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.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

Interstitial Brachytherapy for Orbital Sebaceous Carcinoma.

Sebaceous carcinoma is characterized by its aggressive local tumor behavior and ability to metastasize. Small periocular sebaceous carcinoma are typically treated by excision with cryotherapy. Larger tumors often require adjuvant external beam radiotherapy (EBRT) and/or exenteration surgery. When used alone, EBRT techniques typically exceed the tolerance of critical normal ocular structures. The interstitial orbital brachytherapy-boost technique permits dose escalation to the tumor bed, while minimizing radiation dose to critical normal ocular structures. Here, we present a case of orbital sebaceous carcinoma treated with excision, cryotherapy, and super-thick amniotic membrane fornix reconstruction. Then, after 3 weeks of healing, adjuvant-combined electron interstitial high-dose rate brachytherapy-boost was added to electron-beam radiotherapy to optimize the orbital radiation dose distribution, increase dose to inferonasal orbit, and allow relative sparing of orbital tissues. At 1-year follow-up, there was no evidence of orbital tumor, no significant eye lash loss, normal ocular motility, no radiation retinopathy, optic neuropathy and a visual acuity of 20/20.

The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19.

OBJECTIVE: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I125) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS: I125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS: Local treatment failure and enucleation were relatively infrequent events after I125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part I: Metastasis-Associated Mortality.

PURPOSE: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. MAIN OUTCOME MEASURES: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. RESULTS: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. CONCLUSIONS: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Cancers of the eye.

Ocular cancers are unique among the diseases of the eye, threatening both vision and life. In most cases, the diagnosis can be made utilizing a careful clinical history and specialized ocular examination. Eye cancer diagnosis relies heavily on imaging techniques such as high-frequency ultrasound, fluorescein angiography, anterior and posterior segment optical coherence tomography, computed tomography (CT), and magnetic resonance imaging (MRI). Once the diagnosis is established, treatment decisions depend on the tumor's location, size, local extension, patterns of growth, and secondary complications. Treatment options include observation, local resection, chemotherapy (topical, intravenous, intra-arterial, or intravitreal), and radiation (ophthalmic plaque or external beam). Enucleation or exenteration is only employed if these eye- and vision-sparing treatments are not possible. The core of this comprehensive review is a consecutive series of the most common ocular tumor of each structure of the eye, anterior to posterior, including basal cell carcinoma of the eyelid, squamous conjunctival neoplasia, choroidal melanoma, retinoblastoma, ocular adnexal lymphoma, and metastatic orbital tumors.

Regression Patterns of Iris Melanoma after Palladium-103 (103Pd) Plaque Brachytherapy.

PURPOSE: To evaluate the patterns of regression of iris melanoma after treatment with palladium-103 (103Pd) plaque brachytherapy. DESIGN: Retrospective, nonrandomized, interventional case series. PARTICIPANTS: Fifty patients with primary malignant melanoma of the iris. METHODS: Palladium-103 plaque brachytherapy. MAIN OUTCOME MEASURES: Changes in tumor size, pigmentation, and vascularity; incidence of iris neovascularization; and radiation-related complications. RESULTS: The mean age in the case series was 61.2±14.9 years. The mean tumor thickness was 1.4±0.6 mm. According to the American Joint Committee on Cancer, eighth edition, staging criteria for iris melanoma, 21 tumors (42%) were T1a, 5 tumors (10%) were T1b, and 24 tumors (48%) were T2a. The tumor was melanotic in 37 cases (74%) and amelanotic in 13 cases (26%); of these, 13 tumors (26%) showed variable pigmentation. After brachytherapy, mean tumor thickness decreased to 0.9±0.2 mm. Pigmentation increased in 32 tumors (64%), decreased in 11 tumors (22%), and was unchanged in 6 tumors (12%). For intrinsic vascularity (n = 19), 12 tumors (63%) showed decrease and 7 tumors (37%) showed complete resolution. Appearance of ectropion uveae showed diminution in 15 tumors (43%); newly present corectopia was observed in 6 patients (12%). On high-frequency ultrasound imaging, of the 42 tumors (84%) with low to moderate internal reflectivity, 30 tumors (60%) showed an increase in internal reflectivity on regression. Iris stromal atrophy was noted in 26 patients (52%), progression or new-onset cataract was noted in 22 patients (44%), neovascular glaucoma was noted in 1 patient (2%), and there were no cases of corneal opacity. There was no clinical evidence (0%) of radiation-induced retinopathy, maculopathy, or optic neuropathy. Mean follow-up in this series was 5.2 years (range, 0.5-17 years). CONCLUSIONS: The most common findings related to iris melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, increased tumor pigmentation, and decreased tumor thickness with synchronous increase in internal ultrasonographic reflectivity. No irreversible sight-limiting complications were noted.

Extraocular muscle repositioning and diplopia: associated with ophthalmic plaque radiation therapy for choroidal melanoma.

OBJECTIVE: To evaluate extraocular muscle surgery associated with plaque brachytherapy for choroidal melanoma. DESIGN: Single-center retrospective cohort study. PARTICIPANTS: Three hundred twenty-nine eyes of 329 consecutive patients with clinically diagnosed choroidal melanoma. INTERVENTION: Palladium 103 plaque brachytherapy with or without extraocular muscle surgery. MAIN OUTCOME MEASURES: Type of muscle surgery required for each tumor location, timing, incidence, and duration of diplopia, as well as treatment. RESULTS: Two hundred fifty-four patients (n = 254/329; 77.2%) required muscle surgery. One hundred seven patients (n = 107/329; 32.5%) required surgery on 2 or more muscles. Of 373 muscles repositioned, the lateral rectus muscle (n = 115/373; 30.8%) and inferior oblique muscle (n = 70/373; 18.7%) were the most common, correlating to intraocular tumor location (P<0.001). Only 6 tumors (n = 6/61; 9.5%) originating from the iris and ciliary body required muscle surgery for plaque placement. Of the 312 patients with a preoperative visual acuity better than 20/400, diplopia was reported at the first postoperative visit by 41 patients (n = 41/312; 13.1%), 2 of whom had not undergone muscle surgery. Diplopia resolved spontaneously within 1 month in 18 patients (n = 18/41; 43.9%), between 1 and 6 months in 12 patients (n = 12/41; 29.3%), and at more than 6 months in 5 patients (n = 5/41; 12.2%). Among the 312 patients, persistent diplopia occurred in 6 patients (1.9%), including 1 who had not undergone muscle surgery. Treatment was declined in 1 patient, 3 patients (n = 3/41; 7.3%) were treated with prisms, and 2 patients (n = 2/41; 4.9%) required surgery. CONCLUSIONS: Extraocular muscle surgery frequently is required for plaque brachytherapy. Although transient diplopia occurred in 11.2% of patients, persistent diplopia occurred in only 1.9% of patients and was treatable.

High-Dose-Rate Yttrium-90 (90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma.

Purpose: To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration-cleared, yttrium-90 (Y90) plaque brachytherapy for iris and iridociliary melanoma. Design: A single-center, clinical case series. Participants: Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy. Methods: Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y90 eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression. Main Outcome Measures: Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity. Results: High-dose-rate Y90 plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y90 did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y90 treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8-12.9). High-dose-rate Y90 brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12-24) months. Evidence of local control included a lack of expansion of tumor borders (n = 6, 100%), darkening with or without atrophy of the tumor surface (n = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease. Conclusions: High-dose-rate Y90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

Palladium-103 radiation therapy for small choroidal melanoma.

PURPOSE: To evaluate outcomes after ophthalmic plaque radiation therapy for small choroidal melanomas. DESIGN: Retrospective study, case series. PARTICIPANTS: Seventy-two patients with choroidal melanomas ≥1.5 and ≤2.4 mm apical height and ≤10 mm width treated between 2002 and 2012, with a minimum follow-up of 8 months. METHODS: All patients were treated with palladium-103 plaque brachytherapy. Mean radiation dose to the tumor apex was 82.4 Gy (range, 70.0-102 Gy). MAIN OUTCOME MEASURES: Local control, radiation complications, visual acuity, and metastatic rate. RESULTS: Plaque radiotherapy provided 100% local tumor control and eye retention at a mean 54 months of observation (95% confidence interval, 46-63 months). The most common long-term brachytherapy-related complications were radiation maculopathy (43.1%) and radiation optic neuropathy (20.8%) developing at a mean of 27 months (range, 9-72 months) after irradiation. In this series, 94.4% of patients maintained 20/200 or better vision. There has been no small choroidal melanoma-related metastasis. CONCLUSIONS: Palladium-103 plaque radiation therapy offered excellent local control and visual acuity outcomes for patients with small choroidal melanoma.

Infected epithelial inclusion cyst simulating conjunctival melanoma.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.

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.

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.

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.

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.