Combined photodynamic therapy and transpupillary thermotherapy for small choroidal melanoma.

OBJECTIVE: The objective of this study was to determine whether combining verteporfin-based photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) achieves adequate tumour control while maintaining visual acuity in individuals with small choroidal melanoma of amelanotic, melanotic, and variable pigmentation. DESIGN: Individuals with posterior choroidal melanomas up to 3 mm in height underwent verteporfin-based PDT followed by immediate TTT. Further combined laser therapy was performed if a poor response was noted at 12 weeks or beyond. Tumours that demonstrated significant further growth were treated with brachytherapy or enucleation. A total of 37 eyes of 37 patients from the Terrace Eye Centre in Brisbane, Australia were studied. Average age of participants was 59.62 ± 12.45 years, and 17 of 37 participants were female (46%). METHODS: This was a retrospective, noncomparative interventional study. RESULTS: Seven of the 37 participants (19%) had recurrence of their tumour requiring further brachytherapy or enucleation. There was no statistically significant difference in visual acuity before and after treatment. There were no baseline characteristics that predicted treatment outcome. Ten individuals developed complications including epiretinal membrane (16%), scotoma (8%), cataract (3%), and macular edema (3%). No individuals experienced extraocular extension or progressed to metastatic disease. The mean follow-up time was 49 months. CONCLUSION: Combined PDT and TTT achieved 81% tumour control in this study while preserving visual acuity. However, higher rates of local recurrence compared with brachytherapy warrant close follow-up to identify recurrences early.

Conjunctival Lymphoma.

Lymphoma of the conjunctiva is an ocular malignancy derived from clonal proliferation of lymphocytes. The majority of conjunctival lymphoma is extranodal marginal zone B-Cell lymphoma (EMZL), however diffuse large B-cell (DLBCL), follicular (FL), mantle cell (MCL) and T- cell subtypes are also seen. Clinical manifestations are non-specific, but include unilateral or bilateral painless salmon-pink conjunctival lesions. Approaches to treatment have centered around local immunomodulation, often with Interferon-α2b or Rituximab (anti-CD20 monoclonal antibody) with or without radiation. Although conjunctival lymphoma is generally considered an indolent disease, recent advances in next-generation sequencing have improved clinicians' ability to predict future recurrence or systemic disease through assessment of cytogenic and molecular features. In this paper, we review the classification, clinical features, diagnostic techniques, and emerging strategies for management and prognostication of conjunctival lymphomas.

Choroidal melanoma with synchronous Fuchs' adenoma and novel ATRX mutation.

BACKGROUND: To report a case of Fuchs' adenoma occurring in an eye with a large choroidal melanoma. We have reviewed the literature to describe the clinical presentation, ultrasound characteristics and pathological features of these entities. CASE PRESENTATION: A 69-year-old Caucasian man presented with vision loss from a large choroidal melanoma. Enucleation showed an incidental Fuchs' adenoma in the same eye. Whole-exome sequence analysis was also performed on the patient's blood and melanoma, which showed a rarely-reported ATRX mutation. CONCLUSIONS: Fuchs' adenoma is an under-diagnosed benign age-related hyperplasia of the non-pigmented ciliary epithelium (NPCE). Given its location and characteristics, it can be mistaken for choroidal melanoma and clinicians are reminded how to differentiate between these pathologies and that they may co-exist.

Genomic analysis of adult case of ocular surface giant congenital melanocytic nevus and associated clinicopathological findings.

INTRODUCTION: Conjunctival nevi are the most common tumor of the ocular surface. There are some rare reports of so-called 'giant' conjunctival nevi. We report a case of a 47-year-old female with a cutaneous and ocular surface giant congenital melanocytic nevus and describe her clinical course. CASE DESCRIPTION: This is a retrospective case report of a single patient. A 47-year-old female with a history of biopsy-proven periorbital congenital melanocytic nevus, with an associated giant conjunctival nevus presented for structural and functional rehabilitation. Serial surgeries were performed and excised tissue was sent for histopathological and genetic examination. The conjunctival nevus had a low tumor mutation burden, and of the 647 somatic mutations, only one occurred within a protein coding region, namely NRAS p.Gln61Arg. CONCLUSION: This is the first reported adult case including genomic analysis of an ocular surface giant congenital melanocytic nevus. The case shows a possible association between periorbital congenital melanocytic nevi and giant conjunctival nevi, and underscores the possible role that targeted drug therapies may have in malignant transformation of these conditions.

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).

A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision.

PURPOSE: To determine if a circulating microRNA (miRNA) panel could be used to distinguish between uveal melanoma and uveal nevi. METHODS: We report on a multicenter, cross-sectional study conducted between June 2012 and September 2015. The follow-up time was approximately 3 to 5 years. Blood was drawn from participants presenting with a uveal nevus (n = 10), localized uveal melanoma (n = 50), or metastatic uveal melanoma (n = 5). Levels of 17 miRNAs were measured in blood samples of study participants using a sensitive real-time PCR system. RESULTS: A panel of six miRNAs (miR-16, miR-145, miR-146a, miR-204, miR-211, and miR-363-3p) showed significant differences between participants with uveal nevi compared with patients with localized and metastatic uveal melanoma. Importantly, miR-211 was able to accurately distinguish metastatic disease from localized uveal melanoma (P < 0.0001; area under the curve = 0.96). When the six-miRNA panel was evaluated as a group it had the ability to identify uveal melanoma when four or more miRNAs (93% sensitivity and 100% specificity) reached or exceeded their cut-point. CONCLUSIONS: This miRNA panel, in tandem with clinical findings, may be suited to confirm benign lesions. In addition, due to the panel's high precision in identifying malignancy, it has the potential to augment melanoma detection in subsequent clinical follow-up of lesions with atypical clinical features. TRANSLATIONAL RELEVANCE: Uveal nevi mimic the appearance of uveal melanoma and their transformation potential cannot be definitively determined without a biopsy. This panel is most relevant at the nevus stage and in lesions with uncertain malignant potential as a companion diagnostic tool to assist in clinical decision-making.

Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4.

Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors), supporting its role as a novel driver mutation in UM. PLCB4 p.D630Y mutations are mutually exclusive with mutations in GNA11 and GNAQ, consistent with PLCB4 being the canonical downstream target of the former gene products. Taken together these data suggest that the PLCB4 hotspot mutation is similarly a gain-of-function mutation leading to activation of the same signaling pathway, promoting UM tumorigenesis.

Retrospective study of an as required dosing regimen of intravitreal bevacizumab in neovascular age-related macular degeneration in an Australian population.

PURPOSE: To investigate the efficacy of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration (AMD) using an as required dosing regimen. METHODS: A retrospective study of 210 patients (231 eyes) with choroidal neovascularization resulting from neovasacular AMD. Patients were treated with 1.25 mg intravitreal bevacizumab at a vitreoretinal practice in Adelaide, South Australia. Patients were followed up at 2-4 weeks and then at 1-month intervals; repeat injections were offered in the event of recurrence. Recurrence was defined as either a decrease of best-corrected visual acuity or an increase in macular oedema, subretinal fluid or intraretinal fluid on optical coherence tomography, after complete or partial resolution in previous follow-up visits. Patient data were collected for 12 months of follow up or until the patient's treatment was changed to ranibizumab. RESULTS: Significant improvement in visual acuity and central retinal thickness was demonstrated at 1 month with an improvement of vision from logMAR equivalent 0.76 to 0.68 (P < 0.001) and a decrease of central retinal thickness from 306 µm to 244 µm (P < 0.001). This overall improvement was continued throughout the 12-month follow-up period; however, follow up was poor with 12-month data available for only a small number of patients (7.8%). Ocular and systemic side-effects were rare at 3.5% and 0.4%, respectively. CONCLUSION: Eyes with neovascular AMD treated with intravitreal bevacizumab for up to 12 months had significant functional and anatomical improvement. Further studies need to confirm the long-term safety and efficacy of this treatment.

Sutureless vitrectomy.

Sutureless vitrectomy has rapidly been accepted as an essential part of a vitreoretinal surgical setup. The size and structure of the wound along with near intact conjunctival covering makes the incision self-sealing and safe. This allows the vitrectomy instruments to be used without creating an initial limited peritomy to expose bare sclera, and obviates the need for sutures at the end of the procedure. Wound construction is the essential step in ensuring postoperative wound stability. Both one-step and two-step wound constructions have been described. Key points include an oblique, tunneled approach to ensure a valve-like effect as well as misalignment of conjunctival and scleral wounds by displacing conjunctiva during construction. Advantages include decreased operative times in certain cases and decreased postoperative inflammation, early postoperative rehabilitation, improved patient comfort, and minimal conjunctival damage. Complications are based around wound competence, hypotony, and its relationship to endophthalmitis rates. Early reports highlighted an increase in endophthalmitis though further studies are required to accurately assess the incidence. Endophthalmitis has not been reported in cases that underwent fluid/air exchange. This review focuses on techniques, benefits, complications, personal experiences, and the safety profiles of sutureless vitrectomy systems. A literature review was undertaken using 'Medline' and 'Pubmed'. Search terms included sutureless vitrectomy, 20 gauge, 23 gauge, 25 gauge, and transconjunctival and small gauge vitrectomy.