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.

Cataract surgery outcomes in bangladeshi children.

PURPOSE: To measure visual acuity (VA) outcomes, complication rates, and the social impact of cataract surgery in a cohort who underwent surgery as children in Bangladesh. DESIGN: Case series. PARTICIPANTS: A total of 471 of 850 children from 6 Bangladeshi districts who had been identified as cataract blind using key informants (KIs) between 2004 and 2009 during the Bangladesh Childhood Cataract Campaign (BCCC) together with all those children not included in the BCCC database but in the Child Sight Foundation (CSF) database who had been identified as cataract blind. METHODS: The subjects and families were contacted again by KIs and transported to local examination centers, where parents and subjects were administered a questionnaire and subjects underwent full ocular examination. Where operative data were available (15%), they were analyzed in conjunction with questionnaire and examination findings. Statistical analysis was performed using SPSS Statistics (IBM, Armonk, NY). MAIN OUTCOME MEASURES: Presenting and best-corrected visual acuities (BCVAs), cause(s) of poor outcome, postoperative refraction, and school attendance. RESULTS: A total of 407 of the participants had undergone bilateral surgery as children, with a mean follow-up of 8.8 years. The mean age at examination was 16 years (range, 5-28 years; standard deviation [SD], 4.6 years); 63% of those examined were male; 22% had a binocular presenting VA of >20/60; and 53% were severely visually impaired or blind (VA <20/200). After refraction, 33% had VA >20/60 in their better eye and 33% had VA <20/200. Factors that predicted poor VA in multivariate logistic regression analysis were nystagmus (P < 0.001), longer delay in presentation (P < 0.001), and magnitude of absolute spherical equivalent refractive error (P<0.001). Some 50% had nystagmus, and 69% of those currently aged ≤16 years were attending school. Better acuity was associated with school attendance (P < 0.001), whereas gender was not. CONCLUSIONS: Approximately one third of all participants had a BCVA of ≥20/60 in their better eye. Amblyopia and nystagmus limited visual outcome, indicating the need for earlier detection and treatment. This is the first study to show the link between pediatric cataract outcome and access to education, a millennium development goal.

Posterior scleritis following COVID-19 vaccination or infection simulating uveal melanoma in 8 consecutive patients.

OBJECTIVES: To determine clinical features and outcomes of posterior scleritis masquerading as uveal melanoma following vaccination against COVID-19 and/or COVID-19 infection. SUBJECTS/METHODS: All patients with posterior scleritis referred to our service to rule out intraocular tumour between February 2021 and June 2022, who previously had COVID-19 vaccination and/or infection (n = 8). A retrospective detailed review of patient charts and imaging was carried out. RESULTS: Previous COVID-19 vaccination was documented in 6 patients (75%) and previous COVID-19 infection and vaccination in 2 patients (25%). Demographic features included mean age of 59 years (median 68, range 5-86 years), white race (n = 7, 87%), and male sex (n = 5, 63%). Mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70). The main presenting symptom was blurred vision with pain (n = 5, 63%). Features that suggested scleritis and not uveal melanoma included pain (n = 6, 75%), anterior scleritis (n = 3, 38%), disc oedema (n = 1, 13%), choroidal detachment (n = 3, 38%), choroidal folds (n = 3, 38%), diffusely thickened scleral wall on ultrasonography (n = 2, 25%), Tenon's oedema (n = 5, 63%), and scleral nodule with medium/high internal reflectivity on ultrasonography (n = 4, 50%). Follow-up information at mean of 2 months (range 0.25-7 months) revealed visual acuity at date last seen was mean 0.30 LogMAR (median 0.29, range 0.0-0.54). By 2 months, resolution of "tumour" was noted in 5/6 (83%) patients with follow-up. CONCLUSIONS: Posterior scleritis following COVID-19 vaccination and/or infection can masquerade as choroidal melanoma. At 2 months duration, partial or complete resolution of features with minimal visual consequence was noted.

Association of Fitzpatrick Skin Type with metastatic risk from uveal melanoma in 854 consecutive patients at a single center.

OBJECTIVE: To assess the association of skin color using Fitzpatrick Skin Type (FST) with metastatic risk of uveal melanoma. SUBJECTS: 854 consecutive patients with uveal melanoma and documented FST. METHODS: Retrospective detailed review of patient charts was performed for FST (type I- white, II-fair, III-average, IV-light brown, V-brown, VI-black), clinical details of the patient and the uveal melanoma, tumor cytogenetic classification according to The Cancer Genome Atlas (TCGA), and outcome of melanoma-related metastasis and death. RESULTS: The FST classification was type I (n = 97 patients), type II (n = 665), type III (n = 79), type IV (n = 11), type V (n = 2), type VI (n = 0). A comparison of patient FST (type I vs. II vs. III-V) revealed significant differences in mean age at presentation (64.1 vs. 58.5 vs. 49.8 years, p < 0.001), race white (100% vs. 98% vs. 75%, p < 0.001), presence of ocular melanocytosis (3% vs. 3% vs. 10%, p = 0.01), visual acuity <20/200 at presentation (6% vs. 7% vs. 13%, p = 0.03), genetic results showing TCGA group B tumors (11% vs. 14% vs. 26%, p = 0.01) or TCGA group D tumors (22% vs. 11% vs. 9%, p = 0.01), 10-year incidence of melanoma-related metastasis (25% vs. 15% vs. 14%, p = 0.02) and 10-year incidence of melanoma-related death (9% vs. 3% vs. 4%, p = 0.04). FST was a significant predictor of melanoma-related metastasis (p = 0.02, Hazard ratio 2.3). CONCLUSIONS: Fitzpatrick skin type may be a predictor of melanoma-related metastasis, with metastasis and TCGA Group D tumors being more common in patients with FST I.

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.

Choroidal Melanoma Masquerading as Central Serous Chorioretinopathy.

PURPOSE: To determine the clinical features and outcomes of choroidal melanoma initially masquerading as central serous chorioretinopathy (CSCR). DESIGN: Retrospective case series. SUBJECTS: All patients with choroidal melanoma, initially misdiagnosed as CSCR elsewhere and evaluated by the Ocular Oncology Service at Wills Eye Hospital from 2004 to 2022, were included. METHODS: A retrospective detailed review of patient charts and imaging was performed for all patients included in the study. Paired t tests and chi-squared tests were performed for data analysis. MAIN OUTCOME MEASURES: The primary outcome measures included clinical characteristics, ultrasonography, OCT, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. The secondary outcome measures included treatment results, such as the final visual acuity, tumor control, radiation-related complications, and melanoma-related metastlasis and death. RESULTS: There were 22 patients (mean age, 48 years; 16 men) in this cohort. The mean interval between initial CSCR diagnosis and suspicion of choroidal melanoma was 50 months (median, 50 months; range, 0-242 months). At tumor diagnosis, the melanoma was submacular in 16 (73%) patients and extramacular in 6 (27%) patients. The mean tumor thickness was 3.4 mm (median, 2.5 mm; range, 1.4-10.7 mm), and the mean basal diameter was 9.2 mm (median, 8.0 mm, range, 4.5-22.0 mm). Features enabling differentiation of choroidal melanoma from CSCR (affected versus unaffected eye) included choroidal thickness asymmetry (100% > 300 µm versus 21% > 300 µm; P = 0.005), ipsilateral choroidal surface irregularity (100% versus 0%; P < 0.001), loss of choroidal vascular detail on OCT (100% versus 0%; P < 0.001), presence of multiple pinpoint leaks on angiography (100% versus 0%; P < 0.001), and contralateral lack of autofluoresence abnormalities (75% versus 6%; P = 0.001). Management of the choroidal melanoma included plaque radiotherapy (19, 86%), enucleation (2, 9%), or treatment elsewhere (1, 5%). On follow-up (mean, 6 years), vision loss of ≥ 3 Snellen lines (9 patients, 47%), metastasis (3 patients, 14%), and death (1 patient, 5%) were noted. CONCLUSIONS: Patients with presumed CSCR, especially if chronic, should be evaluated for a possible thin underlying choroidal melanoma with a dilated fundus examination and multimodal imaging.

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.

Iris melanoma outcomes based on the Cancer Genome Atlas (TCGA) classification in 78 consecutive patients.

BACKGROUND: The Cancer Genome Atlas (TCGA) classification of genetic alterations in uveal melanoma is widely used for prognostication. We present novel observations on the impact of TCGA Group specifically for iris melanoma. METHODS: This was a retrospective cohort study at a tertiary referral ocular oncology center. All patients with a diagnosis of iris melanoma who underwent genetic evaluation and assessment for TCGA classification between 20 November 1995 and 5 April 2021 were included. The main outcome measures were visual acuity, secondary glaucoma, tumor recurrence, melanoma-related metastasis and death per TCGA group. RESULTS: There were a total of 78 patients included. The mean patient age was 49.6 years (median 53.0, range 3.0-85.0), mean tumor basal diameter was 6.7 mm (median 6.0, range 1.5-22.0), and mean tumor thickness was 2.6 mm (median 2.5, range 0.5-8.5). Cytology results confirmed iris melanoma (93%) or were inconclusive (7%). The TCGA groups included Group A (n = 36, 46%), Group B (n = 7, 9%), Group C (n = 34, 44%), and Group D (n = 1, 1%). There was no statistically significant difference in outcomes of visual acuity, tumor thickness reduction, secondary glaucoma, tumor recurrence, melanoma-related metastasis or death per individual TCGA group (A vs. B vs. C vs. D) and per bimodal comparison (A/B vs. C/D). CONCLUSIONS: In this analysis, iris melanoma was classified as TCGA group A or B in 55% and as C or D in 45%. The TCGA classification was not predictive of melanoma-related metastasis or death.

Survival analysis following enucleation for uveal melanoma.

OBJECTIVES: To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. SUBJECTS/METHODS: All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. RESULTS: In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p < 0.001) predicted metastatic mortality on multivariable regression analysis. Those who had an insufficient sample of cells gained during FNAB (n = 16) had no different prognosis. CONCLUSIONS: This study confirms, in this population, the poor survival of patients enucleated for uveal melanomas. It confirms the prognostic utility of adding AJCC grade to cytogenetic information. It demonstrates that the lack of sample in patients undergoing FNAB is not related to prognosis.

Ruthenium plaque radiotherapy in the current era of retinoblastoma treatment.

BACKGROUND: Two major treatment modalities for retinoblastoma, intraarterial chemotherapy (IAC) and intravitreal chemotherapy (IVitC), have superseded external beam radiotherapy for eye salvage. In this new setting our objectives were to evaluate the indications for plaque radiotherapy, complications, and recurrence rates. METHODS: Retrospective detailed review of patient's charts was performed for all subjects treated with plaque radiotherapy for retinoblastoma between January 2015 and December 2020. RESULTS: A total of 12 eyes of 12 patients were included. Mean age at plaque insertion was 45 months (median 29, range 17-150). The treatment dose was 40 Gy to the tumor apex. The indication for plaque radiotherapy was salvage therapy in 11 eyes (92%) and primary treatment in one eye (8%). At last follow-up from plaque insertion (mean 36 months, range 3-67), four (33%) patients had visual acuity better than 0.5 LogMAR and four (33%) had visual acuity worse than 1.0 LogMAR. Radiation-related complications were: one (8%) vitreous haemorrhage, two (16%) non-proliferative radiation retinopathy and one (8%) cataract. Recurrence was detected in four (33%) patients at a mean of 7.8 months (median 5, range 1-20) post-plaque. Globe salvage rate was 75%, as three eyes required enucleation, one to treat recurrence of the tumor treated with plaque and two to treat recurrence of other tumors. CONCLUSIONS: In the current era of retinoblastoma management, a role for plaque radiotherapy remains for salvage or primary treatment in eyes with localised active tumor, providing tumor control in 66%. Close observation is recommended to both detect recurrence and radiation-related complications.

Artisan iris-claw intraocular lens implantation in vitrectomised eyes.

OBJECTIVES: To present the visual acuity (VA) results and complication rates following Artisan intraocular lens (IOL) insertion in vitrectomised eyes. METHODS: Outcome data were collected for all vitrectomised patients who had undergone Artisan IOL insertion between January 2014 and May 2019 at Moorfields Eye Hospital. All those with follow-up greater than 2 months were included in the analysis. RESULTS: Sixty-nine eyes from 61 patients were included. Average follow up was 2 years. Fifty-five (80%) eyes had at least one ocular comorbidity prior to Artisan IOL insertion. At final follow up 46 (67%) eyes had best-corrected VA better than 6/12. Sixty-three eyes (91%) either gained or maintained VA. Mean post-operative spherical equivalent was -0.2D. Two (3%) lenses became de-enclavated requiring further surgery. Two (3%) eyes developed acute post-operative cystoid macular oedema. Two (3%) required additional topical IOP-lowering therapy to their pre-operative glaucoma regimen. One eye had mild corneal oedema, which persisted for 1 year following surgery and subsequently resolved. CONCLUSIONS: Artisan IOL insertion is a safe and effective option for the surgical correction of aphakia in vitrectomised eyes lacking capsular support. Refractive results comparable to posterior chamber IOL placement can be achieved with these lenses.

The natural history of conjunctival naevi in children and adolescents.

OBJECTIVE: The objective of this study is to characterise the natural history of conjunctival naevi in a paediatric and adolescent population. METHODS: All children and adolescents referred to Moorfields Ocular Oncology Service for evaluation between January 2015 and 2020 were included. Exclusion criteria included age >20 years old and lack of anterior segment photographs. A total of 77 patients were included with a mean age of 12 years (standard deviation: 3.9; range, 4-20). The main outcome measures were: number of conjunctival naevi that grew, changed in pigmentation, required excisional biopsy, or were histologically malignant. If there was growth, the percentage increase in size was measured. RESULTS: At their first visit, 13% of patients (10/77) were discharged to local follow-up and 10% (8/77) proceeded to excisional biopsy, four further patients underwent excisional biopsy after a period of follow-up. On histopathological assessment, 92% (11/12) of lesions were benign conjunctival naevi. One patient, who had suspicious clinical features at presentation, had conjunctival melanoma. Fifty-nine patients were followed over a median of 1.1 years (interquartile range: 1.54; range, 3 months to 4 years). Eight per cent (5/59) of conjunctival naevi enlarged in diameter by a mean percentage increase in size of 2%, whereas 5% (3/59) showed increased pigmentation and 8.5% (5/59) showed decreased pigmentation. CONCLUSIONS: Growth of conjunctival naevi in children is infrequent (8%) and the large majority of those excised are benign. Because of a lack of evidence, these patients are often followed for years in ophthalmic practice. This series demonstrates that prolonged follow-up may not be necessary.

Detecting Progression of Treated Choroidal Melanomas: Is Ultrasonography Necessary?

Prompt detection and treatment of local treatment failure after radiotherapy for choroidal melanoma optimises any opportunities for conserving vision and the eye, possibly reducing an increased risk of metastatic disease. Long-term surveillance is therefore required but is hampered by the perceived need to perform ultrasonography, which may not be available at a patient's local hospital. The aim of this study was to determine whether local treatment failure can reliably be detected with colour fundus photography alone, and, if so, in which patients. Patients were included in the study if diagnosed with local treatment failure between April 2016 and February 2021 after eye-conserving therapy for choroidal melanoma. Wide-field colour and fundal autofluorescence (FAF) images, optical coherence tomography (OCT), and ultrasonography (US) were analysed by two of the authors (GN and UH). The cohort included 87 patients with local treatment failure. In 75 patients with clear media, tumour progression was detected by colour photography alone in 74 (98.7%) patients. Sensitivity was not increased by the addition of either OCT or AF. One patient with clear media developed extraocular extension detected with US without visible change in the intraocular part of the tumour. In the other 12 patients, US was required because of opaque media and a consequently poor fundal view. Local treatment failure after radiotherapy for choroidal melanoma is detected in 98.7% of cases with colour photography when the media are clear. Ultrasonography is useful when photography is prevented by opaque media or tumours having locations in the far periphery.

Artisan-style iris-claw intraocular lens implantation in patients with uveitis.

PURPOSE: To study the use of iris-claw Artisan intraocular lenses (IOLs) in patients with uveitis. SETTING: Moorfields Eye Hospital, London, England. DESIGN: Retrospective case series. METHODS: Data on all patients with anterior uveitis, intermediate uveitis, and panuveitis who had anterior-fixated Artisan IOL insertion between January 2014 and July 2019 at Moorfields Eye Hospital were assessed. Patients who had less than 2 months of follow-up were excluded from the analysis. RESULTS: The study comprised 11 patients. The mean age of the 7 women and 4 men was 61 years ± 14 (SD). The mean follow-up was 1.7 years. After Artisan IOL insertion, the corrected distance visual acuity (CDVA) improved significantly from 20/200 to 20/50 (P = .02). No patients had a significant flare-up of their uveitis after the surgery, and there were no intraocular pressure-related events. One patient developed cystoid macular edema, which responded to treatment. CONCLUSION: This case series showed the efficacy and safety of Artisan-style IOLs in patients with a history of uveitis. After the Artisan IOL insertions, these patients experienced a significant improvement in CDVA with minimal side effects.