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.

Treatment of metastatic uveal melanoma in 2022: improved treatment regimens and improved prognosis.

PURPOSE OF REVIEW: Until recently, metastatic uveal melanoma was associated with essentially uniform fatality within months. However, recent developments in screening, improved understanding of the genetic underpinnings of metastatic disease, and pivotal medication approvals have improved the disease's rate of fatality. RECENT FINDINGS: Routine implementation of genetic testing at the time of primary tumor treatment via gene expression profiling or chromosomal analysis has identified patients who are at high risk for metastatic disease. Enhanced screening with imaging directed at the liver and lungs has allowed for identification of early disease and lower tumor burden. Significant work on improved liver directed therapy along with systemic chemotherapy and immunotherapy has improved life expectancy. The first systemic immunotherapy specifically for metastatic uveal melanoma was approved this year. This medication, tebentafusp, is likely to improve life expectancy for all patients with metastatic melanoma assuming they have appropriate human leukocyte antigen (HLA) markers. Multiple clinical trials with novel immunotherapeutic agents are promising as well. SUMMARY: The prognosis for patients with uveal melanoma is far better than ever before because of recent developments in the understanding and treatment of metastatic disease.

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.

Photodynamic Therapy with Verteporfin for Choroidal Metastasis Refractory to Radiotherapy.

A 54-year old female with longstanding metastatic breast cancer was referred for management of choroidal metastases. She was first treated with external beam radiotherapy and experienced some response before later suffering progression of her eye disease. We then treated her using full fluence Photodynamic therapy (PDT) with Verteporfin, which resulted in regression of her lesions until she passed away due to other illnesses. This is the first documented successful application of PDT for choroidal metastasis from a primary breast cancer refractory to external beam radiotherapy.

Endoresection utilizing pars plana vitrectomy for benign and malignant intraocular tumors.

PURPOSE OF REVIEW: Endoresection of intraocular tumors is a complicated procedure utilizing pars plana vitrectomy techniques. Though it has potential downsides and complications, there is potential for this technique in the treatment of malignant and benign intraocular tumors. RECENT FINDINGS: Endoresection has been utilized in some form for the last three decades, but recent advances in vitreoretinal surgery have improved the technique. Endoresection is used most commonly to treat posterior uveal melanoma, but success in treating benign tumors, such as astrocytoma or retinal capillary hemangioblastoma has emboldened surgeons to expand its indications. It appears that removal of a malignant tumor, such as uveal melanoma may spare the eye some damaging effects of radiation retinopathy and radiation optic neuropathy. These benefits may occur even when the tumor is treated concurrently with plaque brachytherapy, proton beam irradiation, or stereotactic radiotherapy. The benefits of the technique are tempered, however, by the inherent difficulties associated with performing the surgery. These include potentially severe intraoperative bleeding, recurrent rhegmatogenous retinal detachment with proliferative vitreoretinopathy, air embolism, and recurrence of the tumor at the edge of the resection. Nonetheless, endoresection has recently been used for retinoblastoma in refractory cases in order to spare the globe. SUMMARY: Endoresection is an advanced vitreoretinal surgical technique that has potential advantages in the treatment of malignant and benign intraocular tumors.

Plaque brachytherapy for posterior uveal melanoma in 2018: improved techniques and expanded indications.

PURPOSE OF REVIEW: Plaque brachytherapy remains the dominant globe-sparing therapy of uveal melanoma. This report highlights recent advances, which have expanded plaque brachytherapy's uses as well as improved the surgical technique. RECENT FINDINGS: Plaque brachytherapy is effective for tumors that may previously have demanded enucleation. Plaque brachytherapy can be used to control large melanomas as well as melanomas touching the optic nerve. Improvements in planning and design have made plaque therapy simpler for the surgical operator and may reduce collateral radiation damage to normal ocular structures. The COMS implies a required dose of 85 Gy to the tumor apex for treatment of uveal melanoma. However, multiple reports indicate that lower doses may be equally effective for tumor control while reducing radiation dose to uninvolved structures. Vitreoretinal surgeons can be called upon safely to treat long-term side effects of radiation or tumor death such as intractable vitreous hemorrhage or inflammation. Further, vitreoretinal surgeons have employed tumor endoresection as primary local tumor control or in combination with plaque brachytherapy. SUMMARY: Plaque brachytherapy for uveal melanoma remains highly effective for local tumor control and prevention of metastasis. Indications for plaque brachytherapy have expanded, and the technique has improved.

New concepts in the molecular understanding of uveal melanoma.

PURPOSE OF REVIEW: Uveal melanoma is the most common primary intraocular malignancy, and its metastases are deadly. Significant work has been done to elucidate the molecular framework that causes uveal melanoma development and metastasis. This review is intended to highlight the most recent breakthroughs in the molecular understanding of uveal melanoma. RECENT FINDINGS: Monosomy of chromosome 3 and class 2 gene-expression profile are well-known indicators of melanoma metastasis. However, some patients with disomy 3 and class 1 gene expression profiling (GEP) still develop metastasis. Disomy 3 tumors may be further classified based upon the presence of an SF3B1 mutation. The role of SF3B1 gene is unclear at this time but may be related to the development of late metastases among disomy 3 uveal melanoma. Class 1 GEP tumors have recently been subdivided into class 1a and class 1b, with class 1b tumors carrying a slightly higher risk of metastasis. Among patients with either class 1 or class 2 GEP, the expression of preferentially expressed antigen in melanoma (PRAME) is an independent risk factor for the development of metastasis. Mutation of GNAQ is the most commonly observed mutation in uveal melanoma, regardless of chromosome 3 status or GEP class. Inhibitors or GNAQ may be targets for therapeutic intervention in uveal melanoma. MicroRNA molecules are small noncoding RNA molecules that have been recently demonstrated to function in RNA silencing and posttranscriptional regulation of gene expression. These molecules may play a role in the development of uveal melanoma metastasis. SUMMARY: New findings such as the presence or absence of PRAME, mutations in the SF3B1 gene and microRNA dysregulation have added new layers to our understanding of uveal melanoma. These new concepts will enhance our ability to prognosticate tumor metastasis and may provide targets for therapeutic intervention.

Primary vitreoretinal lymphoma: an update on pathogenesis, diagnosis and treatment.

PURPOSE OF REVIEW: Primary vitreoretinal lymphoma (PVRL) is a subset of primary central nervous system lymphoma in which disease primarily affects the uvea, retina, vitreous and optic nerve. This review discusses recent efforts to clarify the disease's pathogenesis, its diagnosis and its optimal treatment. RECENT FINDINGS: PVRL typically masquerades as a chronic intermediate uveitis in older individuals. Unambiguous diagnosis requires cytologic demonstration of malignant cells in a vitreous or chorioretinal specimen. However, cytokine analysis demonstrating increased interleukin 10 (IL 10) levels or increased IL-10:IL-6 ratio in the aqueous or vitreous, flow cytometry demonstrating a monoclonal cell population, molecular analysis demonstrating gene rearrangements or translocations or combinations of several techniques can be used effectively to aid in diagnosis. Treatment is aimed at eradication of disease within the eyes and prevention of central nervous system (CNS) lymphoma. Whether this should be done with local therapy alone (globe irradiation or intravitreal chemotherapy such as methotrexate or rituximab), or with systemic chemotherapy remains a source of debate. Even with high-dose systemic chemotherapy, CNS disease is prone to recurrence and has a poor prognosis. SUMMARY: New techniques and innovative treatment strategies may streamline time to definitive diagnosis and may lead to prolonged survival with better vision in patients with PVRL.

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.

Attempted auto-enucleation in two incarcerated young men with psychosis.

Auto-enucleation is a sign of untreated psychosis. We describe two patients who presented with attempted auto-enucleation while being incarcerated. This is an observation two-case series of two young men who suffered untreated psychosis while being incarcerated. These young men showed severe self-inflicted ocular trauma during episodes of untreated psychosis. Injuries included orbital bone fracture and dehiscence of the lateral rectus in one patient and severe retinal hemorrhage and partial optic nerve avulsion in the second patient. Auto-enucleation is a severe symptom of untreated psychosis. This urgent finding can occur in a jail setting in which psychiatric care may be minimal.

Current treatments and preventive strategies for radiation retinopathy.

PURPOSE OF REVIEW: Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiation for globe, orbit, and head and neck malignancies. This review discusses the recent efforts of several authors to treat radiation retinopathy once it has developed and efforts to prevent its development with early aggressive management. RECENT FINDINGS: Intravitreal anti-vascular endothelial growth factor agents and intravitreal steroid agents have been used to successfully treat radiation-induced macular edema and neovascular events secondary to radiation retinopathy. The visual outcomes, however, have varied. Recent work has been directed towards prevention of radiation retinopathy prior to its development. This has been done with preventive scatter laser and intravitreal bevacizumab therapy. Effective customization of radiation dose to the tumor has also reduced some collateral radiation damage. Preventive vitrectomy and silicone oil placement at the time of plaque brachytherapy may shield normal ocular structures from radiation injury. SUMMARY: Radiation retinopathy remains a major source of visual morbidity following radiotherapy for malignancies. Promising, albeit unproven, new therapies and preventive efforts may ameliorate the negative visual outcomes.

Acute Central Vision Loss in an IV Drug User.

This report describes the case of a 21-year-old heroin user who presented with a 6-day history of decreased vision in her right eye, preceded by 1 week of headache and tender scalp nodules, neck stiffness, and photophobia. A broad infectious workup for acute vision loss was completed, and she was ultimately presumed to have acquired toxoplasmic chorioretinitis (ocular toxoplasmosis). We review the initial workup for chorioretinitis, and the epidemiology, diagnosis, and treatment of ocular toxoplasmosis. Intravenous drug users may be at increased risk of acquired ocular toxoplasmosis.

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.