Subconjunctival Ocular Argyrosis following Treatment with Ruthenium 106 Brachytherapy for Choroidal Melanoma.

Introduction: Ruthenium-106 (Ru-106) brachytherapy is one of the commonest eye-sparing treatments for choroidal melanoma. These patients require long-term surveillance of the treated tumour remnant to ensure there is no local recurrence. New or progressive pigmented lesions in treated eyes are often regarded as suspicious - especially if there are concerns of extra-scleral extension. Case Presentations: We present two cases of posterior choroidal melanoma treated five and 10 years previously with Ru-106. Both cases developed subconjunctival dark/black lesions on the anterior surface of the eye in the quadrant of the conjunctival peritomy during Ru-106 treatment. Both had similar findings on histopathology: black, non-organic, particulate foreign material of varying confluence deposited on elastin and collagen fibres. Energy dispersive X-ray microanalysis confirmed the material contained silver. Discussion: The Ru-106 applicator consists of a radioactive core of Ru-106 encapsulated within pure silver as a radiation shield. During surgical insertion, stainless steel suture needles and forceps can occasionally scratch the applicator's silver eyelets and scatter microscopic particles of elemental silver into the operative field. These particles were likely deposited within the subconjunctival tissues of these patients during brachytherapy administration, leading to localised ocular argyrosis. Iatrogenic ocular argyrosis should be considered in the differential diagnosis of new pigmented lesions in patients treated with Ru-106 brachytherapy. This study is the first to unequivocally identify the cause of some post-brachytherapy ocular surface pigmentation as caused by silver.

Prevalence of co-existent neoplasia in clinically diagnosed pterygia in a UK population.

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) and pterygia share risk factors and co-exist in only a minority of cases. Reported rates of OSSN in specimens sent as pterygium for histopathological analysis vary between 0% and nearly 10%, with the highest rates reported in countries with high levels of ultraviolet light exposure. As there is a paucity of data in European populations, the aim of this study was to report the prevalence of co-existent OSSN or other neoplastic disease in clinically suspected pterygium specimens sent to a specialist ophthalmic pathology service in London, United Kingdom. METHODS: We performed a retrospective review of sequential histopathology records of patients with excised tissue submitted as suspected "pterygium" between 1997 and 2021. RESULTS: In total, 2061 specimens of pterygia were received during the 24-year period, with a prevalence of neoplasia in those specimens of 0.6% (n = 12). On detailed review of the medical records of these patients, half (n = 6) had the pre-operative clinical suspicion of possible OSSN. Of those cases without clinical suspicion pre-operatively, one was diagnosed with invasive squamous cell carcinoma of the conjunctiva. CONCLUSION: In this study, rates of unexpected diagnoses are reassuringly low. These results may challenge accepted dogma, and influence future guidance for the indications for submitting non-suspicious pterygia for histopathological analysis.

Incidence and survival of uveal melanoma in Northern Ireland: how incomplete data can skew results in rare cancers.

BACKGROUND: The majority of Northern Irish uveal melanoma (UM) patients are diagnosed in Sheffield. This study aims to present incidence and survival outcomes for UM patients from Northern Ireland (NI). METHODS: Collaborative retrospective study between Sheffield and Northern Ireland Cancer Registry (NICR). For UM cases not on both databases, outcomes and survival rates (via Kaplan-Meier analysis) were compared. Anonymised NICR data were used to calculate whole-population incidence of UM for NI. RESULTS: In total, 161 patients from NI were diagnosed in Sheffield, 90 of which were not registered with NICR at the start of this study. Data-omissions were not consistent across patient groups, leading to significant differences between those patients registered and those not. Registered patients had an all-cause 5-year survival rate of only 68.9% compared to 92.5% of those not registered (p < 0.01) and were >17x more likely to have systemic metastases than those not registered (p < 0·001). Following rectification of data-omissions, the European age-standardised incidence rate of UM for NI was 8·6 per million. CONCLUSIONS: This study illustrates the impact of incomplete population-wide data, serving as a real-world lesson in case-identification bias. Rare cancers are at higher risk of omission due to systemic failures as the small numbers involved are not detected by system-wide validation procedures. Following this study, data-transfer agreements between England and NI were actioned, preventing future data-omissions. We present survival and incidence data for UM in NI for the first time, showing the incidence is amongst the highest in Europe, with good survival rates.

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.

To suture or not to suture? Does globe immobilisation technique affect clinical outcome in stereotactic radiosurgery for uveal melanoma?

INTRODUCTION: Stereotactic radiosurgery (SRS) is a valuable treatment option for uveal melanoma, offering excellent tumour control rates and eye preservation. Its efficacy relies upon accurate localisation of the tumour, which is challenging in the mobile eye. Various methods of globe immobilisation have been used, including non-invasive devices, such as eye movement tracking and suction cups, but common practice is to use local anaesthetic block with or without transconjunctival suturing of the extraocular muscles. Some studies have suggested that the addition of muscle suturing to local anaesthetic block provides better immobilisation of the globe, when compared to anaesthetic block alone. Controversy exists regarding the clinical relevance of this observation and ocular oncologists differ in their choice of immobilisation technique. METHODS: In order to establish if the addition of muscle suturing to local anaesthetic block improves clinical outcomes, we performed a retrospective review of all cases that underwent SRS for uveal melanoma over a 10-year period (May 2008 to May 2018). Based on surgeon preference, all patients received either local anaesthetic block plus muscle suturing (Group A) or local anaesthetic block alone (Group B) to induce globe akinesia. Outcomes assessed were primary treatment failure, tumour recurrence, secondary enucleation and death rate. RESULTS: In our cohort of 290 eyes; 118 patients were in group A and 172 patients were in group B. There were no cases of primary treatment failure in either group. With a minimum of 24 months follow-up, only 3 patients experienced tumour recurrence (1 in group A and 2 in group B). There was no significant difference in recurrence, enucleation and all-cause death rates between the two groups. CONCLUSION: Our retrospective review suggests that although extraocular muscle suturing may be considered by some units to provide superior globe immobilisation for SRS, it does not alter the clinical outcome.

Uveal Melanoma and Paraneoplastic Perivascular Dermal Melanocytic Proliferation in the Setting of Bilateral Diffuse Uveal Melanocytic Proliferation: The Potential Role of the Hepatocyte Growth Factor/c-Met Axis in Their Pathogenesis.

Two patients, with non-small cell lung carcinoma treated with pembrolizumab, developed bilateral diffuse uveal melanocytic proliferation (BDUMP) with interesting histopathological features. The first patient developed a right ciliary body mass concurrently with BDUMP. The globe was enucleated. The ciliary body mass was a mitotically active epithelioid uveal melanoma, invading the trabecular meshwork and peripheral corneal stroma, with over 90% of the cells expressing Cyclin D1 protein. The melanoma showed no chromosome 3 or 8 changes. The background uvea showed diffuse, bland spindle cell melanocytic proliferation with much lower Cyclin D1 expression (around 10%). In the choroid, this population was punctuated by islands of pigmented epithelioid cells, some of which were necrotic. All these islands expressed a high level of Cyclin D1, and some islands expressed nuclear preferentially expressed antigen in melanoma (PRAME). The ciliary body mass, epithelioid cell islands, and the BDUMP all expressed c-Met (the receptor for hepatocyte growth factor [HGF]). The features were those of ciliary body melanoma and choroidal melanoma "tumorlets," developing on a background of BDUMP. The second patient developed bilateral periocular skin pigmentation following a diagnosis of BDUMP, which when biopsied, showed dermal islands of paraneoplastic perivascular melanocytic cell proliferation. These cells also expressed c-Met protein. These observations implicate the HGF/c-Met axis in the pathogenesis of BDUMP, the uveal melanomas in the ciliary body and choroid in the first patient and the paraneoplastic dermal melanocytic proliferation in the second patient.

Primary photodynamic therapy for small amelanotic choroidal melanomas: consecutive case series of 69 patients with at least 24-month follow-up.

AIMS: To investigate the success and recurrence rates and visual outcomes in a large case series of amelanotic posterior choroidal melanomas treated by means of primary photodynamic therapy (PDT) with verteporfin. METHODS: Retrospective case series from a single specialist ocular oncology centre. All patients had a clinical diagnosis of choroidal melanoma and were selected for PDT based on tumour characteristics. Included patients had at least 24 months of follow-up from initiation of treatment and all but one had not received treatment prior to PDT. RESULTS: 69 patients were included. Mean tumour thickness was 1.9 mm (range 0.5-4.4), while the mean basal diameter was 6.9 mm (range 2.4-11.0). Included lesions were stage cT1a (n=66) or cT2a (n=3). The mean duration of follow-up from treatment initiation was 57 months (range 24-116 months). Seven lesions (10%) failed to respond to PDT. 10 patients (16%) experienced recurrence during follow-up. Overall success rate in this series was 75% (n=52). 83% of successfully treated patients (n=43) maintained or gained vision by final follow-up. Visual outcomes were significantly better in those patients who received PDT therapy alone in comparison to those who needed other treatments for their melanoma (Fisher's exact test, p=0.004). Unfortunately, one patient (1.4%) in the series developed systemic metastases and died. CONCLUSION: Selected amelanotic posterior uveal melanomas may be successfully treated with PDT with retention of good vision in the majority of cases, maintained with a mean of 57 months (minimum of 24 months) of follow-up.

Cutaneous Malignant Melanoma Metastasis to the Pseudophakic Lens Capsule with Associated Granulomatous Intraocular Inflammation.

Intraocular cutaneous melanoma metastasis (ICMM) is a rare event, accounting for only 5% of all metastases to the eye and orbit. The vast majority of such metastases primarily affect the choroid and vitreoretinal structures. Only three previous cases of predominant lens structure ICMM have been reported in the literature. Histological examination, in all three past cases, was performed on enucleation specimens of painful blind eyes. We present the first case of ICMM to the lens capsule in a comfortable, seeing, pseudophakic eye. This was histologically confirmed following diagnostic pars plana vitrectomy and capsulotomy, and was found to be associated with background granulomatous intraocular inflammation. The potential causes of the granulomatous inflammation are discussed.

Evaluation of 0.2 µg/day fluocinolone acetonide (ILUVIEN) implant in a cohort of previously treated patients with diabetic macular oedema (DMO): a 36-month follow-up clinical case series.

OBJECTIVE: To assess the real-world effectiveness and safety of single injection of a fluocinolone acetonide (FAc) implant in previously treated patients with recurrent diabetic macular oedema (DMO) over a 36-month follow-up period. METHODS AND ANALYSIS: This is a retrospective study conducted at a single ophthalmology department at the Royal Hallamshire Hospital, Sheffield, UK. Data were collected using electronic medical records to identify all patients treated with a FAc implant for DMO between March 2014 and November 2014, followed with a 36-month clinic follow-up. Outcomes measured included mean change in best-recorded visual acuity (BRVA) and central macular thickness (CMT) over the period of 36 months, treatment burden pre-implant and post-implant, and functional and anatomical responder rates. RESULTS: Twenty-six eyes (n=22 patients) were treated with single intravitreal FAc implant followed with 36 months of follow-up. At 24 and 36 months, 86.4% and 75.0% of patients maintained or gained vision post-FAc implant in routine clinical practice. The mean BRVA increased from 41.8 to 54.6 letters at month 24 and 45.8 letters at month 36, with 50.0% and 33.3% of patients achieving a ≥15 letter improvement at months 24 and 36, respectively. The mean CMT reduced from 600.8 µm at baseline to 351.0 µm and 392.5 µm at months 24 and 36, respectively. Overall, a mean of one treatment every 13.33 months post-FAc implant (vs 3.24 months pre-FAc implant) was reported. Eleven eyes had an increased intraocular pressure of ≥10 mm Hg and 12 eyes had an increase to ≥25 mm Hg from baseline. CONCLUSION: These results further support the effectiveness and safety of FAc implant in previously treated patients with persistent or recurrent DMO in a real-world clinical practice.

In vivo diagnosis of intraocular osseous metaplasia in neovascular age-related macular degeneration.

A 75-year-old man presented with deterioration of right eye vision for 6 months. He had no relevant medical history. Fundus examination revealed subretinal fluid, fibrosis, and subretinal hemorrhages. Ocular coherence tomography of the right macula illustrated an underlying subretinal lesion with internal lamellae, resembling trabecular bone elsewhere in the body. Bruch's membrane was clearly intact beneath the lesion, indicating an extrachoroidal location. The lesion appeared highly reflective on B-scan ultrasonography, consistent with ossification. Although initially misdiagnosed as choroidal osteoma, this lesion represents in-vivo intraocular osseous metaplasia at the site of neovascular age-related macular degeneration. The authors believe that similar lesions may have been misdiagnosed as "atypical" osteoma caused by failure to identify their extrachoroidal location.

Conjunctival Blue Naevus in an Anophthalmic Socket.

PURPOSE OF THE STUDY: To describe an unusual brown pigmented lesion of the conjunctiva in an anophthalmic socket in a 16-year-old male. PROCEDURES: A 16-year-old male patient presented with socket irritation whilst wearing an artificial eye due to meibomian gland dysfunction. An area of flat, subepithelial, dark brown pigmentation with irregular and indistinct borders on the bulbar conjunctiva of the anophthalmic socket was seen. The patient believed it had been present for at least 2 years. His past ocular history was of childhood trauma to the right eye at the age of 9 years, and he underwent primary enucleation and hydroxyapatite orbital implant insertion at that time. Unfortunately, the implant extruded and was removed a year later. RESULTS: An incisional biopsy of the pigmented lesion showed a conjunctival, subepithelial bland spindle cell melanocytic lesion, with uniform-sized and -shaped melanosomes. Immunohistochemistry showed the cells to express Melan A and HMB45 and they were negative for CD68 and pan-cytokeratins. The features were of a common blue naevus. CONCLUSION: This is the first documentation of a post-enucleation conjunctival naevus in an anophthalmic socket. We propose a pathogenesis and suggest surveillance as there is a risk of transformation to melanoma.

Case Series Investigating the Efficacy and Safety of Bilateral Fluocinolone Acetonide (ILUVIEN(®)) in Patients with Diabetic Macular Edema: 10 Eyes with 12 Months Follow-up.

INTRODUCTION: This short case series presents the results from 5 patients with bilateral chronic diabetic macular edema (DME), 12 months after they were initially treated with ILUVIEN (®) [0.2 µg/day fluocinolone acetonide (FAc)]. METHODS: Ten eyes from five patients with pseudophakic lenses were investigated. Patients had bilateral, chronic DME and had received prior laser and anti-VEGF therapy. Visual and anatomic outcomes were investigated 12 months post-FAc implant in both eyes. RESULTS: At baseline, central retinal thickness (CRT) was 645.3 ± 176.1 microns (mean ± standard deviation), intraocular pressure (IOP) was 13.7 ± 3.6 mmHg and visual acuity (VA) was 44.5 ± 18.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Mean CRT improved at 6 months (341.7 ± 169.7 microns) and 12 months (287.4 ± 103.1 microns) and there were concurrent improvements in VA (ETDRS letters were 56 ± 16 and 55 ± 16 at 6 and 12 months, respectively). Mean IOP was stable throughout and ≤21 mmHg. Left and right eyes were compared in the 5 patients by plotting changes in CFT, IOP and VA at 12 months, from baseline levels. CONCLUSION: This bilateral case series demonstrates the effectiveness of a sustained, controlled low dose of FAc in the management of bilateral DME over a 12-month period. The FAc implant has shown to work well in treatment of bilateral DME, although longer follow-up of these patients is still needed. FUNDING: Publication charges were funded by Alimera Sciences Ltd.

Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation.

IMPORTANCE: A case showing sustained structural and functional responses 2 years after a single treatment with ILUVIEN (0.2 µg/day fluocinolone acetonide, FAc) despite suboptimal responses to ranibizumab. OBSERVATIONS: A 68-year-old female patient with diabetic macular oedema (DME) from type 2 diabetes mellitus was first diagnosed in October 2010 and had a baseline visual acuity (VA) of 46 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Central foveal thickness (CFT) was 712 microns. The patient was treated with 11 intravitreal injections of ranibizumab (5 in combination with a small-interfering RNA agent), and by March 2014, VA and CFT were largely unchanged (55 ETDRS letters and 774 microns). The patient was treated with ILUVIEN as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab. An implant releasing FAc at a dosage of 0.2 µg/day was administered in March 2014, and the optical coherence tomography indicated that the macula was dry after 7 days (CFT was below 300 microns). This was sustained at 6, 12, and 24 months after the treatment. VA improved by 5 letters within 7 days and by 15 letters within 14 days, and this was maintained after 24 months. Throughout the duration of this study, the intraocular pressure was ≤22 mm Hg, and no glaucoma medication was administered. CONCLUSIONS AND RELEVANCE: In real-life UK practice, this DME patient showed a suboptimal response to multiple intravitreal injections of ranibizumab. When subsequently treated with a single injection of ILUVIEN, there were large and rapid improvements in VA and CFT that were maintained for the following 2 years.