Arun D. Singh’s research while affiliated with Texas Eye Institute and other places

Importance The accuracy of the predicted risk of malignant transformation of a large choroidal nevus or indeterminate melanocytic tumor (IMT) is not known. Objective To estimate the risk of malignant transformation (predicted risk) in a cohort of patients with IMT of known outcomes (observed status; benign [large nevus] or malignant [small melanoma]). Design, Setting, and Participants This was a cohort study of patients from a single center. Patients diagnosed with IMTs that were benign (large nevus) or malignant (small melanoma) were included in the analysis. Those lesions classified as large nevus (benign; 0% risk) had documented stability over 24 or more months. IMTs classified as small melanoma (malignant; 100% risk) had quantified growth or confirmatory pathology. Data were analyzed from October to December 2024. Exposures Prediction of malignant transformation of a large choroidal nevus or IMT. Main Outcomes and Measures The primary outcome included the predicted 5-year Kaplan-Meier probability of malignant transformation using combinations of risk factors of predictive models, the Collaborative Ocular Melanoma Study (COMS) and Wills Eye Hospital (WEH) model. Results A total of 123 patients (median [IQR] age, 63 [56-67] years; 89 male [72%]), 62 with large nevus and 61 with small malignant melanoma, were included in this study. The mean predicted 5-year Kaplan-Meier probability of melanoma for observed melanoma was 0.39 (95% CI, 0.32-0.46) by the COMS model and 0.44 (95% CI, 0.39-0.49) by the WEH model. The difference of −0.05 (95% CI, −0.14 to 0.04) was not statistically significant. However, the mean predicted 5-year Kaplan-Meier probability of melanoma for observed nevus was 0.18 (95% CI, 0.12-0.23) by the COMS model and 0.31 (95% CI, 0.24-0.38) by the WEH model. The difference of −0.13 (95% CI, −0.22 to −0.05) was statistically significant. There was a significant difference in mean 5-year Kaplan-Meier probability of melanoma between observed melanoma and nevus of 0.21 (95% CI, 0.12-0.31) by the COMS model and 0.13 (95% CI, 0.05-0.21) by the WEH model. Optimal cut points of 0.18 and 0.34 for the COMS model and the WEH model, respectively, were identified using the Youden index. The sensitivity was lower for the COMS model than the WEH model (−15.2% difference; 95% CI, −25.6% to −4.8%), and the specificity was higher for the COMS model than the WEH model (11.7% difference; 95% CI, 2.0%-21.4%). Conclusions and Relevance Findings of this cohort study suggest that predicted risk for malignant transformation estimated by 2 different models based on combinations of risk factors was suboptimal and may lead to overtreatment in approximately 30% of patients. These findings support pursuing other methods for prediction that should be validated before use in clinical practice.

Osseous tumors of the uveal tract are relatively rare, benign lesions. Choroidal osteomas usually occur in the region of the posterior pole, typically in younger females, and are more often unilateral than bilateral. Because of their location, they are often associated with significant secondary vision loss, e.g., due to associated choroidal neovascularisation or overlying photoreceptor drop-out. Sclerochoroidal calcification, in contrast, is usually bilateral, found in older patients, and not associated with significant vision loss. This chapter describes the key differential diagnostic features, including ultrasound, angiographic, and OCT imaging findings in these lesions.

Among the ocular complications that are known to occur following the use of radiation therapy for ophthalmic cancers, radiation optic neuropathy (RON) is among the most devastating. Radiation-induced aqueous tear deficiency, dermatitis, cataract, neovascular glaucoma, and retinopathy may be treated with currently available medications and surgical therapies. Radiation optic neuropathy differs from these complications due to its complexity, location, and the biochemical events surrounding its onset. Radiation optic neuropathy develops in approximately 30% of those undergoing plaque brachytherapy for choroidal melanoma and is directly related to the radiation dose, location of the tumor, and the size of the tumor treated. There seems to be no difference in incidence with the type radionuclides used for brachytherapy. RON may be an unavoidable and untreatable complication. However, treatments have been attempted and described in small retrospective case series. Nevertheless, there is some evidence to suggest that downregulation of vaso-occlusive cytokines such as vascular endothelial growth factor (VEGF) and other inflammatory mediators with steroids and anti-VEGF agents (delivered locally) may preserve visual acuity. In addition, early hyperbaric oxygen therapy was shown to be effective in improving or stabilizing vision.

Uveal melanocytes are derived from neural crest and share this embryologic origin with cutaneous melanocytes. The spectrum of observed variants of choroidal melanocytic lesions can be explained on the basis of embryogenesis and migration of uveal melanocytes. Benign melanocytic uveal tumors are generally known as nevi (also spelt as “naevi”). Nevus is a Latin word meaning birthmark or mole and is a general term for a congenital mark on the skin. In ophthalmology, the term nevus refers to an abnormal, hamartomatous cluster of melanocytes. This chapter describes choroidal and ciliary body nevi as well as oculo(dermal) melanocytosis and melanocytoma, which are considered as variants of nevus.

Uveal and conjunctival melanomas comprise approximately 5% of all melanomas. The incidence of uveal melanoma in the United States is similar to that in European countries. The overall mean incidence of uveal melanoma in the United States is 5.2 per million per year with a higher rate in males (6.0 per million per year) as compared to females (4.5 per million per year). Uveal melanoma is more common in the older age group, with a progressively rising age-specific incidence that peaks at the age of 70 years. The age-adjusted annual incidence of uveal melanoma in the United States has remained stable for the last 50 years. Known causes of uveal melanoma include congenital ocular melanocytosis, melanocytoma, and the BAP1 cancer predisposition syndrome, which is associated with cutaneous atypical nevi and melanoma and specific forms of SMN (second malignant neoplasms) such as malignant mesothelioma, meningioma, and lung adenocarcinoma. In the large majority of cases, the etiology is unknown, although ocular melanomas are most common in fair individuals with light-colored eyes.

Iris melanoma is the least frequent of all uveal melanomas. Because of anterior location, iris melanoma is diagnosed and treated when relatively small compared to tumors located in ciliary body and choroid. Melanoma located in the peripheral iris may represent anterior extension of a ciliary body tumor, and therefore it is of paramount importance to examine the ciliary body in cases of iris melanoma when all iris margins of the tumors are not visualized. Iris melanoma may be circumscribed or diffuse. Tapioca iris melanoma is a rare variant of diffuse iris melanoma. Slit-lamp examination, gonioscopy, and ultrasound biomicroscopy (UBM) allow staging of the tumor to guide the most appropriate treatment. Iris melanomas are managed by observation, incisional biopsy, excisional biopsy, or radiotherapy depending upon the size, extent, and visual potential. Iris melanoma tends to be less aggressive in comparison to melanomas in other uveal locations.

Benign melanocytic uveal tumors are generally known as nevi (also spelt as “naevi”). Nevus is a Latin word meaning birthmark or mole and is a general term for a congenital mark on the skin. In ophthalmology, the term nevus refers to an abnormal, hamartomatous cluster of melanocytes. Uveal melanocytes are derived from neural crest and share this embryologic origin with cutaneous melanocytes. This chapter describes benign melanocytic tumors of the iris, including freckles and nevi as well as oculo(dermal) melanocytosis and melanocytoma, which are considered as variants of nevus.

Peripheral nerve sheath tumors of the uveal tract arise mainly in the sheath of peripheral nerves that are found in the uvea. The ciliary nerve is most often affected, and hence, these tumors tend to be located anteriorly in the ciliary body or peripheral choroid in the anatomic location of the long ciliary nerve. There are several systemic predisposing risk factors, which include schwannomatosis, neurofibromatosis 1 (NF1) and 2, and other rare genetic syndromes (PTEN syndrome). The benign tumors can be subclassified as ganglioneuroma, neurofibroma, and schwannoma.

Uveal vascular tumors represent benign hamartomatous disorders and are classified as hemangiomas. Although the iris and ciliary body can be involved, hemangiomas most frequently affect the choroid. Choroidal hemangioma can either be circumscribed or diffuse. In general, uveal hemangioma may be confined to the globe or be a manifestation of a widespread hemangiomatous disorder. Iris vascular anomalies can be classified into five distinct clinicopathological entities: capillary hemangioma, iris cavernous hemangioma, iris microhemangioma, iris arteriovenous malformation, and iris varix. Only a few cases of well-documented ciliary body hemangioma have been published. Circumscribed choroidal hemangioma is usually diagnosed between the second and fourth decade of life when it causes visual disturbances due to the development of exudative retinal detachment or macular edema. In contrast, diffuse choroidal hemangioma is usually evident at birth and generally occurs as a part of neuro-oculo-cutaneous hemangiomatosis (Sturge-Weber syndrome).

Uveal melanoma is a rare, aggressive cancer arising from melanocytes of the uveal tract. It is the most common primary intraocular malignancy in adults. Despite excellent rates of local disease control, nearly 50% of patients will develop metastatic disease, with the most common initial site being the liver. Outcomes are poor following the development of distant disease, with a median survival of under 24 months. Advances in molecular profiling have enabled a more accurate prediction of metastatic risk. Given the poor prognosis associated with metastatic disease, the development of effective adjuvant therapies that prevent the development of recurrence is critical to the management of high-risk patients. In this chapter, we provide a comprehensive review of the historical, current, and future approaches to adjuvant therapy, including chemotherapy, targeted therapy, immunotherapy, epigenetic drugs, liver-directed therapy, and other novel treatment strategies.