Real-world outcomes of allied health professional-led clinic model for assessing and monitoring ocular melanocytic lesions.

BACKGROUND: Naevomelanocytic lesions comprise an increasing workload in ophthalmic secondary care and, although largely benign, carry high risk of mortality in case of malignant transformation. Previous studies highlight the theoretical strength of virtual models in monitoring such lesions and the role of allied health professionals (AHPs). We aim to describe and validate a "real-world" functional clinical model utilising these particular resources. METHODS: New and existing follow-up patients from November 2016 to June 2019 with melanocytic lesions of the uveal tract and conjunctiva were directed into an optometrist-led, consultant-supported, clinic. Diagnostic tests included colour photography, autofluorescence, enhanced-depth imaging and ultrasound biomicroscopy. New patients were examined face-to-face initially, then virtually on subsequent visits. Suspicious lesions were referred to the consultant, with tertiary oncology referrals made as necessary. Clinical concordance between optometrist and consultant, patient satisfaction and outcomes of second opinion requests were audited. RESULTS: Eight hundred and twenty-five patient episodes were encountered: 419 new and 406 follow-up. Between July 1st and August 31st 2018, 72 cases were audited. There was 98.6% concordance between AHP and consultant for diagnosis and management. Referral for consultant second opinion was requested in 18(2%) clinical encounters, with 4(0.5%) referred on to the oncology centre, of which 3 received treatment. Of 65 patients responding to a patient satisfaction survey, 100% were satisfied with their experience and 95% were happy to continue monitoring by the AHP. CONCLUSION: With robust training and assessment, AHP-led service models are a highly efficient in busy units, without compromising patient safety.

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study.

BACKGROUND: To relate conjunctival melanoma characteristics to local control. METHODS: Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: 288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. CONCLUSION: This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma.

IMPORTANCE: Eye cancer staging systems used for standardizing patient care and research need to be validated. OBJECTIVE: To evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018. INTERVENTIONS: Treatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration. MAIN OUTCOMES AND MEASURES: Metastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual. RESULTS: A total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank P < .001). Patients with ulcerated melanomas had significantly higher risk of mortality (hazard ratio, 7.58; 95% CI, 1.02-56.32; P = .04). CONCLUSIONS AND RELEVANCE: This multicenter, international, collaborative study yielded evidence that the conjunctival melanoma staging system in the eighth edition of the AJCC Cancer Staging Manual can be used to accurately estimate metastasis and mortality rates. These findings appear to support the use of AJCC staging as a tool for patient care and research.

Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome.

Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

Abatacept: a potential therapy in refractory cases of juvenile idiopathic arthritis-associated uveitis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common of all systemic conditions associated with childhood uveitis. Visual impairment has been shown to be as high as 40% of which 10% being blind (6/60 or worse). Due to the lack of well-designed randomized control trials for paediatric uveitis and arthritis there are limited comparative data regarding the efficacy of single or combination treatments. Recently, abatacept was shown to control ocular inflammation in a case of psoriatic arthritis- associated uveitis, seven cases of JIA- associated uveitis and in JIA. We present two cases with JIA-associated uveitis who have responded dramatically to abatacept therapy following unsuccessful therapy with other immunosuppressants. Control of arthritis still represents a challenge with this treatment. METHODS: Prospective review of two patients with refractory JIA- associated uveitis not responding to maximum conventional treatment. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group. RESULTS: In case 1, ocular inflammation was brought under control after repeated abatacept infusions. Case 2 showed complete resolution of cystoids macular edema CME and improvement of 5 Snellen's lines in best corrected visual acuity. After 9 months, the ocular condition of both patients remains in remission with steroid sparing. Joint disease was brought to clinical remission in case 2, but not in case 1. CONCLUSIONS: Abatacept is a promising alternative treatment in refractory cases of JIA uveitis but may not be as successful in controlling joint disease. Larger series with long term follow up of biological therapies in paediatric uveitis are essential to assess the efficacy and cost effectiveness.

Paraneoplastic exudative retinal detachment associated with adenocarcinoma of the lung.

PURPOSE: To report a case of bilateral paraneoplastic exudative retinal detachment (ERD) associated with asymptomatic adenocarcinoma of the lung. METHODS: Case report. RESULTS: A 47-year-old man presented with bilateral ERD accompanied by anterior and posterior segment inflammation. Extensive investigations for local and systemic causes of ERD were unrewarding. Only when computed tomography scanning of the thorax was performed were enlarged thorax lymph nodes demonstrated and revealed biopsy-proven adenocarcinoma. CONCLUSIONS: Paraneoplastic phenomena should be considered in patients presenting with ERD. Ocular paraneoplastic pathologies may be the initial manifestation of an underlying malignancy.

Does the presence of an epiretinal membrane alter the cleavage plane during internal limiting membrane peeling?

PURPOSE: To determine whether the presence of a clinically and/or microscopically detectable epiretinal membrane (ERM) alters the cleavage plane during internal limiting membrane (ILM) peeling. DESIGN: Retrospective, observational, immunohistochemical study of ILM specimens using archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: Fifty-one patients who had had ILM excision. METHODS: Fifty-one ILM specimens peeled during vitrectomy for various etiologies were examined by light microscopy. The removal of ILM was assisted using Trypan blue (n = 30), indocyanine green (n = 7), or brilliant blue G (n = 14). Monoclonal antibodies to glial fibrillary acidic protein and to neurofilament protein were used to detect glial or neuronal cells respectively on the vitreous or retinal surfaces of the ILM. Specimens were divided into 2 groups: ILM peeled for full-thickness macular hole (MH; n = 31) and ILM peeled after removal of clinically detectable ERM (n = 20). MAIN OUTCOME MEASURES: Primary outcome measure was the localization of immunohistochemical markers to neuronal or glial cells on the vitreous or retinal surfaces of ILM. The secondary outcome measure was the correlation of the results of the primary measure with the dyes used to facilitate ILM peeling. RESULTS: Glial and/or neuronal cells were detected on the retinal surface of the ILM in 10 of 31 (32%) of the MH ILM specimens and in 13 of 20 (65%) of the ILM peeled after ERM excision; the difference was significant (P = 0.02). There was no association between the presence of neuronal and glial cells with the type of dye used (P = 0.2). Of the 23 ILM specimens with cells attached to the retinal surface, 21 (91%) were associated with clinical and/or histologic evidence of ERM and 2 (9%) were not. The correlation between the presence of cells on the vitreous and the retinal surfaces of ILM was high (P<0.0001). CONCLUSIONS: The findings suggest that ERM may be associated with sub-ILM changes that alter the plane of separation during ILM peeling. This study does not confirm any influence of dyes on the cleavage plane during surgery.

Familial unilateral Brown syndrome.

We present a two-generation family with Brown syndrome. The proband was a six and a half-year-old female who presented with a history of failure of dextro-elevation of her left eye. A full ophthalmic evaluation was consistent with a left Brown syndrome. Family history revealed that her mother was operated on as a child for left Brown syndrome and examination of her four and a half-year-old sibling showed similar affection in the left eye. Autosomal dominant inheritance has been postulated in this condition. To our knowledge this is the first report of three members of a two-generation family with left-sided Brown syndrome. Genetic counseling of Brown syndrome cases is advised; nevertheless, identification of the responsible gene should shed more light on its genetics.