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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.

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 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.

Objective To perform micro-incision, trans-iridal, aspiration-cutter-assisted biopsy for ciliary body tumours. Design Retrospective, nonrandomized, observational, interventional case series. Methods Five consecutive patients undergoing ciliary body tumour biopsy were clinically diagnosed using slit-lamp photography, gonioscopy, high-frequency ultrasound imaging, and systemic radiographic staging. A 1–2 mm clear cornea incision was placed opposite to the central clock hour of the ciliary body tumour. Viscoelastic was infused into the anterior chamber for stabilization and endothelial protection. Then, a 27-gauge aspiration cutter was used to make an iridotomy at the iris root and then extend through the iris into the tumour. Biopsy was performed using mechanical cutting starting at 300 cuts per minute and aspiration at 600 mm Hg. After withdrawal of the cutter from the eye, the effluent tube was flushed into a 3 cc syringe, inspected for specimen under the operating microscope and sent for pathology. Multiple biopsies were performed on each patient. Viscoelastic was removed and Seidel examination of the corneal wound performed. Results Five eyes were biopsied. A mean 3.6 passes were used to obtain tumour tissue. Tumour cells and tissue were obtained in all cases. Cytologic, histopathologic, and immuno-histochemical analysis were performed (100%, n = 5/5). Diagnoses included melanoma (60%, n = 3/5), melanocytoma (20%, n = 1/5), and leiomyoma (20%, n = 1/5). Transient postoperative hyphemas cleared within 1 week (80%, n = 4/5). No secondary glaucoma, infection, or cataracts were noted. Conclusion Aspiration-cutter biopsy through the iris root provided a minimally invasive, safe method for obtaining ciliary body tissue for cytology, histopathology, and immunohistochemical analysis.

Purpose: To provide real-world data on the world-wide-web for patient and doctor awareness. Methods: From December 2017 to January 2020, consecutive patients with choroidal melanoma (CM), iris ciliary body melanoma (ICM), and ocular surface squamous carcinoma (OSSC) had specific outcomes recorded at each return visit. Each result was anonymized, entered in an online portal, and sent to a unique software program where it was used to create real-world data of number of patients, mean vision, local tumor control, eye salvage, systemic metastases, and length of follow-up for our eye cancer center. Results: A HIPAA compliant, internet-based software program was developed and linked to public access web page to collect and analyze near-real-time data pertaining to the treatment, vision, life, and follow-up time of patients. During this period, CM radiation plaque tumor control was 99.7%, median vision 20/25 (mean 20/50) and eye salvage 95.8%. ICM tumor control was 99.1% and the median vision 20/20 (mean 20/20). OSSC tumor control was 100% and the most common vision was 20/20 (mean 20/25). Rates of primary enucleation as treatment were 4.2% for CM, 2.8% for ICM, and 0% for OSSC. All patient results were updated by the ophthalmic oncology fellow at each patient visit as to reflect near-real-time outcomes at our center. Conclusion: Prospective data collection of returning patients was found to be a simple method to reflect patient care outcomes. This method of reporting doctor outcomes offers a measure of transparency for patients and an opportunity to compare results with other clinical practices.

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 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.

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 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.

Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, whereas iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high-frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. We found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment is governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.

In this case-matched study of 28 patients, early treatment with intravitreal anti-VEGF therapy preserved vision by preventing or delaying visually significant radiation maculopathy for high-risk choroidal melanoma patients following plaque radiation therapy.

Purpose: To investigate the safety and tolerability of total anterior segment palladium-103 (103Pd) eye plaque brachytherapy for multifocal iris melanoma. Methods: Interventional case series of 11 patients with multifocal iris melanomas. Anterior segment ultrasound revealed tumor size, location, and intraocular margins. Epicorneal amniotic membrane grafts protected the cornea and decreased pain during total anterior segment 103-Pd ophthalmic plaque brachytherapy. Results: Eleven diffuse iris melanomas were American Joint Committee on Cancer 8th edition–classified as T1 (n = 5, 45.5%) and T2 (n = 6, 54.5%). Plaque radiation was completed to a minimum mean tumor dose of 85 Gy (mean dose rate, 58.1 cGy/h). Ultrasonographic tumor thickness regression was 41% (follow up mean 58.7, median 50, range: 8–139 months). Despite 100% local control and 100% eye retention, one patient (9.1%) developed metastatic disease. Four eyes required cataract surgery. There was no corneal stem-cell deficiency, corneal opacity, radiation maculopathy, or optic neuropathy. While visual acuity prior to treatment was 20/40 or better in 10 (91%), 9 were 20/40 or better (81.9%) at last follow-up. Four (36%) had glaucoma prior to treatment and three eyes developed glaucoma after treatment for a total of 63%. Conclusion: Total anterior segment (103Pd) plaque brachytherapy resulted in local control, good visual acuity, eye and life preservation in the treatment of multifocal iris melanoma.

Objective: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I) 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: I 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 I 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. Ophthalmology 2002;109:2197–2206 © 2002 by the American Academy of Ophthalmology.

Purpose: Current ocular antiseptic practice for intravitreal injection (IVI) employs 5% povidone–iodine (Betadine®) drops which frequently cause ocular discomfort and prolonged irritation. In an effort to improve comfort while maintaining efficacy, we studied a hypochlorous acid (HOCL 0.01%) spray washout prior to injection. Methods: Patients had received a minimum of 3 IVIs prepared with Betadine® antisepsis prior to entry in this study. Their subsequent IVIs were prepared with Betadine® followed by HOCL 0.01% washout. Facets of comfort were measured by a Likert-scaled questionnaire to compare their experiences after IVI. Results: Thirty-seven participants were enrolled. Addition of HOCL 0.01% spray after Betadine® reduced the duration of discomfort (P = 0.001) and need for artificial tears postinjection (P = 0.003). It improved their reported quality of life (P = 0.04) and sleep (P = 0.01). There were neither HOCL-related side effects nor endophthalmitis during this study. Conclusion: Topical HOCL 0.01% spray after topical Betadine® antisepsis significantly improved patient comfort following IVIs.

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.

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.

AimsTo 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.MethodsClinical 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.ResultsOAL 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.ConclusionDisease-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.

ObjectiveTo describe the management of patients with occult anterior uveal melanomas presenting with extrascleral extension.Methods and analysisRetrospective 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.ResultsDuring 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.ConclusionExtrascleral 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.

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., Here, the authors describe a technique using adjuvant interstitial high-dose rate brachytherapy followed by electron-based external beam radiation therapy to increase the dose to a sebaceous carcinoma tumor bed while reducing dose to normal orbital structures.

The literature contains few reports describing autoimmune reactions to intravitreal bevacizumab and no Type-IV delayed hypersensitivity reactions. This was unexpected, as administration of intravenous bevacizumab has frequently caused dermatologic side-effects. This difference was likely attributable in part to the minimum 300-times difference between intravitreal versus intravenous dosing. Here, we present a case of a 52-year-old male who was treated with plaque brachytherapy for a subfoveal choroidal melanoma. The patient was treated with intravitreal bevacizumab for macular edema, retinal detachment and to delay radiation retinopathy. Following his eighth injection, the patient experienced pruritus, rashes, and progressive exacerbations associated with subsequent injections. Cessation of bevacizumab with or without medication (e.g., oral steroid, antihistamine) resulted in complete remission. Switching to periodic intravitreal aflibercept resulted in no additional cutaneous reactions. Physicians administering intravitreal bevacizumab should be aware of this potential systemic side-effect. Its delayed time course facilitates identification and, thus, treatment to resolution.

Purpose: To report that metastatic choroidal melanoma (systemic and intraocular) can respond to systemic immunotherapy. Methods: In 2010, a 64-year-old woman with a choroidal melanoma was treated with palladium-103 plaque brachytherapy. Developing 2.5 years later, radiation maculopathy was suppressed with periodic intravitreal anti–vascular endothelial growth factor injections for five additional years. Development of a new, discrete choroidal melanoma in the same eye prompted radiographic imaging of the orbits, abdomen/pelvis, and chest. Multi-organ metastasis in the eye, the liver, and nodes was treated with systemic combination immunotherapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) intravenous every 3 weeks for four cycles followed by nivolumab (3 mg/kg) intravenous every 4 weeks as maintenance. Subsequent ophthalmic and systemic surveillance were performed. Results: All sites of metastases were found to regress on systemic immunotherapy. For example, ophthalmic ultrasound imaging revealed that the intraocular metastasis was reduced from 6.6 to 1.5 mm in thickness. Synchronously, serial radiographic imaging revealed progressive shrinkage and disappearance of hepatic and nodal metastasis (except for one gastrohepatic node). However, combination stereotactic body radiation therapy (30 Gy) with nivolumab maintenance was found to induce a significant reduction in this remaining node. Continued periodic intraocular anti–vascular endothelial growth factor therapy has suppressed her radiation maculopathy resulting in 20/25 vision, now 8 ½ years after initial plaque therapy. Conclusion: This case shows that metastatic choroidal melanoma can present in the same eye as the primary tumor. It also shows that systemic immunotherapy can control both ocular and systemic metastases as well as prolong both life and sight.

Background Ciliary body tumors can remain undetected and achieve large dimensions. Pigmented ciliary body tumors include: melanoma, leiomyoma and melanocytoma, however correct diagnosis may require tissue diagnosis with immunohistochemical stains. Case presentation Two men presented with identical ciliochoroidal tumors. Both had darkly pigmented dome-shaped anterior uveal masses, exudative retinal detachments and transillumination shadowing. Ocular PET-CT imaging revealed that both were metabolically active consistent with a diagnosis of cancer. However, immunohistochemical examination revealed one a leiomyoma and the other melanoma. Conclusion Uveal leiomyoma can be an indistinguishable doppelganger to ciliochoroidal melanoma, where the diagnosis can only be established by immunohistopathology.

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt 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.ResultsOf 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.ConclusionsThough 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.

To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels.International, multicenter, registry-based retrospective case series.Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents.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.Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy).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; P0.001). 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 P0.001).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.

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).International, multicenter, registry-based retrospective case series.A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.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.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).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 (P0.001). 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; P0.001), cT2b (HR, 16.4; P0.001), and cT3 (HR, 45.0; P0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P0.001).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.

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).International, multicenter, registry-based retrospective case series.A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.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.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.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 (P0.001). 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; P0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease.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.

Purpose To characterize the clinical features of subtype-specific lacrimal gland lymphoma and their effect on patient survival. Design Multicenter retrospective interventional case series. Methods Patient data were collected from 6 international eye cancer centers from January 1, 1980, through December 31, 2017. All patients with histologically verified primary or secondary lymphoma of the lacrimal gland were included. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). Results A total of 260 patients with lacrimal gland lymphoma were identified. The median age was 58 years and 52% of patients were men. Non-Hodgkin B-cell lymphomas constituted 99% (n = 258) and T-cell lymphomas constituted 1% (n = 2). The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n = 177, 68%), follicular lymphoma (FL) (n = 26, 10%), diffuse large B-cell lymphoma (DLBCL) (n = 25, 10%), and mantle cell lymphoma (MCL) (n = 17, 7%). Low-grade lymphomas (EMZL and FL) were most commonly treated with external beam radiotherapy (EBRT), whereas high-grade lymphomas (DLBCL and MCL) were treated with chemotherapy in combination with rituximab and/or EBRT. The prognosis was relatively good with a 5-year OS and DSS of 73.8% and 87.5%, respectively. Lymphoma subtype was a statistically significant predictor for DSS, with EMZL (5-year DSS: 93.4%) having the best prognosis and DLBCL (5-year DSS: 52.6%) having the poorest. Conclusions This is the largest reported collection of data of subtype-specific lacrimal gland lymphoma. The subtype distribution of lacrimal gland lymphoma resembles that of the ocular adnexa. Prognosis is good and the histologic subtype is a significant predictor for disease-specific survival.

Purpose: To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy. Methods: Retrospective interventional case series including 170 consecutive patients treated with 103Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology. Results: The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2–11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0–7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% ( n = 86/170), amelanotic in 10% ( n = 17/170), and variably pigmented in 39% ( n = 67/170). Tumor pigmentation increased in 64% ( n = 106/166), decreased in 18% ( n = 30/166), and was unchanged in 18% ( n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% ( n = 12/120) had decreased tumor-related vascularity and 90% ( n = 108/120) showed complete resolution. Subretinal fluid was present in 34% ( n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% ( n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% ( n = 91/149) showed increased reflectivity on regression. We noted a crescendo–decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis. Conclusion: Findings related to choroidal melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound.

The authors present a case of a pregnant woman with uveal melanoma treated with plaque brachytherapy. Her calculated fetal radiation dose was significantly below accepted levels. The use of the authors' novel, custom-made lead chin shield further diminished irradiation of the fetus. This patient had uncomplicated treatment course, delivered a healthy child full term, achieved local tumor control, and maintained 20/25 vision at 1-year follow-up. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:364–368.]

Purpose.To evaluate a 27-gauge aspiration-cutter technique for biopsy of anterior segment neoplasia. Methods. In this retrospective case review, all patients had clinically diagnosed iris or ciliary body tumors. Each underwent surgical iridectomy biopsy utilizing a modification of the Finger Iridectomy Technique (FIT). Specifically, a beveled clear corneal incision was created with a 27-G inked trocar. Sodium hyaluronate 1 % was infused to posteriorly displace the iris and stabilize the chamber. Then a 27-G aspiration-cutter probe was introduced into the anterior chamber, to a position over the tumor. With the aspiration portal abutting the lesion, surgical iridectomy biopsies were obtained using a cut rate of 300 cuts/min and aspiration of 600 mmHg. After each pass, the probe was removed, its tip placed in balanced salt solution and its contents aspirated into a 3-mL syringe. Each syringe was labeled by pass number and tumor location (by clock hour). After obtaining multiple biopsies, the sodium hyaluronate 1 % was removed and the integrity of the wound checked. Main Outcome Measures. Cytologic, tissue histopathology, and immunohistochemical analyses were performed for diagnostic purposes. Visual acuity, intraocular pressure control and procedure-related complications were secondary outcomes measures. Results. Diagnostic specimens were obtained in all 8 cases (100 %). Diagnoses included unifocal melanoma (62 %), diffuse multifocal melanoma (13 %), and melanocytoma (25 %). All 27-gauge corneal wounds were self-sealing. There was no secondary glaucoma, infection, cataract, or vision loss. Two patients had small transient hyphemas which resolved within 10 days. Conclusions. This study reveals that 27-gauge aspiration-cutter assisted surgical iridectomy biopsy was both minimally invasive and effective. It allowed for partial and full thickness iris biopsy. Compared to larger-gauge aspiration cutter assisted biopsy techniques, this 27-G aspiration-cutter probe allowed for even smaller corneal incisions, rapid recovery and tissue for pathology evaluation. For citation: Scripsema N., Finger P.T. A 27-gauge micro incision biopsy technique for tumors of the iris and ciliary body. Russian ophthalmological journal. 2018; 11 (3): 43-8. doi: 10.21516/2072-0076-2018-11-3-43-48