Detection of Copy-Number Variation in Circulating Cell-Free DNA in Patients With Uveal Melanoma.

PURPOSE: Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes. MATERIALS AND METHODS: ULP-WGS of cfDNA was performed on 29 plasma samples from 16 patients, 14 metastatic UM (mUM) and two non-metastatic, including pre- and post-treatment mUM samples from 10 patients treated with immunotherapy and one with liver-directed therapy. We estimated tumor fraction (TFx) and detected copy-number alterations (CNAs) using ichorCNA. Presence of 8q amplification was further analyzed using the likelihood ratio test (LRT). RESULTS: Eleven patients with mUM (17 samples) of 14 had detectable circulating tumor DNA (ctDNA). 8q gain was detected in all 17, whereas monosomy 3 was detectable in 10 of 17 samples. TFx generally correlated with disease status, showing an increase at the time of disease progression (PD). 8q gain detection sensitivity appeared greater with the LRT than with ichorCNA at lower TFxs. The only patient with mUM with partial response on treatment had a high pretreatment TFx and undetectable on-treatment ctDNA, correlating with her profound response and durable survival. CONCLUSION: ctDNA can be detected in mUM using ULP-WGS, and the TFx correlates with DS. 8q gain was consistently detectable in mUM, in line with previous studies indicating 8q gains early in primary UM and higher amplification with PD. Our work suggests that detection of CNAs by ULP-WGS, particularly focusing on 8q gain, could be a valuable blood biomarker to monitor PD in UM.

Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment.

Introduction: Vision loss is common in patients treated with radiotherapy for uveal melanoma. With proton beam irradiation (PBI), the prescribed dose is delivered to the tumor with a sharp dose reduction outside the target volume. However, radiation complications are likely to develop when tumors are located near the optic nerve or fovea. Treatment with light-activated AU-011 (belzupacap sarotalocan), an investigational drug which specifically targets tumor cells, may avoid these complications. We evaluated outcomes in a historical group of patients who fit eligibility criteria for AU-011 therapy and were treated with PBI. Methods: A consecutive series of patients who received PBI for small choroidal melanoma at a single center between 1986 and 2016 were identified. Consistent with eligibility criteria in clinical trials of AU-011, patients were included when tumor dimensions did not exceed 2.5 mm in maximum thickness and 10.0 mm in largest basal diameter (LBD). Snellen visual acuities were converted to logMAR for analysis. Visual acuity outcomes were analyzed in patients with an initial acuity of logMAR 0.7 or better (equivalent to Snellen 20/100). Rates of visual acuity loss and mortality were calculated using the Kaplan-Meier method. Acuity loss by tumor location was compared using log-rank testing. Rates of tumor recurrence, neovascular glaucoma (NVG), and eye loss were also described. Results: Two hundred and 22 patients were included in the study. The median age was 60.7 years (range 21.3-94.8 years). Median tumor thickness was 2.0 mm (range 1.2-2.5 mm), and median LBD was 8.0 mm (range 4.0-10.0 mm). Median follow-up was 6.9 years (range 1.0-30.2 years). In 204 patients with a baseline logMAR visual acuity of 0.7 or better, the mean baseline acuity was 0.15 (equivalent to Snellen 20/25), which decreased to 0.52 (approximately Snellen 20/70) by 5 years after PBI. Visual outcomes were significantly worse for patients with tumors located within 3 mm of the optic disc and/or fovea. Tumor recurrence (1.4%), NVG (4.5%), and eye loss (2.7%) were uncommon. Discussion: Despite the advantageous dose distribution of protons, over half of patients with small choroidal melanomas located near the optic disc or fovea had a visual acuity equivalent to 20/80 or worse at 5 years after PBI. Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.

Survival of patients with recurrent uveal melanoma after treatment with radiation therapy.

BACKGROUND/AIMS: We evaluated a large cohort of patients treated for local recurrence of choroidal or ciliary body melanomas at the Massachusetts Eye and Ear (MEE) to quantify the risk of melanoma-related mortality associated with recurrence, independent of other risk factors. METHODS: Patients treated with radiation therapy from 1982 to 2017 were identified through the Uveal Melanoma Registry at MEE. Competing risks regression was performed to investigate the risk of melanoma-related mortality associated with recurrence, treating recurrence as a time-varying covariate. RESULTS: Of 4196 patients treated, 4043 patients remained recurrence-free and 153 patients experienced a recurrence (median follow-up: 9.9 years). Median time from initial treatment to recurrence was 30.5 months (range: 2.0-238.7). Seventy-nine (69.9%) patients with recurrences and 826 (37.9%) patients in the recurrence-free group died of metastatic uveal melanoma (p<0.001). Median time from initial treatment to melanoma-related death was 4.9 years (1.0-31.8) for patients who developed recurrences and 4.3 years (0.59-33.8) for patients who did not (p=0.17). Five-year and 10-year probabilities of melanoma-related mortality were 9.5% and 15.0%, respectively, in patients without local recurrences compared with 32.0% and 46.6% in patients with recurrences (p<0.001). CONCLUSION: These data confirm previous reports that local recurrence is associated with an increased risk of dying of melanoma and quantify the risk that can be attributed to local recurrence independent of other risk factors. This group of patients should be strongly considered for adjuvant therapies when available.

Growth rate of indeterminate choroidal lesions prior to melanoma diagnosis.

PURPOSE: Small choroidal melanocytic lesions have a low rate of metastasis and can be reasonably managed with surveillance until they demonstrate evidence of growth or clinical risk factors for melanoma. However, even choroidal nevi are not stationary, with many exhibiting slow growth over time. We sought to quantify the growth rates of indeterminate choroidal lesions that were initially observed prior to a clinical diagnosis of melanoma. METHODS: A single-center retrospective study was performed of patients diagnosed with choroidal melanoma based upon clinical characteristics who were initially followed for indeterminate lesions over at least 6 months. Subjects were included if they had a minimum of two B-scan ultrasound measurements prior to the visit at which melanoma was diagnosed. Demographic and tumor characteristics were collected from the medical record. Growth rates were calculated as the change in lesion thickness in mm per month and were recorded at 6-month intervals; ultrasound measurements less than 1 month apart were excluded. The characteristics of indeterminate lesions with faster versus slower growth rates prior to melanoma diagnosis were compared. RESULTS: Fifty-four patients met inclusion criteria. The mean age at melanoma diagnosis was 67.4 years, and 53.7% were female. Subjects had a median of four B-scan ultrasound measurements prior to melanoma diagnosis (range 2-19) and were followed for a median of 40.6 months (range 9.9-138.0 months). The mean lesion thickness was 1.4 mm (range 0.5-2.2 mm) at presentation, and increased to 2.3 mm (range 1.5-5.7 mm) at melanoma diagnosis. The mean growth rate did not exceed 0.021 mm/month (95% CI: 0.004-0.039; equivalent to 0.25 mm/year) for indeterminate lesions, but increased to 0.057 mm/month (95% CI: 0.043-0.071 mm/month; equivalent to 0.68 mm/year) at the time of melanoma diagnosis. Rapidly growing lesions had a greater tumor thickness and shorter duration of observation at the time of melanoma diagnosis. CONCLUSION: For most indeterminate choroidal lesions eventually diagnosed as melanoma, the lesion thickness was relatively stable for a period of time, then rose significantly between the penultimate visit and the final visit. These findings confirm the recommendation for continued monitoring of suspicious choroidal lesions, as the growth rate may accelerate just prior to melanoma diagnosis. Lesions with a mean growth rate of up to 0.25 mm/year were observed, whereas lesions clinically determined to have transformed into melanoma demonstrated a mean growth rate of 0.68 mm/year. These values provide a baseline for future studies and potential therapies directed at stabilizing or reducing the growth of indeterminate choroidal lesions or small choroidal melanomas. Limitations of this study include its retrospective nature and reliance on clinical diagnostic criteria.

The NLRP3 inflammasome - interleukin 1ß axis in uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1ß axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P < 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1ß secretion than CM, especially when compared to the Hs294t cell line (P < 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1ß compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1ß secretion by melanoma cells and highlight differences between CM and UM.

A Systematic Comparison of Dose Distributions Delivered in 125I Plaque Brachytherapy and Proton Radiation Therapy for Ocular Melanoma.

PURPOSE: To characterize dose distributions with 125I plaque brachytherapy compared with proton radiation therapy for ocular melanoma for relevant clinical scenarios, based on tumor base diameter (d), apical height (h), and location. METHODS AND MATERIALS: Plaque and proton treatment plans were created for 4 groups of cases: (1) REF: 39 instances of reference midsize circular-base tumor (d = 12 mm, h = 5 mm), in locations varying by retinal clock hours and distance to fovea, optic disc, and corneal limbus; (2) SUP: 25 superiorly located; (3) TEMP: 25 temporal; and (4) NAS: 25 nasally located tumors that were a fixed distance from the fovea but varying in d (6-18 mm) and h (3-11 mm). For both modalities, 111 unique scenarios were characterized in terms of the distance to points of interest, doses delivered to fovea, optic disc, optic nerve at 3 mm posterior to the disc (ON@3mm), lens, and retina. Comparative statistical evaluation was performed with the Mann-Whitney U test. RESULTS: Superior dose distributions favored plaque for sparing of (1) fovea in large (d + h ≥ 21 mm) NAS tumors; (2) ON@3mm in REF cases located ≤4 disc diameters from disc, and in NAS overall. Protons achieved superior dose sparing of (1) fovea and optic disc in REF, SUP, and TEMP; (2) ON@3mm in REF >4 disc diameters from disc, and in SUP and TEMP; and (3) the lens center overall and lens periphery in REF ≤6 mm from the corneal limbus, and in TEMP with h = 3 mm. Although protons could completely spare sections of the retina, plaque dose was more target conformal in the high-dose range (50% and 90% of prescription dose). CONCLUSIONS: Although comparison between plaque and proton therapy is not straightforward because of the disparity in dose rate, prescriptions, applicators, and delivery techniques, it is possible to identify distinctions between dose distributions, which could help inform decisions by providers and patients.

Low-dose proton radiotherapy for pediatric choroidal hemangioma: A case series.

Management of pediatric choroidal hemangioma complicated by large exudative retinal detachment can be challenging, with few options available. Limited data have been published on outcomes following proton radiotherapy (PRT) for management of these patients. In this retrospective case series, nine patients were treated with a low-dose PRT regimen of 20 Gy(relative biological effectiveness [RBE]) in 10 fractions, and two were treated with 15 Gy(RBE) in four fractions. Visual acuity improved in seven patients (64%) and remained stable in the remaining four (36%). In patients with imaging follow-up (10 patients), subretinal fluid resolved in nine patients (90%) and tumor thickness decreased or remained stable in 10 (100%). Complications were observed in eight of 11 patients (73%). One patient developed grade 2 cataract; otherwise, no grade ≥2 complications were observed.

The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration.

PURPOSE: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN: Retrospective cohort study. PARTICIPANTS: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES: Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001). CONCLUSIONS: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

A Comparison of Treatment Outcomes after Standard Dose (70 Gy) versus Reduced Dose (50 Gy) Proton Radiation in Patients with Uveal Melanoma.

OBJECTIVE: To compare outcomes in a large patient cohort with small-medium tumors located within 1 disc diameter (DD) of the optic nerve and/or fovea treated with 50 Gy or 70 Gy proton therapy. DESIGN: Retrospective cohort study. SUBJECTS: A total of 1120 patients with uveal melanomas ≤ 15 mm in largest basal diameter, ≤ 5 mm in height, located within 1 DD of the optic nerve and/or fovea, who received primary treatment with protons between 1975 and 2016 at Massachusetts Eye and Ear/Massachusetts General Hospital. METHODS: The rates of outcomes were estimated using the Kaplan-Meier method. Differences between the radiation dose groups were tested using the log-rank test. MAIN OUTCOME MEASURES: Local tumor recurrence, melanoma-related mortality, and visual acuity preservation (≥ 20/200, ≥ 20/40). RESULTS: Local tumor recurrence was observed in 1.8% of the 50 Gy group and 1.5% of the 70 Gy group. The median time to recurrence was 30.7 months for patients treated with 50 Gy and 32.0 months for those treated with 70 Gy (P = 0.28). Five-year rates of vision retention (≥20/40, ≥ 20/200) were 19.4% and 49.3% for patients treated with 50 Gy and 16.4% and 40.7% in those treated with 70 Gy. Ten-year rates of melanoma-related mortality were 8.4% in the 50 Gy group and 8.9% in the 70 Gy group (P = 0.47). CONCLUSIONS: Comparable rates of local control are achieved treating small-medium tumors near the optic nerve and/or fovea with 50 Gy or 70 Gy proton therapy, supporting the use of the lower dose in patients with these tumor characteristics.

Proton beam irradiation of uveal melanoma involving the iris, ciliary body and anterior choroid without surgical localisation (light field).

AIMS: To assess treatment outcomes after proton beam irradiation (PBI) without surgical localisation of uveal melanomas involving the iris, ciliary body and anterior choroid. METHODS: Retrospective chart review of 125 patients evaluated at Massachusetts Eye and Ear and treated with PBI using a light field set-up without localisation surgery between November 1975 and April 2017. The tumours were characterised as follows: iris (n=18, 14.4%), ciliary body (n=12, 9.6%), iridociliary (n=58, 46.4%), ciliochoroidal (n=24, 19.2%) and iridociliochoroidal (n=13, 10.4%). The tumours were measured by transillumination and ultrasonography before treatment. Tumours with posterior margin located less than two disc diameters from the ora serrata were treated using the light field technique. Patient outcomes after PBI were evaluated. RESULTS: Most patients had good vision at the time of tumour diagnosis (69.6% had baseline visual acuity (VA) of ≥20/40). Median VA at last follow-up (median follow-up: 72.1 months) was 20/63. Recurrences occurred in 12 patients (9.6%) at a median time of 4.0 years post-treatment. Recurrences were treated by repeat PBI (n=5) or enucleation (n=7). Secondary enucleation was performed in 18 patients (14.4%), and 61.1% of these were due to complications. Neovascular glaucoma (NVG) developed in 21 patients (16.8%). Of seven patients who developed NVG after anti-vascular endothelial growth factor (anti-VEGF) therapies became available, five were treated with intravitreal Avastin injections (23.8% of patients with NVG). Of 69 patients diagnosed with cataract after treatment, 51 (73.9%) were characterised as radiation-related. Death from metastatic uveal melanoma occurred in 20.8% of the cohort, with a median follow-up of 10.1 years. CONCLUSIONS: Patients treated with PBI using a light field set-up technique experience good outcomes after irradiation. Eye preservation and retention of good VA are seen in the majority of cases, and tumour recurrence is low.

Targeting the YAP/TAZ Pathway in Uveal and Conjunctival Melanoma With Verteporfin.

Purpose: The purpose of this study was to determine whether YAP/TAZ activation in uveal melanoma (UM) and the susceptibility of melanoma cell lines to YAP/TAZ inhibition by verteporfin (VP) is related to the tumor's genetic background. Methods: Characteristics of 144 patients with enucleated UM were analyzed together with mRNA expression levels of YAP/TAZ-related genes (80 patients from the The Cancer Genome Atlas [TCGA] project and 64 patients from Leiden, The Netherlands). VP was administered to cell lines 92.1, OMM1, Mel270, XMP46, and MM28 (UM), CRMM1 and CRMM2 (conjunctival melanoma), and OCM3 (cutaneous melanoma). Viability, growth speed, and expression of YAP1-related proteins were assessed. Results: In TCGA data, high expression of YAP1 and WWTR1 correlated with the presence of monosomy 3 (P = 0.009 and P < 0.001, respectively) and BAP1-loss (P = 0.003 and P = 0.001, respectively) in the primary UM; metastasis development correlated with higher expression of YAP1 (P = 0.05) and WWTR1 (P = 0.003). In Leiden data, downstream transcription factor TEAD4 was increased in cases with M3/BAP1-loss (P = 0.002 and P = 0.006) and related to metastasis (P = 0.004). UM cell lines 92.1, OMM1, and Mel270 (GNAQ/11-mutation, BAP1-positive) and the fast-growing cell line OCM3 (BRAF-mutation) showed decreased proliferation after exposure to VP. Two slow-growing UM cell lines XMP46 and MM28 (GNAQ/11-mutation, BAP1-negative) were not sensitive to VP, and neither were the two conjunctival melanoma cell lines (BRAF/NRAS-mutation). Conclusions: High risk UM showed an increased expression of YAP/TAZ-related genes. Although most UM cell lines responded in vitro to VP, BAP1-negative and conjunctival melanoma cell lines did not. Not only the mutational background, but also cell growth rate is an important predictor of response to YAP/TAZ inhibition by VP.

Checkpoint inhibitor-induced sarcoid choroidal granulomas.

PURPOSE: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. OBSERVATIONS: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. CONCLUSION: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.

Nonresponders to Ranibizumab Anti-VEGF Treatment Are Actually Short-term Responders: A Prospective Spectral-Domain OCT Study.

PURPOSE: To investigate the inter-individual variability in duration of anti-vascular endothelial growth factor (VEGF) treatment effect in neovascular age-related macular degeneration (nvAMD). DESIGN: Prospective observational multi-centered study. PARTICIPANTS: Forty-eight patients with nvAMD treated with anti-VEGF injections were included. Both treatment naive (n=25) as well as patients who had previously received treatment with ranibizumab (n=23) more than one month prior to their enrollment were recruited. METHODS: Patients received injection with ranibizumab (0.5 mg/0.05 ml) and were followed weekly for 4 weeks with spectral-domain OCT (SD-OCT) assessing the time to maximal reduction of central retinal thickness (CRT) and the presence of intraretinal and subretinal fluid. Other data collected included age, gender, visual acuity, axial length, lens status, and previous injections. The Shapiro-Wilk test was used to examine normal distributions for all variables. Correlations were examined by calculating Spearman's correlation coeficient. Distributions of quantitative variables are described as means (±SD). Qualitative variables are summarized by counts and percentage. MAIN OUTCOME MEASURES: Time to maximal reduction of CRT and intra- and subretinal fluid after ranibizumab injection. RESULTS: A total of 48 eyes of 48 patients (age 74.8±8.3 years, 62.5% female, 52% treatment naive, 35.4% pseudophakic) were assessed. Two-thirds (64.6%) reached maximal CRT reduction earlier than the standard 4-week interval: 6.3% at 1 week postinjection, 22.9% at 2 weeks postinjection, and 35.4% at 3 weeks postinjection. Only 35.4% of patients had maximal CRT reduction at 4 weeks. Twenty percent of treatment-naive and 34.8% of non-naive patients had a week-4 CRT that was >35 µm thicker than the earlier occuring lowest CRT value (nadir). The time to maximal CRT reduction was not related to axial length, age, lens status, or history of injections. CONCLUSIONS: Optimal dosing interval for maximal CRT reduction may be less than 4 weeks for a significant proportion of patients. Most patients will be classified as complete responders if intervals less than 4 weeks are used to assess anti-VEGF treatment response. Disease load rather than eye size appears to be the driver of anti-VEGF treatment duration and therefore, dosing interval needs to be optimized in the cohort of short-term responders.

LONG-TERM OBSERVATION OF MULTIFOCAL METASTATIC INTRAOCULAR CARCINOID WITH ACQUIRED IRIS HETEROCHROMIA.

BACKGROUND/PURPOSE: To report a unique case of a pulmonary carcinoid tumor unilaterally metastatic to the iris and ciliary body and bilaterally to the choroid that was conservatively followed. METHODS: A 46-year-old woman presented with bilateral choroidal lesions and a left iris tumor. Ultrasound biomicroscopy disclosed a ciliary body component. A diagnosis of metastatic carcinoid tumor was made based on the clinical features. Rather than an excision, photodynamic therapy, or radiation treatment, as has been reported in all previous cases of carcinoid tumor metastatic to the iris, the patient was observed. RESULTS: Excellent vision was maintained for 8 years. The iris tumor gradually enlarged, but the choroidal lesions remained unchanged. The iris with the carcinoid tumor gradually acquired a brown pigmentation; this is the first reported case of acquired iris heterochromia in the setting of carcinoid tumor. CONCLUSION: We conclude, in cases of metastatic carcinoid in which visual acuity is excellent and the patient is asymptomatic, that observation of the ocular lesions is an acceptable course of action. The iris heterochromia is believed to have been caused by secretory factors produced by the tumor.

Conservative management of suspicious melanocytic lesions of the iris.

PURPOSE: The diagnosis of iris melanoma can be difficult, with no established diagnostic criteria currently available. Careful monitoring of patients with suspicious iris lesions is one approach to managing these tumors. We determined the risk of malignant transformation and melanoma-related mortality in patients under observation to evaluate the validity of this management approach. METHODS: This was a retrospective chart review of patients with suspicious iris lesions diagnosed at Massachusetts Eye and Ear Infirmary (MEE) between 1975 and 2014. All patients with an initial diagnosis of suspicious iris lesion followed and/or treated after malignant transformation at the MEE in this 39-year period were included in the cohort. Rates of malignant transformation and melanoma-related mortality were calculated. Treatment outcomes after proton beam irradiation were evaluated in patients who developed iris melanomas during observation. RESULTS: Two hundred thirty-four patients had a diagnosis of suspicious iris lesion (median follow-up, 5.8 years). Malignant transformation occurred in 16 (6.8%) patients with suspicious lesions during the observation period (median follow-up, 9.9 years). All patients diagnosed with iris melanomas were treated with proton beam irradiation (PBI). Complications after treatment included cataract (18.8%), secondary glaucoma (6.3%), and neovascular glaucoma (12.5%). Two of 16 patients (12.5%) who developed iris melanomas died of metastatic melanoma 32.6 months and 10 years after treatment with PBI. Both cases had been followed regularly to monitor for malignant transformation of their suspicious lesions (8.2 years and 3.2 years before melanoma diagnosis, respectively). CONCLUSIONS: These data suggest that suspicious iris lesions have low malignant potential, and a conservative approach to the management of these lesions is appropriate. Survival does not appear to be compromised with an observational approach, and there is potential for preservation of good visual function because vision-threatening treatments can be avoided.

Evaluation of choroidal lesions with swept-source optical coherence tomography.

AIMS: The aim of our study was to image choroidal lesions with swept-source optical coherence tomography (SS-OCT) and to identify the morphological characteristics associated with optimal visualisation. METHODS: This was a prospective, cross-sectional study. Patients with choroidal melanocytic lesions <3 mm in thickness on B-scan ultrasonography were recruited. All participants underwent SS-OCT. On SS-OCT we evaluated qualitative (eg, lesion outline, detection of scleral-choroidal interface and quality of the image) and quantitative (measurement of maximum lesion thickness and the largest basal diameter) parameters. Probability of optimal image quality was examined using ordered logistic regression models. The main outcome measure was quality of the choroidal lesion images on SS-OCT, defined as: optimal, suboptimal or poor. RESULTS: We included 85 choroidal lesions of 82 patients. There were 24 choroidal lesions (29%) for which image quality was classified as optimal, 31 lesions (37%) as suboptimal and 30 lesions (36%) as poor. The factors associated with optimal image quality were distance closer to the fovea (OR 0.76, p<0.001), posterior pole location (OR 3.87, p=0.05), lower ultrasonography thickness (OR 0.44, p=0.04), lighter lesion pigmentation (OR 0.12, p=0.003) and smaller lesion diameter (OR 0.73, p<0.001). In the multivariable analysis, closer distance to the fovea (OR 0.81, p=0.005), lighter lesion pigmentation (OR 0.11, p=0.01) and smaller lesion diameter (OR 0.76, p=0.006) remained statistically significant. CONCLUSION: SS-OCT is useful in imaging most choroidal melanocytic lesions. Image quality is best when the choroidal lesion is closer to the fovea, has a smaller diameter and a lighter choroidal pigmentation.