesothelioma-related metastasis. Likewise, magnetic resonance imaging of the abdomen showed no evidence of hepatic metastasis. CONCLUSION: BAP1 tumor predisposition syndrome can promote risk of uveal melanoma and malignant peritoneal mesothelioma. Cancer screening for these malignancies is warranted.

Biopsy for molecular risk stratification in uveal melanoma: Yields and molecular characteristics in 119 patients.

BACKGROUND: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples. METHODS: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and post-enucleation (n = 62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry. RESULTS: Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p = 0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p = 0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (Tb  = 0.742, p = 0.005). However, epithelioid morphology was not associated with either monosomy 3 (p = 0.07) or BAP1 aberrancy (p = 0.24) for in vivo biopsies. CONCLUSIONS: All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test.

ASSOCIATION OF VITREORETINAL LYMPHOMA WITH SYSTEMIC LYMPHOMA.

PURPOSE: To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL). METHODS: Single-center retrospective review of medical records. RESULTS: Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate. CONCLUSION: We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.

UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES.

BACKGROUND/PURPOSE: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma. METHODS: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified. RESULTS: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment. CONCLUSION: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.

Ultra-low-dose (boom-boom) radiotherapy for choroidal lymphoma in three consecutive cases.

PURPOSE: To describe the outcome of ultra-low-dose (boom-boom) radiotherapy for choroidal lymphoma. METHODS: Retrospective series of three consecutive patients with biopsy-proven choroidal lymphoma treated with ultra-low-dose radiotherapy. RESULTS: The three patients (two male, one female) of mean age 70 years (range, 64-74 years) demonstrated presenting visual acuity in the affected eye between 20/40 and 20/50. The choroidal lymphoma was unilateral in all cases and presented with multifocal yellow patchy choroidal infiltration, located in all four quadrants and measuring mean 2.9 mm (range, 1.9-4.0 mm) in thickness by ultrasonography. Anterior epibulbar extension of 5 mm diameter was noted in one case. By enhanced depth imaging optical coherence tomography, the choroidal infiltration demonstrated classic undulating appearance (n = 3), with subretinal fluid (n = 2) and intraretinal edema (n = 1). There was no systemic lymphoma in any case. Biopsy was performed in all three cases and was diagnostic (n = 1) or suggestive (n = 2) of B-cell lymphoma. Management involved ultra-low-dose radiotherapy (4 Gy delivered in two fractions, "boom-boom"). On follow-up (mean = 14 months, range = 6-24 months), complete tumor regression on ophthalmoscopy was documented in all three cases, with enhanced depth imaging optical coherence tomography and ultrasonography demonstrating evidence of lymphoma resolution and visual acuity improvement to 20/25-20/40. There were no radiation complications. CONCLUSION: In this small case series, ultra-low-dose (boom-boom) radiotherapy was effective for choroidal lymphoma with favorable response and minimal side effects.

Intraocular schwannoma with extrascleral extension.

PURPOSE: To report a rare case of intraocular schwannoma with extrascleral extension in a patient with juvenile idiopathic arthritis and to review the literature for this topic. METHODS: Case report. RESULTS: A 19-year-old male with a history of juvenile idiopathic arthritis was referred for diagnosis and management of an episcleral mass, initially thought to be focal nodular scleritis. The ocular surface of the right eye revealed an elevated amelanotic episcleral nodule inferonasally, with thin strands of overlying sclera, feeding episcleral vessels, and measuring 11 mm × 11 mm in diameter and 5 mm in thickness. Ophthalmoscopic examination revealed a minimally pigmented ciliochoroidal tumor measuring 13 mm in diameter and 11.4 mm in total thickness and without associated subretinal fluid, orange pigment, or drusen. Ultrasound biomicroscopy and anterior-segment optical coherence tomography confirmed a solid mass with scleral disruption and extraocular extension. Shave biopsy revealed palisading spindle cells and interspersed eosinophilic fibrillary cytoplasmic processes, forming Verocay bodies. The specimen stained positive for S-100 and negative for Melan-A, consistent with benign schwannoma. Observation was recommended. CONCLUSION: Intraocular schwannoma is a rare, benign uveal tumor that can demonstrate extrascleral extension, mimicking inflammatory and malignant neoplastic processes. Clinical diagnosis is challenging, and tissue biopsy is required for definite diagnosis.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

PURPOSE: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). METHODS: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. RESULTS: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. CONCLUSION: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

Incidence and predictors of ophthalmic artery occlusion in intra-arterial chemotherapy for retinoblastoma.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children. OBJECTIVE: To determine the incidence of ophthalmic artery (OA) occlusion in patients treated with selective ophthalmic artery catheterization (OAC) for chemotherapy infusion for retinoblastoma. Also, to evaluate technical, anatomical, tumorous, and patient-related factors that are predictors of OA occlusion. METHODS: A retrospective chart review was performed for patients diagnosed with intraocular retinoblastoma and managed with intra-arterial chemotherapy (IAC). RESULTS: The total study cohort included 208 retinoblastoma tumors of 208 eyes in 197 consecutive patients who underwent 688 attempted IAC infusions overall with a total of 624 successful OAC infusions. The total incidence of ophthalmic artery thrombosis was 11.1% (23/208). The numbers of successful OAC procedures before diagnosing OA occlusion were one OAC in six cases (27.3%), two in seven cases (31.8%), three in four cases (18.2%), four in one case (4.5%), five in two cases (9.1%), and six in one case (4.5%). CONCLUSIONS: Local factors relating to the chemotherapy and selective microcatheterization of the OA are essential factors in the development of OA thrombosis, as seen by the association of OA thrombosis with the frequency of IAC.

The Use of Alternative Routes for the Delivery of Intra-Arterial Chemotherapy for Retinoblastoma.

BACKGROUND: The introduction of intra-arterial chemotherapy (IAC) for treatment of retinoblastoma considerably changed the paradigm by which this disease is managed, with event-free survival rates being above 70%. OBJECTIVE: To analyze efficacy of IAC treatment using alternative approaches to ophthalmic artery catheterization (OAC), such as external carotid artery approach or balloon-assisted drug delivery. METHODS: This is a retrospective chart review for subjects receiving IAC for retinoblastoma. The primary approach was OAC. In cases in which selective OAC was not feasible, alternative routes including catheterization of the external carotid artery or use of a balloon-assisted drug infusion were used. RESULTS: This study included 197 consecutive patients with 207 retinoblastomas who underwent 658 IAC procedures overall. The mean age at diagnosis was 24 mo, and 54.5% of the study population was male. Success rate with IAC was 97% (639). Alternative approaches to OAC were, in total, 42 cases (6.4%)-external carotid artery catheterization and use of ICA balloon were performed in 22 (3.3%) and 20 (3%) cases, respectively. A mean of 3.1 IAC cycles were performed for each patient. In total, there were 23 technical failures of the primary OAC technique (3.4%). Periprocedural adverse events occurred in 4 procedures (0.6%). Use of an alternative technique for chemotherapy delivery other than selective OAC in at least one IAC cycle was not a predictor of enucleation. CONCLUSION: IAC is a safe and effective treatment option for retinoblastoma. Chemotherapy delivery using alternative techniques is as effective as selective OAC.

Wide-Field (15â€Š× 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

PURPOSE: The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA). DESIGN: Single-centre retrospective review. METHODS: Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA). RESULTS: At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P < 0.001, and 46% vs 48%, P = 0.001, respectively), peripapillary region (66% vs 77%, P < 0.001, and 66% vs 72%, P = 0.001, respectively), and papillomacular bundle (60% vs 68%, P < 0.001, and 61% vs 64%, P = 0.03, respectively). Comparison (no CERR vs controls) revealed nonsignificant foveal avascular zone enlargement (1.20 vs 0.23 mm, P = 0.16) and reduction of CVD in the superficial plexus (46% vs 47%, P = 0.008), and not the deep plexus (48% vs 48%, P = 0.42) of the total wide-field. Comparison of irradiated eyes (CERR vs no CERR) showed reduction of CVD in the superficial and deep plexus of the total wide-field (43% vs 46%, P < 0.006, and 46% vs 48% P < 0.02, respectively), peripapillary region (66% vs 74%, P < 0.001, and 66% vs 72% P < 0.01, respectively), and superficial plexus in the papillomacular bundle (60% vs 65%, P = 0.03). CONCLUSIONS: Following plaque radiotherapy for choroidal melanoma, wide-field swept-source optical coherence tomography angiography demonstrates retinal microvascular abnormalities in the CVD in eyes with and without CERR. These findings are important in early detection and monitoring of radiation retinopathy.

Ophthalmic artery catheterization for retinoblastoma treatment: does reflux affect tumor response?

BACKGROUND: Intra-arterial chemotherapy (IAC) for retinoblastoma (Rb) has been established as a primary treatment for the disease. To determine whether the presence of reflux into the ICA is associated with tumor response or with any other adverse events in pediatric retinoblastoma patients. METHODS: A retrospective chart review was performed for patients diagnosed with Rb and managed with ophthalmic artery catheterization (OAC). RESULTS: The total study cohort included 205 Rb tumors of 205 eyes in 194 consecutive patients who underwent 624 successful intra-arterial chemotherapy infusions using OAC. Of the 205 eyes, 65 eyes (32.7%) underwent 157 OAC procedures constituted group A (no reflux), 64 eyes (31.2%) underwent 236 OAC procedures constituted group B (variable pattern), and 74 eyes (36.1%) underwent 231 OAC procedures constituted group C (reflux). There was no significant difference in baseline characteristics between the three cohorts. Also, there was no significant difference in tumor characteristics between the three groups, except for genetic status. There was no significant difference between the three groups in terms of tumor response at completion of the treatment regimen. Complete tumor response was achieved at 70.2% in Group A, at 83.3% in Group B, and at 78.5% in group C (P=0.39). Similarly, eye enucleation occurred at 38.5% in group A, 31.8% in group B, and 31.5% in group C. None of the patients in both groups had any neurological adverse events or new onset of seizures. CONCLUSIONS: The presence of reflux, which may complicate the procedure and prolong it, was not associated with poor outcomes in our analysis.

Clinical Features Predictive of Survival in Patients With Vitreoretinal Lymphoma: Analysis of 70 Patients at a Single Ocular Oncology Center.

PURPOSE: The aim of this study was to identify clinical factors predictive of time to central nervous system (CNS) lymphoma or death in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective cohort study. METHODS: Patients with VRL (n = 95 patients) from Januray 1, 1984 to July 30, 2018 were identified at a single ocular oncology center and records were retrospectively reviewed. Outcomes included Kaplan-Meier estimated time to CNS lymphoma and death. RESULTS: There were 95 patients with VRL diagnosed at mean age 67 years, of which 70 patients had follow-up with the ocular oncology service. Mean time to CNS lymphoma in patients with isolated VRL was 56 months and did not differ by age, sex, bilateral ocular involvement, retinal infiltration, subretinal pigment epithelial (sub-RPE) infiltration, or treatment with prophylactic systemic chemotherapy (P > 0.05). Mean time to death was 66 months and did not differ when comparing those with CNS lymphoma diagnosed before VRL versus after VRL versus no CNS lymphoma at any time (67 vs 60 vs 64 months, P > 0.05). Presence of sub-RPE infiltration was associated with shorter mean time to death (46 vs 76 months, P = 0.04, odds ratio 1.9). Older patient age was associated with increased risk of death (odds ratio 1.0, P = 0.02). The mean time to death did not differ by sex, bilateral ocular involvement, retinal infiltration, timing of CNS or systemic lymphoma, or treatment with prophylactic systemic chemotherapy (P > 0.05). CONCLUSIONS: Patients with VRL presenting with sub-RPE infiltration could have shorter mean survival time. Further studies are required to confirm these findings and determine whether sub-RPE infiltration is associated with more aggressive CNS lymphoma.

Lipid-Producing Ciliochoroidal Melanoma with Expression of HMG-CoA Reductase.

Uveal melanoma (UM) is the commonest primary intraocular malignancy in adults. There is limited published data on lipid production in UM. Here, we describe the clinical, histological, immunohistochemical, and molecular findings in a ciliochoroidal melanoma with lipid production and expression of the enzyme HMG-CoA reductase. This case highlights an unusual UM tumour phenotype with a high-risk molecular metastatic profile and discusses tumour lipogenesis and activation of the mevalonate pathway as a potential therapeutic target in managing lipidised ciliochoroidal UM.

Visual acuity outcomes in Coats disease by classification stage in 160 patients.

PURPOSE: To assess visual outcomes of Coats disease by classification stage. METHODS: A retrospective review was conducted on consecutive patients with Coats disease, classified according to Shields classification and with available Snellen visual acuity before and after treatment. RESULTS: There were 160 eyes with Coats disease (stage 1 (n=2) vs stage 2A (n=17) vs stage 2B (n=22) vs stage 3A1 (n=26) vs stage 3A2 (n=40) vs stage 3B (n=42) vs stage 4 (n=9) vs stage 5 (n=2)). By comparison, more advanced stage showed greater frequency of poor presenting visual acuity (<20/200) (0% vs 0% vs 50% vs 35% vs 38% vs 83% vs 100% vs 100%, p<0.001) and higher mean intraocular pressure (17 vs 15 vs 15 vs 15 vs 15 vs 15 vs 37 vs 26, p<0.001). More advanced stage was less likely managed with laser photocoagulation (100% vs 87% vs 48% vs 62% vs 74% vs 35% vs 0% vs 0%, p<0.001) and more likely with cryotherapy (0% vs 47% vs 81% vs 81% vs 82% vs 88% vs 50% vs 100%, p=0.001). More advanced stage was associated with lower frequency of visual acuity ≥20/40 (100% vs 71% vs 5% vs 42% vs 23% vs 5% vs 0% vs 0%, p<0.001) and greater frequency of visual acuity <20/200 (0% vs 12% vs 36% vs31 % vs 45% vs 88% vs 0% vs 100%, p<0.001). CONCLUSION: Visual acuity in eyes with Coats disease parallels staging with more advanced stage demonstrating poorer visual acuity at presentation and final visit.