15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.

PURPOSE: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD). METHODS: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52. RESULTS: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (-31.9 µ m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 µ m compared with week 14. By week 52, improvements in BCVA and CST were lost. CONCLUSION: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.

Annulus-shaped I-125 plaque brachytherapy for conjunctival melanoma.

Purpose: To report successful ring-shaped iodine-125 plaque brachytherapy for conjunctival melanoma. Observations: Eye Physics (EP) plaque brachytherapy, designed with Plaque Simulator software, proved to be an effective treatment modality with some corneal irritation and no recurrence at 12-months post radiation. Conclusion and importance: Management of conjunctival melanoma is complicated by the lack of gold standard adjuvant treatments. I-125 EP plaque brachytherapy represents a viable option for these malignancies. Specifically, ring-shaped plaque geometries allow for targeted radiotherapy.

Chorioretinal Biopsy-Proven Ocular Sarcoidosis in a Patient with a History of B-Cell Lymphoma.

The purpose of this report is to describe biopsy-proven ocular sarcoidosis (OS) in a 67-year-old patient with a history of sarcoidosis and diffuse large B-cell lymphoma (DLBCL). Nonspecific posterior chorioretinal lesions in a patient with prior malignancy necessitated chorioretinal biopsy to rule out metastatic lymphoma. The association between sarcoidosis and malignancy remains unclear and can complicate management of similar patients with nonspecific posterior segment findings. Chorioretinal biopsy may, therefore, be required to rule out malignancy in patients with a leading history.

Radiation therapy for uveal melanoma: a review of treatment methods available in 2021.

PURPOSE OF REVIEW: Radiation therapy has become the standard of care for the treatment of uveal melanoma. We intend to outline the current radiation therapy methods that are employed to treat uveal melanoma. We will outline their relative benefits over one another. We will also provide some background about radiation therapy in general to accustom the ophthalmologists likely reading this review. RECENT FINDINGS: Four main options exist for radiation therapy of uveal melanoma. Because the eye is a small space, and because melanomas are relatively radioresistant, oncologists treating uveal melanoma must deliver highly focused doses in high amounts to a small space. Therapies incorporating external beams include proton beam therapy and stereotactic radiosurgery. Stereotactic radiosurgery comes in two forms, gamma knife therapy and cyberknife therapy. Radiation may also be placed directly on the eye surgically via plaque brachytherapy. All methods have been used effectively to treat uveal melanoma. SUMMARY: Each particular radiotherapy technique employed to treat uveal melanoma has its own set of benefits and drawbacks. The ocular oncologist can choose amongst these therapies based upon his or her clinical judgment of the relative risks and benefits. Availability of the therapy and cost to the patient remain significant factors in the ocular oncologist's choice.

An amelanotic choroidal melanoma arising in a young man with tattoo-associated sarcoidosis.

PURPOSE: To describe a patient with an amelanotic choroidal melanoma, originally misdiagnosed as a choroidal granuloma, following his systemic diagnosis of tattoo-associated sarcoidosis. OBSERVATIONS: The amelanotic choroidal tumor, suspected to be a granuloma, failed initial steroid treatment. Full-thickness chorioretinal biopsy demonstrated histologic presence of uveal melanoma and tumor genetics via GEP analysis demonstrated a PRAME negative, Class 1A lesion. The amelanotic choroidal melanoma was treated successfully with I-125 plaque brachytherapy. CONCLUSION AND IMPORTANCE: Despite a systemic diagnosis which predisposes a patient to uveal granuloma, amelanotic choroidal melanomas can still occur and should be considered. The association of uveal melanoma and sarcoidosis remains rare and of unclear significance.

A case of giant cell arteritis presenting with nodular posterior scleritis mimicking a choroidal mass.

PURPOSE: Herein we present a case of giant cell arteritis presenting with nodular posterior scleritis and exudative retinal detachment mimicking a choroidal mass. OBSERVATIONS: A 67-year-old man presented with sudden onset left-sided periorbital pain, blurry vision, and a choroidal lesion in the posterior pole. Despite treatment with high-dose oral prednisone for suspected nodular posterior scleritis mimicking a choroidal mass, the vision in his left eye did not recover, and he developed optic nerve pallor on exam. Further evaluation revealed an ESR of >140 mm/hr (Upper limit of normal = 20 mm/hr), a CRP of 113 mg/L (Upper limit of normal = 9 mg/L), and a temporal artery biopsy consistent with GCA. The patient was started on methotrexate and the oral steroids were slowly tapered. CONCLUSIONS: Given the potential for GCA to present with scleritis and the potential for nodular posterior scleritis to mimic a choroidal mass, presence of a painful choroidal lesion with optic nerve swelling should prompt an evaluation for GCA to prevent permanent and bilateral vision loss.

BILATERAL UVEAL METASTASES SECONDARY TO PROSTATE ADENOCARCINOMA.

PURPOSE: To report a patient with bilateral uveal metastases secondary to previously quiescent prostate adenocarcinoma with a 22-month follow-up. METHODS: Retrospective chart review was performed for this patient. RESULTS: Androgen deprivation therapy and external beam radiation therapy were shown to manage ocular symptoms in a sixty-nine-year-old man previously diagnosed with adenocarcinoma of the prostate. CONCLUSION: Uveal metastases can be the first site of systemic metastasis even long after initial diagnosis and treatment of prostate adenocarcinoma; the 17 years between this patient's treatment for adenocarcinoma and commencement of his ocular symptoms is the longest interval reported. Hormonal therapy, in conjunction with radiation therapy, can successfully reduce tumor burden in these patients and improve visual symptoms over time.

Local Anesthesia With Blunt Sub-Tenon's Cannula Versus Sharp Retrobulbar Needle for Vitreoretinal Surgery: A Retrospective, Comparative Study.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of a blunt sub-Tenon's cannula for local anesthesia before vitreoretinal surgery compared to a sharp retrobulbar needle. PATIENTS AND METHODS: Retrospective, comparative study of all patients undergoing vitreoretinal surgery at the Medical College of Wisconsin between August 2009 and November 2013. Institutional review board approval was obtained. RESULTS: Of 940 surgeries performed with a sub-Tenon's cannula, 99% (938 of 940) were completed. Of the 771 surgeries performed with a sharp retrobulbar needle, 99% (770 of 771) were completed. Factors associated with use of a sharp retrobulbar needle over sub-Tenon's cannula were presence of prior scleral buckle (P < .01) and inclusion of scleral buckle placement in the procedure (P < .01). No case of globe perforation, severe retrobulbar hemorrhage, or severe conjunctival chemosis was observed in either group. CONCLUSION: Blunt sub-Tenon's cannula appears as effective and safe as a sharp retrobulbar needle for local anesthesia during vitreoretinal surgery. Vitreoretinal surgeons may wish to consider a blunt sub-Tenon's cannula for local surgical anesthesia.

Unusual multifocal pigmented lesions of the uvea in a patient with ocular melanocytosis.

PURPOSE: To report findings of unusual multifocal pigmented lesions in a single patient with sector uveal melanocytosis. METHODS: Retrospective case report of an otherwise healthy 64-year-old man with unusual uveal pigmentation. Complete ocular examination, including slit-lamp biomicroscopy, ophthalmoscopy, optical coherence tomography, and ultrasound biomicroscopy, was performed. RESULTS: Slit-lamp examination disclosed inferior sector pigmentation of the iris. Ophthalmoscopy showed multiple discrete, deeply pigmented, inferior choroidal lesions, and ultrasound biomicroscopy confirmed a small inferior ciliary body mass. The findings were consistent with sector uveal melanocytosis, believed to be the same as a diffuse melanocytoma. CONCLUSION: Melanocytoma is typically a unilateral, unifocal lesion that occurs on the optic disc but can be located anywhere in the uveal tract. This is a case of unusual pigmented uveal lesions, likely representing a variant of sector uveal melanocytosis or multiple diffuse uveal melanocytomas.

Decreased striatal c-Fos accompanies latent inhibition in a conditioned taste aversion paradigm.

Latent inhibition (LI) is a phenomenon whereby previous exposure to a stimulus retards subsequent acquisition of a conditioned response to that stimulus. The present study investigated the neuronal substrates of LI as assessed in a conditioned taste aversion paradigm by comparing regional c-Fos activation in pre- vs. non-pre-exposed animals. The LI paradigm involved a pre-exposure phase in which water-deprived rats were allowed access to either water (non-pre-exposed; NPE) or 5% sucrose (pre-exposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. Two hours following the onset of the test phase, animals were perfused and their brains processed for c-Fos immunohistochemistry. PE animals drank significantly more sucrose on the test day, indicating the presence of LI. PE animals had significantly fewer FLI-positive cells in the striatum than NPE animals; however, no differences were seen in the nucleus accumbens. This difference in FLI was not due to a difference in sucrose consumption on the test day as there was no correlation between c-Fos and amount of sucrose consumed in the PE group. These data are consistent with previous data supporting a role for the striatum in the disruption of LI as assessed by CTA.