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

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

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

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

A five-year study of slotted eye plaque radiation therapy for choroidal melanoma: near, touching, or surrounding the optic nerve.

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.

Refractory squamous cell carcinoma of the conjunctiva treated with subconjunctival ranibizumab (Lucentis): a two-year study.

PURPOSE: To test the safety, tolerability, and efficacy of subconjunctival ranibizumab (Lucentis [Genentech, Inc.]) for squamous cell carcinoma of the conjunctiva and cornea. METHODS: Five patients with recurrent squamous cell carcinoma of the conjunctiva and cornea enrolled in this nonrandomized, single center, phase I pilot study as an alternative to radiation or exenteration. Subconjunctival ranibizumab (0.5 mg) was given on a monthly or twice monthly basis. Patients were examined for safety, tolerability, and efficacy using visual acuity, blood pressure, urinalysis, comparative slit lamp biomicroscopy with photography, and high frequency ultrasound imaging. RESULTS: Five male patients with biopsy-proven squamous conjunctival carcinoma were found to have recurrent disease. Each patient had been initially treated with combinations of primary excision (n = 1) or excision and cryotherapy (n = 4), and all (n = 5) had failed separate courses of both topical interferon a and mitomycin 0.02%. Tumors were multifocal and involved between 8 and 12 clock hours of the limbus. A median of 22 injections (range 12-27) was given over a mean 19 months (range 6-24). Three patients had a complete response (no clinically apparent disease) during the 2-year study, while 2 failed treatment despite demonstrating an initial partial response. Treatment was well-tolerated, as 4 patients demonstrated stable or improved visual acuity, and none had significant systemic or ocular side effects. CONCLUSIONS: This 2-year study demonstrated that subconjunctival ranibizumab induced regression of squamous cell carcinoma of the conjunctiva and cornea. Therefore, antivascular endothelial growth factor chemotherapy may offer a new strategy, complement excision and cryotherapy, or provide an alternative to radiation and/or exenteration. Further, larger investigations utilizing a larger group of patients are needed to determine the ideal dose, route of drug delivery, and case selection.

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

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

Palladium-103 plaque therapy for multifocal iris melanoma: Radiation of the entire anterior segment of the eye.

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.

Hypochlorous acid antiseptic washout improves patient comfort after intravitreal injection: A patient reported outcomes study.

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.

Palladium-103 ophthalmic plaque radiation therapy for choroidal melanoma: 400 treated patients.

PURPOSE: To describe 18 years of experience with palladium-103 ((103)Pd) ophthalmic plaque brachytherapy. DESIGN: Retrospective case series. PARTICIPANTS: From 1990 to 2007, 400 patients were diagnosed with uveal melanoma, found negative for metastatic disease, and treated. Episcleral (103)Pd radiation was delivered to a mean apical radiation dose of 73.3 Gy over 5 to 7 continuous days. INTERVENTION: Palladium-103 ophthalmic plaque brachytherapy. MAIN OUTCOME MEASURES: Patients were evaluated for local tumor control, visual acuity, radiation damage (retinopathy, optic neuropathy, cataract), and metastatic disease. RESULTS: A total of 272 tumors (68%) were located at or posterior to the equator. There were 186 (46.5%) T1 tumors, 156 (39%) T2 tumors, 50 (12.5%) T3 tumors, and 8 (2%) T4 tumors. Patients were followed for a maximum of 205 months (mean, 51.1 months). Fourteen patients required secondary enucleation (5 for tumor growth and 9 for glaucoma pain control). The local control rate was 96.7%. Life table analysis of patients with 20/200 or better before treatment (n = 357) suggests that 79% and 69% are expected to retain that acuity for 5 and 10 years, respectively. Life table analysis demonstrates a probability that 92.7% and 86.6% of patients will be free of metastatic disease at 5 and 10 years, respectively. CONCLUSIONS: In a nonrandomized phase I clinical evaluation, (103)Pd ophthalmic plaque radiotherapy was used to treat 400 patients with uveal melanoma. In this series, results after (103)Pd ophthalmic plaque radiotherapy were superior to those reported for alternative forms of radiation.

Reactive keratoma of the central corneal epithelium.

PURPOSE: The authors present a unique corneal tumor. METHODS: A 75-year-old gardener presented with a 1-year history of a slowly growing central corneal lesion with progressive visual loss. We performed an ophthalmic examination, slit lamp photography, high-frequency ultrasonography, and culture with sensitivity (followed by therapeutic scrape biopsy). RESULTS: Clinical examination revealed a gray-white central corneal tumor without extension to the limbus. No significant tumor neovascularization or intraocular inflammation was noted. High frequency ultrasound revealed no penetration of the corneal stroma. The tumor was removed with a platinum spatula. Histopathology revealed simple hyperkeratosis characterized by stratified hyperkeratotic corneal epithelium with metaplastic granular layer characteristic of epidermis. Few and focal clusters of passenger bacteria were found (as seen in cutaneous leukoplakia). Cultures revealed a few Gram-positive cocci and no fungus. A human papilloma virus wide-screen spectrum assay (in situ hybridization) was negative. CONCLUSIONS: The authors present a benign keratoma of the central corneal epithelium. High frequency ultrasound and scrape biopsy histopathologic techniques were used to diagnose and treat this keratoleukoma caused by a reactive keratoma as well as improve his vision.

Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.

PURPOSE: To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM). DESIGN: Retrospective, interventional case series. METHODS: Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease. One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months. Punctal plugs limited systemic absorption. The main outcome measure was tumor regression by clinical examination and comparative slit-lamp photography. RESULTS: Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-International Union Against Cancer stages T2 [n = 3] and T3 [n = 2]) were included. Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy. Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects. Two additional patients (who could not tolerate topical mitomycin C) were switched to topical interferon alfa-2b. They experienced transient chemical conjunctivitis and have no signs of recurrence (mean, 15 months of follow-up). The fifth had recurrent tumor despite multiple surgeries. This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjunctivitis). No systemic side effects were noted. CONCLUSIONS: We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b. A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy.

Intravitreal anti-VEGF therapy for macular radiation retinopathy: a 10-year study.

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.

High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy.

PURPOSE: To evaluate the safety and tolerability and treatment efficacy of high-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. METHODS: A phase I to II open-label, nonrandomized prospective clinical trial was performed on 10 eyes of 10 patients with recalcitrant radiation retinopathy who were failing standard dose anti-vascular endothelial growth factor (VEGF) therapy. External beam or plaque brachytherapy-associated retinopathy was characterized by persistent macular edema or leakage on optical coherence tomography or fluorescein angiography. Intravitreal 2.0 mg ranibizumab was given monthly up to 12 months and monitored for tolerability and change in best-corrected visual acuity (BCVA), central foveal thickness, and clinical signs of radiation retinopathy. RESULTS: Seven patients completed the 1-year study and received all 12 injections; 3 withdrew from the study due to worsening retinopathy (1 after external beam, 2 following plaque). Treatment was well-tolerated with no severe adverse reactions. A total of 70% had stable (n = 3) or improved (n = 4) BCVA. Mean change in BCVA was +3.3 letters at 6 months and +0.7 letters at 1 year. Mean improvement in central foveal thickness (CFT) was -19.3% (range -57 to +15%) at 1 year. Initial mean CFT was 428 µm (range 192-776); final mean CFT was 333 µm (range 190-532). A total of 80% demonstrated a statistically significant (p<0.05) reduction in CFT. CONCLUSIONS: Regardless of radiation source, intravitreal injections of 2.0 ranibizumab induced significant reductions in macular edema and maintained or improved BCVA in most patients who were failing standard dose anti-VEGF therapy.

Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy.

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.

Initial PET/CT staging for choroidal melanoma: AJCC correlation and second nonocular primaries in 333 patients.

PURPOSE: To report on whole body positron emission tomography/computed tomography (PET/CT) screening for metastasis at diagnosis of primary uveal melanoma. METHODS: Since August 2003, 333 consecutive patients were diagnosed with uveal melanoma and underwent whole body screening for metastatic disease with PET/CT along with liver function tests and physical examination. Abnormal findings prompted further biopsies, blood tests, imaging, or clinical evaluations for confirmation. The presence of metastatic disease and second cancers were evaluated. RESULTS: Using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) 7th edition criteria, 104 tumors were classified T1 (31%), 162 T2 (49%), 37 T3 (11%), and 30 T4 (9%). Seven of 333 (2.1%; 95% confidence interval [CI] 0.8-4.3) patients had metastatic melanoma. One tumor was a T3 and 6 were T4. Thus, 3% of T3 and 20% of T4 melanomas were found to have metastases at the time of initial diagnosis. Ten patients (3.3%; 95% CI 0.9-5.5) had synchronous second cancers and 28 (8.4%) concurrent benign lesions. The most common metastatic sites were liver (7/7) and bone (2/7). DISCUSSION: This study suggests that PET/CT improves the yield of detecting both extrahepatic metastases, especially from tumors defined as AJCC-T4, and synchronous primary cancers, irrespective of the size of the uveal melanoma. With respect to liver metastases, PET/CT demonstrated high sensitivity and positive predictive values, indicating an overall better performance than conventional screening procedures.

[(18)F]Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) physiologic imaging of choroidal melanoma: before and after ophthalmic plaque radiation therapy.

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.

Subfoveal choroidal melanoma: pretreatment characteristics and response to plaque radiation therapy.

OBJECTIVE: To evaluate the clinical presentation, tumor characteristics, and response to palladium 103 plaque radiation therapy for subfoveal choroidal melanomas. METHODS: Retrospective case series of 50 patients diagnosed as having subfoveal melanoma and treated with plaque brachytherapy. Patients underwent evaluation for tumor characteristics, visual acuity, radiation damage, local tumor control, and metastatic disease. RESULTS: Patients were followed up for a median of 54 (SD, 49.3) months. Forty-nine tumors (98%) were dome shaped. Subretinal fluid (overlying or a dependent exudative retinal detachment) was evident in 34 of 45 patients (76%). Treatment involved an apical radiation dose of 82.8 Gy (delivered across 5-7 days), resulting in a mean dose of 157.7 Gy to the fovea. Pretreatment median visual acuity was 20/50, which declined to 20/180 at last follow-up. Visual acuity was better than 20/200 in 33 patients (66%) at baseline and 25 (50%) at last follow-up; 13 patients (26%) lost 6 or more lines of vision. Twenty-eight patients (56%) developed radiation retinopathy; 16 (32%) required secondary intervention for radiation retinopathy, including intravitreal antivascular endothelial growth factor therapy, laser treatment, cryotherapy, or pars plana vitrectomy. The local tumor control rate of subfoveal tumors was 92%. Four patients (8%) required secondary enucleation. Metastasis developed in 2 patients (4%). CONCLUSIONS: Subfoveal choroidal melanomas in this series are almost exclusively dome shaped and likely to have an associated exudative retinal detachment. They are amenable to plaque radiation therapy. However, this tumor location is associated with a high incidence of radiation maculopathy and a low incidence of radiation cataract.

Systemic bevacizumab (Avastin) for exudative retinal detachment secondary to choroidal melanoma.

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.