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.

Conjunctival Merkel cell carcinoma: case report and review of the literature.

Merkel cell carcinoma (MCC) of the conjunctiva is rare. We report the case of a 73-year-old man who presented with unilateral foreign body sensation and blurred vision. A rapidly enlarging conjunctival lesion was identified and excised. The histopathological diagnosis was poorly differentiated squamous cell carcinoma, later reclassified as neuroendocrine / Merkel cell carcinoma following excision on subsequent recurrence. The patient developed lymph node and widespread metastatic disease. The challenges of diagnosing MCC at this site are discussed and the literature on treatment options for this aggressive disease is reviewed.

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.

Ocular Surface Fibroma: Clinical, Histopathological, and Immunohistochemical Features of 10 Cases.

AIM: To describe the clinical, histological, and immunohistochemical (IHC) features of a series of 10 cases of ocular surface fibroma (OSF) and correlate the findings with other similar histological entities. METHOD: The patient demographics and features of the lesions were analysed from the clinical notes. All cases in the series had routine diagnostic excisional biopsies with standard histopathological and IHC evaluation. Each case was analysed by histology and immunohistochemistry with antibodies to: CD34, Factor XIIIa, desmin, smooth muscle actin, S100, Melan-A, ß-catenin, neurofilament, and Ki67. RESULTS: OSF occurred on the bulbar, tarsal, or forniceal conjunctiva, and typically presented as a white, pink, or yellow sheet-like or nodular lesion. The most common symptom was irritation or a foreign-body sensation. Lesions ranged in size from 4 to 13 mm. Only 1/10 cases showed a recurrence after an incomplete excision. Histologically, OSF comprised bland spindle cells in a collagen stroma. The spindle cells were CD34-positive (in 10/10 cases) and a smaller subset was positive for Factor XIIIa (6/10 cases). Normal resident spindle cells in the conjunctival stroma, Tenon's capsule, and tarsal plate were positive for CD34 and Factor XIIIa, implicating these cells in the origin of OSF. CONCLUSION: OSF is a benign lesion of resident CD34- and Factor XIIIa-positive spindle cells in the conjunctiva and Tenon's capsule. We have called to attention another lesion to be included by clinicians in the differential diagnosis of benign ocular surface lesions composed of CD34- and Factor XIIIa-positive spindle cells.

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).

Efficacy of porcine acellular dermal matrix in the management of lower eyelid retraction: case series and review of the literature.

PURPOSE: To investigate the efficacy of Permacol™, a decellularized porcine dermal-derived membrane, as a spacer in the management of lower eyelid retraction. The efficacy of sizing and insertion was investigated, as well as complications. The literature was also reviewed to compare this material with other porcine-derived grafts in use for the management of lower eyelid retraction. METHODS: This was a retrospective case series observing all patients who received lower eyelid Permacol implants by the two senior authors (AAM, TGH) for the management of lower eyelid retraction. Patient demographics, indications for surgery, graft size, degree of postoperative lid advancement, and complications were reviewed. RESULTS: A total of 12 patients (16 eyelids) received Permacol implants for correction of lower eyelid retraction during the study period of 18 months (January 2015 to July 2017). Ten procedures were related to thyroid eye disease, 3 for reconstruction, 2 postcosmetic lower lid blepharoplasty, and one acquired anophthalmic socket. The average preoperative inferior scleral show (ISS) was 1.74 mm, and the average postoperative ISS was 0.82 mm. There was a mean lower eyelid elevation of 0.91 mm (p < 0.005, Wilcoxon signed rank test) and mean ratio of graft height:preoperative ISS was 3.8:1 over a median of 8 months follow-up. CONCLUSIONS: Permacol is a safe and effective alternative to autologous tissues for use as a spacer in patients with lower eyelid retraction of varying etiologies. It does undergo some resorption with time, however this can be predicted and incorporated into surgical planning; we recommend an implant height:ISS ratio of 4:1.

Management of recurrent sebaceous gland carcinoma.

OBJECTIVE: To evaluate the incidence and management of recurrent periocular sebaceous gland carcinoma at a tertiary ocular oncology service in the United Kingdom. METHODS: This was a retrospective cohort study of 62 patients with sebaceous gland carcinoma treated between 2004 and 2017. A total of 10 eyes were treated for local recurrence. The following variables were recorded: age and sex of patient; tumour location, histological subtype; recurrence type; treatment and outcome. RESULTS: Of the 62 cases with eyelid SGC, 10 (16%) had recurrences during the study period and satisfied inclusion criteria. There were six (60%) females and four males in the recurrent group. The mean time interval between initial excision and tumour recurrence was 37 months (median 23 months; range 4 to 84 months). Four patients received cryotherapy to the lids and conjunctiva to control recurrent disease and two patients were treated with topical or intralesional chemotherapy. Four patients (40%) underwent orbital exenteration during the study period. Metastasis occurred in 20% over a mean follow-up of 113 months (median 106; range 47-184 months). CONCLUSIONS: The risk factors for local recurrence of SGC after wide excision with paraffin section control were reported, and an approach to these recurrent lesions was proposed. The results of this study will help guide surgeons dealing with the medical and surgical conundrum of recurrent disease. The risk of recurrence is highest in the first 2 years after initial excision.

Paraneoplastic Granulomatous Vitritis: Elaboration of 8 Cases.

PURPOSE: To describe the clinical features in a series of 8 patients with cytologically proven granulomatous vitritis in the context of systemic malignancy. DESIGN: Retrospective case review series from 2004 through 2018 to identify all cases of cytologically proven granulomatous vitritis and to analyze its disease associations and causes. PARTICIPANTS: Twenty-three patients with a cytologic diagnosis of granulomatous vitritis were identified, 8 of whom demonstrated systemic malignancy. MAIN OUTCOME MEASURES: To identify a clinical profile of the 8 cases of granulomatous vitritis occurring in the setting of systemic malignancy, focusing on the timing of the eye presentation compared with the timing of the systemic malignancy. METHODS: Patients with a cytologic diagnosis of granulomatous vitritis seeking treatment from 2004 through 2018 were included in this retrospective case series. Case notes were recalled and reviewed for demographic features, medical history, presenting symptoms, investigations, surgical procedures, and follow-up. RESULTS: Twenty-three patients were diagnosed cytologically with granulomatous vitritis. Ten of 23 patients (43%) showed autoimmune and infectious causes, 5 of 23 patients (22%) showed were idiopathic causes, and 8 of 23 patients' (35%) disease was associated with systemic malignancy. In the latter group, the median age at presentation was 70 years (range, 55-89 years). Six patients showed bilateral disease, and the remaining 3 showed unilateral disease. Three of 8 patients showed primary systemic malignancy diagnosed after eye symptoms and 5 of 8 showed malignancy before the eye symptoms. These latter 5 patients all demonstrated a major relapse, metastasis, or both at the time of eye symptoms. CONCLUSIONS: Paraneoplastic vitritis is primarily a disease of older age, with 67% of those affected older than 65 years. Ophthalmologists should maintain a high index of suspicion of paraneoplastic cause in bilateral posterior segment inflammation of uncertain origin, presenting for the first time, or heralding malignancy recurrence or metastasis in known cases of malignancy.

A Case of a Cavitary Iris Melanoma with Aqueous Cytological Modulation.

Malignant melanoma is the most common primary malignant tumour of the iris, but represents a small proportion of all uveal melanomas. The authors describe a 34-year-old male with a pigmented lesion of the iris. The lesion remained stable for 7 years, but the patient re-presented after this time with sudden enlargement of the mass and hyphaema. Excisional biopsy confirmed cavitary melanoma of the iris. This is the first reported case of cavitation in a primary iris melanoma. The patient has not had any further adjuvant treatment and remains metastasis free at 5 years of follow-up.

Staged excision of primary periocular basal cell carcinoma: absence of residual tumour in re-excised specimens: a 10-year series.

AIMS: The aim is to study staged periocular basal cell carcinoma (BCC) excision in a tertiary oculoplastic referral centre in Sheffield, UK. In particular, we examined patients with close or positive margins and no tumour seen on re-excision to identify demographics and tumour characteristics in this population. METHODS: A retrospective review of medical records of 437 cases of staged periocular BCC excisions over a 10-year period (2007-2017) was carried out. Patients had surgical excision with 3 mm clinically clear margins. Staged excision was performed for all cases included in this study. Standard reconstruction techniques were employed. Histopathology was analysed for tumour type, subtype and stage. RESULTS: Over the 10-year period, of the 437 periocular BCCs, 156 had close or involved margins. Residual tumour was found in 29 (18.6%), whereas in 122 eyelids of 120 patients (78.2%) no residual tumour was identified on histological examination. Micronodular (54.1%) and nodular (23.7%) growth patterns of BCC, as well as lower eyelid location (72.1%), were the most prevalent in this population. Two patients (1.6%) had recurrence of BCC over a mean follow-up of 57 months (range 1-125 months). CONCLUSIONS: A significant proportion of BCCs transected on initial excision show no residual tumour in the re-excision specimens. In the interval between initial excision and re-excision, there may be eradication of the residual tumour. The exact mechanisms for this are unclear, however, and re-excision remains the appropriate recommended course in the presence of involved surgical margins of periocular BCC, particularly when high-risk tumour subtypes are encountered.

Hemangioblastoma of the optic nerve.

Optic nerve hemangioblastoma is a rare tumor that is usually unilateral and most commonly occurs in the context of von Hippel-Lindau disease. Differential diagnosis is based on clinical history and imaging. Magnetic resonance imaging with gadolinium enhancement is the most useful imaging modality as it can reveal flow voids and an absence of dural attachment, differentiating optic nerve hemangioblastoma from other more commonly encountered optic nerve tumors. Optic nerve hemangioblastoma are usually well-circumscribed vascular lesions composed of stromal cells and vascular endothelial cells. These lesions are diagnosed at a mean age of 37 years and can be asymptomatic, but over time, patients may develop reduction in vision, proptosis, and pain. Surgical excision is well described via orbital, transsphenoidal, or transcranial approaches. Given the risks associated with surgery, a stepwise conservative approach is advocated by most clinicians in the absence of severe symptoms. Although uncommon, this optic nerve tumor should be considered in young patients presenting with pain, proptosis, and optic nerve pallor, with or without a history of von Hippel-Lindau disease.

Optic Nerve Haemangioblastoma: Signs of Chronicity.

Optic nerve haemangioblastomas remain exceedingly rare extrinsic tumours of the optic nerve, often associated with von Hippel-Lindau disease. The authors report a 25-year-old female with a slowly progressive unilateral optic nerve lesion, causing reduced vision and bilateral optic tract oedema. A diagnosis of optic nerve haemangioblastoma with piloid gliosis was made histologically after surgical resection. This is the first reported case of such dual pathology occurring in the optic nerve. The patient has been monitored without further adjuvant treatment, and has not had a recurrence to date, at 6 years of follow-up.

Temporary suture tarsorrhaphy at the time of orbital ball implantation.

PURPOSE: Conjunctival chemosis is a common, usually benign, complication of ocular and oculoplastic surgery. After enucleation, evisceration, or secondary ball implant, however, conjunctival edema can cause conformer extrusion, forniceal eversion, and shortening which may complicate the future fitting of a prosthesis. This longitudinal chart review aimed to estimate the efficacy of a temporary suture tarsorrhaphy to minimize postoperative edema and improve conformer retention. METHODS: We retrospectively reviewed the charts of 415 consecutive patients undergoing enucleation, evisceration, and secondary ball implantation between 1990 and 2016. Three-hundred twenty-eight patients had complete data which was analyzed for age, gender, surgical details, complications, and follow-up. RESULTS: We identified 328 eyes that underwent enucleation (48%), evisceration (3%), or secondary implantation (49%) during the study period. Eighty-nine patients had a suture tarsorrhaphy at the time of surgery, and 239 did not. There was a statistically significant incidence of postoperative conjunctival edema in the no tarsorrhaphy group. There was also a significantly increased rate of conformer loss associated with conjunctival edema. Need for further surgery was not uncommon with 64% and 43% of patients requiring a secondary procedure in the no tarsorrhaphy and tarsorrhaphy groups respectively. CONCLUSIONS: Temporary suture tarsorrhaphy is a simple and effective procedure that reduces conjunctival edema and increases conformer stability when performed at the time of enucleation, evisceration, or secondary ball implantation.

Squamous cell carcinoma in the anophthalmic socket: a series of four cases with HPV-16 profiling.

PURPOSE: To present the clinical and histological features of squamous cell carcinoma (SCC) in the anophthalmic socket in four adult patients, and to determine the presence of human papillomavirus infection (HPV). METHODS: Retrospective case series of four adult patients with SCC of the anophthalmic socket. P16 immunohistochemistry and HPV testing was carried out in all cases. The authors report clinical findings, histopathology, management and outcomes for all four patients with conjunctival SCC. Previously reported cases of conjunctival SCC in anophthalmic sockets were reviewed. RESULTS: Four adult patients presented with eyelid lumps, discharge or change in prosthesis fit. Common examination findings included papillomatous changes, eyelid masses and epithelial changes. Three out of the four cases (75%) were positive for p16 by immunohistochemistry and the same cases positive for HPV-16 DNA. All patients received cryotherapy, topical or intralesional chemotherapy. Two patients proceeded to exenteration for control of invasive disease. CONCLUSIONS: To the authors' knowledge, this is the largest series of SCC in the anophthalmic socket with comprehensive annotation of HPV status. Although socket conjunctiva is protected from environmental radiation, there is still a risk of neoplastic transformation in this tissue, thus patient education and regular checking of sockets by ophthalmologists should be undertaken as a preventative measure. The potential role of HPV in these tumours warrants further investigation.

Recognition and Management of Acute Dacryocystic Retention.

PURPOSE: Acute noninfectious dacryocystic retention is an under-recognized condition heralded by painful lacrimal sac swelling, obstruction, and epiphora. This longitudinal chart review aimed to estimate the incidence of this condition in an urban Australian population, while further defining the signs and symptoms of the disease and options for management. METHODS: We retrospectively reviewed the charts of 1,593 consecutive patients presenting with acquired nasolacrimal duct obstruction and epiphora between 1990 and 2015. The records of patients with acute dacryocystic retention were analyzed for age, gender, clinical features, and management. RESULTS: Of all patients presenting with nasolacrimal duct obstruction, 20 were found to have acute dacryocystic retention. The mean age was 42.2 ± 9.3. There was an equal distribution of laterality, and only 2 cases (10%) were bilateral. There was a statistically significant female predominance, and most patients presented reporting 2 to 3 previous episodes. At presentation, 30% of patients reported spontaneous passage of a dacryolith. Despite this, 70% of affected patients required surgical management, with a 64% incidence of stones noted at the time of dacryocystorhinostomy. CONCLUSIONS: Acute dacryocystic retention is an uncommon, but even less frequently identified condition, most common in middle-aged women. Improved understanding of this condition and its natural history is likely to enhance patient counseling and avoid ineffective use of antibiotics in affected patients.