Unusual Presentation of Unilateral Choroidal Melanoma with Bilateral Vasculitis in Young Individual: A Case Report and Review of Literature.

Ocular melanoma stands as the predominant primary intraocular malignancy, albeit infrequently exhibiting ipsilateral inflammatory manifestations. In this article, we present an exceptional case involving a middle-aged male who presented with unilateral ocular choroidal melanoma alongside bilateral retinal vasculitis. The patient initially received temporary steroid treatment, followed by brachytherapy, which contributed to the resolution of vasculitis symptoms. The study aims to document the atypical occurrence of bilateral retinal vasculitis, which could potentially masquerade as melanoma, emphasizing the need for heightened vigilance and further investigations when encountering choroidal masses in its presence. Future research endeavors are warranted to better understand the incidence of such occurrences in this context.

Multispectral Fundus Photography of Choroidal Nevi With Trans-Palpebral Illumination.

Purpose: The purpose of this study was to investigate the spectral characteristics of choroidal nevi and assess the feasibility of quantifying the basal diameter of choroidal nevi using multispectral fundus images captured with trans-palpebral illumination. Methods: The study used a widefield fundus camera with multispectral (625 nm, 780 nm, 850 nm, and 970 nm) trans-palpebral illumination to examine eight subjects diagnosed with choroidal nevi. Geometric features of nevi, including border clarity, overlying drusen, and lesion basal diameter, were characterized. Clinical imagers, including scanning laser ophthalmoscopy (SLO), autofluorescence (AF), and optical coherence tomography (OCT), were utilized for comparative assessment. Results: Fundus images depicted nevi as dark regions with high contrast against the background. Near-infrared (NIR) fundus images provided enhanced visibility of lesion borders compared to visible fundus images and SLO images. Lesion-background contrast measurements revealed 635 nm SLO at 11% and 625 nm fundus at 42%. Significantly enhanced contrasts were observed in NIR fundus images at 780 nm (73%), 850 nm (63%), and 970 nm (67%). For quantifying the diameter of nevi, NIR fundus images at 780 nm and 850 nm yielded a deviation of less than 10% when compared to OCT measurements. Conclusions: NIR fundus photography with trans-palpebral illumination enhances nevi visibility and boundary definition compared to SLO. Agreement in diameter measurements with OCT validates the accuracy and reliability of this method for choroidal nevi assessment. Translational Relevance: Multispectral fundus imaging with trans-palpebral illumination improves choroidal nevi visibility and accurately measures basal diameter, promising to enhance clinical practices in screening, diagnosis, and monitoring of choroidal nevi.

Disinsert, retract and rotate technique of plaque brachytherapy.

BACKGROUND: Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed. PURPOSE: The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas. SYNOPSIS: The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration. HIGHLIGHTS: In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque. VIDEO LINK: https://youtu.be/YMIg3rYyp2o.

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.

POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

CHOROIDAL NEVUS ASSOCIATED WITH VITELLIFORM DEPOSITION IN A PATIENT WITH AUTOSOMAL DOMINANT BEST DYSTROPHY.

BACKGROUND/PURPOSE: To describe the clinical, optical coherence tomography (OCT), fundus autofluorescence and ultrasound findings of a patient with a choroidal nevus actively exuding vitelliform material in the setting of autosomal dominant Best dystrophy (BD). METHODS: The patient's clinical course was followed over time with ophthalmic examinations and multimodal imaging. RESULTS: A 71-year-old male patient with BD was referred for evaluation of a choroidal nevus in the right eye. Dilated fundoscopic examination showed a small pigmented choroidal nevus in the temporal periphery. Over a 3-year period, the nevus developed progressive deposition of vitelliform material along its inferior border. Meanwhile, OCT and fundus photography showed only slight growth. Ultrasound showed no change in height; basal measurements were confounded by the increased vitelliform deposits. Genetic testing confirmed a heterozygous mutation in the BEST1 gene and electrophysiology was consistent with BD. CONCLUSIONS: Dysfunction of the retinal pigment epithelium associated with BD may cause novel presentations of other conditions such as choroidal nevi. The implication for malignant transformation of a choroidal nevus associated with vitelliform deposit accumulation in this context is unknown.

An immunotherapeutic artificial vitreous body hydrogel to control choroidal melanoma and preserve vision after vitrectomy.

Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.

Optical Density Ratio of Subretinal Fluid in Choroidal Melanomas Versus Choroidal Naevi Assessed by Optical Coherence Tomography.

Purpose: The purpose of this study was to determine whether optical density ratio (ODR) of subretinal fluid (SRF) on optical coherence tomography (OCT) differs between choroidal naevi and melanomas. Methods: One hundred ninety-nine patients (one eye per patient) presenting choroidal melanoma or choroidal naevus with SRF on OCT, evaluated between February and June 2019, were retrospectively included. Other retinal conditions, opaque media, and low-quality OCT were excluded. Mean pixel intensity of SRF (range = 0-255) was quantified using a semi-automated procedure by a masked observer on standard horizontal OCT sections. Mean vitreous intensity served as the reference for ODR. Results: One hundred twenty-eight patients with choroidal melanoma and 71 patients with choroidal naevus were included in this study. ODR (mean ± SD) was higher in melanomas (181 ± 64) than in naevi (78 ± 48, P < 0.0001). ODR was correlated to lesion thickness (P < 0.0001, r = 0.27), largest basal diameter (P = 0.028, r = 0.16) and, among naevi, to the number of risk factors for growth into melanoma (P = 0.032, r = 0.22). Among 110 patients with naevi or melanoma who underwent fluorescein angiography, ODR was 120.7 ± 550.1 in eyes presenting angiographic pinpoints versus 14.19 ± 26.0 in eyes that did not (P = 0.06). Fourteen eyes with naevi that transformed into melanoma over 3 years had a mean baseline ODR of 94.7 ± 243.5 compared to 4.01 ± 9.74 in 28 matched naevi eyes of similar size that did not transform (P = 0.027). Conclusions: SRF ODR is higher in choroidal melanoma compared to choroidal naevi. This OCT-derived imaging marker is also higher in choroidal naevi with the potential to transform into melanoma, compared to stationary naevi.

Malignant choroidal melanoma with vitreous seeds: supported by histopathology and field emission scanning electron microscopy study.

Aim: To report an exceptionally rare case of malignant choroidal melanoma with vitreous seeding, supported by histopathological and field emission scanning electron microscopic (FESEM) studies. Case report: A 58-year-old male with painless diminution of vision in his left eye for past 1 month was found to have a brown retrolental mass lesion on slit lamp examination in the left eye. Detailed fundus examination revealed choroidal melanoma in the left eye with pigmented seeds extending into the vitreous cavity and associated exudative retinal detachment. Ocular imaging was consistent with the diagnosis. Results: The eyeball was enucleated and the tumor was considered as stage IIB (AJCC 8th edition classification). Metastatic workup of the patient was negative. One half of the eyeball was subjected to field emission scanning electron microscopy to further study the nature and appearance of vitreous seeds. Discussion: Vitreous seeding in choroidal melanoma has been reported only in a handful of cases in literature. Histopathological confirmation of vitreous seeds was done in our case and morphological detailing was performed using FESEM study. Conclusions: Treatment naïve choroidal melanoma can very rarely have vitreous seeds. Early enucleation in such cases carries a favorable prognosis.

Choroidal Nevus Features Associated with Subspecialty Referral.

OBJECTIVE: To identify choroidal nevus features associated with referral to a retina or ocular oncology subspecialist. DESIGN: Population-based retrospective cohort study. SUBJECTS: Patients diagnosed with choroidal nevus. METHODS: Population-based retrospective cohort study of residents of Olmsted County, Minnesota, with an incident diagnosis of choroidal nevus from January 1, 2006, to December 31, 2015 using the Rochester Epidemiology Project, a medical record linkage system. Tumor features and patient demographics associated with referral to a retina or ocular oncology subspecialist were assessed. Wilcoxon rank sum test, chi-square test, and Fisher exact test were used for statistical analysis. MAIN OUTCOME MEASURES: Tumor features and patient demographics associated with referral to subspecialty care. RESULTS: There were 826 incident diagnoses of choroidal nevus, of which 88 cases (11%) were referred, with highest level of referral being retina in 29 cases (33%) and ocular oncology in 59 cases (67%). None of the analyzed demographic features were associated with choroidal nevus referral to subspecialty care. Tumor features associated with referral (vs. not referred) included greater mean basal diameter (4.6 mm vs. 2.4 mm, P < 0.001), greater mean tumor thickness (0.7 mm vs. 0.1 mm, P < 0.001), greater distance to optic disc (6.9 mm vs. 3.4 mm, P = 0.02), halo around nevus (5.7% vs. 0.4%, P < 0.001), and drusen on OCT (51% vs. 25%, P = 0.002). Presence of orange pigment (8% vs. 0%, P = 0.14), subretinal fluid (9% vs. 2.5%, P = 0.09), and low internal reflectivity on A-scan (7.7% vs. 0%, P = 1.00) were not found more frequently in the subspecialty referral group. CONCLUSIONS: Greater basal diameter and mean tumor thickness of choroidal nevus were associated with referral to retina or ocular oncology. However, several features associated with increased risk of malignant transformation were not associated with subspecialty referral. These findings highlight the importance of educating eye care providers about high-risk tumor features associated with choroidal nevus transformation to melanoma. In the primary eye care setting where not all multimodal imaging may be available, we encourage color photography and OCT with referral for any features of basal diameter > 5 mm, presence of subretinal fluid, or thickness too large for capture by enhanced-depth imaging OCT. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

[OCT classification of choroidal nevi]. / OKT-klassifikatsiya nevusov khorioidei.

Choroidal nevi (CN) are commonly divided into non-suspicious (stable) and suscpicious (progressive). However, there are still no clear data on OCT patterns of nevi progression, their transformation into initial melanomas. PURPOSE: The study aims to determine the types of OCT patterns of CN and to evaluate their prognostic value. MATERIAL AND METHODS: The study included 50 patients with CN (53 nevi). The height of 19 nevi evaluated with ultrasonography was 1.33±0.43 mm, diameter - 5.47±1.68 mm. RESULTS: CN is an area of local increase in reflectivity of the choroid; its widening and elevation of the tomographic section were observed in 72% of nevi. In more than half of all cases a distinct hyperreflective border was revealed between the CN and adjacent choroid. In two thirds of all cases the choriocapillaris layer was preserved and visualized mainly along the edge of lesion. Analysis of OCT scans showed distinct differences, which allowed designation of four OCT types of CN: 1) nevi with typical OCT pattern; 2) nevi with changes in retinal pigment epithelium (RPE); 3) nevi with neuroepithelial detachment; 4) nevi with atypical OCT pattern. CONCLUSION: Based on the analysis of OCT images of the determined types of nevi, it can be assumed that all of them initially had typical OCT pattern. With enlargement of the nevi and increase in the duration of its presence in the choroid, dystrophic processes in the adjacent retina and changes in RPE begin to occur. Disturbed pumping ability of the damaged RPE results in disruption of the trophism of adjacent retina, which leads to development of atrophic changes. Nevi with atypical OCT pattern should be considered as a sign of long-term benign process in the choroid that will cause atrophic changes in the choroid and adjacent retina, while nevi with changes in RPE and with neuroepithelial detachment - as a risk factor for transition to choroidal melanoma.

PIGMENTATION IN FOCAL SCLERAL NODULE.

PURPOSE: To report a case of pigmentation in focal scleral nodule (FSN). METHODS: This is a single case report. RESULT: An asymptomatic 61-year-old woman was referred with small, partially pigmented raised lesion located at the superior margin of the optic nerve head. The lesion's clinical and multimodal imaging features were consistent for FSN including a dome-shaped elevation confined to the sclera with overlying choroidal thinning. However, the pigmentation within our lesion is a novel finding in FSN that has not been described before. CONCLUSION: To our knowledge, we report the first case of pigmentation in FSN. It is likely that our case was a typical FSN that then became pigmented, with melanosomes involving the flanges of the lesion where thin choroid remains. The understanding that FSN can be partially pigmented may eventually help unravel the origins of this poorly understood lesion.

Bacillary layer detachment with malignant choroidal tumors: a case series.

PURPOSE: To study the incidence and characteristics of bacillary layer detachment (BALAD) occurring with the two most common choroidal malignancies, choroidal metastasis and choroidal melanoma. METHODS: A retrospective multicentric record analysis. Eyes with a diagnosis of choroidal melanoma or choroidal metastasis that had good-quality fundus photography and spectral domain optical coherence tomography (OCT) scans of the macular and tumor regions allowing for delineation of the retinal layers were included for analysis. Qualitative image evaluation was done by two independent graders for the presence, location, and OCT features of BALAD, as well as any associated intraretinal or subretinal fluid. Demographic and clinical data were also retrieved. RESULTS: Of the 11 eyes with choroidal metastasis and 7 eyes with choroidal melanoma that were included in the final analysis, 6 (54.5%) and 1 (14.3%) had BALAD, respectively. The BALAD co-localized with the subretinal fluid in all cases and with the intraretinal fluid in 1/3 cases (33.3%), was foveal in location in 3 eyes (42.9%), was overlying the tumor in 6 eyes (85.7%), and varied in number and size. Reflectivity within the BALAD was consistently higher than the vitreous and adjacent subretinal fluid, and discernable suspended hyperreflective particles were noted in 5 eyes (71.4%). CONCLUSION: BALAD is relatively common with choroidal metastasis. The OCT features described supplement our recognition of this new entity.

Long term results of photodynamic therapy in intraocular tumors.

PURPOSE: To report long term results of photodynamic therapy (PDT) as treatment for intraocular tumors METHODS: Retrospective interventional case series of 15 patients. All patients treated with standard-fluence PDT (83 s; 50 J/cm2) using verteporfin. OUTCOME MEASURES: Tumor diameter, tumor thickness, subretinal fluid resolution, best-corrected visual acuity,intraocular pressure and PDT complications. RESULTS: 10 patients (66.7% of total patients) were diagnosed with choroidal hemangioma, 3 patients (20% of total patients) were diagnosed with choroidal melanoma, and 2 patients (13,3% of total patients) were diagnosed with choroidal osteoma.. Mean follow-up time was 33±18 months. The mean visual acuity was determined as 1.29 ± 0.98 logMAR in the examinations just before the PDT application. At the end of the follow-up period, the mean visual acuity was calculated as 1.41 ± 1.07 logMAR. While VA increased in 3 (20%) patients and decreased in 5 (33.3%) patients; It was determined that VA value did not change after treatment in 7 (46.7%) patients. The mean lesion diameter before PDT was 6573 ± 2115 µm (range; 1500-10,000 µm). The mean tumor thickness before PDT was 3624 ± 1404 µm (range; 600-6000 µm). The mean lesion diameter after treatment was 6026 ± 2521 µm (range; 0-9000 µm), and the mean tumor thickness after treatment was 2280 ± 1740 µm (range; 0-6000 µm).After the PDT, tumor size decreased in 8 (53.3%) patients, increased in 3 (20%) patients, and no change in tumor size was observed in 4 (26.7%) patients. Mean IOP values of all patients were 14.06 ± 3.17 mmHg before treatment; after treatment, it was measured as 13.46 ± 1.70 mmHg. After the treatment, geographic atrophy developed in 1 (6.7%) patient, cystoid macular edema developed in 1 (6.7%) patient, Retinal Pigment Epithelium (RPE) and choroidal atrophy developed in 1 (6.7%) patient. CONCLUSION: There are not enough cases of each to clearly distinguish between these 3 types of ocular cancers.However PDT may be a good option in the treatment of intraocular tumors with the chance of selective treatment and successful response.

Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma.

Purpose: Choroidal melanoma (CM) and ciliary body melanoma (CBM) are the two most common subtypes of uveal melanoma. Starting from the observation that CBM tends to have a higher metastatic potential than CM, we hypothesized that specific cytogenetic abnormalities could be associated with tumor location - reflecting distinct genetic signatures that would drive the risk of distant spread. Methods: Chromosomal alterations were investigated by molecular cytogenetic techniques in 217 and 97 patients with CM and CBM, respectively. Cox proportional hazards regression analysis was used to identify the independent predictors of distant metastasis. Results: Patients with CBM had larger tumor sizes (P < 0.001), higher disease stages (P < 0.001), and more frequently showed distant metastasis (P = 0.002) than those with CM. On analyzing the entire study cohort, we found that specific chromosomal alterations - including chromosome 8p loss (P < 0.001), 1p loss (P < 0.001), and monosomy 3 (P < 0.005) - were independent predictors of distant metastasis. Based on a decision-tree learning algorithm, we identified three specific subgroups of patients with uveal melanoma at high risk of distant spread. Monosomy 3 occurred significantly more frequently in patients with T3 CBM tumors. Conclusions: Specific cytogenetic abnormalities - including chromosome 8p loss, 1p loss, and monosomy 3 - are independent risk factors for distant metastasis in uveal melanoma. Larger tumor size at presentation and monosomy 3 contribute to a higher metastatic risk in patients with CBM.

Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects.

Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro models compared to real clinical cases. Among the several potential mechanisms examined, particular attention was paid to histologic alterations and molecular cascades. Physical or biochemical resistance to vascular invasion from the choroid offered by Bruch's membrane, the role of fibroblast growth factor 2 and vascular endothelial growth factor, resident or recruited stem-like/progenitor cells, and other angiogenic promoters were taken into account. Even if the exact mechanisms are still partially obscure, experimental models are progressively enhancing our understanding of neovascularization etiology. Choroidal neovascularization (CNV) over melanoma, osteoma, and other tumors is not rare and is not contraindicative of malignancy as previously believed. In addition, CNV may represent a late complication of either benign or malignant choroidal tumors, stressing the importance of a long follow-up.

Metastatic and aggressive renal cell carcinoma mimicking a unilateral choroidal tuberculoma.

Ocular metastases from systemic tumors are uncommon. The choroid is the most frequent target, with a preference for elderly individuals. Lung cancer is the predominant primary tumor that metastasizes to the eyes in males, although other ocular conditions such as uveitis and retinal lesions can mimic secondary tumor implants in ocular tissues. On fundoscopy, choroidal metastasis resembles other infectious processes, especially choroidal tuberculoma. Therefore, patients presenting with choroidal masses should undergo detailed clinical examinations, especially if the mass is the first manifestation of a systemic and severe disease. In this report, we describe a young man with a metastatic choroidal tumor secondary to papillary renal cell carcinoma mimicking a unilateral choroidal tuberculoma.

Extrascleral extension of choroidal melanoma after iodine-125 brachytherapy treatment: a case series.

BACKGROUND/OBJECTIVES: The purpose of this study is to report cases of choroidal melanoma that developed extrascleral tumour recurrence after treatment with iodine-125 brachytherapy. SUBJECTS/METHODS: In this single-institution retrospective observational case series, all instances of biopsy-confirmed orbital melanoma after known intraocular melanoma were reviewed. Tumour characteristics, clinical course, time to recurrence, cytogenetics of initial tumour and recurrence, and presence of intraocular recurrence were documented. RESULTS: Five cases of orbital melanoma following treatment with plaque radiotherapy are described. Tumour staging was Ia (1), IIa (2), and IIb (2). The primary lesion in four of the five appeared to have undergone complete regression for an average of 2 years, with the orbital melanoma developing after this interval. Recurrence of the intraocular tumour was seen in conjunction with an extrascleral component in two cases. Four cases ultimately underwent enucleation or exenteration; three had evidence of direct extension of tumour through the sclera. Four cases in this series had molecular characteristics associated with high metastatic risk (three patients with monosomy 3, one with BAP1 mutation). CONCLUSIONS: High-risk tumour biology may predispose to late appearance of extrascleral melanoma despite optimal treatment and adequate control of the intraocular tumour. Extended follow-up with detailed orbital examination and imaging is recommended for this population.

Presumed incipient choroidal melanoma: proposed diagnostic criteria and management.

AIMS: To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT). METHODS: Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010-2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-term follow-up. RESULTS: The median LBD and thickness were 1.6 mm (range 0.9-2.3) and 0.20 mm (range 0.15-0.29), respectively. The median age was 57 years (range 47-78). Seven tumours were classified as de novo melanomas and two as transformed naevi. The median time from first observation to diagnosis was 3.3 years (range 2.2-7.3), LBD growth rate 0.25 mm/year (range 0.11-0.72) and 34 per cent/year (range 10-1437), and TDT 609 days (range 97-1612). The estimates matched those reported for uveal melanoma (median TDT 521 days, 90th percentile 2192) and exceeded those for growing naevi (median growth rate 0.04 mm/year, 90th percentile 0.12; 1.1 per cent/year, 90th percentile 2.6). The predicted median age at de novo appearance was 51 years (range 32-63). No tumour grew after TTT during a median follow-up of 2.1 years (range 0.6-8.7). CONCLUSIONS: In this series, relative growth rate and TDT best qualified as diagnostic criteria for an incipient choroidal melanoma. Too small for brachytherapy, they could be managed with TTT.