Trends in the Clinical Presentation of Uveal Melanoma During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: The objective was to evaluate factors associated with clinical presentation of uveal melanoma (UM) during the initial two years of the coronavirus disease 2019 pandemic. PATIENTS AND METHODS: This was a multi-site, retrospective cohort study of patients treated for uveal melanoma during the first (early) and second (late) year of the pandemic compared with the year prior (control). RESULTS: A total of 48, 67, and 75 patients were in the control, early, and late cohorts, respectively. The early cohort had a higher frequency of large tumors (control: 29.2%, early: 40.3%, late: 29.3%; P < 0.001) at presentation. Both the early and late cohorts had higher rates of enucleation (control: 8.33%, early: 20.9%, late: 18.67%; P ≤ 0.0338) compared to the control cohort. CONCLUSIONS: While there was an increase in large tumors along with a rise in enucleation during the first year of the pandemic, enucleation rates remained elevated even while tumor sizes normalized. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Telemedicine retinopathy of prematurity severity score (TeleROP-SS) versus modified activity score (mROP-ActS) retrospective comparison in SUNDROP cohort.

Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP's totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.

Endoscopic enucleation and clinicopathologic correlation of a small choroidal melanoma hiding massive extrascleral extension.

Purpose: To report the unusual case of a previously stable choroidal nevus, closely followed for over 15 years, which underwent malignant transformation into small choroidal melanoma with massive extrascleral extension. Observations: A 67-year-old Caucasian female was referred to the Stanford Ocular Oncology Service with concern for malignant transformation of a previously stable choroidal nevus in her left eye. Her funduscopic examination demonstrated a dome-shaped choroidal lesion with overlying associated lipofuscin and subretinal fluid, consistent with a diagnosis of small choroidal melanoma. By B-scan ultrasonography, the lesion measured 8.0 × 6.0 mm in base and 2.1 mm in thickness. B-scan ultrasonography also disclosed an associated retroscleral mass, which appeared contiguous with the intraocular melanoma and was confirmed on subsequent orbital magnetic resonance imaging. A decision was made to proceed with enucleation. Under direct endoscopic visualization, the globe and extrascleral mass were fully isolated, mobilized, and removed in toto. At 24 months post-enucleation, the patient remains disease-free without evidence of systemic metastasis or local recurrence. Conclusions/importance: This case describes a small choroidal melanoma hiding massive extrascleral extension, underscoring the value of B-scan ultrasonography. This case also describes the unique management of choroidal melanoma with extrascleral extension using endoscopic enucleation. Performing enucleation under direct endoscopic visualization ensures complete resection and prevents inadvertent transection of the extrascleral component.

Update in Molecular Testing for Intraocular Lymphoma.

The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. In cases with intraocular involvement, vitreous biopsy plays a pivotal role. Several diagnostic tests are employed to confirm a diagnosis and include cytologic evaluation, immunohistochemistry, flow cytometry, and cytokine analysis. The limitations of these conventional diagnostic tests stem from the often paucicellular nature of vitreous biopsy specimens and the fragility of malignant cells ex vivo. Several emerging molecular techniques show promise in improving the diagnostic yield of intraocular biopsy, possibly enabling more accurate and timely diagnoses. This article will review existing diagnostic modalities for intraocular lymphoma, with an emphasis on currently available molecular tests.

Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy.

Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

Stimulating Tear Production: Spotlight on Neurostimulation.

Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far-from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.

Cell-free fetal DNA testing and its correlation with prenatal indications.

BACKGROUND: The prenatal test of cell-free fetal DNA (cffDNA) is also known as noninvasive prenatal testing (NIPT) with high sensitivity and specificity. This study is to evaluate the performance of NIPT and its clinical relevance with various clinical indications. METHODS: A retrospective analysis was conducted on 14,316 pregnant women with prenatal indications, including advanced maternal age (≥35 years), maternal serum screening abnormalities, the thickened nuchal translucency (≥2.5 mm) and other ultrasound abnormalities, twin pregnancy/IVF-ET pregnancy, etc. The whole-genome sequencing (WGS) of maternal plasma cffDNA was employed in this study. RESULTS: A total of 189 (1.32%) positive NIPT cases were identified, and 113/189 (59.79%)cases were confirmed by invasive prenatal testing. Abnormal serological screening (53.14%) was the most common indication, followed by elderly pregnancy (23.02%). The positive prediction value for T21, T18, T13, sex chromosome abnormalities, other autosomal aneuploidy abnormalities, and CNV abnormalities were 91.84, 68.75,37.50, 66.67, 14.29, and 6.45%, respectively. The positive rate and the true positive rate of nuchal translucency (NT) thickening were the highest (4.17 and 3.33%), followed by the voluntary requirement group (3.49 and 1.90%) in the various prenatal screening indications. The cffDNA concentration was linearly correlated with gestational age (≥10 weeks) and the positive NIPT group's Z-score values. CONCLUSIONS: whole-genome sequencing of cffDNA has extremely high sensitivity and specificity for T21, high sensitivity for T18, sex chromosome abnormalities, and T13. It also provides evidence for other abnormal chromosomal karyotypes (CNV and non-21/18/13 autosomal aneuploidy abnormalities). The cffDNA concentration is closely related to the gestational age and determines the specificity of NIPT. Our results highlight NIPT's clinical significance, which is an effective prenatal screening tool for high-quality care of pregnancy.

BAP1 Germline Mutation Associated with Bilateral Primary Uveal Melanoma.

PURPOSE: To describe the occurrence of bilateral primary uveal melanoma in 2 patients with mutation on the gene encoding BRCA1-associated protein 1 (BAP1). METHODS: Retrospective chart review of patients with bilateral primary uveal melanoma and subsequent positive germline BAP1 mutation. RESULTS: There were 2 patients with bilateral uveal melanoma and BAP1 germline positivity. Neither patient demonstrated oculodermal melanocytosis. Patient 1 underwent enucleation of his right eye (OD) at the age of 44 years for a 9.6-mm-thick choroidal melanoma. He returned 4 years later with a 10.0-mm-thick choroidal melanoma in his left eye (OS) and was treated with plaque radiotherapy. He had a strong family history of cancer, and clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 18-month follow-up, visual acuity was 20/200 OS without evidence of systemic metastasis. Patient 2 initially presented at age 54 years with extensive, diffuse iris melanoma OD, initially treated with plaque radiotherapy, but local recurrence after 3 years necessitated enucleation. Four years later, a 6.0-mm-thick ciliary body melanoma OS was found and successfully treated with plaque radiotherapy. Clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 8-year follow-up, visual acuity was 20/40 OS without evidence of local recurrence or systemic metastasis. The patient expired secondary to an unrelated brain infarction. CONCLUSION: Bilateral uveal melanoma is exceedingly rare. Patients with bilateral uveal melanoma, especially when coincident with remote systemic cancers or a family history of cancer, should be evaluated for germline BAP1 mutation. Lifelong monitoring for related systemic malignancies is advised.

Photoreceptor morphology and correlation with subretinal fluid chronicity associated with choroidal nevus.

BACKGROUND: Subretinal fluid (SRF) can be associated with choroidal nevus and can cause progressive change in the morphology of overlying photoreceptors. METHODS: A retrospective observational study was performed using optical coherence tomography to assess nevus and SRF features, as well as photoreceptor morphology over time. RESULTS: There were 232 choroidal nevi that presented with or developed SRF. Photoreceptor morphology at presentation was classified as normal (n=60, 26%), shaggy (elongated) (n=73, 31%), retracted (stalactite appearance) (n=76, 33%), or absent (n=23, 10%). There was a progression in photoreceptor morphology with increasing SRF chronicity (p=0.003). For nevus presenting with normal photoreceptors and later developed SRF (n=60), photoreceptors became shaggy in 29 (48%), retracted in 24 (40%), and absent in 7 (12%) after 15, 19 and 22 months, respectively. For nevus presenting with SRF and shaggy photoreceptors (n=73), progression to retracted photoreceptors occurred in 31 (42%) after a mean of 22 months; for nevus with SRF and retracted photoreceptors (n=76), progression to absent photoreceptors occurred in 19 (25%) after a mean of 34 months; and for nevus with absent photoreceptors (n=23), photoreceptor morphology showed no change after mean follow-up of 33 months. Risk of nevus growth to melanoma was not associated with photoreceptor morphology at presentation (p=0.19). CONCLUSION: In eyes with choroidal nevus and SRF, there is a longitudinal evolution in photoreceptor morphology from normal to shaggy to retracted then absent with increasing SRF chronicity. SRF chronicity, as indicated by photoreceptor morphology on presentation, did not correlate with nevus growth to melanoma.

Nomogram for visual acuity outcome after iodine-125 plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma in 1131 patients.

AIMS: To develop a nomogram for prediction of visual acuity outcome following plaque radiotherapy for uveal melanoma. METHODS: Retrospective review of uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab injections at 4-month intervals for 2 years duration. Two nomograms for poor visual acuity outcome (Snellen <20/200) were developed based on (1) Clinical risk factors. (2) Or clinical and treatment risk factors. RESULTS: There were 1131 included cases. The most important clinical risk factors (points for nomogram) for poor visual acuity outcome included subretinal fluid involving four quadrants (100), tumour thickness >4 mm (69), presenting visual acuity ≤20/30 (65), non-Caucasian race (58), tumour shape mushroom, bilobed, or multilobulated (57), and insulin-dependent diabetes (54). Risk of poor visual acuity at 2 years and 4 years increased from 11% and 24% with 40 points to 97% and >99% with 304 points. A second analysis was performed using both clinical and treatment risk factors. The most important factors included presenting visual acuity ≤20/30 (100), tumour largest basal diameter >11 mm (80), radiation dose rate to tumour base ≥164 cGy/hour (78), tumour thickness >4 mm (76), insulin-dependent diabetes (75) and abnormal foveolar status by optical coherence tomography at presentation (72). Risk of poor visual acuity at 2 years and 4 years increased from 6% and 14% with 56 points to 88% and 99% with 496 points. CONCLUSIONS: A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at https://fighteyecancer.com/nomograms/.

Retinal haemangioblastoma associated with peripheral non-perfusion: widefield fluorescein angiography analysis of 41 cases.

AIMS: To investigate the association of peripheral retinal non-perfusion with retinal haemangioblastoma. METHODS: Medical and widefield fluorescein angiography records of patients diagnosed with retinal haemangioblastoma from 1990 to 2018 were reviewed for patient demographics, tumour features, fluorescein angiography features and characteristics of peripheral retinal non-perfusion. RESULTS: There were 41 eyes of 40 patients with retinal haemangioblastoma imaged by widefield fluorescein angiography during this time period. Of 41 eyes, 14 (34%) had haemangioblastoma-associated peripheral retinal non-perfusion on fluorescein angiography. A comparison of eyes with versus without non-perfusion revealed younger mean age at presentation (28 vs 43 years old, p=0.05), increased prevalence of von Hippel-Lindau (VHL) disease (62% vs 22%, p=0.01), greater mean largest tumour basal diameter (3.7 vs 2.5 mm, p=0.04), greater tumour distance from optic nerve (8.4 vs 1.9 mm, p<0.01) and increased prevalence of vascular leakage from the tumour (86% vs 52%, p=0.03). After mean follow-up of 97 versus 71 months (p=0.52), eyes with non-perfusion were significantly more likely to develop neovascularisation (40% vs 0%, p<0.01) and experience a three-line or greater decrease in visual acuity (60% vs 11%, p<0.01). CONCLUSION: Peripheral retinal non-perfusion can be associated with retinal haemangioblastoma, and could be more common with larger, more peripheral tumours in younger patients with VHL disease. Eyes with haemangioblastoma-associated peripheral non-perfusion could be more likely to develop neovascularisation and lose visual acuity.

RETINAL CAVERNOUS HEMANGIOMA WITH INTRALESIONAL PHLEBOLITHS.

PURPOSE: To report a case of retinal cavernous hemangioma with intralesional phleboliths, simulating retinoblastoma. METHODS: A healthy 5-month-old girl developed left esotropia and was noted to have atraumatic vitreous hemorrhage with underlying partially calcified mass, suspicious for retinoblastoma. RESULTS: On examination, the visual acuity was fix and follow in the right eye and absent fixation in the left eye. Evaluation of the right eye revealed normal findings. The left eye demonstrated healthy anterior segment and dense vitreous hemorrhage with no view of the postequatorial structures, but with hazy view of the flat peripheral retina and a superonasal retinal mass, covered with fresh hemorrhage. Three white intralesional flecks, consistent with calcification, each measuring 300 µm, were visualized. B-scan ultrasonography confirmed the dense mass with several foci of calcification, suspicious for retinoblastoma, despite poor visualization on funduscopy. Prophylactic intravenous chemotherapy was delivered for globe salvage and systemic protection. At 12-month follow-up, the hemorrhage showed resolution, revealing a superonasal dark blue multilobulated mass with saccular aneurysms, measuring 16 mm in diameter, and with 3 phleboliths (intralesional calcification). Fluorescein angiography demonstrated early and midphase hypofluorescence with late-phase filling and with plasma-erythrocyte separation in some larger aneurysms, characteristic of retinal cavernous hemangioma. CONCLUSION: Retinal cavernous hemangioma can be associated with intralesional calcification (phleboliths).

Malignant transformation of choroidal nevus according to race in 3334 consecutive patients.

Purpose: To evaluate choroidal nevus demographics, clinical features, imaging features, and the rate of transformation into melanoma by race. Methods: In this observational case series,: There were 3334 participants (3806 choroidal nevi) at a single tertiary-referral center evaluated between January 2, 2007, and August 7, 2017. Retrospective chart and multimodal imaging review was performed. Patient demographics, tumor features, and outcomes were compared between different races using Chi-squared test, Fisher's exact test, t-test, and analysis of variance. The main outcome measure was clinical features of choroidal nevus and the rate of transformation into melanoma by race. Results: Of the 3334 patients, there were Caucasian (n = 3167, 95%) and non-Caucasian (n = 167, 5%). The non-Caucasian races included African-American (n = 27, <1%), Hispanic (n = 38, <1%), Asian (n = 15, <1%), Asian Indian (n = 2, <1%), Middle Eastern (n = 4, <1%), and unknown (n = 83, 3%). By comparison (Caucasian versus vs. non-Caucasian), there were differences in the mean age at presentation (61 vs. 56 years,P < 0.0001), female sex (63% vs. 52%,P < 0.01), dysplastic nevus syndrome (<1% vs. 1%,P < 0.01), and previous cutaneous melanoma (5% vs. 1%,P= 0.03). A comparison of tumor features revealed differences in presence of symptoms (12% vs. 20%,P < 0.01) and ≥3 nevi per eye (3% vs. <1%,P= 0.04). A comparison of imaging features showed no differences. A comparison of outcome of nevus transformation into melanoma revealed no difference (2% vs. 3%,P= 0.29). However, of those nevi exhibiting growth to melanoma, ultrasonographic hollowness was less frequent in Caucasians (29% vs. 67%,P= 0.04). Conclusion: In this analysis of 3334 patients with choroidal nevus, we found differences in the mean age of presentation, sex, dysplastic nevus syndrome, previous cutaneous melanoma, presence of symptoms, and multiplicity of nevus per eye by race. However, there was no difference in the rate of transformation into melanoma by race.

Retinoblastoma in older patients: A retrospective comparative analysis of 100 consecutive patients based on age.

PURPOSE: To describe comparative clinical features, treatment, and outcomes of retinoblastoma in patients initially diagnosed at age 4 or older. METHODS: Retrospective case series. RESULTS: There were 101 eyes in 100 consecutive patients age ≥4 years diagnosed with retinoblastoma. Mean patient age at diagnosis was 6.6 years (median 5.3, range 4.0-41.0 years). Tumors were predominantly classified (International Classification of Retinoblastoma) as group D (31%) or E (65%). Patients were divided by age into 3 groups: young (4-6 years [65%]), middle (>6-8 years [23%]), and older (>8 years [12%]). Comparing by age group (young vs. middle vs. older), mean tumor basal diameter (19.9 vs. 17.3 vs. 17.0 mm, p = 0.05) and mean tumor thickness (11.0 vs. 9.4 vs. 7.0 mm, p < 0.01) were greatest in the youngest group. Distance to the optic nerve (1.5 vs. 1.7 vs. 5.0 mm, p = 0.01) and foveola (1.9 vs. 1.8 vs. 6.0 mm, p < 0.01) were greatest in the oldest age group. Objective findings of leukocoria and strabismus were more common in younger patients, while older patients complained of subjective findings, like decreased vision (19% vs. 30% vs. 60%, p < 0.01) and floaters (3% vs. 4% vs. 17%, p = 0.05). Primary treatment included enucleation (76%) and other modalities (24%). Globe salvage rate was 13%, with no significant difference by age. Comparison of globe salvage by revealed significant improvement between 1974-2008 (6%) and 2009-2017 (38%, p < 0.01). CONCLUSION: Retinoblastoma in older patients (>8 years) tends to be smaller and more peripherally located, with more subjective presenting symptoms.

Retinoblastoma vascular perfusion and intra-arterial chemotherapy cycle requirements.

IMPORTANCE: Retinoblastoma is a life- and sight-threatening malignancy. BACKGROUND: To assess the relationship between tumour perfusion and intra-arterial chemotherapy (IAC) requirements to achieve retinoblastoma control. DESIGN: Retrospective case series at the Ocular Oncology Service of Wills Eye Hospital (Philadelphia, Pennsylvania). PARTICIPANTS: Fifty-nine eyes of 55 patients. METHODS: Review of medical and fluorescein angiography (FA) records for retinoblastoma treated with primary or secondary IAC from 2012 to 2017. Vascular supply of the main tumour was evaluated in the pre-treatment FA. MAIN OUTCOME MEASURES: Tumour fluorescence was classified as partial <67% or complete tumour perfusion >67%. Partially vs completely perfused tumours were compared for IAC cycle requirements. RESULTS: There were 59 eyes of 55 patients with pre-treatment FA managed with IAC. Partially perfused tumours (n = 20, 34%) required fewer IAC infusions than completely perfused tumours (n = 39, 66%) (2.5 vs 3.7 infusions, P = .02), even after adjustment for confounding factors (tumour diameter, thickness and drug scheme, adjusted P = .04). Tumour perfusion correlated with number of IAC cycles required for tumour control (r = 0.46, P < .001). For primary IAC (n = 18, 31%), tumour perfusion was not associated with number of IAC cycles (P = .63). For secondary IAC (n = 41, 69%), partially perfused tumours (n = 15, 37%) required fewer IAC infusions than completely perfused tumours (n = 26, 63%) (2.1 vs 3.7 infusions, P < .01). CONCLUSIONS AND RELEVANCE: FA demonstrating partial retinoblastoma tumour perfusion is associated with fewer IAC cycle requirements for secondary but not primary IAC. FA might be useful in judging anticipated treatment cycles of retinoblastoma managed with primary or secondary IAC.

Precision Intravitreal Chemotherapy for Localized Vitreous Seeding of Retinoblastoma.

PURPOSE: To describe and evaluate the effectivity of a novel precision intravitreal injection technique for select cases of localized vitreous seeding in retinoblastoma. METHODS: Patients with localized vitreous seeds from retinoblastoma received intravitreal chemotherapy via a precision injection technique (P-IVitC) intended to optimize local delivery of melphalan to target seeds. The needle was inserted trans-pars plana and chemotherapy deposited within 3 mm of the target seed(s) under indirect ophthalmoscopic guidance. Without subsequent globe manipulation, the head was then positioned to promote gravity-dependent settling of chemotherapy. RESULTS: There were 8 eyes of 8 patients treated with P-IVitC for active vitreous seeds following adequate solid tumor control with intravenous chemotherapy (n = 3, 38%) or intra-arterial chemotherapy (n = 5, 63%). Viable vitreous seeds were primarily solitary spheres (n = 6, 75%) and measured an average of 2.7 mm in diameter. Vitreous seed resolution (n = 8, 100%) was noted after a mean of 2.6 injections (median 2; range 1-3) of 20 µg melphalan. There was no recurrence at a mean follow-up of 10.0 months. Only 1 eye had an associated complication (focal retinal pigment epithelial mottling, n = 1, 13%). CONCLUSIONS: With direct delivery of chemotherapy to within 3-4 mm of vitreous seed activity, P-IVitC provided complete control of localized vitreous seeds with minimal toxicity.

CHOROIDAL NEVUS TRANSFORMATION INTO MELANOMA PER MILLIMETER INCREMENT IN THICKNESS USING MULTIMODAL IMAGING IN 2355 CASES: The 2019 Wendell L. Hughes Lecture.

PURPOSE: To analyze risk of nevus transformation into melanoma per millimeter increment. METHODS: Retrospective analysis of 3,806 choroidal nevi for transformation into melanoma per incremental millimeter thickness (flat [≤1.0 mm], thin [1.1-2.0 mm], thicker [2.1-3.0 mm], and thickest [>3.0 mm]) RESULTS:: The median nevus thickness was 1.4 mm, and nevi were categorized (flat, thin, thicker, and thickest) in 1,140 (30%), 2052 (54%), 555 (15%), and 59 (<1%), respectively. There were differences in tumor diameter (2.5, 4.8, 7.5, and 9.3 mm; P < 0.01), optical coherence tomography detection of overlying subretinal fluid (<1, 4, 15, and 11%; P < 0.01), overlying retinal edema (<1, 3, 14, and 25%; P < 0.01), overlying drusen (23, 49, 64, and 64%; P < 0.01), overlying retinal pigment epithelial detachment (1, 4, 4, and 9%; P < 0.01), and overlying lipofuscin hyperautofluoresence (<1, 3, 6, and 7%; P < 0.01). Choroidal nevus transformation into melanoma (n = 90/2,355 cases, 3.8%) was found by Kaplan-Meier 7-year estimates (2.2, 6.1, 31.7, and 34.5%; P < 0.0001) and by hazard ratio (HR) compared with nevus ≤1.0 mm (not available, 4.7 [P = 0.01], 35.7 [P < 0.0001], and 52.0 [P < 0.0001]). For all thicknesses, those with growth displayed increase in mean basal diameter of 2.4 mm and thickness of 1.1 mm, optical coherence tomography increase in subretinal fluid (65%), autofluorescence increase in lipofuscin (40%), and ultrasonography increase in hollowness (30%). Multivariable risk factors, recalled by the mnemonic "To Find Small Ocular Melanoma Doing IMaging" (TFSOM-DIM) representing Thickness >2 mm (ultrasonography), Fluid subretinal (optical coherence tomography), Symptom vision loss (Va), Orange pigment (autofluorescence), Melanoma hollow (ultrasonography), and DIaMeter >5 mm, revealed factors per incremental thickness category (compared with flat) including thin (Fluid overlying, HR 6.1; DIaMeter >5 mm, HR 3.3), thicker (Fluid subretinal ≤3 mm from nevus, HR 5.7; Melanoma acoustic hollowness, HR 2.7), and thickest (Orange pigment, HR 9.1). CONCLUSION: Each incremental increase in choroidal nevus thickness demonstrated risk of growth into melanoma with HR (compared with flat) 4.7 for thin, 35.7 for thicker, and 52.0 for thickest. The increase from ≤2.0 mm to >2.0 mm thickness conferred the greatest rise for transformation.