Victoria M L Cohen

The success of primary chemotherapy for group D heritable retinoblastoma

Aims: To report the ocular survival and event-free survival following primary multiagent chemotherapy for group D, heritable bilateral retinoblastoma (RB). Methods: The RB database was used to identify children with heritable, bilateral RB treated with primary chemotherapy (six cycles of vincristine, etoposide and carboplatin). Only Group D eyes with more than 12 months’ follow-up were analysed. The timing, number and type of salvage treatments were recorded. Kaplan–Meier estimates for the ocular survival and event-free survival (percentage of eyes that avoided external beam radiotherapy and/or enucleation) were performed as a function of time. Results: Of 18 group D eyes, two (11%) were treated successfully with chemotherapy alone, nine (50%) underwent successful salvage treatment, and seven (39%) were enucleated. The median time from completing chemotherapy to enucleation was 9 months (range 4 to 25 months). Ocular survival was 67% at 2 years. External beam radiotherapy proved successful salvage treatment in five of nine eyes, so the event-free survival was 34% at 2 years. Conclusion: Multiagent chemotherapy alone is rarely sufficient for the preservation of group D eyes. External beam radiotherapy and plaque radiotherapy remain important salvage treatments for advanced, heritable retinoblastoma.

Prospective study of sentinel lymph node biopsy for conjunctival melanoma

Background To report our experience with sentinel lymph node biopsy for staging patients with conjunctival melanoma. Methods A prospective review of patients with conjunctival melanoma who underwent sentinel lymph node biopsy at St Bartholomews Hospital from May 2008 to May 2012. The selection criterion for sentinel node biopsy depended on the tumour thickness (≥2 mm) and location of the conjunctival melanoma. The main outcome measures were the incidence of sentinel lymph node positivity and the procedure-related complications. Results In 4 years, 26 out of 70 patients met the selection criteria for sentinel lymph node biopsy. 4 patients declined and 22 patients consented for the procedure. Technetium-99m failed to identify a sentinel lymph node in four of the 22 patients (18%). Of the remaining 18 patients, two were found to have subclinical micrometastasis in regional lymph nodes. Median follow-up was 20 months (range 6–36 months). No false-negative events were observed. Complications of the procedure included transient blue staining of the epibulbar surface in five patients and transient facial nerve palsy in one patient. Conclusions Sentinel lymph node biopsy is a safe procedure with minimal complications. It should be considered for the staging of conjunctival melanomas, especially melanomas in non-limbal location or conjunctival melanomas ≥2 mm thick.

Predicting local control of choroidal melanomas following 106Ru plaque brachytherapy

Background We evaluated the control rate of choroidal melanomas treated with 106Ru plaque brachytherapy to identify the risk factors associated with local recurrence and lack of response. Methods A retrospective review of 106Ru plaque brachytherapy for patients with choroidal melanoma treated at St Bartholomews Hospital, London. Survival analysis was used to assess associations between evaluated age, sex, location, foveal proximity, tumour base and height, presence of lipofuscin and subretinal fluid, apex dose, radiation rate and type of plaque with time to local recurrence. Logistic regression analysis was used to assess to evaluate the association between the same set of variables and lack of tumour response. Results From January 2002 to December 2006 189 patients were treated. The follow-up ranged from 12 to 78 (median 33) months. None of the patients received adjuvant diode laser thermotherapy. The control rate was 85.7% (14 recurred while 13 did not respond). Of the patients who had local recurrence, univariate survival analysis demonstrated an association with younger patients, foveal proximity, preoperative subfoveal fluid and tumour base >11 mm. Age and foveal proximity remained significant in a Cox multiple variable model (p=0.03). Of the patients who did not respond, logistic regression analysis showed that lack of response was associated with a tumour height >5 mm, confirmed through multiple variable analysis (p=0.027). Conclusions Tumours that are close to the fovea in young patients appear more likely to show local recurrence. Tumour height >5 mm was the only prognostic factor that determined lack of response. These results may be used to select which tumours require adjuvant therapy.

Uveal Melanoma UK National Guidelines

The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

Bilateral granulomatous uveitis in association with common variable immunodeficiency

Editor,—We report a case of bilateral granulomatous uveitis, which prompted extensive diagnostic review in a 20 year old woman with a long history of recurrent infection and idiopathic thrombocytopenia. Investigations allowed the definitive diagnosis of common variable immunodeficiency with granulomas (granulomatous antibody deficiency syndrome.) To our knowledge this is the first reported case of granulomatous uveitis in association with granulomatous antibody deficiency (GAD). We discuss the features of GAD, and how it may be distinguished from sarcoidosis. ### CASE REPORT A 20 year old woman presented with sudden onset blurred vision. Examination revealed a bilateral granulomatous uveitis with mutton-fat keratic precipitates and anterior chamber cells. Two weeks later she developed bilateral optic disc swelling with multifocal areas of choroidal pallor in her left eye (Fig 1). There was no vitritis …

Ocular adnexal lymphoma. What is the evidence for an infectious aetiology

Ocular adnexal lymphoma is classified as non-Hodgkin’s lymphoma, the most common primary subtype of which is the low-grade extranodal marginal zone B-cell lymphoma of the MALT type (mucosa-associated lymphoid tissue).1 MALT lymphomas were first recognised in 1983;2 they occur in tissues normally devoid of lymph nodes such as the skin, gastric mucosa, lung, thyroid and salivary gland.3 The incidence increases with age and is highest among Asians and Pacific Islanders.4 Since 1975, the incidence of ocular NHL has increased approximately 6% per year, and ocular adnexal MALT lymphoma is increasing more rapidly than MALT lymphoma at other sites.4 It is possible that this may be related to a new infectious aetiology. Many MALT lymphomas at non-ocular sites are associated with an infectious aetiology supporting the model of antigen-driven lymphomagenesis.3 An infection triggers chronic antigen stimulation of B cells and the production of antibodies; later, the proliferation of B cell clones becomes antigen-independent, and with uncontrolled proliferation, malignant transformation can occur.3 Borrelia burgdorferi and Campylobacter jejuni have been associated with marginal zone lymphoma of the skin and small intestine, respectively.5 6 However, the most frequently cited example is that of gastric MALT lymphoma where eradication of Helicobactor pylori, a cause of chronic gastritis, results in the resolution of early stage gastric MALT lymphoma.7 Interestingly, some extra-gastric, non-ocular MALT lymphomas have regressed following H pylori -eradicating antibiotic therapy.8 9 This finding led many to speculate that H pylori may have a role in ocular adnexal lymphoma. Although Ferreri and associates10 showed that H pylori antibiotic eradication was not effective treatment for ocular adnexal MALT lymphoma (OA MALT lymphoma), there is some published evidence for the role of H pylori in OAL. Chan et al …

Primary photodynamic therapy with verteporfin for small pigmented posterior pole choroidal melanoma

PurposeThe purpose of the study was to investigate the outcomes of primary photodynamic therapy (PDT) for small pigmented posterior pole choroidal melanoma.Patients and methodsProspective interventional consecutive case series of 15 patients with small pigmented posterior pole choroidal melanoma, who were treated with three sessions of PDT and followed-up thereafter. Risk factors for failure were assessed and outcome measures at presentation were compared to those at last follow-up visit.ResultsTumor control was achieved in 12 (80%) patients in a median follow-up time of 15 months (mean 14, range 8–18). Three patients failed treatment, diagnosed in a median time of 5 months (mean 4, range 3–6), after first PDT. In all failed cases, lesions were 100% pigmented; de novo melanoma rather than transformed nevi and showed a radial growth pattern rather than increased thickness. All failed cases were subsequently successfully treated with radiotherapy. In this cohort, subretinal fluid (SRF) was significantly reduced (P<0.001), vision did not deteriorate (P=0.11) and even improved in patients with subfoveal SRF at presentation (P=0.018), tumor height significantly decreased (P=0.037) and no complications were recorded.ConclusionPrimary PDT was found to be a safe and efficient treatment modality for small pigmented posterior pole choroidal melanoma, achieving short-term tumor control in 80% of patients. PDT offers patients the opportunity to preserve vision by avoiding the retinopathy associated with conventional radiation treatments for choroidal melanoma. However, the long-term local control of these tumors remains uncertain.

Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary to choroidal osteoma

PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography—where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3–10 injections of bevacizumab. Median follow-up was 9 months (3–15 months). Visual acuity improved in 5 patients, by 2–6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 μm (6 to −230 μm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group

PURPOSE To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN Retrospective, multicenter observational study. PARTICIPANTS Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Metabolic activity of primary uveal melanoma on PET/CT scan and its relationship with monosomy 3 and other prognostic factors

Purpose To correlate the metabolic activity of primary uveal melanoma on positron emission tomography (PET)/CT scan with known clinical and pathological prognostic factors. Methods A retrospective cohort analysis of eyes enucleated for uveal melanoma that underwent preoperative imaging with a PET/CT scan was performed. Tumour dimensions were recorded and classified using Collaborative Ocular Melanoma Study (COMS) and American Joint Committee on Cancer (AJCC) Tumour - Nodes - Metastases (TNM) criteria. Metabolic activity was determined by measurement of the maximal standardised uptake value (SUVmax) on PET/CT scans. SUVmax of >2.5 and >4 was also used as cut-off value for metabolic positivity. Chromosome 3 and 8 status was determined using fluorescence in situ hybridisation analysis. Pearson correlation, χ2 test and non-parametric tests were used. p<0.05 was considered statistically significant. Results Seventy-six uveal melanomas were imaged preoperatively with a PET/CT scan. Overall 92% of tumours had a SUVmax >2.5 and 67% had a SUVmax >4. Monosomy 3 was found in 35 melanomas, of which 94% had an SUVmax >2.5 and 80% had an SUVmax >4. Only 57% of disomy 3 melanomas had an SUVmax >4. SUVmax was significantly increased in tumours with monosomy 3 (p=0.043) but not in tumours with chromosome 8 gain (p=0.49). SUVmax and increasing tumour size were positively correlated (p<0.05). Using the AJCC criteria, there was a significant difference in SUVmax among prognostic groups (p=0.024). There was no correlation with histopathological cell type (p=0.923). Conclusions Metabolic activity of uveal melanoma on PET/CT scan is positively correlated with monosomy 3, increasing tumour size and TNM prognostic groups. No association with chromosome 8 gain or histopathology cell type was noted. SUVmax >4 is a relative but not an absolute indicator of monosomy 3 status.