Faculty Bibliography

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

Importance: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. Objective: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). Design, Setting, and Participants: This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. Main Outcomes and Measures: Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. Results: One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). Conclusions and Relevance: Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

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

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

OBJECTIVE: To evaluate extraocular muscle surgery associated with plaque brachytherapy for choroidal melanoma. DESIGN: Single-center retrospective cohort study. PARTICIPANTS: Three hundred twenty-nine eyes of 329 consecutive patients with clinically diagnosed choroidal melanoma. INTERVENTION: Palladium 103 plaque brachytherapy with or without extraocular muscle surgery. MAIN OUTCOME MEASURES: Type of muscle surgery required for each tumor location, timing, incidence, and duration of diplopia, as well as treatment. RESULTS: Two hundred fifty-four patients (n = 254/329; 77.2%) required muscle surgery. One hundred seven patients (n = 107/329; 32.5%) required surgery on 2 or more muscles. Of 373 muscles repositioned, the lateral rectus muscle (n = 115/373; 30.8%) and inferior oblique muscle (n = 70/373; 18.7%) were the most common, correlating to intraocular tumor location (P<0.001). Only 6 tumors (n = 6/61; 9.5%) originating from the iris and ciliary body required muscle surgery for plaque placement. Of the 312 patients with a preoperative visual acuity better than 20/400, diplopia was reported at the first postoperative visit by 41 patients (n = 41/312; 13.1%), 2 of whom had not undergone muscle surgery. Diplopia resolved spontaneously within 1 month in 18 patients (n = 18/41; 43.9%), between 1 and 6 months in 12 patients (n = 12/41; 29.3%), and at more than 6 months in 5 patients (n = 5/41; 12.2%). Among the 312 patients, persistent diplopia occurred in 6 patients (1.9%), including 1 who had not undergone muscle surgery. Treatment was declined in 1 patient, 3 patients (n = 3/41; 7.3%) were treated with prisms, and 2 patients (n = 2/41; 4.9%) required surgery. CONCLUSIONS: Extraocular muscle surgery frequently is required for plaque brachytherapy. Although transient diplopia occurred in 11.2% of patients, persistent diplopia occurred in only 1.9% of patients and was treatable.

IMPORTANCE The clinical features of the follicular subtype of ocular adnexal lymphoma (OAL) have not been previously evaluated in a large cohort. OBJECTIVE To characterize the clinical features of follicular OAL. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective multicenter study that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). MAIN OUTCOMES AND MEASURES Overall survival, disease-specific, and progression-free survivals were the primary end points. RESULTS Ninety-eight eligible patients with follicular OAL were included; 60 (61%) were women. The median patient age was 63 years (range, 32-96 years). Sixty-nine patients (70%) had primary OAL, 19 (19%) had OAL in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma, and 31 (45%) had stage IIE lymphoma. Patients with disseminated lymphoma had stage IIIE (9 of 19 [47%]) and stage IV (10 of 19 [53%]) disease, whereas patients with a relapse of systemic lymphoma presented with stage IE (8 of 10 [80%]), stage IIE (1 of 10 [10%]), and stage IIIE (1 of 10 [10%]) disease. Patients with primary follicular lymphoma (n = 69) and those with isolated ocular relapse (n = 9) were treated with external beam radiation therapy (EBRT) (35 of 78 [45%]) or EBRT plus chemotherapy (22 of 78 [28%]). Patients presenting with stage IIIE-IV follicular lymphoma (n = 20) most frequently received chemotherapy (9 of 20 [45%]) or EBRT plus chemotherapy (4 of 20 [20%]). The 10-year overall survival for the entire study cohort was 60%. Primary patients treated with EBRT had a better disease-specific survival compared with patients receiving ERBT plus chemotherapy (10-year disease-specific survival, 94% vs 40%; P = .02 by log-rank test). CONCLUSIONS AND RELEVANCE Follicular OAL was more commonly found in elderly female patients. These tumors were equally noted to involve the conjunctiva, lacrimal gland, and orbit. Patients with ocular adnexal follicular lymphoma primarily treated with EBRT had a more favorable long-term disease-specific survival.

The authors describe a case report of idiopathic asymptomatic giant retinal cyst with underlying hyperpigmentation. Low- and high-frequency ultrasound (ultrasound biomicroscopy) revealed an anechoic giant cyst with two hyper-reflective traction bands between the ciliary body and the anterior base of the retinal cyst. There was no retinal detachment.

PURPOSE: To investigate if orbital extension of uveal melanoma can be treated with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: This study is a retrospective analysis of the results of a clinical case series was performed on 10 patients. Each underwent primary enucleation for uveal melanoma, was discovered to have orbital extension, and consented for HDR brachytherapy. By American Joint Committee on Cancer (AJCC) initial tumor grading, there was one each (T1c, T2c, T2d, and T3d, three T4c, and two T4d-staged uveal melanomas. One was AJCC-staged R2 due to orbital recurrence presenting 16 months after enucleation. 192Ir HDR brachytherapy involved transcutaneous circumferential orbital incisions allowing for evenly spaced brachytherapy catheters into the orbit. A target dose of 32.85 Gy (range, 32.85-34 Gy) was delivered in 9-10 twice-daily fractions (range, 3.4-3.65 Gy per fraction) over 5 consecutive days. Data analysis included but was not limited to radiation therapy methods, local tumor control, side effects, and metastatic rate. RESULTS: In the 9 patients who tolerated treatment, there has been no orbital recurrence at a median follow-up of 18 months (range, 1-62 months). Four patients died of metastatic disease (one presented with a treated solitary liver metastasis before brachytherapy). There was no significant eyelash or eyebrow loss. There was no radiation-induced eyelid erythema, orbital infection, or contracted sockets. All orbits accepted and maintained ocular prostheses. CONCLUSIONS: Brachytherapy was used as an alternative to external beam radiation treatment for postenucleation orbital melanoma. This series reports complete local control, few side effects, and excellent cosmetic results.

IMPORTANCE Patients with larger choroidal melanomas are being treated with plaque radiation therapy. OBJECTIVE To report the methods and results of palladium-103 brachytherapy for American Joint Committee on Cancer, 7th edition, T3- and T4-sized choroidal melanomas. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of the results of a clinical case series over a 10-year period of 47 consecutive patients with uveal melanoma. The patients were treated at The New York Eye Cancer Center, Beth Israel Comprehensive Cancer Center, or The New York Eye and Ear Infirmary between 2002 and 2012 and had a minimum follow-up of 6 months. Tumors had a mean preoperative apical tumor height of 8.6 mm and a mean largest basal diameter of 15.8 mm. MAIN OUTCOMES AND MEASURES We analyzed, but were not limited to, data on the methods of radiation therapy, local tumor control, adverse effects, vision retention, and metastatic rate. RESULTS All patients completed therapy and received the prescribed tumor apex dose. At a median of 47 months (range, 6-125 months), the rate of local control was 91% and the rate of eye retention was 89%. The most common long-term brachytherapy-related complication was radiation maculopathy (66% of patients), followed by radiation optic neuropathy (51% of patients). One or both of these complications were diagnosed at a mean time of 16 months (range, 2-36 months) after brachytherapy. Secondary cataract developed in 36% of patients. Glaucoma developed in 17% of patients and resulted in enucleation in 4% of patients. The mean pretreatment visual acuity was 20/50 (range, 20/12.5 to hand motions), which evolved to a mean visual acuity of 20/100 (range, 20/20 to no light perception). Overall, 25 of 47 patients (53%) maintained 20/200 or better vision. Metastatic melanoma developed in 32% of patients. CONCLUSIONS AND RELEVANCE Palladium-103 ophthalmic plaque radiation therapy can be used as an eye- and vision-preserving treatment for relatively large American Joint Committee on Cancer T3- or T4-sized choroidal melanomas.