The Fight Tumour Blindness Registry: Efficient capture of high-quality real-world data in uveal melanoma.

OBJECTIVE: To describe the development of a web-based data collection tool to track the management and outcomes of uveal melanoma patients. DESIGN: Description of a clinical registry. PARTICIPANTS: Patients with uveal melanoma. METHODS: A panel of expert ocular oncologists, with input from other relevant specialties and individuals with expertise in registry development, collaborated to formulate a minimum data set to be collected to track patient centred, real-world outcomes in uveal melanoma. This data set was used to create the Fight Tumour Blindness! (FTB!) registry within Save Sight Registries. RESULTS: The data set to be collected includes patient demographics and medical history, baseline visit, follow-up visit including tumour treatment, metastatic staging and surveillance, pathology, and patient-reported questionnaires. The inbuilt mechanisms to ensure efficient and complete data collection are described. CONCLUSIONS: The FTB! registry can be used to monitor outcomes for patients with uveal melanoma. It allows benchmarking of outcomes and comparisons between different clinics and countries.

Apical dose versus volume dose of Ruthenium-106 brachytherapy for uveal melanoma.

OBJECTIVE: Ruthenium-106 brachytherapy is commonly used to treat uveal melanomas. Most centres prescribe a radiation dose to the tumour apex that is calculated with the tumour located in the centre of the plaque. Recent work suggests that D99%-the minimum radiation dose delivered to 99% of tumour volume-may be a better predictor of tumour control than apex dose. Both dosing regimens may be affected by tumour and treatment variables differently. We explored the effect of differences in these variables on volume and apex dose using a 3-dimensional planning model. METHODS: The time required to deliver 100 Gy to the tumour apices of representative tumours ranging from 2- to 6-mm thickness with central plaque positioning was calculated in Plaque Simulator™. This treatment time was used for further calculations, including D99% with central plaque placement, and apical and tumour volume doses when tumour and plaque characteristics were altered, including eccentric plaque placement, either away from (tilt) or along (offset) scleral surface, tumour shape, and plaque type. RESULTS: D99% was always greater than the apex dose when plaques were placed centrally, and the difference increased with tumour thickness. Increasing degrees of tumour offset reduced apical dose and D99%, with a greater effect on apical dose for thicker and D99% for thinner tumours, respectively. Differences in tumour shape and plaque type had idiosyncratic effects on apical and volume dosing. CONCLUSION: D99% and apex dose are affected by tumour and treatment characteristics in different ways, highlighting the complexity of radiation delivery to uveal tumours.

Globe Salvage and Vision Preservation by Neoadjuvant Darovasertib and Crizotinib in Uveal Melanoma.

PURPOSE: To report the effective use of neoadjuvant darovasertib and crizotinib in a patient with a large uveal melanoma (UM) in his only functional eye. DESIGN: Case report. SUBJECTS: One patient with T4b UM. INTERVENTION: Neoadjuvant darovasertib and crizotinib, followed by plaque brachytherapy. MAIN OUTCOME MEASURES: Objective tumor response and conversion from planned enucleation to placement of fovea- and optic nerve-sparing plaque brachytherapy. RESULTS: A patient with a history of left eye blindness from retinal artery occlusion presented with rapidly declining right eye vision due to a primary UM measuring 18 mm in maximal diameter and 16.5 mm in maximal thickness. To salvage vision, neoadjuvant treatment was initiated using darovasertib and crizotinib. After 6 months of neoadjuvant treatment, which included intraocular lens replacement for tumor-associated cataract, the tumor regressed to 14.1 mm in maximal diameter and 2.6 mm in maximal thickness, enabling treatment with plaque brachytherapy rather than enucleation. CONCLUSIONS: The combination of darovasertib and crizotinib for UM is an effective neoadjuvant strategy that warrants further investigation as an approach to improve visual outcomes from the treatment of primary UM. FINANCIAL DISCLOSURE: The other authors have no proprietary or commercial interest in any materials discussed in this article.

De novo choroidal osteoma after laser photocoagulation of a peripapillary choroidal neovascular membrane.

We describe the case of a 76-year-old man who developed an asymptomatic choroidal osteoma in the left eye 10 years after receiving retinal laser photocoagulation for treatment of a peripapillary choroidal neovascular membrane. The choroidal osteoma presented as a progressively enlarging, well-circumscribed yellow lesion adjacent to the region of retinal fibrosis. Optical coherence tomography showed a choroidal lesion with superficial lamellations and ultrasonography demonstrated increased echogenicity. The choroidal osteoma was not encroaching on the fovea and is currently being monitored. This is only the third report of a de novo choroidal osteoma developing subsequent to retinal laser photocoagulation.

Long-term visual outcomes after ruthenium plaque brachytherapy for posterior choroidal melanoma.

BACKGROUND: To assess the long-term visual outcomes in patients with posteriorly located choroidal melanoma treated with ruthenium plaque brachytherapy between January 2013 and December 2015. METHODS: A retrospective review was conducted on consecutive patients treated with ruthenium plaque brachytherapy for post-equatorial choroidal melanoma with available Snellen visual acuity before and after treatment, and the development and treatment of radiation complications. RESULTS: There were 219 patients with posterior choroidal melanoma treated with ruthenium plaque brachytherapy. Median follow up was 56.5 months, range 12-81 months. Final visual acuity was ≥6/12 in 97 (44.3%) patients, 6/12 to 6/60 in 57 (26.0%), <6/60 in 55 (25.1%) and 10 (4.6%) eyes were enucleated. Radiation maculopathy was the most common radiation complication encountered, occurring in 53 (24.2%) patients. Of these, final visual acuity was 6/12 in 10 patients (18.9%), 6/12 to 6/60 in 26 (49.1%), <6/60 in 16 (30.2%) and 1 eye (1.9%) was enucleated. Twenty-five (47%) with radiation maculopathy were treated with intravitreal anti-angiogenic therapy, 27 (51%) were monitored and one (2%) was treated with scatter photocoagulation. Eyes treated with intravitreal anti-angiogenic therapy had better final vision than those observed or treated with retinal laser (chi-square, p = 0.04). On multivariate analysis, close proximity to the optic nerve and fovea, and large or notched plaque type was associated with final vision worse than 6/12. CONCLUSION: Most patients treated with ruthenium plaque brachytherapy for posterior choroidal melanoma retain 6/60 vision, with almost half retaining 6/12 vision at long term follow up.

The MOLES system to guide the management of melanocytic choroidal tumours: can optometrists apply it?

CLINICAL RELEVANCE: Although melanocytic choroidal tumours of the choroid are a common eye pathology, no standardised protocol exists for their management in the community. BACKGROUND: Choroidal naevi are found in approximately 6% of the adult White population, whereas choroidal melanomas are rare, with an annual incidence of 5-10/million/year. Multimodal imaging has advanced the understanding of malignancy imaging biomarkers, but distinguishing between a small melanoma and naevus remains difficult and an algorithm for their management by community practitioners has not been uniformly adopted. One of the authors (BD) devised the MOLES scoring system, which indicates malignancy likelihood according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. When applied by ocular oncologists, the system accurately distinguishes choroidal naevi from melanomas. The aim of this study was to evaluate whether community optometrists can appropriately manage patients with melanocytic choroidal tumours using this system. METHODS: Clinical images of 25 melanocytic choroidal tumours were presented in an online survey, including colour fundus photographs, fundus autofluorescence, optical coherence tomography, and B-scan ultrasound images. Using the MOLES system, 39 optometrists diagnosed tumours as naevus or probable melanoma and decided between community monitoring and ophthalmologist referral. Responses were compared to MOLES grading of the same clinical images by ocular oncologists. RESULTS: Using MOLES, optometrists correctly identified 389/406 probable melanomas (95.8% sensitivity) and 331/516 choroidal naevi (64.1% specificity); correctly referred 773/778 tumours to an ophthalmologist (99.4% sensitivity); and correctly managed 80/144 lesions (55.6% specificity) in the community. CONCLUSION: Optometrists safely applied the MOLES scoring system in this survey. Further measures are indicated to reduce choroidal naevi over-referral and evaluate MOLES system usage in clinical optometric practice, where some imaging modalities may not be readily available.

Quantifying the effect of eccentric ruthenium plaque placement on tumor volume dose.

Purpose: Ruthenium-106 brachytherapy is a common treatment for small to medium-sized uveal melanomas. In certain clinical contexts, plaques may be placed eccentrically to tumor center. The effect of plaque decentration, a common radiation dose measurement in radiotherapy: D98%, the percentage of the tumor volume receiving at least 98% of the prescribed dose (a commonly used term in radiation oncology), is unknown. We investigated this using two commonly used plaques (CCA and CCB; Eckert & Ziegler, BEBIG GmbH) in silico. Material and methods: Using a Plaque Simulator™ (Eye Physics) plaque modelling software, treatment time required to deliver 100 Gy D98% with central plaque placement was calculated for both plaque models, treating tumors with basal dimensions of 10 mm (CCB plaque only) and 7 mm (CCA and CCB plaques), and a range of thicknesses. D98% was calculated for plaque-tumor edge distances of 0-5 mm. Additionally, we defined minimum plaque-tumor edge distances, at which D98% fell by 10% and 5% (safety margins). Results: D98% decreased as plaque-tumor edge distance decreased, i.e. as plaque eccentricity increased. Minor (< 1 mm) plaque decentration caused minimal D98% changes across tumor thicknesses. Safety margins did not follow a consistent pattern. Conclusions: Eccentric plaque placement reduces the radiation dose delivered to choroidal tumors. Both tumor (thickness, diameter) and plaque (size, location) characteristics are important D98% modulators. Further investigation of the effect of these characteristics and dose to organs at risk is essential.

Case Series: Presumed Choroidal Melanoma Diagnosis Expedited by Documented Growth on Serial Optical Coherence Tomography.

SIGNIFICANCE: These cases highlight the importance of monitoring choroidal nevi with benign imaging characteristics and the potential to quantify horizontal growth using optical coherence tomography (OCT), in the absence of color fundus photography. PURPOSE: This study aimed to present reports of two patients with pigmented choroidal tumors with low malignant potential based on their multimodal imaging features at the time of referral, but access to prior OCT imaging confirmed horizontal growth consistent with melanoma. CASE REPORTS: Two patients with pigmented, dome-shaped, subfoveal tumors were referred. Both tumors had basal diameters greater than 5 mm but no other risk factor for growth at the time of referral. Screening OCT scans had been taken of each patient's macula more than 5 years before referral, but color fundus photography was not available for either. Repeat OCT scanning at the time of referral showed horizontal growth of the tumors consistent with melanoma. As per the "To Find Small Ocular Melanoma-Do Imaging" risk factor assessment, the 5-year risk of growth of both tumors would be estimated at 11% at the time of referral, and in the absence of the documented horizontal growth on OCT scanning, the patients would have been monitored for growth. After discussion of the risks and benefits, both patients elected for their tumors to be managed as choroidal melanomas and underwent ruthenium plaque brachytherapy. CONCLUSIONS: Horizontal growth of choroidal tumors can be established using sequential OCT scans in the absence of color fundus photography. Access to prior imaging can expedite the diagnosis of choroidal melanoma, potentially allowing patients to be treated earlier.

Ultra-low dose external beam radiotherapy for presumed choroidal lymphoma: a case report.

Primary choroidal lymphoma is a rare, slowly progressive intraocular malignancy. Most are low grade B cell lymphomas, often involving tissues adjacent to the choroid such as the subconjunctival space, lacrimal gland or orbit. Ideally, these lesions are biopsied to establish histopathological diagnosis. The most accessible ocular structure is biopsied. Obtaining tissue by transvitreal choroidal biopsy imparts a small but significant risk of ocular morbidity, including the need for multiple surgeries, retinal detachment and vision loss.External beam radiotherapy (EBRT) is a common and effective treatment of low-grade lymphomas. EBRT has been found to very successfully treat primary marginal zone lymphomas of the ocular adnexa, which are typically of the same cell type as most primary choroid lymphomas. Ultra-low dose EBRT, most commonly using a total dose of 4 Gy, has been shown to be as effective as higher doses of radiotherapy for follicular or marginal zone lymphomas. The use of this low dose regimen for conjunctival lymphomas has been recently explored. The role of EBRT, and especially ultra-low dose EBRT, for treatment of primary choroidal lymphoma has been confined to case reports.We describe a case of presumed primary choroidal lymphoma diagnosed on clinical findings alone as the risks of ocular biopsy were deemed too high, and report outcome following treatment with ultra-low dose EBRT.

Distinguishing Choroidal Nevi from Melanomas Using the MOLES Algorithm: Evaluation in an Ocular Nevus Clinic.

OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of the MOLES scoring system in differentiating choroidal melanomas from nevi according to Mushroom shape, Orange pigment, Large tumor size, Enlarging tumor, and Subretinal fluid (SRF). METHODS: Color photographs, fundus-autofluorescence images, and optical coherence tomography of 222 melanocytic choroidal tumors were reviewed. Each MOLES feature was retrospectively scored between 0 and 2 and tumors categorized as "common nevus," "low-risk nevus," "high-risk nevus," and "probable melanoma" according to the total score. MOLES scores were compared with the experts' diagnosis of melanoma. RESULTS: The MOLES scoring system indicated melanoma in all 81 tumors diagnosed as such by ocular oncologists (100% sensitivity) and nevus in 135 of 141 tumors given this diagnosis by these experts (95.7% specificity). Of the 6 tumors with discordant diagnoses, 4 had basal diameters exceeding 6 mm, all with SRF and/or orange pigment, and 2 small tumors showed either significant SRF with traces of orange pigment, or vice versa. CONCLUSIONS: The MOLES system for diagnosing melanocytic choroidal tumors compares well with expert diagnosis but needs to be evaluated when deployed by ophthalmologists and community optometrists in a wide variety of working environments.

A Case Series of "Solitary Idiopathic Choroiditis" and Proposal of a Nomenclature Change to "Idiopathic Scleroma".

OBJECTIVE: To define the characteristics of solitary idiopathic choroiditis (SIC) in a consecutive series of patients and propose a nomenclature change to idiopathic scleroma. MATERIALS AND METHODS: Electronic patient records were retrospectively interrogated to identify all patients diagnosed with SIC between 2002 and 2019 in a tertiary referral ophthalmic hospital in the United Kingdom. RESULTS: Thirty-four eyes of 34 patients were found to have SIC. The mean age at diagnosis was 48 years (range 24-78) and 23 patients (68%) were female. All lesions were located posterior to the equator, most frequently in the inferotemporal quadrant (13 eyes, 38%). The lesions had a mean largest basal diameter of 1.2 ± 0.4 disc diameters (range 0.5-2) and their distance to the optic disc had a mean of 1.2 ± 0.9 disc diameters (range 0-3.3). All lesions were intrascleral on enhanced depth imaging optical coherence tomography, demonstrating a hypo-reflective zone within the sclera, with an underlying hyper-reflective zone in some cases. No lesion enlarged or developed features consistent with active inflammation after a median follow-up time of 0.9 years (range 0-16.8). DISCUSSION/CONCLUSION: Optical coherence tomography shows SIC to be an intrascleral lesion. Furthermore, we found no evidence of any inflammatory component. A nomenclature change to idiopathic scleroma is appropriate to prevent unnecessary investigation.

Reply to Comment on Roelofs, K.A.; et al. "Detecting Progression of Melanocytic Choroidal Tumours by Sequential Imaging: Is Ultrasonography Necessary?" Cancers 2020, 12, 1856.

We thank Capasso et al [...].

Estimating malignancy risk of melanocytic choroidal tumours detected in the Australian National Eye Health Survey.

Clinical relevance: The malignant potential of choroidal melanocytic tumours detected incidentally in the community is thought to be low, but this has not been assessed using a validated screening tool. An accurate characterisation of the malignant potential of these lesions has implications for resource allocation, service provision, education, and training.Background: MOLES (Mushroom shape, Orange Pigment, Large size, Enlargement, and Subretinal fluid) categorises tumours as 'common naevus', 'low-risk naevus', 'high-risk naevus', and 'probable melanoma'. The MOLES system recommends that patients with common naevi (score = 0) undergo review by a community optometrist every two years, ideally with sequential colour photography. For the remaining patients (score ≥ 1), specialist imaging and assessment are recommended, with referral triaged as non-urgent for patients with low-risk (score = 1) or high-risk naevi (score = 2) and urgent for patients with probable melanoma (score > 2).Methods: Lesions flagged as choroidal melanocytic tumours on retinal photographs taken during the Australian National Eye Health Survey were retrospectively analysed by an ocular oncologist. Each lesion was assigned a MOLES score and categorised as common, low-risk, high-risk or probable melanoma.Results: Seventy-seven choroidal naevi were identified. Seventy-five (97%) of the choroidal naevi were categorised as common naevi, with a MOLES score of 0. Two (3%) choroidal naevi had a score of 1 and diagnosed as low-risk naevi due to their size. No naevi had a score of 2 or more.Conclusion: All choroidal naevi detected in this nationally representative population survey were innocuous. This suggests that the vast majority of choroidal melanocytic tumours that are incidentally detected in Australia can be managed in primary eye care settings without the need for specialist referral. MOLES provides a simple evidence-based method for choroidal naevi assessment in primary care.

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma.

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive.

Circumscribed choroidal haemangioma: Indocyanine green angiography features on scanning laser ophthalmoscopy versus traditional digital fundus photography.

BACKGROUND AND OBJECTIVE: Circumscribed choroidal haemangioma (CCH) has several characteristic clinical and angiographic features. We aimed to compare indocyanine green angiography (ICG) findings of CCH captured on a traditional digital camera system (DCS) to newer scanning laser ophthalmoscopy (SLO) platforms. STUDY DESIGN/MATERIALS AND METHODS: A total of 35 patients over a 10-year period diagnosed with CCH using ICG were included (18 imaged with DCS and 17 with SLO). RESULTS: On early ICG frames, intrinsic vessels were apparent in two-thirds (12/18; 67%) of the DCS group compared with all of eyes in the SLO group (p = 0.020). In addition, at maximal hyperfluorescence, most eyes imaged with DCS had a feathery appearance (16/18; 89%) compared with those in the SLO group which all (17/17; 100%) displayed a granular appearance (p < 0.001). The presence of hot spots at maximal hyperfluorescence was also more common in the SLO group (12/17; 71%) versus the DCS group (0/18; 0%) (p < 0.001). Finally, intrinsic vessels and vascular loops could be identified throughout the entire duration of the ICG in 100% of the SLO cases (17/17) versus only 11% (2/18) of DCS cases (p < 0.001). CONCLUSIONS: The visualization of intrinsic vessels, vascular loops, and "hot spots" in CCH is significantly enhanced with SLO compared with DCS. Many characteristic mid-late angiographic findings of CCH are more optimally visualized on SLO which may negate the need for late frames (>30 min) without compromising diagnostic accuracy.

Intra-Scleral Blue Nevus Arising within Oculodermal Melanocytosis: Melanoma or Not?

We report a 61-year-old female who presented to our service with recent growth of a thickened, pigmented, sub-conjunctival lesion within an area of ocular melanocytosis in her left eye. Lamellar sclerectomy was performed. Histopathological assessment revealed a localized melanocytic proliferation with features of blue nevus arising within the area of ocular melanocytosis. There was a small zone of cells showing cytological atypia and expansion of the scleral stroma. We believe this case to be the first report of intrascleral blue nevus arising within an area of ocular melanocytosis. Given the cytological atypia, the blue nevus may perhaps represent an intermediate stage within a progression from ocular melanocytosis towards melanoma. Patients with oculodermal melanocytosis merit regular long-term surveillance for early detection of melanoma, not only in the uvea, but also in the orbit and potentially the ocular surface.