Sara E. Lally

Survey of 520 eyes with uveal metastases.

OBJECTIVE The purpose of this investigation is to report the clinical features of patients with uveal metastases seen at a major ocular oncology center. DESIGN/PARTICIPANTS A retrospective chart review was performed on all patients with uveal metastases evaluated at an ocular oncology outpatient facility over a 20-year period. MAIN OUTCOME MEASURE To assess the systemic and ophthalmic features of uveal metastases. RESULTS A total of 950 uveal metastases were diagnosed in 520 eyes of 420 consecutive patients. Of the 950 metastatic foci, the uveal involvement included iris in 90 (9%), ciliary body in 22 (2%), and choroid in 838 (88%). The total number of uveal metastases per eye was 1 (71%) in 370 eyes, 2 (12%) in 63 eyes, and 3 or more (17%) in 87 eyes. The mean number of uveal metastases per eye was two (median, one). Iris metastases presented most often as a yellow-to-white solitary nodule in the inferior quadrant. Ciliary body metastases typically presented as a solitary, sessile, or dome-shaped yellow mass in the inferior quadrant, but were difficult to visualize directly. The choroidal metastases typically were yellow in color, plateau shaped, and associated with subretinal fluid. In the 479 eyes with choroidal metastases, the epicenter of the main tumor was found in the macular area in 59 eyes (12%), between the macula and equator in 383 eyes (80%), and anterior to the equator in 37 eyes (8%). The mean size of the main (largest) choroidal tumor in each eye was 9 mm in base and 3 mm in thickness. At the time of ocular diagnosis, 278 patients (66%) reported a history of a primary cancer and 142 patients (34%) had no history of a cancer. Subsequent evaluation of these 142 patients after the ocular diagnosis of uveal metastasis showed a primary tumor in the lung in 50 patients (35%), breast in 10 (7%), others in 9 (6%), and no primary site was found in 73 patients (51%). Nearly half of the patients with no known primary site eventually died of diffuse metastatic disease. In the entire group of 420 patients, the uveal metastasis came from a primary cancer of the breast in 196 (47%), lung in 90 (21%), gastrointestinal tract in 18 (4%), kidney in 9 (2%), skin in 9 (2%), prostate in 9 (2%), and other cancers in 16 (4%). In 73 cases (17%), the primary site was never established despite systemic evaluation by medical oncologists. CONCLUSIONS Iris, ciliary body, and choroidal metastases have typical clinical features that should suggest the diagnosis. The choroid is the most common site for uveal metastases, and the tumors occur most often in the posterior pole of the eye with an average of two tumors per eye. Approximately one third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung cancers represent more than two thirds of the primary tumor sites.

Intra-arterial Chemotherapy for Retinoblastoma: Report No. 1, Control of Retinal Tumors, Subretinal Seeds, and Vitreous Seeds

OBJECTIVE To describe tumor control following intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS A retrospective interventional series in which 17 patients were treated with ophthalmic artery injection of melphalan, 5 mg, was undertaken to determine retinoblastoma control. RESULTS Of 190 children with retinoblastoma, 17 (9%) were treated with IAC. Catheterization was successful in 37 of 38 attempts. The treatment was primary in 13 cases (1 failed catheterization) and secondary in 4. The median retinoblastoma base was 20 mm and the median retinoblastoma thickness was 9.0 mm. Iris neovascularization was present in 5 cases. Following IAC, complete response of the main tumor was found in 14 cases (88%) and partial response was found in 2 (12%). Eyes with complete response and followed up for a minimum of 1 year (n = 10) showed no solid tumor recurrence. Of 11 eyes with subretinal seeds, 9 (82%) had complete response, 1 (9%) had partial response, and 1 (9%) had recurrence. Of 9 eyes with vitreous seeds, 6 (67%) had complete response, 2 (22%) had partial response, and 1 (11%) had recurrence. Globe salvage was achieved in 8 of 12 eyes (67%) treated with primary IAC, including 2 of 2 group C eyes, 4 of 4 group D eyes, and 2 of 6 group E eyes according to the International Classification of Retinoblastoma. Globe salvage was achieved in 2 of 4 eyes (50%) treated secondarily after failure of other methods. CONCLUSIONS Of 12 eyes managed with IAC as primary treatment, globe salvage was achieved in 67%. Eyes classified as group C or D showed 100% globe salvage, whereas group E had 33% salvage. Of 4 eyes managed with IAC as secondary treatment, globe salvage was achieved in 50%.

Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma.

OBJECTIVE To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy. DESIGN Retrospective interventional case series. PARTICIPANTS A total of 70 eyes of 67 patients. INTERVENTION Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary. MAIN OUTCOME MEASURES Tumor control and treatment complications. RESULTS The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death. CONCLUSIONS Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.

Conjunctival Melanoma: Outcomes Based on Tumor Origin in 382 Consecutive Cases

PURPOSE To evaluate prognostic factors based on origin of conjunctival melanoma. DESIGN Interventional case series. PARTICIPANTS Three hundred eighty-two consecutive patients. METHODS Retrospective chart review. MAIN OUTCOME MEASURES Melanoma-related metastasis and death. RESULTS The melanoma arose from primary acquired melanosis (PAM; n = 284; 74%), from pre-existing nevus (n = 26; 7%), and de novo (n = 72; 19%). The mean tumor base was 11 mm for melanoma arising from PAM, 6 mm for melanoma arising from nevus, and 10 mm for those arising de novo. At 5 years (10 years), melanoma metastasis occurred in 19% (25%) in melanoma arising from PAM (P = 0.003), 10% (26%) in melanoma from nevus (P = 0.193), and 35% (49%) in those de novo. Factors predictive of metastasis by multivariable analysis included tumor origin de novo (P = 0.001), palpebral location (P<0.001), nodular tumor (P = 0.005), and orbital invasion (P = 0.022). At 5 years (10 years), melanoma-related death occurred in 5% (9%) in melanoma arising from PAM (P<0.001), 0% (9%) in melanoma arising from nevus (P<0.057), and 17% (35%) in those arising de novo. Factors predictive of death by multivariable analysis included tumor origin de novo (P<0.001), fornix location (P = 0.04), and nodular tumor (P = 0.001). CONCLUSIONS Melanoma arising de novo carries a higher risk of melanoma-related metastasis and death compared with those cases arising from PAM or nevus.

Original articleIntra-arterial Chemotherapy for Retinoblastoma in 70 Eyes: Outcomes Based on the International Classification of Retinoblastoma

OBJECTIVE To analyze our 5-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma as primary or secondary therapy. DESIGN Retrospective interventional case series. PARTICIPANTS A total of 70 eyes of 67 patients. INTERVENTION Ophthalmic artery chemotherapy infusion under fluoroscopic guidance was performed using melphalan (3, 5, or 7.5 mg) in every case, with additional topotecan (1 mg) and/or carboplatin (30 or 50 mg) as necessary. MAIN OUTCOME MEASURES Tumor control and treatment complications. RESULTS The mean patient age at IAC was 30 months. The treatment was primary in 36 eyes and secondary in 34 eyes. Those primary therapy eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 1), C (n = 4), D (n = 17), or E (n = 14). The secondary therapy eyes had failed previous intravenous chemotherapy (n = 34) in every case. Each eye received a mean of 3 IAC sessions per eye (median, 3; range, 1-7 sessions). After IAC with a mean follow-up of 19 months, globe salvage was achieved in 72% of primary-treated cases and in 62% of secondary-treated cases. Specifically, primary therapy achieved globe salvage for group B (100%), group C (100%), group D (94%), and group E (36%). Of all 70 eyes, complete regression was achieved for solid tumor in 48 of 51 eyes (94%), subretinal seeds in 40 of 42 eyes (95%), and vitreous seeds in 34 of 39 eyes (87%). After each catheterization (n = 198), the main complications included transient eyelid edema (5%), blepharoptosis (5%), and forehead hyperemia (2%). More lasting complications included vitreous hemorrhage (2%), branch retinal artery obstruction (1%), ophthalmic artery spasm with reperfusion (2%), ophthalmic artery obstruction (2%), partial choroidal ischemia (2%), and optic neuropathy (<1%). Over the past 3 years, the combined incidence of ophthalmic, retinal, and choroidal vascular ischemia was reduced to 1%. There was no patient with stroke, seizure, neurologic impairment, limb ischemia, secondary leukemia, metastasis, or death. CONCLUSIONS Five-year experience with IAC indicates that this technique is remarkably effective for the management of retinoblastoma as both a primary and a secondary treatment.

Interferon for ocular surface squamous neoplasia in 81 cases: outcomes based on the American Joint Committee on Cancer classification.

Purpose: To assess the efficacy of interferon alpha-2b (IFN&agr;2b) in the management of ocular surface squamous neoplasia (OSSN). Methods: This is a retrospective, nonrandomized interventional case series study of 80 patients with 81 tumors treated with IFN&agr;2b eye drops and/or injection combined with surgical excision when necessary. The main outcome measure was complete response or partial response based on the American Joint Committee on Cancer classification. Results: The OSSN was classified as Tis (n = 10, 12%), T1 (n = 13, 16%), T2 (n = 6, 7%), T3 (n = 51, 63%), and T4 (n = 1, 1%). IFN&agr;2b was used as immunotherapy alone (n = 22, 27%) or combined with surgery (n = 59, 73%). Overall (n = 81), complete response was achieved in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4. Specifically for immunotherapy (n = 22), IFN&agr;2b alone achieved complete response in 75% (3/4) Tis, in 100% (8/8) T1, and in 70% (7/10) T3. Planned IFN&agr;2b plus surgery (n = 59) achieved control in 100% (6/6) Tis, in 100% (5/5) T1, in 100% (6/6) T2, in 100% (41/41) T3, and in 100% (1/1) T4. Tumor recurrence was noted in 5% (4/81) of cases over a median follow-up of 1 year. Ocular side effects included conjunctival hyperemia (n = 4, 5%), ocular irritation (n = 3, 4%), superficial punctate keratitis (n = 3, 4%), and conjunctival follicles (n = 1, 1%). Systemic side effects included postinjection flu-like syndrome for 1 day (n = 7, 9%). Conclusions: IFN&agr;2b, when appropriately combined with surgical excision for OSSN, provides complete control in 95% of cases overall, specifically in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4.

Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

Purpose of review The management of retinoblastoma is complex and involves strategically chosen methods of enucleation, radiotherapy, chemotherapy, laser photocoagulation, thermotherapy, and cryotherapy. Chemotherapy has become the most common eye-sparing modality. There are four routes of delivery of chemotherapy for retinoblastoma, including intravenous, intra-arterial, periocular, and intravitreal techniques. The purpose of this review is to discuss the current rationale for each method and the anticipated outcomes. Recent findings The diagnosis of retinoblastoma should be clinically established prior to embarking on a chemotherapy protocol. There are over 25 conditions that can closely simulate retinoblastoma in a young child. In addition, enucleation is an acceptable method for management, particularly with advanced retinoblastoma. Intravenous chemotherapy is generally used for germline mutation (bilateral, familial) retinoblastoma with excellent tumor control for groups A, B, and C and intermediate control for group D eyes. Intra-arterial chemotherapy is used as primary therapy in selected cases for nongermline mutation (unilateral) retinoblastoma with excellent control, and also used as secondary therapy for recurrent solid retinoblastoma, subretinal seeds, and vitreous seeds. Periocular chemotherapy is employed to boost local chemotherapy dose in advanced bilateral groups D and E eyes or for localized recurrences. Intravitreal chemotherapy is used for recurrent vitreous seeds from retinoblastoma. Patients at high risk for metastases should receive intravenous chemotherapy. Summary Chemotherapy is effective for retinoblastoma and the targeted treatment route depends on the clinical features and anticipated outcomes.

Giant ocular surface squamous neoplasia managed with interferon alpha-2b as immunotherapy or immunoreduction.

OBJECTIVE To evaluate the efficacy of interferon alpha-2b (IFNα2b) for extensive ocular surface squamous neoplasia (OSSN). DESIGN Retrospective, interventional case series. PARTICIPANTS Eighteen eyes in 18 patients. METHODS Each patient with giant OSSN (a single tumor ≥15 mm basal diameter or ≥6 limbal clock-hours) was managed with topical IFNα2b (1 million IU/ml) 4 times daily or with injection IFNα2b (a portion of 10 million IU/ml vial) with follow-up every 1 to 3 months. MAIN OUTCOME MEASURES Tumor response, recurrence, and treatment complications were evaluated. RESULTS Eighteen patients with giant OSSN (median diameter [MD], 20 mm; median clock-hours [MCH], 6) were treated with topical IFNα2b (n = 12), injection IFNα2b (n = 3), or both (n = 3). The IFNα2b achieved complete tumor control (immunotherapy) in 13 eyes and partial tumor control with reduction in size (immunoreduction) in 5 eyes. Topical IFNα2b alone (n = 12) provided complete immunotherapy in 7 eyes (MD, 12 mm; MCH, 9) over a median period of 5 months and immunoreduction by 74% in 5 eyes (MD, 20 mm; MCH, 3), allowing for subsequent surgical excision (n = 3), photodynamic therapy (n = 1), or cryotherapy (n = 1) for tumor control. Injection IFNα2b alone (n = 3; median, 1 injection) provided complete control of giant tarsal conjunctival OSSN (MD, 20 mm) over a 1-month period. A combination of topical and injection IFNα2b (n = 3; median, 3 injections) completely resolved larger tumors (MD, 30 mm; MCH, 6) over a 6-month period. Complications of IFNα2b included transient flu-like symptoms (n = 3), corneal epithelial defect (n = 2), and conjunctival hyperemia (n = 1). During a median follow-up of 11 months, there were no tumor recurrences, but 2 new tumors appeared at a remote site from the original tumor, requiring operative intervention. CONCLUSIONS In 72% of giant OSSNs IFNα2b achieved complete control (immunotherapy); there was a reduction in size (immunoreduction) in 28% of giant OSSNs.

Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes.

IMPORTANCE Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients. In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis. OBJECTIVE To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma. DESIGN, SETTING, AND PATIENTS Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008. EXPOSURES Enucleation, plaque radiotherapy, local resection, or thermotherapy. MAIN OUTCOMES AND MEASURES Metastasis and death. RESULTS Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%). The melanocytosis involved the sclera (92%), iris (17%), choroid (12%), eyelid (8%), and temporal fossa (1%). Eyes with melanoma and oculo(dermal) melanocytosis had a relative risk for metastasis 1.6 times greater compared with those with no melanocytosis (P < .001). Metastasis of uveal melanoma was 2.8 times higher in patients with iris melanocytosis (P < .001), 2.6 times higher with choroidal melanocytosis (P = .02), and 1.9 times higher with scleral melanocytosis (P < .001). By Kaplan-Meier estimates, metastasis in patients with oculo(dermal) melanocytosis vs no melanocytosis was 2% vs 1.8% at 1 year, 27% vs 15% at 5 years, and 48% vs 24% at 10 years (P < .001). By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis. All patients with oculo(dermal) melanocytosis should undergo ophthalmic examination and imaging on a twice-yearly basis because this could help with the early detection of melanoma.

Reply re: "American Joint Committee on Cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes".

Purpose: The aim of this study was to evaluate conjunctival melanoma outcomes based on American Joint Committee on Cancer classification. The study design constituted a nonrandomized interventional case series. Methods: This was a retrospective chart review comprising 343 participants, and the main outcome measures were melanoma local recurrence, lymph node metastasis, distant metastasis, and death. Results: On the basis of the American Joint Committee on Cancer classification (seventh edition), conjunctival melanoma was classified as T1 (196 [57%]), T2 (110 [32%]), T3 (37 [11%]), and T4 (0). The mean tumor basal diameter increased with tumor staging with 8.5 mm for T1, 12.7 mm for T2 (p = 0.0003), and 16 mm for T3 (p < 0.0001). The melanoma arose from primary acquired melanosis (T1 = 71%; T2 = 84%; T3 = 81%), preexisting nevus (T1 = 8%; T2 = 5%; T3 = 3%), or de novo (T1 = 21%; T2 = 12%; T3 = 16%). Outcomes at 5 years (Kaplan–Meier) revealed melanoma local recurrence/new tumor in 44% T1, 78% T2 (p < 0.0001), and 76% T3 (P=0.0044); regional lymph node metastasis in 17% T1, 52% T2 (p < 0.0001), and 49% T3 (p = 0.0092); melanoma-related distant metastasis in 11% T1, 35% T2 (p < 0.0001), and 42% T3 (p = 0.0018); and melanoma-related death in 5% T1, 20% T2 (p = 0.0655), and 23% T3 (p = 0.0526). Based on American Joint Committee on Cancer classification, factors predictive of melanoma recurrence included T2 stage (p < 0.0001), and T3 stage (p = 0.0061). After adjusting for tumor origin, factors predictive of regional lymph node metastasis, melanoma-related distant metastasis, and melanoma-related death included melanoma arising de novo (p < 0.0001; p < 0.0001; p < 0.0001), T2 stage (p < 0.0001; p < 0.0001; p = 0.007), and T3 stage (p = 0.005; p = 0.0014; p = 0.0342). Conclusion: The American Joint Committee on Cancer staging predicts prognosis of conjunctival melanoma. Melanoma classified as T2 and T3 (compared with T1) showed significantly higher rates of local recurrence, regional lymph node metastasis, distant metastasis, and death.