Understanding choroidal nevus risk factors for transformation into melanoma.

A choroidal nevus is a common intraocular tumor in the United States, found in approximately 5% of Caucasian adults. The three main risks of melanocytic choroidal nevus include vision loss from a subfoveal nevus, development of subretinal fluid, and transformation of nevus into melanoma, a malignant counterpart. We explore clinical risk factors that predict benign melanocytic choroidal nevus transformation into a malignant choroidal melanoma. Based on a large analysis of 2,355 cases that were monitored longitudinally using multimodal imaging, the most recent list of clinical features includes tumor Thickness greater than 2 mm on ultrasonography, subretinal Fluid on optical coherence tomography, Symptomatic vision loss 20/50 or worse, Orange pigment on fundus autofluorescence, Melanoma hollow on ultrasonography, and DIaMeter greater than 5 mm on fundus photography. These factors are remembered with a mnemonic of the capital letters TFSOM-DIM for "To Find Small Ocular Melanoma Doing Imaging." Analysis of these factors demonstrated a Kaplan-Meier mean five-year risk of 1% with no risk factors, 11% with any one factor, 22% with any two factors, 34% with any three factors, 51% with any four factors, and 55% with any five factors. There was no patient with six risk factors. Of those with combinations of four risk factors, six of 15 combinations yielded a 70%-100% rate of transformation; of those with combinations of five risk factors, two of five combinations yielded a 70%-100% rate of transformation. Choroidal nevus carries a risk for evolving into melanoma, and understanding of clinical and imaging features predictive of this outcome is highly important.

Conjunctival melanoma: Insights into classification, outcomes, and biomarkers.

Conjunctival melanoma is quite rare, estimated at approximately 0.5 incidence per 1 million persons per year. This malignancy arises from a pre-existing nevus (7%), primary acquired melanosis (74%), or de novo without pre-existing condition (19%) and develops most often in patients with Fitzpatrick skin types I (23%) and II (62%). At initial presentation, the tumor size is approximately 13 mm in cross-sectional diameter and has 3-mm thickness, involving the bulbar (97%), forniceal (30%), tarsal (28%), or caruncular (11%) regions, often with corneal (54%) and rarely with orbital (4%) involvement. According to the eighth edition of the American Joint Committee on Cancer (AJCC), the tumor is classified as T1 (63%), T2 (18%), T3 (20%), and T4 (0%). Outcomes depend on several factors including patient age, AJCC classification, orbital invasion, and type of initial surgery, whereas tumor origin and Fitzpatrick skin type do not appear to impact outcomes. Older patients (≥70 years of age) demonstrate larger tumors, greater recurrence, and greater vision loss. Analysis of 425 patients by AJCC classification (T1 versus T2 versus T3) revealed increasing T category with greater lymph node metastasis (3% versus 13% versus 25%; P < .001), tumor-related systemic metastasis (13% versus 45% versus 40%; P < .001), and tumor-related death (8% versus 22% versus 37%; P < .001). Data of patients with orbital invasion revealed significantly greater 10-year rates of exenteration (P < .001), distant metastasis (P = .0005), and death (P = .001). Studies have demonstrated biomarkers related to conjunctival melanoma include mutations in BRAF, NRAS, ATRX, and NF1. Future therapies might be directed against these mutations or with small-molecule inhibitors and/or immunotherapy. In summary, conjunctival melanoma is a rare but ominous malignancy, imparting moderate risk for lymph node and systemic metastasis as well as death, depending on tumor features and classification. The first surgery is highly important in prevention of tumor seeding, recurrence, and metastasis.

Iris melanoma: Review of clinical features, risks, management, and outcomes.

Primary uveal melanoma is rare and affects approximately 8,000 persons per year worldwide. This malignancy can involve the iris, ciliary body, and choroid. Of these three structures, the iris is the least commonly affected site, representing only 4% of all uveal melanomas. Iris melanoma can arise from iris melanocytic nevus, iris melanocytosis, or de novo. In a longitudinal study of 1,611 patients with iris nevus, transformation into melanoma, using Kaplan-Meier estimates, was found in 2.6% by five years and in 4.1% by 10 years. The factors that predicted growth of iris melanocytic nevus into melanoma are denoted by a letter (ABCDEF) guide: A for age ≤40 years old at presentation (hazard ratio [HR] = 3, P = .01), B for blood (hyphema) (HR = 9, P < .0004), C for clock hour of tumor inferiorly (tumor location) (HR = 9, P = .03), D for diffuse flat tumor configuration (HR = 14, P = .02), E for ectropion uveae (HR = 4, P = .002), and F for feathery ill-defined margins (HR = 3, P = .02). At diagnosis, iris melanoma has a mean cross-sectional diameter of 5.5 mm and thickness of 2.1 mm, often with tumor seeding (28%) and secondary glaucoma (35%). We provide a comprehensive review of iris nevus and melanoma to explore relevant demographic and clinical data, risk factors for tumor growth, management, and prognosis, with the hope that clinicians will be more comfortable in understanding this rare malignant condition.

Conditional Metastasis of Uveal Melanoma in 8091 Patients over Half-Century (51 Years) by Age Group: Assessing the Entire Population and the Extremes of Age.

Purpose: To evaluate cumulative incidence of metastasis at specific timepoints after treatment of uveal melanoma in a large cohort of patients and to provide comparison of conditional outcomes in the youngest and oldest cohorts (extremes of age). Methods: Retrospective analysis of 8091 consecutive patients with uveal melanoma at a single center over a 51-year period. The patients were categorized by age at presentation (0-29 years [n = 348, 4%], 30-59 years [n = 3859, 48%], 60-79 years [n = 3425, 42%], 80 to 99 years [n = 459, 6%]) and evaluated for nonconditional (from presentation date) and conditional (from specific timepoints after presentation) cumulative incidence of metastasis at five, 10, 20, and 30 years. Results: For the entire population of 8091 patients, five-year/10-year/20-year/30-year nonconditional cumulative incidence of metastasis was 15%/23%/32%/36%, and the conditional incidence improved to 6%/15%/25%/30% for patients who did not develop metastasis in the first three years. For the extremes of age (0-29 years and 80-99 years), the nonconditional cumulative incidence of metastasis revealed the younger cohort with superior outcomes at 8%/15%/19%/27% and 21%/29%/29%/29%, respectively (P < 0.001). The conditional incidence (at one-year and two-year timepoints with metastasis-free survival) showed persistent superior younger cohort survival (P < 0.001, P = 0.001), but no further benefit for patients with three-year metastasis-free survival at 4%/12%/16%/24% and 7%/18%/18%/18%, respectively (P = 0.09). Conclusions: Non-conditional metastasis-free survival analysis for patients with uveal melanoma revealed the youngest cohort to have significantly better survival than the oldest cohort, and this persisted into one-year and two-year conditional metastasis-free survival but diminished at the three-year conditional timepoint.

Metastatic tumours to the eye. Review of metastasis to the iris, ciliary body, choroid, retina, optic disc, vitreous, and/or lens capsule.

Metastasis to the eye can involve the choroid (90%), ciliary body (2%), iris (8%), and retina, optic disc, vitreous, and/or lens capsule (<1-4%). The mean number of uveal metastasis per eye (1.7), mean tumour base (11.6 mm) and thickness (3.2 mm), tumour colour (86% yellow), and presence of subretinal fluid (72%), are all clinical features suggestive of the diagnosis. Imaging with ultrasonography demonstrates an echodense mass (80%) and optical coherence tomography shows a "lumpy bumpy" choroidal surface (64%), both important diagnostic features. Uveal metastases typically emanate from primary cancer of the breast (37%), lung (27%), kidney (4%), gastrointestinal tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), and other sites (3%). Occasionally, fine needle aspiration biopsy is employed if the primary site is not known. In 16% of cases, the primary site remains unknown. Rarely, metastases affect the retina, vitreous, and lens capsule, most often originating from cutaneous melanoma and in patients previously treated with checkpoint inhibitor therapy. Kaplan-Meier analysis in a series of 1111 patients with uveal metastasis revealed 32% survival at 3 years and 24% at 5 years. Patients with uveal metastasis from carcinoid tumour showed most favourable survival at 5-years (92%), whereas pancreatic and kidney cancer demonstrated least favourable survival (0%). The 5-year survival was better for females (versus (vs.) males) (31% vs. 21%) and older adults (vs. children) (40% vs. 0%). In this review, we examine several large-cohort publications on the topic of ocular metastasis.

Choroidal Melanoma Masquerading as Central Serous Chorioretinopathy.

PURPOSE: To determine the clinical features and outcomes of choroidal melanoma initially masquerading as central serous chorioretinopathy (CSCR). DESIGN: Retrospective case series. SUBJECTS: All patients with choroidal melanoma, initially misdiagnosed as CSCR elsewhere and evaluated by the Ocular Oncology Service at Wills Eye Hospital from 2004 to 2022, were included. METHODS: A retrospective detailed review of patient charts and imaging was performed for all patients included in the study. Paired t tests and chi-squared tests were performed for data analysis. MAIN OUTCOME MEASURES: The primary outcome measures included clinical characteristics, ultrasonography, OCT, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. The secondary outcome measures included treatment results, such as the final visual acuity, tumor control, radiation-related complications, and melanoma-related metastlasis and death. RESULTS: There were 22 patients (mean age, 48 years; 16 men) in this cohort. The mean interval between initial CSCR diagnosis and suspicion of choroidal melanoma was 50 months (median, 50 months; range, 0-242 months). At tumor diagnosis, the melanoma was submacular in 16 (73%) patients and extramacular in 6 (27%) patients. The mean tumor thickness was 3.4 mm (median, 2.5 mm; range, 1.4-10.7 mm), and the mean basal diameter was 9.2 mm (median, 8.0 mm, range, 4.5-22.0 mm). Features enabling differentiation of choroidal melanoma from CSCR (affected versus unaffected eye) included choroidal thickness asymmetry (100% > 300 µm versus 21% > 300 µm; P = 0.005), ipsilateral choroidal surface irregularity (100% versus 0%; P < 0.001), loss of choroidal vascular detail on OCT (100% versus 0%; P < 0.001), presence of multiple pinpoint leaks on angiography (100% versus 0%; P < 0.001), and contralateral lack of autofluoresence abnormalities (75% versus 6%; P = 0.001). Management of the choroidal melanoma included plaque radiotherapy (19, 86%), enucleation (2, 9%), or treatment elsewhere (1, 5%). On follow-up (mean, 6 years), vision loss of ≥ 3 Snellen lines (9 patients, 47%), metastasis (3 patients, 14%), and death (1 patient, 5%) were noted. CONCLUSIONS: Patients with presumed CSCR, especially if chronic, should be evaluated for a possible thin underlying choroidal melanoma with a dilated fundus examination and multimodal imaging.

Tissue Glue Adhesion for Plaque Radiotherapy of Uveal Melanoma in Humans: An Initial Experience.

Purpose: The aims of this study were to study use of tissue glue instead of conventional suturing and to secure I-125 plaque in human eyes with uveal melanoma. Methods: We studied 6 patients with choroidal melanoma undergoing plaque radiotherapy who were found to have thin sclera intraoperatively. Following tumor localization and plaque placement, tissue glue was applied over and around the plaque surface. The plaque was held securely in all cases. Conjunctivoplasty was performed with 7-0 vicryl sutures to ensure complete coverage and stability of the plaque. At the time of plaque removal, the tissue glue clot was in place with plaque secured. The clot and plaque were removed without difficulty. Results: In all 6 cases, the tissue glue secured the plaque in place for the required radiation duration (mean 117.6 h (hrs), median 103.1 h, range 101.6-162.5 h) delivering a tumor apex dose (mean 63.6 cGy/h, median 69.6 cGy/h, range 44.7-70.5 cGy/h). At the time of plaque removal, the plaque was in the designated position without displacement in all cases. There were no toxicities from the tissue glue. Conclusions: Tissue glue can serve as an alternative for fixation of plaque radiotherapy to the sclera without the need for suturing. This technique might be useful in eyes with thin sclera.

Coats plus syndrome with new observation of drusenoid retinal pigment epithelial detachments in a teenager.

Purpose: To describe a case of Coats Plus Syndrome (CPS), a vision and life threatening disease belonging to a family of diseases known as the Telomere Biology Disorders. Observations: A 15-year-old girl with a history of small for gestational age, short stature, microcephaly, thinning/greying of scalp hair, skin hyperpigmentation, nail ridging, and multiple pathological fractures presented with bilateral Coats-like retinopathy. We discovered a new observation of multiple peripheral pinpoint retinal pigment epithelial detachments (PEDs). Further genetic testing revealed CTC1 gene mutation and she was diagnosed with Coats plus syndrome with features of dyskeratosis congenita, a telomere biology disorder. Conclusion and importance: Patients with bilateral Coats-like retinopathy and associated systemic features suggestive of CPS should be evaluated through genetic testing to diagnose this disease and treat vision and life threatening manifestations as early as possible. In this report, we also document, for the first time, multiple pinpoint PEDs that could be related to an accelerated aging process with telomere dysfunction.

Retinal cavernous hemangioma in a newborn: an unusual presentation of a rare tumor.

Retinal cavernous hemangioma (RCavH) is an uncommon, benign, vascular tumor of venous aneurysms. It can be sporadic or inherited in an autosomal-dominant pattern as part of an oculoneurocutaneous syndrome. Some affected patients are asymptomatic, and others have symptoms related to retinal dragging and vitreous hemorrhage. In the case presented here, the tumor was located in the anterior retina overhanging the ciliary body with lens involvement and heterochromia. The differential diagnosis included traumatic hemorrhage, persistent fetal vasculature, juvenile xanthogranuloma, retinoblastoma, medulloepithelioma, and others. Fluorescein angiography documented the slow-filling cavernous aneurysms of RCavH.

Assessment of patient follow-up from student-run free eye clinic to county ophthalmology clinic.

The Ophthalmology Student Interest Group at Indiana University School of Medicine provides a free student-run eye screening clinic for an underserved community in Indianapolis. Patients with abnormal findings are referred to the ophthalmology service of the local county hospital for further evaluation. This retrospective chart review studied 180 patients referred from our free eye clinic to follow up at the ophthalmology service of a local county hospital from October 2013 to February 2020. This study investigated factors impacting follow-up of patients by analyzing demographics, medical history, insurance coverage, and final diagnoses at follow-up. Thirty-five (19.4%) of 180 patients successfully followed up at the local county hospital with an average time to follow-up of 14.4 (± 15.9) months. Mean patient age was 51 (± 13.6) with nearly equal numbers of males and females. The most common diagnoses at follow-up included refractive error (51.4%), cataract (45.7%), and glaucoma (28.6%). Patients with diabetes diagnoses or Healthy Indiana Plan insurance coverage had increased probability of follow-up. This study reveals gaps in timely follow-up to the local county hospital, demonstrating the current limitations of our free clinic in connecting patients to more definitive care and the need for an improved referral process.

A seven-year analysis of the role and impact of a free community eye clinic.

BACKGROUND: The Indiana University Student Outreach Clinic (IUSOC) Eye Clinic is a monthly student-run eye clinic that provides free visual screening to the Near East Side community of Indianapolis, IN, USA. Screening includes assessments of visual acuity, intraocular pressure, peripheral visual fields, refraction, and non-mydriatic fundus photography. METHODS: This is a retrospective chart review of 875 patients seen at the IUSOC Eye Clinic from October 2013 to February 2020. Data on demographics, insurance coverage, ocular history, physical examination, suspected diagnosis, referral status, and glasses provided were collected and analyzed. RESULTS: 875 patients were seen at the IUSOC Eye Clinic from October 2013 to February 2020. 39.2% of the patients seen at the clinic reported being uninsured. 61.4% of patients were found to have visual acuity of 20/40 or worse, while 51.3% of patients were found to have a near visual acuity of 20/40 or worse. 20.3% of patients were referred to the local county hospital for further evaluation by an ophthalmologist, 14.4% of patients received free glasses prescriptions, and 27.9% of patients received free reading glasses. Common reasons for referral for further ophthalmology evaluation included glaucoma, decreased visual acuity, and diabetic retinopathy. An estimated value of services provided over the seven years of the clinic was 1271 relative value units. CONCLUSION: The IUSOC Eye Clinic fills an important role in advancing ocular health and preventing irreversible blindness in an underserved Indianapolis community. Additionally, the clinic demonstrates an educational model for involving medical student volunteers.