Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture.

A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races.

Rescue intra-arterial chemotherapy following retinoblastoma recurrence after initial intra-arterial chemotherapy.

PURPOSE: To determine the efficacy of rescue intra-arterial chemotherapy (IAC) for retinoblastoma recurrence following failed initial IAC. METHODS: Retrospective, non-comparative, interventional case series of 12 eyes in 12 patients. INTERVENTION: Rescue IAC employed chemotherapy agents of melphalan (5mg, 7.5mg) alone or with additional topotecan (1mg). MAIN OUTCOME MEASURE: Tumor control and globe salvage. RESULTS: The median patient age at initial presentation was 16 months. At initial examination, the International Classification of Retinoblastoma grouping was group B (n=1), group D (n=7), or group E (n=4). The initial IAC was primary in 5 cases (42%) and secondary following failure of intravenous chemotherapy in 7 (58%). In all cases, initial IAC was delivered using melphalan 3mg (n=3), melphalan 5mg (n=7), or combination melphalan 5mg/topotecan 1mg (n=2) for a median of 3 cycles. The mean interval from initial IAC to recurrence necessitating rescue IAC was 5 months (median 4, range 2-10 months). Of the 12 patients, 3 (25%) had undergone previous enucleation of the opposite eye and the rescue IAC was planned for the only remaining eye. Rescue IAC was delivered for recurrent solid tumor (n=1), recurrent subretinal seeds (n=7), recurrent vitreous seeds (n=1), or combination recurrent subretinal/vitreous seeds (n=3). IAC was technically successful through the ophthalmic artery in 9 cases (75%) or the middle meningeal artery in 3 (25%). Rescue IAC involved median 3 cycles (mean 3, range 2-4 cycles) of higher dose melphalan in 4 cases (33%) or combination melphalan/topotecan in 8 (67%). At mean follow-up of 20 months (median 14 months, range 7-36 months), complete tumor control was achieved in 9 eyes (75%) and globe salvage in 8 eyes (67%). Of the 3 failure eyes, all were initially groups D or E, previously treated with initial IAC, and 2 had previous intravenous chemotherapy. There were 4 eyes that came to enucleation for persistent subretinal/vitreous seeds (n=3) or neovascular glaucoma without viable tumor (n=1). There was no case of cerebrovascular stroke, systemic metastasis, or death. CONCLUSION: Rescue IAC following retinoblastoma recurrence after initial IAC provided tumor control in 75% of cases and globe salvage in 67%. Rescue IAC can be considered in children who fail initial IAC, especially if the opposite eye has been enucleated.

Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation.

Polypoidal choroidal vasculopathy following photodynamic therapy for choroidal hemangioma.

PURPOSE: To report a case of circumscribed choroidal hemangioma (CCH) that responded to photodynamic therapy (PDT) but 3 years later developed polypoidal choroidal vasculopathy (PCV) with exudative retinopathy. METHODS: Case report. RESULTS: A 59-year-old woman with a juxtapapillary CCH in her left eye was treated with a single 83-second, 7.5 mm PDT laser spot at 689 nm (50 J/cm2) 15 minutes after the injection of intravenous verteporfin (6 mg/m2). Three years later, the patient presented with photopsia in her left eye. Fundus examination of the left eye showed CCH regressed completely to a flat atrophic scar. There was diffuse macular edema and exudative retinopathy along the inferotemporal vascular arcade. On indocyanine green angiography, there were hyperfluorescent dilated choroidal vessels inferior to the foveola with late staining and leakage consistent with PCV. Hypofluorescence superior and nasal to the optic disc at the site of the treated hemangioma, consistent with choroidal ischemia, was observed. She was treated with 1.25 mg (0.05 cc) intravitreal bevacizumab. After 21 months of follow-up, the exudative retinopathy and macular edema completely regressed. CONCLUSIONS: PDT is an effective treatment for CCH. Side effects of PDT for CCH are rare but include PCV.

Autofluorescence of choroidal melanoma in 51 cases.

AIM: To describe the autofluorescence features of choroidal melanoma. DESIGN: Non-comparative case series. PARTICIPANTS: 51 consecutive patients. METHODS: Standard fundus photography and autofluorescence photography (580 nm excitation, 695 nm barrier filter) were performed on all patients. Clinical features were correlated with autofluorescence features. MAIN OUTCOME MEASURE: Autofluorescence features of choroidal melanoma and overlying retinal pigment epithelium (RPE). RESULTS: The mean patient age was 59 years. The choroidal melanoma was a mean of 3.6 mm from the optic disc and 2.6 mm from the foveola. The mean tumour basal dimension was 11 mm and the mean tumour thickness was 4 mm. The choroidal melanoma showed intrinsic hypoautofluorescence (39%), isoautofluorescence (6%) and hyperautofluorescence (55%). Slightly increased hyperautofluorescence of the melanoma was found in pigmented tumours (versus non-pigmented), those with greater thickness and basal dimensions, and those with overlying disrupted RPE. Related RPE hyperplasia and atrophy showed hypoautofluorescence, drusen, RPE detachment and subretinal fluid showed slight hyperautofluorescence, and orange pigment displayed the brightest hyperautofluorescence. CONCLUSIONS: Choroidal melanoma generally shows slight intrinsic hyperautofluorescence and the brightness increases with pigmented tumours, larger tumours, and those associated with disrupted RPE. Overlying orange pigment shows remarkably bright hyperautofluorescence.

Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy: a report of three cases.

PURPOSE: To report three cases of bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy. METHODS: Retrospective, single-center case series. RESULTS: Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm-thick choroidal melanoma in the right eye (OD) and treated with plaque radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was treated with plaque radiotherapy. Final visual acuity was light perception OD and 20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a 7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow-up. No patient showed ocular melanocytosis. Stable tumor regression was achieved in all six eyes. Metastatic disease did not develop in any case over 16 years of follow-up. CONCLUSIONS: Monitoring of both eyes of patients with uveal melanoma is important for the remote possibility of melanoma in the second eye. In these three patients, plaque radiotherapy allowed for preservation of the globes and some vision.

Involution of retinochoroidal shunt vessel after radiotherapy for optic nerve sheath meningioma.

PURPOSE: To illustrate the development and involution of retinochoroidal shunt vessel of the optic disc in a patient with primary optic nerve sheath meningioma. CASE REPORT: A 38-year-old woman presented with gradual onset of blurred vision in her right eye. Examination revealed a right relative afferent pupillary defect and mild edema of the right optic disc. Computed tomography (CT) showed changes consistent with a primary optic nerve sheath meningioma affecting the orbital portion of the right optic nerve. Patient was observed without treatment and subsequently developed a retinochoroidal shunt vessel on her right optic disc. With progression of the meningioma towards the optic chiasm, treatment with stereotactic radiosurgery was done. Following treatment, the optic disc gradually became pale and the retinochoroidal shunt vessel decreased in caliber with complete involution three years after radiotherapy.

Choroidal melanoma metastatic to the contralateral choroid.

PURPOSE: To report metastasis of choroidal melanoma to the contralateral choroid. METHODS: Interventional case report. In a 49-year-old Caucasian female, a primary choroidal melanoma, left eye, was diagnosed and treated with Ruthenium-106 plaque radiotherapy. The choroidal melanoma showed excellent regression with flattening of the mass and adjacent chorioretinal atrophy. RESULTS: Fifteen years after brachytherapy for choroidal melanoma, left eye, the patient developed a metastatic melanoma to the contralateral choroid as the first sign of metastasis. No history of oculo(dermal) melanocytosis or cutaneous melanoma existed. Systemic evaluation disclosed multiple metastases confined to the liver. CONCLUSION: Metastasis to the contralateral choroid can be the first sign of metastasis from choroidal melanoma.

Circumscribed choroidal hemangioma: clinical manifestations and factors predictive of visual outcome in 200 consecutive cases.

PURPOSE: To review the clinical features and management of circumscribed choroidal hemangioma and determine factors predictive of poor visual outcome. DESIGN: Retrospective consecutive noncomparative interventional case series. PARTICIPANTS: Two hundred consecutive patients with circumscribed choroidal hemangioma. MAIN OUTCOME MEASURES: The main outcome measures were analyzed in 155 patients with follow-up of at least 3 months and included complete resolution of subretinal fluid, worsening of visual acuity (more than 2 Snellen lines), and poor final visual acuity (20/200 or worse). RESULTS: The patients were seen at a mean age of 45 years with symptoms of decreased visual acuity (81%), visual field defect (7%), metamorphopsia (3%), floaters (2%), progressive hypermetropia (1%), photopsia (1%), pain (1%), and no symptoms (6%). The referring diagnoses were choroidal hemangioma (29%), choroidal melanoma (29%), choroidal metastasis (9%), retinal detachment (6%), central serous chorioretinopathy (5%), and others. The tumor had a median base of 6.0 mm and median thickness of 3.0 mm. Secondary retinal detachment in the foveal region was present in 81% of the patients. Initial treatment included observation (51%), laser photocoagulation (44%), plaque radiotherapy (4%), external beam radiotherapy (1%), surgical repair of retinal detachment (1%), and enucleation for painful neovascular glaucoma (1%). Kaplan-Meier estimates revealed complete resolution of subretinal fluid in 60% patients at 5 years and 76% patients at 10 years follow-up. By multivariable analysis, clinical factors predictive of complete resolution of subretinal fluid included shorter duration of symptoms (P = 0.03) and inferior quadrant location of tumor (P = 0.001). At initial presentation, 82 of 155 (53%) patients had poor visual acuity (20/200 or worse), and 73 of 155 (47%) patients had good to moderate visual acuity (20/100 or better). Of those 82 patients with poor initial vision, poor final vision was found in 54% at 5 years and 80% at 10 years. Of the 73 patients with good to moderate initial vision, poor final vision was found in 12% at 5 years and 43% at 10 years. By multivariable analysis, clinical factors predictive of poor final visual acuity included poor initial visual acuity (P < 0.001), failure of previous laser photocoagulation before referral (P = 0.01), and tumor management with observation after referral (P = 0.02). Worsening of visual acuity (by more than 2 Snellen lines) was observed in 8% at 5 years and 28% at 10 years of those 82 patients who were initially seen with poor vision. Worsening of visual acuity was found in 10% at 5 years and 30% at 10 years of those 73 patients who initially were seen with good to moderate vision. CONCLUSIONS: Circumscribed choroidal hemangioma is a rare intraocular tumor. In 38% of cases, this tumor is initially misinterpreted before referral as choroidal melanoma or metastasis. Visual acuity is poor in more than 60% of patients at 10 years, despite successful control of associated subretinal fluid in 76% patients.

Clinical spectrum of primary ophthalmic rhabdomyosarcoma.

PURPOSE: To review the clinical presentation, histopathologic analysis, management, and ocular and systemic outcome of rhabdomyosarcoma affecting the ocular region. DESIGN: Retrospective, noncomparative, consecutive, interventional case series. PARTICIPANTS: Thirty-three consecutive patients with primary ophthalmic involvement of rhabdomyosarcoma from a single tertiary care center specializing in ocular oncology. MAIN OUTCOME MEASURES: Final visual acuity, treatment complications, local recurrence, and distant metastasis. RESULTS: The mean age at presentation was 10 years (median, 7 years; range, 1 month-68 years). At presentation, 8 patients (24%) were older than age 10 years and 4 patients (12%) were older than 20 years. The rhabdomyosarcoma was primarily located in the orbit in 25 cases (76%), conjunctiva in 4 cases (12%), eyelid in 1 case (3%), and uveal tract in 3 cases (9%). Symptoms or signs related to the tumor were present for a mean of 5 weeks and included proptosis in 10 patients (30%), eyelid swelling in 7 patients (21%), and blepharoptosis in 6 patients (18%). The initial diagnosis before referral to us included rhabdomyosarcoma in 8 cases (24%), conjunctivitis in 5 cases (15%), orbital or preseptal cellulitis in 5 cases (15%), idiopathic orbital inflammatory pseudotumor in 4 cases (12%), and others. Using the Intergroup Rhabdomyosarcoma Study Group staging and treatment protocols, the tumor was classified as group I in 4 cases (12%), group II in 12 cases (36%), group III in 16 cases (48%), and group IV in 1 case (3%). Treatment included surgical debulking and various regimens of chemotherapy and radiotherapy for the periocular tumors and enucleation for the three intraocular tumors. Local tumor recurrence was detected in 6 patients (18%). Orbital exenteration was necessary for tumor recurrence in 2 cases (6%). Long-term visual outcome of the 28 patients who maintained their globe was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 patients (18%), and 20/200 to no light perception in 12 patients (43%). Regional lymph node metastasis was detected in 2 patients (6%), one at initial visit and one after therapy. Distant metastasis occurred in 2 patients (6%), one detected at initial visit and one after therapy. With mean follow-up of 8.3 years, tumor-related death occurred in 1 patient (3%). CONCLUSIONS: Rhabdomyosarcoma can present in the orbit, eyelid, conjunctiva, and uveal tract. After treatment, local tumor recurrence occurs in 18%, metastasis in 6%, and death in 3%.

Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors.

OBJECTIVE: To evaluate the clinical factors predictive for tumor recurrence and treatment complications in a large series of children who underwent plaque radiotherapy for retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The participants included 141 children with retinoblastoma who were managed on the Oncology Service at Wills Eye Hospital with plaque radiotherapy between July 1976 and June 1999. MAIN OUTCOME MEASURES: Tumor recurrence and treatment complications. RESULTS: There were 208 tumors managed with plaque radiotherapy. The mean patient age at plaque treatment was 19 months. Prior treatment to the retinoblastoma of concern was delivered to 148 tumors (71%) and included various combinations of treatments such as intravenous chemoreduction, external beam radiotherapy, laser photocoagulation, thermotherapy, and cryotherapy. For 72 retinoblastomas (35%), more than one therapeutic method had failed to achieve tumor control before the use of plaque radiotherapy. Of the 208 retinoblastomas managed with plaque radiotherapy, Kaplan-Meier estimates of tumor control were 83% at 1 year and 79% at 5 years. Of the 60 tumors treated only with plaque radiotherapy (primary treatment), recurrence at 1 year was 12%. Of the 148 tumors treated after failure of other methods (secondary treatment), specific Kaplan-Meier estimates of tumor recurrence at 1 year was detected in 8% of tumors previously treated with chemoreduction, 25% of tumors previously treated with external beam radiotherapy, 34% tumors previously treated with both chemoreduction and external beam radiotherapy, and 8% of tumors previously treated with laser photocoagulation, thermotherapy, or cryotherapy (methods other than chemoreduction and external beam radiotherapy). Using multivariable analysis, the risks for tumor recurrence included the presence of tumor seeds in the vitreous, presence of subretinal tumor seeds, and increasing patient age. Using Kaplan-Meier estimates, radiation complications at 5 years of follow-up included nonproliferative retinopathy in 27%, proliferative retinopathy in 15%, maculopathy in 25%, papillopathy in 26%, cataract in 31%, glaucoma in 11%, and scleral necrosis in 0%. CONCLUSIONS: Plaque radiotherapy for retinoblastoma provides tumor control in 79% of cases at 5 years of follow-up. It is particularly useful for those tumors that fail treatment with chemoreduction, laser photocoagulation, thermotherapy, and cryotherapy. Tumors in young patients without vitreous or subretinal seeding show the best long-term control.

Intraocular surgery after treatment of retinoblastoma.

OBJECTIVES: To analyze the results of intraocular surgery in patients treated for retinoblastoma and to assess the ocular and systemic outcomes. DESIGN: Retrospective noncomparative case series. PATIENTS: Forty-five consecutive patients who underwent an introcular surgery after treatment for retinoblastoma. MAIN OUTCOME MEASURES: (1) Recurrence of retinoblastoma, (2) need for enucleation, and (3) systemic metastasis. Overall outcome was defined as favorable in the absence of any of these measures and unfavorable in the presence of 1 or more. RESULTS: Thirty-four patients (76%) underwent a single procedure of cataract surgery, a scleral buckling procedure, or pars plana vitrectomy and 11 (24%) underwent a combination of 2 or more surgical procedures. In all, 16 patients (36%) achieved final visual acuity better than 20/200. Unfavorable outcomes included recurrence of retinoblastoma in 14 patients (31%), enucleation in 16 (36%), and systemic metastasis in 3 (7%). Five patients (20%) who underwent cataract surgery, 5 (63%) who underwent a scleral buckling procedure, and 9 (75%) who underwent pars plana vitrectomy manifested an unfavorable outcome. The median interval between completion of treatment for retinoblastoma and intraocular surgery was 26 months in patients with a favorable outcome vs 6 months in those with an unfavorable outcome. CONCLUSIONS: Intraocular surgery after treatment for retinoblastoma may be justified in certain exceptional clinical situations. Cataract surgery is safe and effective in most cases. However, the need for a scleral buckling procedure and pars plana vitrectomy may be associated with a higher risk for recurrence of retinoblastoma, enucleation, and systemic metastasis, and a cautious approach is warranted.