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.

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.

AUSTRALIAN AND NEW ZEALAND STUDY OF PHOTODYNAMIC THERAPY IN CHOROIDAL AMELANOTIC MELANOMA.

PURPOSE: To evaluate the safety and efficacy of primary photodynamic therapy (PDT) for posterior choroidal amelanotic melanomas. METHODS: Patients with posterior choroidal amelanotic melanomas up to 6 mm in height were treated with PDT using verteporfin as the photosensitizing agent. Treatment was repeated every 3 months until the tumor was flat up to a maximum of 6 treatments. Tumor response and recurrence was assessed by clinical examination, photography, and ultrasonography. Patients were monitored 3 monthly for a minimum of 3 years. RESULTS: Thirty-six of 41 (88%) patients had complete regression after an initial course of PDT. Of them, 20 (56%) had no recurrence, 3 (8%) had recurrences that were successfully treated with further PDT, and 13 (36%) had recurrences that failed or were not amenable to further PDT. None of the measured baseline characteristics predicted treatment outcomes. There was no reduction in visual acuity due to PDT. The mean follow-up time was 3.5 years. CONCLUSION: In this large series, primary PDT was highly effective in achieving initial regression of posterior choroidal amelanotic melanomas. Photodynamic therapy is a vision-preserving treatment option for these tumors; however, patients need to be followed up closely because there is a significant rate of recurrence.

A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion - an 18-month prospective cohort study.

BACKGROUND: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). METHODS: Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. RESULTS: Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. CONCLUSIONS: The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015.

Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial.

BACKGROUND: Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision. METHODS: Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months. RESULTS: The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month. CONCLUSIONS: IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked. TRIAL REGISTRATION: Clinical trials.gov NCT00167518, September 5, 2005.

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.

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.

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.

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.

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.

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.

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.