Unilateral conjunctival Classic Kaposi Sarcoma following a COVID 19 booster.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as "bubbling" in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

Yttrium-90 Episcleral Plaque Brachytherapy for Choroidal Melanoma.

Purpose: To describe the first use of high-dose-rate yttrium-90 disc brachytherapy for choroidal melanoma. Methods: A 72-year-old patient had a cT1-category choroidal melanoma characterized by the presence of orange pigment, increasing subretinal fluid (SRF), and enlarging tumor thickness. It was treated with single-session, light-guided, light-defined yttrium-90-disc brachytherapy. Results: A specialized handheld applicator provided with 4 encircling lights was used to guide plaque placement and localize treatment. Unlike low-dose-rate plaques, high-dose-rate yttrium-90 required only 3 minutes 39 seconds. In this case, treatment did not require episcleral sutures, muscle relocation, outpatient dwell time, or a second surgery. High-dose-rate treatment improved radiation safety by eliminating perioperative exposure to health care personnel, the community, and the family. At the 13-month follow-up, the SRF and tumor thickness were diminished. There was no secondary cataract, radiation retinopathy, maculopathy, or optic neuropathy, and the visual acuity was 20/20. Conclusions: Yttrium-90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of a choroidal melanoma.

Choroidal metastasis: Radiation and bevacizumab at presentation.

Purpose: To reveal early intervention outcomes for patients describing with choroidal metastasis. Methods: A retrospective interventional case series on 27 eyes of 22 patients treated for choroidal metastasis with external beam radiation therapy (EBRT) With and without intravitreal injections. The prescribed radiation dose was a mean and median 30 Gy (range of 30-40 Gy in 180-200 cGy daily fractions). Outcome measures included change in tumor thickness, subretinal fluid, visual acuity, radiation oculopathy, and survival. Results: Decreased vision was the most common presenting symptom (n = 20/27, 74%). Pre-treatment vision for subfoveal lesions was a mean 20/400, median 20/200, and range 20/40 to hand motions (HM). Pre-treatment vision for extrafoveal tumors were a mean 20/40, median 20/25, range 20/20 to counting fingers (CF) which improved to a mean 20/32, median 20/20, range 20/12.5 to 20/200. Local control, with ultrasonographic height regression (44.5%; mean: 2.7-1.5 mm), was observed in all eyes at mean follow-up of 16 months (range: 1-72 months). Intravitreal anti-vascular endothelial growth factor (anti-VEGF) was given in nine cases (n = 9/27, 33%) to slow the growth of the metastasis and suppress their exudative detachments and to treat radiation maculopathy in 10 cases (n = 10/27, 37%). Late radiation complications included keratoconjunctivitis sicca in four cases (n = 4/27, 15%), exposure keratopathy in two cases (n = 2/27, 7%), and radiation retinopathy in 10 cases (n = 10/27, 37%). Of the 23 phakic eyes, four (n = 4, 17%) developed cataract. Conclusion: Radiation therapy with or without intravitreal anti-VEGF injections was a safe and effective treatment for choroidal metastasis. It was associated with local tumor control, reduction of secondary retinal detachments, and vision preservation.

First clinical implementation of Yttrium-90 Disc Brachytherapy after FDA clearance.

PURPOSE: Herein, we study if high-dose-rate (HDR) yttrium-90 (90Y) brachytherapy could be utilized by medical physicists, radiation oncologists, and ophthalmic surgeons. METHODS AND MATERIALS: Yttrium-90 (90Y) beta-emitting brachytherapy sources received United States Food and Drug Administration clearance for episcleral treatment of ocular tumors and benign growths. Dose calibration traceable to the National Institute of Standards and Technology as well as treatment planning and target delineation methods were established. Single-use systems included a 90Y-disc affixed within specialized, multifunction, handheld applicator. Low-dose-rate to high-dose-rate prescription conversions and depth-dose determinations were performed. Radiation safety was evaluated based on live exposure rates during assembly and surgeries. Clinical data for radiation safety, treatment tolerability, and local control was collected. RESULTS: Practice parameters for the medical physicist, radiation oncologist, and ophthalmic surgeon were defined. Device sterilizations, calibrations, assemblies, surgical methods, and disposals were reproducible and effective. Treated tumors included iris melanoma, iridociliary melanoma, choroidal melanoma, and a locally invasive squamous carcinoma. Mean calculated 90Y disc activity was 14.33 mCi (range 8.8-16.6), prescription dose 27.8 Gy (range 22-30), delivered to depth of 2.3 mm (range 1.6-2.6), at treatment durations of 420 s (7.0 min, range 219 s-773 s). Both insertion and removal were performed during one surgical session. After surgery, each disc-applicator- system was contained for decay in storage. Treatments were well-tolerated. CONCLUSIONS: HDR 90Y episcleral brachytherapy devices were created, implementation methods developed, and treatments performed on 6 patients. Treatments were single-surgery, rapid, and well-tolerated with short-term follow up.

Tarsoconjunctival flap for scleromalacia related to treatments for conjunctival melanoma.

Purpose: To describe the use of a tarsoconjunctival pedicle flap for the repair of scleral melt secondary to treatment of conjunctival melanoma. Observation: A 67-year-old woman developed progressive scleromalacia after multiple treatments for an American Joint Committee on Cancer cT2d category conjunctival melanoma. Prior to referral, she underwent synchronous topical chemotherapy (interferon, 5-fluorouracil, mitomycin). Then, incomplete tumor regression led to excision with adjuvant cryotherapy. Lastly, systemic metastasis treated with systemic immunotherapy provided durable remission. However, her multiple treatments (e.g., topical chemotherapy, resection, cryotherapy) were associated with progressive nasal bulbar scleromalacia treated by conjunctival advancement and amniotic membrane grafts. Sclera reinforcement was achieved after a tarsoconjunctival flap was affixed to the eye to cover, and thus vascularize the scleral defect. The tarsoconjunctival flap provided 5 years of tectonic support. Conclusions and Importance: Tarsoconjunctival pedicle flaps can provide scleral integrity for a patient with progressive scleral melting.

Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned.

Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.

Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.

OBJECTIVE: To investigate vascular and morphologic optic disc changes after slotted plaque radiation therapy for choroidal melanoma involving the optic disc. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Thirty-nine patients with choroidal melanoma involving the optic nerve. METHODS: Each melanoma was treated with palladium-103 slotted plaque brachytherapy (incorporating and/or surrounding the optic nerve sheath) between 2005 and 2019. Imaging of the optic nerve before and after radiation allowed for documentation and evaluation of optic nerve pallor and cup-to-disc ratio (CDR) changes. Optical coherence tomography (OCT) CDR measurements and intraocular pressure (IOP) were recorded pretreatment and at follow-up. Of these patients, 22 also had OCT angiography (OCT-A) images with sufficient quality for evaluation of blood vessel density and length. Differences in cup-to-disc measurements were correlated with changes in OCT-A-measured vessel density and length. RESULTS: Following slotted plaque radiation therapy, there was no significant increase in IOP or optic nerve pallor. OCT and colour photography revealed significant increases (both p < 0.001) in CDR from pretreatment to the last follow-up. Increased CDRs on OCT were significantly correlated to OCT-A-measured change in vessel length (p = 0.027). Similarly, increased CDR ratios on fundus photography were significantly correlated with OCT-A-measured change in vessel density (p = 0.043) and length (p = 0.019). CONCLUSION: Fundus photography and OCT measurements revealed increased optic disc cupping following slotted plaque radiation therapy. Cupping was associated with OCT-A evidence of synchronous progressive peripapillary vascular occlusion and attenuation. Therefore, slotted plaque radiation-induced peripapillary and papillary ischemia was associated with increased CDR ratios and optic disc cupping.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Specific location of ocular adnexal lymphoma and mortality: an international multicentre retrospective study.

AIMS: To examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes. METHODS: Clinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality. RESULTS: OAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location. CONCLUSION: Disease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.

Laser treatment for choroidal melanoma: Current concepts.

Laser treatment has offered a relatively nonsurgical alternative for eye, life, and vision-sparing treatment of malignant melanoma of the choroid. Historically, the most commonly used forms of lasers were xenon-arc, argon laser, krypton laser, and the more recent transpupillary thermotherapy (TTT) and photodynamic therapy (PDT). Melanomas selected for laser treatment tend to be smaller and visibly accessible, which means these tumors are usually located in the posterior choroid. Laser treatments have been associated with both local tumor destruction and side effects. Unlike radiation therapy, laser treatment has been commonly associated with retinal traction, hemorrhage, chorioretinal neovascularization, and extra scleral tumor extension, as well as higher rates of local treatment failure. In addition, however, laser-treatment has been successfully used to treat tumor-related retinal detachments, radiation retinopathy, and neovascular glaucoma. We review the world's experience of ophthalmic laser treatment for choroidal melanoma, offer safety and efficacy guidelines, as well as a comparison of laser treatment to radiation therapy outcomes.

Occult anterior uveal melanomas presenting as extrascleral extension.

OBJECTIVE: To describe the management of patients with occult anterior uveal melanomas presenting with extrascleral extension. METHODS AND ANALYSIS: Retrospective case series including five patients with small pigmented nodular mass on the episclera. Each lesion was documented by slit-lamp photography and measured with high-frequency ultrasound imaging (ultrasound biomicroscopy). Diagnosis of uveal melanoma was confirmed by biopsy with lamellar sclerectomy. Immediate scleral patch graft repair was performed. Later, each tumour was treated with palladium-103 ophthalmic plaque brachytherapy. The mean plaque diameter was 12 mm (median, 12; range, 10-14). A mean apex prescription dose of 87 Gy (median, 84.5; range, 82.3-99.2) to a tumour depth of 2 mm from the inner sclera delivered over 7 continuous days. The main outcome measures were best-corrected visual acuity, changes in tumour and scleral characteristics and complications. RESULTS: During each surgery, residual tumour was visualised within an emissary passageway at the deep plane of scleral resection. At a mean of 80 months (median, 57; range, 24-159) follow-up, no patients experienced graft infection, scleromalacia or rejection. Biopsy was required to establish the diagnosis, transillumination failed, and therefore ultrasound measurements were used to determine the plaque size required to treat the relatively occult intraocular component. Despite these challenges, there were no cases of local tumour recurrence, secondary enucleation or metastatic disease. Attributed to cataract surgery, visual acuities improved in three patients and two were stable. CONCLUSION: Extrascleral uveal melanoma extension can occur with undetectable, occult intraocular tumours. In these cases, plaque radiation effectively induced local tumour control, preserved vision and prevented metastasis.

Palladium-103 plaque brachytherapy for retinoblastoma: Long term follow up.

Purpose: Radiation has been used in the treatment of retinoblastoma. Herein, we present the novel use of palladium-103 plaque brachytherapy as primary treatment. Observation: An 8-year-old asymptomatic girl presented was found to have a solitary peripheral retinoblastoma in her right eye. She was treated with primary palladium-103 plaque brachytherapy (47.4 Gray over 5 consecutive days). A secondary, vitreous hemorrhage noted 46 months after irradiation was successfully controlled by laser tumor-demarcation. With 19-years follow up, there has been no clinical scleropathy, or local tumor recurrence. The eye yields 20/20 vision and there has been no systemic metastasis. Conclusion and importance: Palladium-103 plaque brachytherapy successfully controlled retinoblastoma, while preserving the globe, vision, and life.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

OCT-A evaluation of radiation vasculopathy following slotted plaque brachytherapy.

PURPOSE: To determine a reliable diagnostic method to reveal and monitor subclinical progression of neural and perineural radiation vasculopathy. METHODS: A retrospective cross-sectional study, where optical coherence tomography angiography (OCT-A) imaging data was collected and analyzed from 22 consecutive patients that had been treated with circumneural slotted plaque brachytherapy for peripapillary, juxtapapillary, or circumpapillary choroidal melanomas. Pre-operative dosimetry of palladium-103 radiation dose to the optic nerve and fovea were collected. Quantified differences in OCT-A-measured vessel density and length in treated verses untreated contralateral control eyes were collected. Vessel density and length were correlated to radiation dose, plaque slot depth, visual acuity outcomes, and circumpapillary retinal nerve fiber layer thickness. RESULTS: Patients had post-irradiation follow-up of median 39 months, interquartile range 62 months). The mean optic disc radiation dose was 89.9 Gy ± 39.2 (86.5, 30.8-189.0). In comparison to controls, OCT-A imaging revealed significant differences in radial peripapillary capillary vessel density (18 µm2 in case eyes, 34 µm2 in control eyes; p < 0.001) and length (10 µm in case eyes, 14 µm in control eyes; p < 0.001). Change in vessel density did not show a significant correlation to radiation dose, slot depth, or visual acuity. However, change in vessel length was significantly correlated to radiation dose (p = 0.049) and change in visual acuity (p < 0.001). CONCLUSIONS: OCT-A imaging revealed that radial peripapillary capillary vessel density and length were significantly reduced after circumneural irradiation for choroidal melanoma. Therefore, OCT-A imaging can be used to monitor progression of papillary vasculopathy associated with radiation optic neuropathy.

Patients presenting with metastases: stage IV uveal melanoma, an international study.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS: Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS: Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.