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

Purpose: To 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.

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.

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

To evaluate the safety and tolerability and treatment efficacy of high-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy.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.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 (plt;0.05) reduction in CFT.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.

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P

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.

Two common variants in the gene encoding complement factor H (CFH), the Y402H substitution (rs1061170, c.1204C>T)(1-4) and the intronic rs1410996 SNP(5,6), explain 17% of age-related macular degeneration (AMD) liability. However, proof for the involvement of CFH, as opposed to a neighboring transcript, and knowledge of the potential mechanism of susceptibility alleles are lacking. Assuming that rare functional variants might provide mechanistic insights, we used genotype data and high-throughput sequencing to discover a rare, high-risk CFH haplotype with a c.3628C>T mutation that resulted in an R1210C substitution. This allele has been implicated previously in atypical hemolytic uremic syndrome, and it abrogates C-terminal ligand binding(7,8). Genotyping R1210C in 2,423 AMD cases and 1,122 controls demonstrated high penetrance (present in 40 cases versus 1 control, P = 7.0 × 10(-6)) and an association with a 6-year-earlier onset of disease (P = 2.3 × 10(-6)). This result suggests that loss-of-function alleles at CFH are likely to drive AMD risk. This finding represents one of the first instances in which a common complex disease variant has led to the discovery of a rare penetrant mutation.

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.

Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 x 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 x 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD. Hum Mol Genet

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.

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 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.

Purpose To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. Design Sibling correlation study and genome-wide association study (GWAS). Participants For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. Methods Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. Main Outcome Measures Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. Results The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree ( P = 4.2×10 –5 ), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3×10 –9 ), which was confirmed in the replication samples (OR, 1.38; P = 7.4×10 –14 for combined discovery and replication analysis). Conclusions Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

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.

To report on whole body positron emission tomography/computed tomography (PET/CT) screening for metastasis at diagnosis of primary uveal melanoma.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.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).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.

In 2009, thousands of attorneys working in the nation's top-tiered law firms were laid off in response to the economic recession. As a result, the majority of associates reported being troubled by their firms' lack of transparency regarding financial issues and layoffs. Given the secrecy surrounding employment decisions in many of the nation’s top law firms, this Note explores the ability of private attorneys to unionize, situating the possibility in a historical and economic context, and addresses practical considerations that may arise during formation of a private attorney labor union. This paper won third place in the 2009-2010 Louis Jackson Memorial National Student Writing Competition in Employment and Labor Law.

Two patients were diagnosed as having unilateral iris pigment epithelial (IPE) cysts that were documented to enlarge and induce angle closure. Transpupillary IPE cystotomies were performed using the Nd:YAG laser as a prophylactic measure to prevent angle-closure glaucoma. Anterior chamber anatomy and cyst dimensions were assessed before, during, and after long-term follow-up using slit-lamp biomicroscopy, gonioscopy, and 20- or 35-MHz high-frequency ultrasound imaging. Cystotomy resulted in immediate, visible deflation of both IPE cysts with subsequent resolution of angle closure. The cyst contents appeared clear and no secondary inflammation or glaucoma occurred. No evidence of cyst recurrence has been noted during 3 and 8 years of follow-up, respectively. Transpupillary Nd:YAG laser cystotomy offered a minimally invasive and effective treatment for angle closure induced by progressive IPE cysts.

To examine how tumor characteristics and dose affect cataract development after plaque radiation therapy.Three hundred and eighty-four patients were diagnosed with uveal melanoma and treated with palladium-103 ((103)Pd) plaque radiation therapy. Of these, 282 (74%) inclusion met exclusion criteria for follow-up time, tumor location, and phakic status. Then patient-, ophthalmic-, and radiation-specific factors (patient age, diabetes, hypertension, tumor location, tumor dimensions, and lens dose) were examined (by a Cox proportional regression model) as predictors for the development of radiation-related cataract.Radiation cataract developed in 76 (24%) of patients at a mean follow-up of 39.8 months (range, 1-192). Patients with anteriorly located tumors were noted to have a higher incidence of cataract at 43.0% (43 of 100 patients) vs. 18.1% (33 cataracts per 182 patients) for posteriorly located tumors (p0.0001). However, multivariate Cox proportional modeling showed that increasing patient age at time of treatment (p for trend = 0.0003) and higher lens dose (p for trend = 0.001) were the best predictors (biomarkers) for radiation cataract.Although anterior tumor location, greater tumor height, and increased patient age (at treatment) were associated with significantly greater risk for radiation cataract, dose to lens was the most significant factor.

Background and Objective: To evaluate optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) imaging for optic nerve head drusen (ONHD). Patients and Methods: Nine consecutive eyes with ONHD were imaged. Each underwent visual field testing, 20-MHz B-scan ultrasonography, photography, and OCT/SLO imaging of the nerve head. Similar evaluation was performed on 12 matched, disease-free control eyes for comparison. Results: OCT/SLO imaging of ONHD demonstrated lucencies (100%), variable amounts of displacement, and thickening of the overlying nerve fiber layer, as well as disorganization of the adjacent retinal pigment epithelium (44%). Optic nerve head topography was measured (using horizontal and vertical electronic calipers). Mean disc diameter was 1.81 mm (range: 1.49 to 2.12 mm). All ONHD demonstrated anterior displacement of the base of the optic nerve cup (shallowing) compared to controls. The cup base was a mean +0.32 mm anterior to the retinal pigment epithelium for ONHD versus −0.23 mm for normal controls. Conclusion: OCT/SLO revealed unique and clinically helpful views of ONHD.

Fundus autofluorescence imaging (FAF) in a case of diffuse uveal melanocytic proliferation is described in this study. It is a rare chorioretinopathy associated with systemic cancer, for which the exact pathological mechanisms are poorly understood. FAF-imaging revealed a diffuse background of hyper-autofluorescence associated with diffuse orange pigment deposition and islands of persistent hypo-fluorescence corresponding to loss of retinal pigment epithelium (RPE). In this disorder, increasingly smaller spots of FAF hypo-fluorescence were found from the center to the periphery of the affected retina. Fluorescein angiography demonstrated a negative of the FAF-images. FAF hypo-autofluorescence corresponded to optical coherence tomography (OCT) thinning or absence of the RPE-layer. Conversely, FAF hyper-autofluorescence correlated to thickening of the RPE-layer on OCT. The case demonstrates that FAF can be useful for the diagnosis of diffuse uveal melanocytic proliferation and offers greater insight into the pathophysiology of this disease.

To determine how tumor characteristics and radiation dose affect the incidence of radiation maculopathy (RM).Retrospective, consecutive case series.A consecutive case series of 384 uveal melanomas irradiated (mean apical dose, 71.2 Gy) were followed up for a mean 47.2 months. Tumor locations included: 122 (32%) centered anterior to the equator, 27 (7%) equatorial, and 235 (61%) posterior. Tumor sizes were American Joint Committee on Cancer class T1 (n = 180), T2 (n = 150), T3 (n = 47), and T4 (n = 7).RM occurred in 8 (7%) eyes with anterior uveal melanomas. In contrast, it was found in 82 (41%) eyes with posterior tumors. Multivariate analysis revealed the risk related to posterior location was greater compared with anterior location with a hazard ratio of 6.66 (95% confidence interval [CI], 4.94 to 22.50; P = .0001). Tumor height (6.0 mm) also demonstrated a high risk for RM (hazard ratio, 4.5; 95% CI, 2.68 to 10.17; P = .0001). A significant dose-response relationship was found between dose to fovea and RM (P = .0005, for trend). As compared with a dose of35 Gy, the risk of RM was 1.74 (95% CI, 0.98 to 3.1) for doses from 35 to 70 Gy, and the risk of RM was 2.43 (95% CI, 1.48 to 4.0) for doses of 70 Gy or more. Of interest, those anterior melanomas with RM had a mean apical height of 9.4 mm, as compared with a mean height of 3.3 mm for anterior tumors not associated with RM. Visual acuity was preserved if the fovea dose was less than 35 Gy.This study suggests that tumor location, tumor thickness, and radiation dose to the fovea are risk factors for the development of RM.

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.

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. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose The aim of this study was to describe autofluorescence characteristics of 30 suspicious choroidal nevi. Methods Fundus autofluorescence (FAF) images were reviewed retrospectively on 30 consecutive cases of suspicious choroidal nevi. Autofluorescence imaging was achieved using a fundus camera-based system with a barrier filter of 695 nm and excitation of 580 nm. All nevi exhibited one or more of the following characteristics: tumor thickness, basal dimension greater than 5 mm, subretinal fluid, posterior location, ophthalmic symptoms, or lipofuscin (orange pigment). Results Suspicious choroidal nevi were found to have specific FAF features. Orange pigment was noted in 67% of the nevi and appeared as very bright hyperfluorescent areas. Overlying retinal pigment epithelium hypertrophy and atrophy were noted in 50% and appeared darkly hypofluorescent. Subretinal fluid (17%) and drusen (17%) both appeared mildly hyperfluorescent. Conclusions Orange pigment was the most hyperfluorescent FAF finding. Because the presence of orange pigment is a known risk factor for malignant transformation, the use of camera-based FAF imaging may improve our ability to identify those choroidal nevi that will transform into malignant melanoma. More long-term follow-up studies will be required to determine the exact prognostic value of our findings.

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.

Background Positron-emission tomography/computed tomography (PET/CT) is a unique imaging tool that aids in the detection of cancerous lesions. It is currently and widely used for cancer staging (both initial and follow-up). Here we report our findings of second primary cancers incidentally discovered during PET/CT staging of patients with choroidal melanomas. Methods We performed a retrospective case review of 139 patients with uveal melanoma who were subsequently evaluated by whole-body [18-fluorine-labeled] 2-deoxy-2-fluoro-D-glucose (18FDG) PET/CT imaging. In this series, 93 were scanned before treatment and 46 during the course of their follow-up systemic examinations. Their mean follow-up was 50.9 months. Results Six patients (4.3%) had second primary cancers revealed by PET/CT imaging. Three patients (50%) were synchronous (found at initial staging), and the remaining 3 patients (50%) were metachronous (found at follow-up staging). Second primary cancers were found in the lung, breast, uterus, colon, and thyroid. Conclusions Although whole-body PET/CT scans were ordered as part of the staging process of patients with diagnosed choroidal melanoma, both synchronous and metachronous second primary cancers were found. PET/CT has become an indispensable tool for staging, diagnosis, and treatment planning for choroidal melanoma. The possibility of detecting second primary cancers should also be considered valuable.

Aims: To correlate the clinical, ultrasound and pathological features of the eyes first evaluated by 18-fluorine-labelled 2-deoxy-2-fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography and then enucleated for choroidal melanoma. Methods: 14 consecutive patients enucleated for choroidal melanoma were examined. At presentation, clinical, ultrasound and PET/computed tomography imaging were carried out. Ultrasound was used to measure the tumour size and evaluate the tumour shape and intrinsic vascularity (blood flow). Histopathological and immunohistochemical evaluations included tumour cell type, necrosis, glycogen content, vascularity and extrascleral extension. Results: 13 tumours were T3 and one T2 (American Joint Committee on Cancer – International Union against Cancer). The mean tumour height was 10.6 (range 3.5–17.7) mm with a largest basal dimension of 19.3 (range 14.5–30) mm. Patients having melanoma with the highest six standardised uptake values ((SUV) ⩾4.0) were (on average) >10 years older, their melanomas had larger basal dimensions and were epithelioid-cell type; three melanomas were centred anterior to the equator; three contained enlarged blood vessels (>150 μm in diameter); and three formed extrascleral extension. Patients with the two highest SUV tumours died due to metastatic melanoma. Conclusion: PET/computed tomography imaging offers a physiological assessment of glucose metabolism in primary choroidal melanomas. Increased FDG PET/computed tomography SUV was positively correlated with known clinical, pathological and ultrasound features linked to metastatic potential of choroidal melanoma.

Background The aim of this study was to evaluate early insertion of ocular prostheses for aesthetic rehabilitation after enucleation and review current methods of enucleation surgery. Methods Twelve patients with large intraocular malignancies were treated by enucleation with implant. At the end of surgery, a medium-size conformer was inserted onto the closed conjunctival wound (just before applying a pressure dressing). The pressure dressing was removed 3 to 5 days after surgery. Immediately after bandage removal, the patients saw themselves in a mirror and were offered placement of a relatively small ocular prosthesis. Patients were asked if they preferred their aesthetic appearance with or without the prosthesis. Results Eight patients (67%) tolerated introduction of the prosthesis at the time of removal of their pressure dressing (3 to 5 days after enucleation surgery). Because of discomfort, 4 were able to receive their prostheses at their second postoperative visit (day 12 or 13). The manipulation at prosthesis insertion and subsequent wearing was found to have no effect on wound closure, final prosthetic fittings, or movement of the permanent prosthesis. All patients were pleased with the cosmetic benefit afforded by early introduction of the prosthesis and preferred their appearance to that of their eye with the conformer. Conclusions Early replacement of the conformer by an ocular prosthesis allows for cosmetic rehabilitation and improved quality of life.

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.

Objective To evaluate size, characteristics, and regression of iris and iridociliary melanomas on high-frequency ultrasound images before and after plaque brachytherapy. Methods Retrospective review of high-frequency ultrasound characteristics of 24 consecutive iris and iridociliary melanomas before and after radiation therapy. Results The median tumor thickness before radiation therapy was 2.3 mm (range, 1.4-4.3 mm). Nineteen iris melanomas (79%) involved the ciliary body, 18 (75%) involved the iris pigment epithelium, 11 (46%) were club shaped, and 4 (17%) caused disinsertion of the iris root. At a median follow-up of 30 months after plaque brachytherapy, the mean tumor thickness had diminished to 1.2 mm (median, 1.2 mm; range, 0.9-1.9 mm). While all tumors exhibited a reduction in thickness, no tumors showed additional regression after 30 months past treatment. Fourteen tumors (58%) were noted to have increases in internal reflectivity. There was 1 failure of local control (at 6 years), successfully treated by a second application of plaque brachytherapy. Conclusion High-frequency ultrasonography revealed unique tumor characteristics, quantified tumor size, and demonstrated tumor response to radiation therapy.

Objective To evaluate the high-frequency B-scan ultrasonographic characteristics of squamous conjunctival neoplasia (conjunctival intraepithelial neoplasia and squamous cell carcinoma). Methods Each of 11 patients was examined with 20- and/or 50-MHz ultrasonography in a retrospective consecutive case series. Main Outcome Measures Ultrasonographic findings with clinical and histopathologic correlations. Results Eleven eyes of 11 patients (8 men) were affected. Disease involved the right eye in 6 (55%) of the patients and the left eye in 5 (45%) of the patients; it was multifocal in 5 (45%) of the eyes. All tumors extended to, or primarily involved, the limbal conjunctiva. One patient developed superficial spread overlying a functioning partial-thickness filtering bleb, 1 developed intraocular extension, 1 developed scleral invasion, and 3 developed orbital involvement before treatment. Results of ultrasonographic examinations showed that the superficial aspect of the smaller limbal tumors appeared as fusiform thickening of the conjunctiva. In all patients, the tumor surface was highly reflective in contrast to the characteristically low reflectivity seen within the tumor stroma. Intraocular tumor extension was variably reflective, but evidenced by blunting of the anterior chamber angle and thickening of the uvea. Orbital extension was viewed as low reflective tumor extension into the relatively hyperechoic orbital tissues. Conclusions High-frequency ultrasonography may be used to assess the extent of squamous conjunctival neoplasia. While the 50-MHz system offered better resolution, 20-MHz ultrasonography allowed for a wider and deeper field of view. High-frequency ultrasonography was useful in determining tumor thickness, shape, and internal reflectivity, and especially in revealing tumor extension into the sclera, eye, and orbit.