Faculty Bibliography

The diagnosis and treatment of orbital and periorbital malignancies are challenging. These tumors can result in blindness, death, and significant cosmetic deformities. Herein, we present the most common ocular malignancies and a systematic approach to diagnosis. Further, we integrate the seventh edition American Joint Committee on Cancer staging system, biomarkers, and multidisciplinary approaches to treatment.

Schwannoma is a proliferation of neoplastic Schwann cells. Whereas schwannomas of the head and neck region are common, intraocular tissues are rarely affected. Uveal schwannoma has been aptly called a "pseudomelanoma", reflecting the difficulty in its clinical distinction from uveal malignant melanoma. Most of our current knowledge on intraocular schwannoma is limited to case reports, short case series, and non-comprehensive literature reviews. Three isolated reports of uveal schwannoma with extrascleral extension exist in literature, but the prognostic significance of this growth pattern is unknown. We present a patient with choroidal schwannoma with extrascleral extension and review 46 previously reported cases of uveal schwannomas to delineate clinical and pathologic characteristics of these intraocular tumors with a specific emphasis on schwannoma with extraocular extension.

OBJECTIVE: To evaluate the outcome of scleral patch grafts in a series of patients undergoing management for uveal and ocular surface tumors. DESIGN: Case series. PARTICIPANTS: Ten patients underwent scleral patch grafting. Five patients had uveal melanoma with extrascleral extension, 2 patients had scleromalacia secondary to plaque radiotherapy for uveal melanoma, 2 patients had suspicious uveoscleral nevi, and 1 patient had invasive conjunctival squamous cell carcinoma with scleral necrosis. METHODS: Retrospective, interventional, noncomparative chart review of patients undergoing treatment for ocular tumors followed by scleral grafts in a tertiary eye care center in the United States between September 2003 and January 2011. Sclera was reconstructed with allogenic scleral grafts. Clinical observations were performed after grafting. MAIN OUTCOME MEASURES: Structural integrity, appearance, and stability of the grafts. RESULTS: Ten patients were reviewed. All melanoma cases received plaque radiotherapy with palladium 103. The cases with nevi and squamous cell carcinoma underwent local resection with cryotherapy as primary treatment. In 8 cases, scleral grafting was performed as part of the initial surgery. In all of these cases, satisfactory anatomic and functional outcomes were achieved. In 2 cases with scleromalacia secondary to radiotherapy for uveal melanoma, grafts were placed several years after the initial treatment. In these 2 cases, one showed signs of graft retraction, whereas another showed graft thinning. No patients experienced graft infection, rejection, or tumor recurrence. CONCLUSIONS: In this series, scleral grafts were well accepted when placed as part of the primary tumor management despite synchronous radiotherapy, scleral resection, or cryotherapy. Grafting was less successful when performed as a late procedure for radiation-induced scleromalacia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Dosimetry of eye plaques for ocular tumors presents unique challenges in brachytherapy. The challenges in accurate dosimetry are in part related to the steep dose gradient in the tumor and critical structures that are within millimeters of radioactive sources. In most clinical applications, calculations of dose distributions around eye plaques assume a homogenous water medium and full scatter conditions. Recent Monte Carlo (MC)-based eye-plaque dosimetry simulations have demonstrated that the perturbation effects of heterogeneous materials in eye plaques, including the gold-alloy backing and Silastic insert, can be calculated with reasonable accuracy. Even additional levels of complexity introduced through the use of gold foil "seed-guides" and custom-designed plaques can be calculated accurately using modern MC techniques. Simulations accounting for the aforementioned complexities indicate dose discrepancies exceeding a factor of ten to selected critical structures compared to conventional dose calculations. Task Group 129 was formed to review the literature; re-examine the current dosimetry calculation formalism; and make recommendations for eye-plaque dosimetry, including evaluation of brachytherapy source dosimetry parameters and heterogeneity correction factors. A literature review identified modern assessments of dose calculations for Collaborative Ocular Melanoma Study (COMS) design plaques, including MC analyses and an intercomparison of treatment planning systems (TPS) detailing differences between homogeneous and heterogeneous plaque calculations using the American Association of Physicists in Medicine (AAPM) TG-43U1 brachytherapy dosimetry formalism and MC techniques. This review identified that a commonly used prescription dose of 85 Gy at 5 mm depth in homogeneous medium delivers about 75 Gy and 69 Gy at the same 5 mm depth for specific (125)I and (103)Pd sources, respectively, when accounting for COMS plaque heterogeneities. Thus, the adoption of heterogeneous dose calculation methods in clinical practice would result in dose differences >10% and warrant a careful evaluation of the corresponding changes in prescription doses. Doses to normal ocular structures vary with choice of radionuclide, plaque location, and prescription depth, such that further dosimetric evaluations of the adoption of MC-based dosimetry methods are needed. The AAPM and American Brachytherapy Society (ABS) recommend that clinical medical physicists should make concurrent estimates of heterogeneity-corrected delivered dose using the information in this report's tables to prepare for brachytherapy TPS that can account for material heterogeneities and for a transition to heterogeneity-corrected prescriptive goals. It is recommended that brachytherapy TPS vendors include material heterogeneity corrections in their systems and take steps to integrate planned plaque localization and image guidance. In the interim, before the availability of commercial MC-based brachytherapy TPS, it is recommended that clinical medical physicists use the line-source approximation in homogeneous water medium and the 2D AAPM TG-43U1 dosimetry formalism and brachytherapy source dosimetry parameter datasets for treatment planning calculations. Furthermore, this report includes quality management program recommendations for eye-plaque brachytherapy.

PURPOSE: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). DESIGN: Prospective, multicenter study. PARTICIPANTS: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. TESTING: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. MAIN OUTCOME MEASURES: Patients were managed for their primary tumor and monitored for metastasis. RESULTS: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. CONCLUSIONS: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.

PURPOSE: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by (103)Pd plaque radiotherapy. METHODS AND MATERIALS: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. RESULTS: Thirty patients were followed for a median 36 months (range, 12-90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extending into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75-100 Gy), lens dose 43.5 Gy (range, 17.8-60 Gy), fovea dose 1.8 Gy (range, 1.3-5 Gy), and central optic disc dose 1.7 Gy (range, 1.3-4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was >/=20/25 in 28 patients (93%) at a median 36 months' follow-up. CONCLUSION: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after (103)Pd treatment of iris and iridociliary melanomas.

Purpose. To evaluate aspiration cutter-assisted small-incision anterior orbitotomy. Methods. Three patients with orbital adnexal tumors underwent orbital biopsy through a 3-mm incision in the eyelid skin (n=2) or conjunctival fornix (n=1). Standard aspiration cutters were introduced into anterior and posterior orbital tumors utilizing a bimanual technique. Multiple passes were made into the tumor. Fresh specimens were analyzed for adequacy prior to the end of surgery. Cytopathology, histopathology, and immunohistochemical analysis were performed. Results. Aspiration cutter technique biopsies were diagnostic in 2 of 3 cases. Diagnoses were orbital lymphoma, metastatic endometrial adenocarcinoma, and metastatic prostate cancer. The 20-G aspiration cutter yielded the most tissue. No sutures were required for the small incisions. Conclusions. Sutureless, aspiration cutter biopsy offered benefits commonly associated with fine needle aspiration biopsy, controlled aspiration, and enclosed mechanical cutting

OBJECTIVE To evaluate the predictive value of the seventh edition American Joint Committee on Cancer (AJCC) staging system for conjunctival melanoma. METHODS Retrospective, observational case series of 42 eyes of 42 patients with conjunctival melanoma studied by reviewing medical records, pathology reports, and color photographs. The main evaluated outcomes were demographic information, laterality, tumor size, thickness, pathologic diagnosis, seventh edition AJCC stage (clinical and pathologic), recurrence, metastasis, and duration of follow-up. RESULTS There was no sex preference, and the median age was 61 years. Recurrent disease was noted in 33% of patients (n = 14 of 42), with 64% occurring at a median of 2.5 years (range, 1-5 years) after primary treatment. Metastasis was noted in 19% of patients. The significant predictive factors for high risk of tumor recurrence were tumors involving more than 1 quadrant (P = .02), tumors thicker than 0.5 mm (P = .04), and tumor multifocality (P = .04). The significant predictive factors for high risk of tumor metastasis were tumors thicker than 0.5 mm (P = .005), tumor invasiveness (P = .04), pathologic diagnosis of conjunctival melanoma rather than melanoma in situ (P = .04), and tumor recurrence (P < .001). Similarly, increasing AJCC T stages (clinical and pathologic) were associated with unfavorable outcomes. For example, clinical stage-related recurrence rates were 19% (Tis), 27% (T1), 33% (T2), and 75% (T3). Clinical stage-related lymphatic and distant metastasis rates were 0% (Tis), 20% (T1), 0% (T2), and 63% (T3). CONCLUSIONS Advanced AJCC T-stage (clinical and pathologic) tumors were at higher risk for recurrence and metastasis. In this study, the seventh edition AJCC staging system was predictive of local control and systemic spread of conjunctival melanoma.