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Purpose To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by 103 Pd plaque radiotherapy. Methods and Materials This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results Thirty patients were followed for a median 36 months (range, 12–90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extending into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75–100 Gy), lens dose 43.5 Gy (range, 17.8–60 Gy), fovea dose 1.8 Gy (range, 1.3–5 Gy), and central optic disc dose 1.7 Gy (range, 1.3–4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was ≥20/25 in 28 patients (93%) at a median 36 months' follow-up. Conclusion Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after 103 Pd treatment of iris and iridociliary melanomas.

Purpose To investigate the value of whole-body positron emission tomography/computed tomography (PET/CT) as a screening tool for patients with uveal metastasis. Design Retrospective observational case series. Methods setting: Clinical practice. study population: Eighteen patients with uveal metastatic tumors were evaluated. Patients had no history of malignancy or a past medical history of malignancy without known active metastasis or known systemic cancer. intervention: Whole-body PET/CT was used as a screening tool to evaluate the intraocular tumor, to evaluate for multi-organ metastatic disease, and for cancer staging. main outcome measures: Detection and PET/CT uptake of primary tumors and metastatic disease. Results PET/CT imaging uncovered previously occult primary nonocular cancers (11/18, 61%), revealed progression of known primary systemic cancer (7/18, 39%), and confirmed multi-organ metastases in all cases (18/18, 100%). PET/CT findings were used to direct nonocular, confirmatory biopsy in 67% of cases (12/18). No uveal biopsies were required. PET/CT revealed lymph nodes and bone as the most common metastatic sites. The intraocular tumor was detectable in 28% of cases. Small, non-avid tumors and those within the hypermetabolic, PET-avid brain were falsely negative. Conclusion This study suggests that whole-body PET/CT can be useful for clinical evaluation of patients with uveal metastases. It allowed for screening of the entire body and directed extraocular biopsy. Commonly used for tumor staging, PET/CT aided in the detection of the primary cancer in patients with metastatic uveal tumors.

Objective To evaluate slotted eye plaque radiation therapy for choroidal melanomas near the optic disc. Design A clinical case series. Participants Twenty-four consecutive patients with uveal melanomas that were near, touching, or surrounding the optic disc. Intervention Slotted eye plaque radiation therapy. Main Outcome Measures Recorded characteristics were related to patient, clinical, and ophthalmic imaging. Data included change in visual acuity, tumor size, recurrence, eye retention, and metastasis. Results From 2005 to 2010, 24 consecutive patients were treated with custom-sized plaques with 8-mm–wide, variable-depth slots. Radiation doses ranged from 69.3 to 163.8 Gy (mean, 85.0 Gy) based on delivering a minimum tumor dose of 85 Gy. All treatments were continuously delivered over 5 to 7 days. Mean patient age at presentation was 57 years. Tumors were within 1.5 mm of the optic nerve (n = 3, 13%), juxtapapillary (n = 6, 25%), touching ≥180 degrees (n = 7, 29%), or circumpapillary (n = 8, 33%). Ultrasound revealed dome-shaped tumors in 79% of patients, collar-button tumors in 17% of patients, irregular tumor in 1 patient (4%), and intraneural invasion in 2 patients. Mean initial largest basal dimension was 11.0 mm (standard deviation [SD] ± 3.5 mm; median, 11.4 mm; range, 5.9–16.4 mm). Mean initial tumor thickness was 3.5 mm (SD ± 1.7 mm; median, 3.0 mm; range, 1.4–6.9 mm). Initial visual acuities were a median 20/25 (range, 20/20 to hand motions) and decreased to a median 20/40 (range, 20/20 to no light perception). At a mean follow-up of 23 months, 12 patients required periodic intravitreal bevacizumab to suppress radiation optic neuropathy (RON) or maculopathy. To date, there has been a 100% local control rate. No patients have required secondary enucleation for recurrence or neovascular glaucoma. No patients have developed metastasis. Conclusions Slotted plaque radiation therapy allows peripapillary, juxtapapilary, and circumpapillary choroidal melanomas (and a safety margin) to be included in the radiation targeted zone. Normalization of the plaque position beneath the tumor appears to increase RON and improve local control. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6–8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

Objective To evaluate clinical and histopathologic factors of squamous conjunctival neoplasia associated with recurrence. Design Retrospective, clinical case series. Participants One hundred one eyes of 99 patients with squamous conjunctival dysplasia, carcinoma in situ, or squamous cell carcinoma. Methods Review of the medical records, pathology reports, and color photographs. Main Outcome Measures Demographic information, laterality, tumor size, extension, pathologic diagnosis, seventh edition of the American Joint Committee on Cancer Classification (AJCC) staging system stage, treatment methods, recurrence, and duration of follow-up. Results Malignant squamous conjunctival neoplasia was seen most commonly in males at a median age of 71 years. Recurrences were seen in 12.9% (n = 13/101), with 92.3% occurring 6 to 12 months after primary treatment. Recurrence was not correlated significantly to age, gender, laterality, clinical appearance or focality of the tumor at presentation. However, tumors larger than 5 mm in diameter, tumors extending more than 2 mm onto the cornea, and tumors with local invasion (corneal, scleral, intraocular or orbital invasion) were associated with a higher risk of recurrence. Increasing AJCC T-stage was correlated strongly to the incidence of recurrence ( P = 0.0006). Rates were 1.7% for Tis-staged tumors, 0% for T1- and T2-staged tumors, 34.3% for T3-staged tumors, and 50% for T4-staged tumors. Histopathologic diagnosis was correlated to recurrence ( P = 0.037). None of the tumors defined histologically as dysplasia showed recurrence, whereas 12.8% of carcinoma in situ tumors and 22.2% of squamous cell carcinoma tumors recurred. Although the overall recurrence rate was 12.9%, the rate for tumors treated primarily at the authors' center was 4%, significantly less than the recurrence rate in previously operated tumors ( P = 0.0003). Lymph nodes demonstrated positive results in 1%, and in no patient did distant metastasis develop. Conclusions Advanced AJCC T-stage, locally invasive tumors, and more pathologically aggressive tumors were at higher risk for recurrence. Inadequate initial therapy also was an important risk factor for recurrence. Treatment strategies should be affected by tumor staging at presentation. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose To present an interventional case report on the use of plaque brachytherapy for adenocarcinoma of the nonpigmented ciliary epithelium. Methods and materials A 36-year-old woman with unilateral right eye pain and finger counting vision was noted to have an anterior segment intraocular mass. It extended between the iris and lens and into the pupillary aperture. High-frequency ultrasound imaging revealed a ciliary body origin. A minimally invasive biopsy technique allowed for a cytology and histopathology diagnosis of primary adenocarcinoma of the ciliary epithelium. Treatment was performed with palladium-103 ophthalmic plaque brachytherapy (80-Gy apex). Main outcome measures include visual acuity, local control, radiation complications, and metastatic disease. Results The patient presented with counting fingers vision, focal angle closure, cataract, and a 5.5-mm thick ciliary body malignancy. At 3 years after radiation therapy and 2.5 years after cataract extraction, her visual acuity was improved to 20/30 and the tumor residua stabilized at 60% of its initial thickness. There has been neither radiation-related keratopathy, retinopathy, optic neuropathy nor metastatic disease. Conclusions Plaque brachytherapy was used to treat primary adenocarcinoma of the ciliary epithelium. With 3-year followup, there has been excellent local control, preservation of the eye, and recovery of vision.

To report on intravitreal bevacizumab treatment for external beam radiation therapy (EBRT)-related radiation maculopathy.Three patients (4 eyes) with EBRT-related maculopathy were treated with periodic (4- to 8-week) intravitreal injections of bevacizumab (1.25 mg in 0.05 cc). Outcome measures included best-corrected Early Treatment Diabetic Retinopathy Study visual acuity, retinal examination, fundus photography, fluorescein angiography, and optical coherence tomography.Patients were diagnosed with Stage 3 radiation maculopathy occurring 12, 19, and 48 months after irradiation. One received 50 Gy of 6-MV photon EBRT for a maxillary carcinoma, the second 30.6 Gy of 6-MV photon EBRT for intraocular lymphoma, and the third 72 Gy proton beam irradiation for adenoid cystic carcinoma of the lacrimal gland. With up to 33 months follow-up, visual acuities improved (8 and 11 letters) in 2 eyes, gained 5 letters in 1 eye and 1 decreased 5 letters from 20/16 to 20/20. All cases demonstrated clinical findings of decreased intraretinal hemorrhages, cotton-wool spots, and retinal edema. There were no significant ocular or systemic side effects.Intravitreal anti-VEGF therapy was associated with reductions of EBRT-related retinopathy. No ocular or systemic side effects were noted. Anti-VEGF therapy may be considered radiation maculopathy secondary to EBRT.

Background Multiple myeloma is the most common plasma cell tumor; however, ocular plasmacytomas are rare and can appear in almost any structure of the eye. We present 3 cases, including 2 with unique ophthalmic ultrasound images of ocular plasmacytoma. Case Reports Three patients with ocular manifestations of multiple myeloma are described. All were noted to have known synchronous systemic disease. In this study, patients presented with epibulbar (n = 2), iridociliary (n = 1), and orbital (n = 2) plasmacytomas. Presenting signs included clinically visible tumor (n = 2), blurred vision (n = 2), diplopia (n = 2), and glaucoma (n = 1). The iridociliary plasmacytoma was defined by high-frequency 35-MHz ultrasonography that revealed 360° of anterior chamber involvement, secondary angle-closure, and extent of iridociliary invasion. In another case, low-frequency B-scan ultrasonography found multiple myeloma of the orbit. Ocular manifestations of multiple myeloma, histopathology, treatment, and prognosis are described. Conclusion Ocular manifestations of plasma cell neoplasms are rare. In multiple myeloma, plasmacytomas can present as a solitary tumor, as an initial sign of systemic disease, or as recurrence. This study presents 3 cases in which epibulbar, orbital, and iridociliary plasmacytoma with secondary glaucoma were presenting signs of uncontrolled multiple myeloma.

Purpose. To evaluate the safety and effect of systemic anti-vascular endothelial growth factor bevacizumab (Avastin) in treatment of exudative retinal detachment secondary to choroidal melanoma. Methods. Two patients were definitively treated with ophthalmic plaque radiation therapy and subsequently given 10 mg/kg intravenous bevacizumab every 2 weeks for 3 or 4 cycles. Results. Complete resolution of the exudative retinal detachments occurred 1.2 months and 6.5 months after completion of systemic bevacizumab and 4.7 and 10 months after plaque therapy. The first patient's visual acuity improved from counting fingers at 1 foot to 20/80 (at 40 months), while his tumor regressed from 9.2 to 3.7 mm in apical height. The second patient's initial acuity was 20/20 and final acuity was 20/80 (at 35 months), while her tumor height regressed from 12.2 to 6.3 mm. No exudative retinal detachment, intraocular or systemic tumor recurrence was noted up to 40 and 35 months, respectively. Acute side effects of intravenous bevacizumab therapy included hypertension, headaches, and amenorrhea, which shortly resolved after completion of therapy. Conclusions. This pilot study suggests that systemic bevacizumab was associated with transient systemic effects as well as resolution of choroidal melanoma-related exudative retinal detachment.

Purpose To evaluate changes in [ 18 F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) standardized uptake values (SUV) in uveal melanoma before and after plaque brachytherapy. Methods and Materials A cohort of 217 patients diagnosed with uveal melanoma and eligible for ophthalmic plaque brachytherapy underwent preoperative PET/CT to evaluate their intraocular tumor and screen for metastasis. Subsequent to undergoing plaque brachytherapy, patients' PET/CT SUV were periodically reevaluated over 42 months. Results In this series, 37 (17%) choroidal melanoma patients were found to have an SUV of >2.0. Of these, 18 patients were able to undergo interval follow-up PET/CT scanning. There were 3 patients with T2, 11 patients with T3, and 4 patients with T4 melanomas according to 7th edition AJCC-UICC criteria. Mean apical thickness was 8.8 mm (range, 3-12.3 mm), and the largest mean tumor diameter was 15.1 mm (range, 12-19.9 mm). The mean initial SUV was 3.7 (range, 2.1-7.3). Patients were followed for a median 16 months (range, 6-42 months). The median time to a tumor SUV of 0 was 8.0 months (range, 6-18 months). There was one case of one interval increase in SUV that diminished after circumferential laser treatment. Conclusions Intraocular PET/CT imaging provides a physiological assessment of tumor metabolism that can be used to evaluate changes after treatment. In this study, ophthalmic plaque radiation therapy was associated with extinguished tumor PET/CT SUV over time. PET/CT imaging can be used to assess choroidal melanomas for their response to treatment.

Purpose: To investigate dosimetric differences among several clinical treatment planning systems (TPS) and Monte Carlo(MC) codes for brachytherapy of intraocular tumors using I 125 or P 103 d plaques, and to evaluate the impact on the prescription dose of the adoption of MC codes and certain versions of a TPS (Plaque Simulator with optional modules). Methods: Three clinical brachytherapy TPS capable of intraocular brachytherapytreatment planning and two MC codes were compared. The TPS investigated were Pinnacle v8.0dp1, BrachyVision v8.1, and Plaque Simulator v5.3.9, all of which use the AAPM TG-43 formalism in water. The Plaque Simulator software can also handle some correction factors from MC simulations. The MC codes used areMCNP5 v1.40 and BrachyDose/EGSnrc. Using these TPS and MC codes, three types of calculations were performed: homogeneous medium with point sources (for the TPS only, using the 1D TG-43 dose calculation formalism); homogeneous medium with line sources (TPS with 2D TG-43 dose calculation formalism and MC codes); and plaque heterogeneity-corrected line sources (Plaque Simulator with modified 2D TG-43 dose calculation formalism and MC codes). Comparisons were made of doses calculated at points-of-interest on the plaque central-axis and at off-axis points of clinical interest within a standardized model of the right eye. Results: For the homogeneous water medium case, agreement was within ∼ 2 % for the point- and line-source models when comparing between TPS and between TPS and MC codes, respectively. For the heterogeneous medium case, dose differences (as calculated using the MC codes and Plaque Simulator) differ by up to 37% on the central-axis in comparison to the homogeneous water calculations. A prescription dose of 85 Gy at 5 mm depth based on calculations in a homogeneous medium delivers 76 Gy and 67 Gy for specific I 125 and P 103 d sources, respectively, when accounting for COMS-plaque heterogeneities. For off-axis points-of-interest, dose differences approached factors of 7 and 12 at some positions for I 125 and P 103 d , respectively. There was good agreement ( ∼ 3 % ) among MC codes and Plaque Simulator results when appropriate parameters calculated using MC codes were input into Plaque Simulator. Plaque Simulator and MC users are perhaps at risk of overdosing patients up to 20% if heterogeneity corrections are used and the prescribed dose is not modified appropriately. Conclusions: Agreement within 2% was observed among conventional brachytherapy TPS and MC codes for intraocular brachytherapydose calculations in a homogeneous water environment. In general, the magnitude of dose errors incurred by ignoring the effect of the plaque backing and Silastic insert (i.e., by using the TG-43 approach) increased with distance from the plaque’s central-axis. Considering the presence of material heterogeneities in a typical eye plaque, the best method in this study for dose calculations is a verified MC simulation.

Background and Objective: To correlate fundus autofluorescence (FAF) characteristics of metastatic choroidal tumors with optical coherence tomography/scanning laser ophthalmoscope (OCT/SLO). Patients and Methods: A retrospective review of 10 choroidal metastases in 9 patients. Results: All tumors were amelanotic, although 8 exhibited surface pigmentation. FAF imaging revealed hyperautofluorescence in areas of focal pigmentation and subretinal fluid with hypoautofluorescent margins (n = 5) corresponding to OCT evidence of retinal pigment epithelial (RPE) thickening and subretinal fluid. Loss of RPE was FAF imaging hypoautofluorescent. FAF images changed with tumor growth. OCT best revealed elevation of the RPE and retina, RPE thickening and folds, and retinal detachment. Conclusion: FAF imaging best defined surface characteristics and tumor margins. FAF imaging hyperautofluorescence correlated to focal hyperpigmentation, subretinal fluid, and advancing tumor edges. OCT better demonstrated intraretinal findings (atrophy, subretinal fluid, and increased and lost RPE). This study shows that FAF imaging and OCT reveal unique tumor characteristics of choroidal metastasis.

A 39-year-old female presented with a painless yellow-pink tumor on her right eye. High-frequency ultrasound imaging revealed an epibulbar lesion with homogenous low internal reflectivity and no evidence of intraocular invasion. The patient underwent excisional biopsy leading to a pathology diagnosis of myxoma. Additional surgical margins as well as adjuvant cryotherapy margins were followed by extensive conjunctival repair. Herein, we report on a conjunctival myxoma with unique ultrasonographic findings.

Objective To correlate combined optical coherence tomography (OCT) and scanning laser ophthalmoscope (SLO) imaging to clinical and histopathologic characteristics of optic disc melanocytoma (ODM). Design Retrospective, consecutive clinical case analysis. Participants Twenty patients with ODM were evaluated. Testing All underwent ophthalmic examinations including a best-corrected visual acuity, slit-lamp examination, dilated ophthalmoscopy, fundus photography with angiography, B-scan ultrasonography, and combined OCT and SLO imaging. Main Outcome Measures One eye, treated by enucleation, was evaluated by pathologic analysis and was correlated to its combined OCT and SLO images. These findings were correlated to clinical and OCT information from 19 patients with ODM. Results Histopathologic and combined OCT and SLO features included: disruption of the internal limiting membrane, disorganization of the retina (overlying the tumor), and visualization of the tumor's subretinal surface. Compressive and infiltrative changes in the optic nerve, peripapillary choroid, and retina were correlated directly to combined OCT and SLO images. To varying degrees, these histopathologic findings were seen on combined OCT and SLO. However, the pigment of the ODMs blocked OCT reflectance deep to the tumor's surface. Conclusions This study demonstrated that OCT and SLO findings could be correlated directly with histopathologic characteristics. Imaging with OCT can be used to diagnose and correlate secondary retinal, superficial, and subretinal tumor characteristics. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Importance To our knowledge, the clinical features of ocular adnexal mantle-cell lymphoma (OA-MCL) have not previously been evaluated in a large multicenter cohort. Objective To characterize the clinical features of OA-MCL. Design, Setting, and Participants This retrospective multicenter study included patient data collected from January 1, 1980, through December 31, 2015, at 6 eye cancer centers in 4 countries. Medical records of 55 patients with OA-MCL were reviewed; the median length of follow-up was 33 months. Main Outcomes and Measures Overall survival, disease-specific survival, and progression-free survival were the primary end points. Results Fifty-five patients were included; ocular adnexal MCL was found to be most common in older individuals (mean age, 70 years) and men (n = 42 of 55; 76%). Patients with OA-MCL frequently presented with disseminated lymphoma (n = 34 of 55; 62%), and were likely to experience stage IVE disease (n = 35 of 55; 64%), with bilateral involvement (n = 27 of 55; 47%), tumor masses (n = 27 of 36; 75%), and involvement of the orbit (n = 32 of 55; 58%). Chemotherapy with or without external beam radiation therapy was the most frequently used treatment. Overall survival rates for the entire cohort were 65% at 3 years (95% CI, 52%-78%) and 34% at 5 years (95% CI, 21%-47%). Disease-specific survival after 5 years was 38% for the entire cohort (95% CI, 25%-51%); the disease-specific survival adjusted by eye cancer center was better in patients who had received rituximab in addition to the chemotherapy regimen (hazard ratio, 3.3; 95% CI, 1.0-14.7;P = .06). The median progression-free survival was 2.3 years (95% CI, 1.8-2.7 years) in patients who experienced recurrence after primary treatment, and 4.1 years (95% CI, 3.9-4.3 years) in patients who presented with a relapse of systemic lymphoma in the ocular adnexal region. Conclusions and Relevance These results suggest that the distinctive features of OA-MCL are its appearance in older male individuals, advanced stage and bilateral manifestation at the time of diagnosis, and aggressive course. The prognosis of patients with OA-MCL might be improved by addition of rituximab to chemotherapy treatment.

Context.—The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer commissioned the Ophthalmic Oncology Task Force to modify and update the ophthalmic chapters of the 7th edition of the AJCC Cancer Staging Manual. Objective.—To review the existing eyelid carcinoma chapter in the 6th edition of the AJCC Cancer Staging Manual for its clinical and research utility and to seek evidence-based revisions with the strongest medical foundation to use in updating the anatomically based TNM cancer staging system manual. Data Sources.—The 4-year Ophthalmic Oncology Task Force consisted of 45 tumor specialists from 10 countries and an extensive internal and external peer review process. The 10-member Carcinoma of the Eyelid team included a diverse group of international authors. The group included extensive representation by clinicians, pathologists, surgeons, radiation therapists, and cancer registrars, all with advanced, ophthalmic cancer–related areas of subspecialty. Data sources included the above expertise applying a worldwide medical literature search, with no discrimination based on language, country of origin, discipline source, specialty source, or surgical practice. Conclusions.—Revisions were made to the TNM classification in areas with the strongest basis in evidence and practical effect. Lymph node staging data were expanded markedly to reflect its significant prognostic value. T3 and T4 were redefined and stage groupings were added that applied current understanding in tumor biology, respected site-specific risk factors, and provided greater correlation with the common language of the overall AJCC Cancer Staging Manual. Evidence-based biomarkers and data-field modifiers were included to capture additional pathologically and clinically substantiated prognostic factors.

Purpose:To examine the incidence of retinoblastoma for regional variations by race.Methods:Age-adjusted incidence rates, rate ratios, and 95% confidence intervals were determined in 109 regions from 1993 to 1997 using compiled data from the International Agency for Research on Cancer.Results:The rate ratio was 1.12 (range: 0.35 to 4.15) between white populations in the United States and Europe/Australia, 0.98 (range: 0.37 to 2.65) between Hispanic populations in Spain and the United States, and 1.44 (range: 0.29 to 1.79) between Hispanic populations in Uruguay and the United States. The rate ratio between Hispanic and white populations within the United States was 0.94 (range: 0.33 to 2.56). No differences were significant.Conclusions:Because retinoblastoma is a genetic disease, its incidence is similar among varied populations.

To describe whole-body 18-fluorodeoxyglucose (FDG) positron emission tomography/computed radiographic tomography (PET-CT) imaging of ophthalmic patients with systemic sarcoidosis.Four systemic sarcoidosis patients were evaluated with PET-CT for staging. Two had been treated for conjunctival melanoma and two had been referred for atypical choroidal tumors. PET-CT images were studied for presence of tumor or tissue with increased standardized uptake values, indicating increased metabolic activity.In all cases, PET-CT revealed focal systemic lesions with increased uptake (SUV range 1.7-5.9 kg/mL). Cases 1 and 2 had a previous diagnosis of sarcoidosis (without ocular involvement), while cases 3 and 4 were diagnosed during their work-up. PET-CT revealed the presence and distribution of systemic sarcoid granulomas.In this series, PET-CT staged patients with eye cancer and systemic sarcoidosis and aided in differentiating between a metastatic choroidal tumor and uveal sarcoid granuloma. PET-CT offers a method to assess the presence and distribution of systemic sarcoidosis.

Aim: To evaluate 18-fluoro-2-deoxyglucose (FDG) whole-body positron emission tomography/computed radiographic tomography (PET/CT) for lymph node and metastatic staging of patients with conjunctival melanoma. Methods: Fourteen patients with T3 (n = 13) and T4 (n = 1) conjunctival melanoma (as defined in Chapter 42 of the AJCC staging manual) were staged for metastatic disease with PET/CT imaging with fusion. The patients had lymph node and clinical staging evaluations before PET/CT imaging. PET/CT images were studied for the presence and distribution of metastatic conjunctival melanoma (determined by standardised uptake values) and later confirmed by biopsy. MRI imaging was performed if abnormalities were noted on PET/CT images. Results: Fourteen patients with conjunctival melanoma underwent PET/CT imaging. Seven were newly diagnosed (presurgical screening), and seven had undergone prior treatment (follow-up group). Only one patient with conjunctival melanoma (7.1%) was found to have metastatic disease on PET/CT imaging. Abnormal foci were found in the liver, lung, peritoneal cavity, lumbar spine as well as a supraclavicular node (T4N1M4). All liver function tests were normal. The mean length of follow-up after PET/CT imaging was 13 months (range 4–30 months). Conclusions: PET/CT imaging did not reveal any regional or systemic metastasis among 14 patients with advanced, diffuse and multifocal disease.

Purpose To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6–12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% ( n = 18). Three patients discontinued therapy. Each was legally blind before treatment ( n = 1), experienced little to no subjective improvement ( n = 2), or was poorly compliant ( n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti–vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy.

A 60-year-old woman with endometrioid adenocarcinoma (stage FIGO II) presented with left eye pain. A hysterectomy was to be preceded by pelvic radiation therapy (45 Gy). Ophthalmic examination with high frequency ultrasonography revealed a ciliary body tumor with iris extension. Positron emission tomography and computed tomography fusion revealed multifocal metastatic disease. A Finger iridectomy technique ciliary body tumor biopsy revealed metastatic endometrioid adenocarcinoma. Treatment with external beam radiation therapy (3,060 cGy in 17 daily fractions) resolved her ocular disease. Subsequent and rapidly evolving systemic carcinomatosis with brain involvement resulted in her death. This is the first reported case of endometrioid adenocarcinoma of the uterus metastatic to the uveal tract. [Ophthalmic Surg Lasers Imaging 2008;39:246-249.] AUTHORS From Hacettepe University School of Medicine (MA), Sihhiye, Turkey; the New York Eye Cancer Center (MA, PTF), New York, New York; and the New York Eye and Ear Infirmary (TM), New York, New York. Accepted for publication December 4, 2007. Supported by the EyeCare Foundation, Inc., New York, New York. Address correspondence to Paul T. Finger, MD, The New York Eye Cancer Center, 115 East 61st Street, New York, NY 10065.

Purpose To report long-term experience with intravitreal anti–vascular endothelial growth factor treatment for radiation maculopathy. Methods From 2005-2015, 120 consecutive patients underwent intravitreal anti-VEGF therapy for radiation maculopathy. Inclusion criteria included a diagnosis of uveal melanoma treated with plaque radiotherapy and subsequent macular radiation vasculopathy (exudate, retinal hemorrhage, intraretinal microangiopathy, neovascularization, edema). Anti-VEGF therapy involved continuous injections in 4- to 12-week intervals with doses of 1.25 mg/0.05 mL, 2.0 mg/0.08 mL, 2.5 mg/0.1 mL, or 3.0 mg/0.12 mL of bevacizumab as well as 0.5 mg/0.05 mL or 2.0 mg/0.05 mL of ranibizumab. Goals were maintenance of visual acuity and normative macular anatomy. Safety and tolerability (retinal detachment, hemorrhage, infection), visual acuity, central foveal thickness on optical coherence tomography imaging, and clinical features of radiation maculopathy were analyzed. Results Progressive reductions in macular edema, hemorrhages, exudates, cotton-wool spots, and microangiopathy were noted. At last follow-up, 80% remained within 2 lines of their initial visual acuity or better, with a mean treatment interval of 38 months (range 6-108 months). Kaplan-Meier analysis of the probability of remaining within 2 lines of initial visual acuity was 69% at 5 years and 38% at 8 years of anti-VEGF therapy. Discontinuation of therapy was rare. Relatively few acute or long-term side effects were noted, allowing for good long-term patient accrual. Conclusions Continuous intravitreal anti-VEGF therapy in patients with radiation maculopathy was well-tolerated and preserved vision. In most cases, reductions or resolution of retinal hemorrhages, cotton-wool spots, and retinal edema were noted for up to 10 years.

PurposeTo assess of the effect of local recurrence of uveal melanoma on metastasis using a multicenter international tumor registry.DesignRetrospective study using an online tumor registry.ParticipantsPatients with uveal melanoma diagnosed between 2001 and 2011.MethodsA committee was formed to create uveal melanoma patient-specific data fields. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma and adequate records to allow tumor staging by American Joint Committee on Cancer (AJCC) criteria and follow-up for metastatic melanoma.Main Outcome MeasuresLocal tumor recurrence and metastatic uveal melanoma.ResultsOf 3809 total entries, 3217 patients with ciliary body and choroidal (CBC) melanoma and 160 with iris melanoma were evaluated. There was a median follow-up of 3.7 years (95% confidence interval [CI], 3.5–3.8). One hundred fifty-two patients (4.7%) with CBC melanoma experienced local recurrence, with a cumulative incidence of 11%. Kaplan-Meier point estimates for remaining free of local recurrence were 99% (95% CI, 99–99) at 1 year, 93% (95% CI, 92–94) at 5 years, and 89% (95% CI, 86–91) at 10 years. Five- and 10-year metastasis-free Kaplan-Meier estimates for the recurrence-free group were 87% (95% CI, 86–89) and 82% (95% CI, 79–84), and those for the local recurrence group were 71% (95% CI, 62–78) and 62% (95% CI, 49–72). The difference between these 2 groups was statistically significant (P < 0.001). Furthermore, local tumor recurrence increased the risk of metastasis by a hazard ratio (HR) of 6.28 (95% CI, 4.4–8.9; P < 0.001). Local recurrence was detected up to 9.8 years after treatment. Extrascleral extension also was associated with local recurrence (HR, 3.2; 95% CI, 1.5–6.7; P = 0.003), but higher AJCC T-size category was not (P = 0.63). Five patients (n = 5/161 [3.1%]) with iris melanoma demonstrated local recurrence and 1 metastasized.ConclusionsInternational multicenter data sharing was used to evaluate the effect of local tumor recurrence on metastatic rate. In that local tumor recurrence was associated with a significantly higher risk of systemic metastasis, effective initial treatment and long-term surveillance of treated uveal melanoma patients is necessary.

Although an accurate uveal melanoma staging system is needed to improve research and patient care, the evaluation of eye cancer staging systems requires international multicenter data sharing to acquire a statistically significant analysis.To assess patient mortality outcomes associated with uveal melanoma staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual.A committee was formed to create patient-specific data fields for patients with uveal melanoma. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma from April 1, 2001, to April 1, 2011, adequate records to allow tumor staging by the AJCC criteria, and follow-up for metastatic melanoma.Primary treatments included local resection, radiation therapy, and enucleation.Metastasis after initial tumor staging with 5- and 10-year Kaplan-Meier metastasis-free point estimates, depending on AJCC prognostic stages I through IV, tumor size category, and subclassification (defined by the presence of ciliary body involvement and/or extrascleral extension).A total of 3809 patients were entered into the database. Of these, 3377 records (88.7%) were complete. Primary ciliary body and choroidal melanoma was the diagnosis for 3217, and 160 had primary iris melanoma. Tumor size categories were T1 in 1115 (34.7%) of the 3217 patients, T2 in 1128 patients (35.1%), T3 in 789 patients (24.5%), and T4 in 185 patients (5.8%). The 5- and 10-year Kaplan-Meier metastasis-free point estimates by tumor size categories were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for T1 tumors, 85% (95% CI, 82%-88%) and 80% (95% CI, 75%-84%) for T2 tumors, 77% (95% CI, 73%-80%) and 68% (95% CI, 60%-74%) for T3 tumors, and 61% (95% CI, 49%-71%) (5-year only) for T4 tumors, respectively. Increasing tumor size was consistent with increased metastasis risk (P .001). Subclassifications were significantly associated with increased risk of metastasis (P.001). The AJCC prognostic and anatomical groupings were as follows: stage I, 1030 (32.0%); stage IIA, 1095 (34.0%); stage IIB, 710 (22.1%); stage IIIA, 282 (8.8%); stage IIIB, 79 (2.5%); and stage IIIC, 21 (0.7%). The 5- and 10-year Kaplan-Meier metastasis-free estimates for prognostic stages were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for stage I, 89% (95% CI, 86%-91%) and 84% (95% CI, 80%-88%) for stage IIA, 79% (95% CI, 75%-83%) and 70% (95% CI, 62%-76%) for stage IIB, 67% (95% CI, 59%-73%) and 60% (95% CI, 51%-68%) for stage IIIA, 50% (95% CI, 33%-65%) and 50% (95% CI, 33%-65%) for stage IIIB, and 25% (95% CI, 4%-53%) (5-year only) for stage IIIC, respectively. The 160 iris melanomas were too few for subgroup analysis.Multicenter, worldwide, Internet-based data sharing was used to study a heterogenous patient population in ophthalmic oncology. Our results support the continued use of the 7th edition of the AJCCCancer Staging Manual for uveal melanoma.

The use of a method based on fuzzy granular computing to process ultrasound image stack and also ultra-sound single images is proposed. Fuzzy granularity has been employed with success in the determination of speckle laser activity, this determination is usually temporal and requires a stack of consecutive time frames of the sample. In this proposal a spatial method is also presented, based on the computing of intensity grains inside a sliding window in the image. To test the performance of the method, we apply it to corn kernels images obtained with dynamic laser speckle and a set of ultra-sound (US) images of an eye with melanoma. Temporal and spatial approaches would allow identifying regions of interest in the corn grain and benign and malignant tumors within the eye ultrasound images.

Objectives To report the use of whole-body positron emission tomography fused with computed tomography (PET/CT) for the diagnosis and staging of orbital lymphoma. Design Retrospective observational case series. Participants Four patients with biopsy-proven orbital lymphoma were evaluated by 18-fluoro-2-deoxyglucose whole-body PET/CT imaging. Methods Positron emission tomography/CT images were studied for the presence of glucose uptake. Foci were considered suspicious based on their standardized uptake values (SUVs). Physiologic images (PET) and their anatomic counterparts (CT) were fused to allow form and function to be evaluated on the same diagnostic page. Main Outcome Measures Positron emission tomography/CT images were assessed for foci with abnormally high SUVs that correlated with biopsy-proven lymphoma. Results Positron emission tomography/CT detected orbital lymphoma in 3 patients (75%). It also revealed systemic lymphoma in 2 of the 4 patients. The 2 patients found to have systemic lymphoma were diagnosed to have extranodal marginal zone B-cell orbital lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Similarly, the 2 with negative PET/CT results also had orbital MALT-type lymphoma. We found that PET/CT imaging helped guide further management in all 4 patients. Conclusions Positron emission tomography/CT should be considered as a new method of diagnosing, staging, and restaging patients with orbital lymphomas.

Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease.

Aims: To develop a minimally invasive, maximally effective method to biopsy anterior segment tumours. Methods: A 25 gauge aspiration cutter (vitrector) was used to biopsy anterior segment tumours. The probe was introduced under sodium hyaluronate 1% and through a 1 mm incision. Aspiration (600 mm Hg) cutting (300 cpm) was performed to obtain specimens for cytology and histopathology. Results: Diagnostic material was obtained in nine of 10 (90%) cases. Diagnoses included iris naevus, iris stroma, malignant melanoma, melanocytoma, epithelial inclusion cyst, and sarcoid granuloma. All corneal wounds were self sealing. One patient developed a transient postoperative increase in intraocular pressure. Within the follow up of this study, no patients suffered intraocular haemorrhage, infection, cataract or vision loss. Conclusion: The Finger iridectomy technique was a minimally invasive and very effective biopsy technique. Aspiration cutting yielded relatively large pieces of tissue (and cells) used for cytopathological and histopathological evaluation. Small incision surgery allowed for rapid rehabilitation and no significant complications.

The Collaborative Ocular Melanoma Study (COMS) developed a standardized set of eye plaques that consist of a 0.5 mm thick bowl-like gold alloy backing with a cylindrical collimating lip. A Silastic seed carrier into which 125I seeds are loaded was designed to fit within the backing. The carrier provides a standardized seed pattern and functions to offset the seeds by 1.0 mm from the concave (front) surface of the carrier. These Silastic carriers have been found to be difficult to load, preclude flash sterilization, and are a source of dosimetric uncertainty because the effective atomic number of Silastic is significantly higher than that of water. The main dosimetric effect of the Silastic carrier is a dose-reduction (compared to homogeneous water) of approximately 10%-15% for 125I radiation. The dose reduction is expected to be even greater for 103Pd radiation. In an attempt to improve upon, yet retain as much of the familiar COMS design as possible, we have developed a thin "seed-guide" insert made of gold alloy. This new insert has cutouts which match the seed pattern of the Silastic carrier, but allows the seeds to be glued directly to the inner surface of the gold backing using either dental acrylic or a cyanoacrylate adhesive. When glued directly to the gold backing the seeds are offset a few tenths of a millimeter further away from the scleral surface compared to using the Silastic carrier. From a dosimetric perspective, the space formerly occupied by the Silastic carrier is now assumed to be water equivalent. Water equivalency is a desirable attribute for this space because it eliminates the dosimetric uncertainties related to the atomic composition of Silastic and thereby facilitates the use of either 125I and/or 103Pd seeds. The caveat is that a new source of dosimetric uncertainty would be introduced were an air bubble to become trapped in this space during or after the surgical insertion. The presence of air in this space is modeled and the dosimetric impact discussed. Another unintended consequence of water equivalency is that some fluorescent x rays emitted from the gold backing can now reach the eye. These very low energy x rays were virtually eliminated by absorption in Silastic. When loaded with 125I seeds the modified plaque appears to produce dose distributions that are almost the same as those of the original COMS plaque and the maximum dosimetric uncertainty introduced by an air bubble is about 2%. Dose distributions calculated for a modified plaque loaded with 103Pd seeds show that dose to healthy ocular structures distal to the tumor apex can be reduced compared to 125I. Clearly, it is faster and easier to glue seeds into the reusable gold seed-guide insert than it is to load the COMS-Silastic carrier.

Aim: To evaluate the use of scatter laser photocoagulation to prevent radiation related retinopathy, maculopathy, and loss of vision. Methods: This was an interventional case series. 66 eyes with posterior choroidal melanomas treated by ophthalmic plaque radiation therapy were reported. Of these patients, 50 were selected because they developed radiation retinopathy; 45 of these were treated with sector scatter laser photocoagulation to regress clinically evident radiation retinopathy. 16 additional patients (considered to be “high risk” to develop radiation retinopathy) were also treated. Results: Radiation retinopathy was noted to appear at a mean interval of 26 months following plaque treatment. Laser photocoagulation regressed radiation retinopathy in 29 (64.4%) of the 45 patients treated after the onset of radiation retinopathy (17 with only retinopathy, 10 with a combination of retinopathy and maculopathy, and two with only maculopathy). Of the 16 patients who received laser treatment before clinical evidence of retinopathy, one developed radiation maculopathy and two retinopathy without maculopathy (all three responded to additional laser photocoagulation). In the 45 patient group, vision loss of more than three lines was attributable to radiation maculopathy in seven (15.5%). None of the patients in the prophylactic laser group lost more than three lines of vision as a result of maculopathy. Conclusion: Sector scatter argon laser photocoagulation induced regression of radiation retinopathy. Though early treatment of radiation retinopathy appears to be more effective, a more long term and prospective randomised study will be needed to prove efficacy.

Twenty-three normal eyes were examined with the Intensity Profiling technique of 3D I-Scan and 52 normal eyes with the Automated technique of OTI-Scan 1000 ultrasound systems (Ophthalmic Technologies Inc., Toronto, Ontario, Canada). With the eye looking straight, the probe was applied on the temporal sclera. Scanning generated 3D image files. Coronal optic nerve measurements were obtained 3 mm behind the globe. The mean optic nerve sheath diameter was 4.8 mm (standard deviation = 0.6; range, 3.9 to 5.9 mm) with the Intensity Profiling technique, and 5.4 mm (standard deviation = 0.4; range, 4.4 to 6.0 mm) with the Automated technique. 3D ultrasound imaging can be used to obtain optic nerve measurements in vivo. Both the Intensity Profiling and the Automated techniques yielded measurements similar to current magnetic resonance imaging and computed tomography scan reports. Coronal "C-scan" sectioning can be used as a screening tool to measure optic nerve diameter prior to magnetic resonance imaging or computed tomography. [Ophthalmic Surg Lasers Imaging 2005;36:142-146.]

Melanocytic conjunctival tumors include a wide range of lesions that vary in their clinical and histopathologic features. Their management depends on numerous factors, including their location, focality, tumor dimensions (including depth), histopathologic characteristics, recurrences, growth, and the presence of metastasis.

Purpose Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy. Design Case report. Methods A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy. Results One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25. Conclusion Although systemic chemotherapy can be used to treat intraocular metastasis, external beam radiation may provide more prompt resolution of vision-threatening tumors.

Purpose To evaluate the use of 3-dimensional ultrasound C-scan imaging for optic nerve diameter measurements. Design Prospective observational case series. Participants Thirty-eight normal eyes of 32 healthy adults. Methods Coronal C-scans of 38 normal optic nerves were imaged 3 mm behind the globe. Main outcome measures Optic nerve sheath diameter (ONSD) and optic nerve diameter (OND). Results Mean ONSD was 4.8 mm (range: 3.9–5.9; SD 0.6), whereas mean optic OND was 1.9 mm (range: 1.8–2.1; SD 0.1). Mean ONSDs were 4.9 mm (male), 4.5 mm (female), 5.0 mm (subjects younger than 50 years), and 4.6 mm (subjects 50 and older). Conclusion Coronal C-scans generated from 3-dimensional ultrasound can be used to measure the optic nerve diameters in adult eyes.

Aim: To report 7 year results of ophthalmic plaque radiotherapy for exudative macular degeneration. Methods: In a phase I clinical trial, 30 patients (31 eyes) were treated with ophthalmic plaque irradiation for subfoveal exudative macular degeneration. Radiation was delivered to a mean 2 mm from the inner sclera (range 1.2–2.4) prescription point calculated along the central axis of the plaque. The mean prescription dose was 17.62 Gy (range 12.5–24) delivered over 34 hours (range 18–65). Early Treatment Diabetic Retinopathy Study (ETDRS) type standardised visual acuity determinations, ophthalmic examinations, and angiography were performed before and after treatment. Clinical evaluations were performed in a non-randomised and unmasked fashion. Results: At 33.3 months (range 3–4), 17 of 31 (55%) eyes had lost 3 or more lines of vision on the ETDRS chart, five (16%) had improved 3 or more lines, and the remaining nine (29%) were within 2 lines of their pretreatment visual acuity measurement. Overall, 45% of patients were within or improved more than 2 lines of their initial visual acuity. Five eyes developed macular scars, eight developed subsequent neovascularisation or haemorrhage, and three progressed through therapy. Two patients were lost to follow up. The most common finding of patients followed for 6 or more months (n = 18 of 29 (62%)) was regression or stabilisation of the exudative process. No radiation retinopathy, optic neuropathy, or cataracts could be attributed to irradiation. Conclusion: Ophthalmic plaque radiation can be used to treat exudative macular degeneration. At the dose and dose rates employed, most patients experienced decreased exudation or stabilisation of their maculas. No sight limiting radiation complications were noted during 7 year follow up. Owing to the variable natural course of this disease, a prospective randomised clinical trial should be performed to evaluate the efficacy of plaque radiation therapy for exudative macular degeneration.

This article presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with choroidal melanomas.Members of the ABS with expertise in choroidal melanoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report.Episcleral plaque brachytherapy is a complex procedure and should only be undertaken in specialized medical centers with expertise in this sophisticated treatment program. Recommendations were made for patient selection, techniques, dose rates, and dosages. Most patients with very small uveal melanomas (2.5 mm height and10 mm in largest basal dimension) should be observed for tumor growth before treatment. Patients with a clinical diagnosis of medium-sized choroidal melanoma (between 2.5 and 10 mm in height and16 mm basal diameter) are candidates for episcleral plaques if the patient is otherwise healthy and without metastatic disease. A histopathologic verification is not required. Small melanomas may be candidates if there is documented growth; some patients with large melanomas (10 mm height or16 mm basal diameter) may also be candidates. Patients with large tumors or with tumors at peripapillary and macular locations have a poorer visual outcome and lower local control that must be taken into account in the patient decision-making process. Patients with gross extrascleral extension, ring melanoma, and tumor involvement of more than half of the ciliary body are not suitable for plaque therapy. For plaque fabrication, the ophthalmologist must provide the tumor size (including basal diameters and tumor height) and a detailed fundus diagram. The ABS recommends a minimum tumor (125)I dose of 85 Gy at a dose rate of 0.60-1.05 Gy/h using AAPM TG-43 formalism for the calculation of dose. NRC or state licensing guidelines regarding procedures for handling of radioisotopes must be followed.Brachytherapy represents an effective means of treating patients with choroidal melanomas. Guidelines are established for the use of brachytherapy in the treatment of choroidal melanomas. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose reporting policies. These guidelines will be modified as further clinical results become available.

Objective To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I(125)) 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(125) 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(125) 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.

Background: Vitreoretinal lymphoma (VRL) is an unusual presentation of primary central nervous system lymphoma and a subcategory of intraocular lymphoma (IOL). The etiology and epidemiology of this rare malignancy is unknown. Methods: We diagnosed 10 subjects with VRL in our clinical practices in New York City (NYC) during 2010-2013. Upon systematic collection of demographic and exposure history, 6 patients reported residence in regions proximal to the Chernobyl nuclear disaster (4 Ukraine, 1 Poland, 1 Moldova). We studied clinical variables including presentation, diagnostic parameters, therapies and survival of this case series. To provide context, we examined population-based incidence data from the Surveillance, Epidemiology and End Results (SEER) program to determine age-adjusted incidence rates of IOL (there is no unique code for VRL) per 100,000 person-years in the United States (US) during 1992-2013. New York State (NYS) rates are not reported to SEER and were examined separately using NYS Cancer Registry (NYSCR). Incidence trends using 10-year intervals (1992-2002 and 2003-2013) were also analyzed. Results: All six subjects (5 females) were diagnosed with diffuse large B-cell lymphoma with bilateral presentation. Diagnosis in all cases was made by immunohistochemical analysis on tumor specimen obtained by vitreous fine needle aspiration, vitreous biopsy or stereotactic brain biopsy. Median age at diagnosis was 76 years (range, 62-84 years). Median interval from Chernobyl accident (1986) to diagnosis was 26 years (range, 24-27 years). We identified no other common exposure or environmental risk factor. There were 68 cases of primary IOL during 1992-2013 in the 13 SEER areas. IOL rates per 100,000 person-years for both sexes were highest among Asian/Pacific Islanders (0.010 for males and 0.014 for females) followed by whites (0.009 for males and 0.008 for females) and (based on small numbers) by blacks. Analysis of incidence trends showed an increase in rates among Asian/Pacific Islander females from 0.005 in 1992-2002 to 0.018 in 2003-2013 and among males from 0.006 to 0.013. Rates among whites increased for both genders. Analysis of NYSCR data revealed 44 cases of primary IOL. IOL rates per 100,000 person-years for both genders were highest among whites (0.010 for males and 0.012 for females) followed by Asian/Pacific Islanders (0.007 for males and females). Analysis of trends revealed increase in rates for both genders and racial groups. Conclusions: Our analyses highlight the rarity of VRL and reveal an increase in incidence, particularly among Asian/Pacific Islanders where IOL rates tripled within two decades. Based on incidence rates, 8 cases of IOL (with a subset being VRL) are expected in 4 years in NYS. Our observation of 10 cases of VRL in 4 years in our practices in NYC is unanticipated. The sole common environmental factor we identified was residence in regions proximal to the Chernobyl nuclear disaster. Citation Format: Sanford Kempin, Paul Finger, Robert Gale, John Rescigno, Jeffrey Rubin, Walter Choi, Rebecca Fisher, Alexander Aizman, Ilona Genis, Roxana Moslehi* (Corresponding Author). A case series of vitreoretinal lymphoma in New York City with exposure to Chernobyl nuclear disaster decades earlier [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 259. doi:10.1158/1538-7445.AM2017-259

PURPOSE The perfect intravitreal injection delivers an exact amount of medication with the least risk to vision and the eye. We examined 2 different methods of intravitreal injection to determine if an angled transscleral entry for intravitreal injection results in less egress of intravitreal contents, including medication. METHODS In a crossover controlled trial at an outpatient clinical facility within a major ophthalmology referral center, we treated 10 patients. The surgical technique involved injecting 0.05 mL of bevacizumab injected in one eye by both an orthogonal (straight in) and oblique (angled) technique. The intraocular pressure (IOP) was measured immediately before and after each monthly injection. RESULTS Orthogonal injections raised the IOP significantly less (mean 24.6 mm Hg or 126%) than oblique injections (29.6 mm Hg or 152%) (p = 0.045). There were no reported differences in injection-related pain or adverse effects between the techniques. CONCLUSIONS Oblique or angled injections caused a larger IOP rise than straight or orthogonal injections. This finding suggests that oblique injections are self-sealing, deliver a higher dose of medication, or prevent vitreous reflux as well as close a potential portal of entry for pathogens.

In the twenty-first century, cancer staging is essential for clinical management to decrease tumor morbidity and reduce patient mortality. Staging serves as a common scientific language within which statistically significant answers can be obtained about diagnostic and therapeutic choices. This chapter details the staging process of orbital malignancies. Clinical (cTNM), Pathologic (pTNM), Retreatment (rTNM), and Autopsy (aTNM) classifications are reviewed. Herein, we explain why prospective data collection is required to continuously evolve staging and how staging will accelerate research, save vision and save lives.

Radiation therapy has played an important role in the management of benign and malignant orbital tumors. These include sinus, intraocular and adnexal tumors, those with orbital extension and orbital inflammatory processes. While external beam radiation therapy is the gold standard in treatment of orbital tumors, new techniques such as brachytherapy boost appear to increase local control and decrease secondary radiation complications. This chapter details the common modalities of radiation utilized in treatment of orbital tumors.

BACKGROUND AND OBJECTIVE: To report outcomes of intravitreal bevacizumab therapy in radiation-associated neovascular glaucoma (NVG). PATIENTS AND METHODS: In this retrospective interventional case series, 12 eyes with NVG after radiation therapy for ocular malignancy were treated with periodic intravitreal injections of 1.25 mg bevacizumab. Outcome measures included changes in iris neovascularization, intraocular pressure (IOP), visual acuity, and pain. RESULTS: One month after the first injection, iris neovascularization regressed in nine of 12 eyes (75%), and IOP decreased in eight of 12 eyes (67%) by a mean of 10.1 mm Hg. Patients were monitored for a mean of 26.5 months after their first injection. Six eyes subsequently underwent enucleation for pain control (four eyes; 66%), chronic uveitis (one eye; 17%), and tumor recurrence (one eye; 17%). All remaining patients experienced deterioration in visual acuity (range: 20/160 to no light perception), but pain control was good and IOP normalized in four patients. CONCLUSION: Intravitreal bevacizumab therapy should be considered for patients with radiation-associated NVG who wish to avoid enucleation. [ Ophthalmic Surg Lasers Imaging Retina. 2015;46:201–207.]

The authors describe a case in which drusenoid retinal pigment epithelial detachments (DRPEDs) melted after plaque radiation therapy for an unrelated choroidal melanoma. The patient had a history of bilateral macular DRPEDs prior to palladium-103 plaque therapy. The choroidal melanoma was located in the temporal macula. The central fovea was calculated to receive an incidental radiation dose of 34 Gy. Six months after treatment, an ipsilateral, unilateral reduction of DRPEDs was first noted by comparative fundus photography and optical coherence tomography. From his initial evaluation to his last follow-up, the patient’s visual acuity slightly improved from 20/20 to 20/16. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:84–86.]

To evaluate extraocular muscle surgery associated with plaque brachytherapy for choroidal melanoma.Single-center retrospective cohort study.Three hundred twenty-nine eyes of 329 consecutive patients with clinically diagnosed choroidal melanoma.Palladium 103 plaque brachytherapy with or without extraocular muscle surgery.Type of muscle surgery required for each tumor location, timing, incidence, and duration of diplopia, as well as treatment.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 (P0.001). 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.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.

Chemotherapy has been used to treat a multitude of eye cancers. We attempted to review the role of chemotherapy in the treatment of ocular, adnexal, and orbital malignancies by conducting an extensive search of the medical literature. Unfortunately, the published reports typically contain few patients with limited follow-up, precluding definitive recommendations. For most eye cancers, multicenter trials will offer the potential to gather the numbers of patients required to determine the clinical utility of chemotherapy.

Neovascular age-related macular degeneration is the most common cause of severe irreversible blindness in the Western world in people older than age 50. Laser photocoagulation is the only proven treatment for this disease; however, fewer than 20% of patients are eligible for this treatment because the majority of choroidal neovascularization membranes are not visible by ophthalmoscopy or angiography. In addition, many patients elect not to undergo this treatment because laser treatment of subfoveal neovascular membranes results in immediate and permanent central visual loss. Several treatments are under investigation, including external-beam radiation therapy. There are multiple publications of early trials using radiation therapy, but to date there is only one randomized published study. This article reviews these trials and summarizes the status of radiation therapy as a treatment for macular degeneration.