Long-term Outcomes of Small Pigmented Choroidal Melanoma Treated with Primary Photodynamic Therapy

PURPOSE: To report the long-term outcomes of patients with small, pigmented posteriorly located choroidal melanoma undergoing primary treatment using photodynamic therapy (PDT) with verteporfin at the London Ocular Oncology Service. DESIGN: Retrospective interventional consecutive case series SUBJECTS: All patients undergoing primary treatment using PDT with verteporfin from April 2014 and December 2015 and followed until December 2019. METHODS: This is a long-term follow up study of the same cohort of patients previously reported by our group in 2017 and 2018. MAIN OUTCOME MEASURE: Local tumor control, visual outcomes and metastasis-free survival. RESULTS: Twenty-six patients were included with a mean (± SD) age and tumour thickness of 62 ± 14 years and 1.3 ± 0.5 mm, respectively. Tumours were posteriorly located (mean distance to optic nerve and fovea = 2.0 ± 2.2 and 1.6 ± 1.5 mm, respectively) and the majority were fully pigmented (73%). Overall, patients were followed for a median [IQR, range] of 49.5 [15.3, 7.0 - 66.0] months from first PDT to last follow up. Over the course of this study, 14/26 (54%) have developed a local recurrence at a median of 20.0 months [20.5, 4.7 - 60.9 months]. The most common pattern of recurrence was an isolated increase in basal dimensions (9/14; 64%). Median [IQR] final LogMAR visual acuity of the whole cohort was 0.2 [0.5]. The only statistically significant difference in baseline and outcome characteristics between treatment failures and non-failures was distance to fovea (median [IQR]: 0.5 [1.3] versus 2.5 [2.8]; P = 0.002) and final LogMAR visual acuity (median [IQR]: 0.50 [0.80] versus 0.00 [0.14]; P-value = 0.002), respectively. CONCLUSIONS: While treatment of small pigmented posterior choroidal melanoma with PDT effectively preserves visual acuity, five-year treatment-success calculated by Kaplan-Meier analysis was only 38.4%. Recurrences after PDT tend to occur along the tumor edges, often with minimal increase in thickness. Given the substantial risk of treatment failure, primary PDT with vertepofrin is recommended in exceptional cases of choroidal melanoma, where other treatments with greater tumor control are not a feasible option

Effect of Feronia elephantum (Corr) Fruit Pulp Extract on Indomethacin-induced Gastric Ulcer in Albino Rats

Purpose: To investigate the activity of Feronia elephantum fruit pulp extract (which is used in folk medicine) against indomethacin-induced gastric ulcer in rats. Methods: The fruit pulp was extracted with ethanol and the anti-ulcer activity of the extract in indomethacin-induced gastric ulceration in Swiss albino rats was evaluated. The parameters assessed were pH and acid concentration of gastric contents, and gastric ulcer index. Ranitidine was used as the reference anti-ulcer drug. Acute toxicity studies were also carried out. Results: The extract (500 mg/kg, p.o.) inhibited indomethacin-induced gastric ulceration by decreasing acid concentration of gastric fluid while elevating its pH (p < 0.01), and compared well with the standard drug, ranitidine (p < 0.001). However, its anti-ulcer activity was not as potent as that of ranitidine. Acute toxicity studies showed thatthere was no mortality following the administration of the extract in a dose range of 250 - 5000 mg/kg, p.o. Conclusion: Feronia elephantum fruit pulp extract has potent antiulcer activity with low toxicity. Its anti-ulcer property probably acts via a reduction in gastric acid secretion. The results obtained support the use of this herbal material in folk medicine.Keywords: Anti-ulcer; Feronia elephantum (Corr.); Indomethacin; Ulcer; Gastric acidit

Primary photodynamic therapy with verteporfin for pigmented posterior pole cT1a choroidal melanoma: a 3-year retrospective analysis

AIMS: To investigate the outcomes of primary photodynamic therapy (PDT) for pigmented posterior pole cT1a choroidal melanoma. METHODS: Retrospective interventional consecutive case series of 26 patients (26 eyes) with pigmented posterior pole cT1a choroidal melanoma, who were treated with 3 sessions of PDT and followed-up thereafter. RESULTS: Included were 11 males and 15 females that presented at a median age of 66 years (mean: 64) with transformed naevi (n=11) or suspicious lesions (n=15) with ≥3 risk factors for growth, with lipofuscin in all. In all cases, diagnosis was clinically based (no tissue biopsy). Tumour control was achieved in 16 (62%) patients in a median follow-up time of 29 months (mean: 27). Ten patients failed treatment by form of radial expansion, diagnosed in a median time of 13 months (mean: 12) from last treatment. By Kaplan-Meier analysis, success rate after 1, 2 and 3 years was 85%, 59% and 51%, respectively. On statistical analysis, number of suspicious features was found to be the only risk factor predicting failure (P=0.046). One patient developed macula-sparing branch retinal artery occlusion after treatment. Following PDT, subretinal fluid resolved in all cases and visual acuity significantly improved in all treatment-success cases (P=0.043). There were no cases of metastatic spread. CONCLUSION: Primary PDT resulted in tumour regression of small, pigmented choroidal melanoma in 62% after a mean of 27 months. Treatment was more effective in tumours with three or less risk factors for growth, and resulted with fluid elimination and significant improvement in vision in treatment-success cases

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

Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma

PURPOSE: To report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL). METHODS: Retrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year). RESULTS: From April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5-34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5-104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma). CONCLUSIONS: Intravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this

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

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