Lazaros Konstantinidis

Retinal pigment epithelium tears after intravitreal injection of ranibizumab for predominantly classic neovascular membranes secondary to age-related macular degeneration.

Acta Ophthalmol. 2010: 88: 736–741

Whole anterior segment proton beam radiotherapy for diffuse iris melanoma

Aim To report the results of whole anterior segment proton beam radiotherapy (PBR) for diffuse iris melanoma. Methods Between 2000 and 2011, 12 patients with iris melanoma received PBR to the entire iris and ciliary body. Results Patients had a mean age of 57 years and a median follow-up of 3.5 years (range 1–11.6 years). Tumour iris involvement was 1–4 h in five patients, 5–8 h in four and 9–12 h in three. Angle involvement was 6–8 h in five patients and 9–12 h in seven. The visual acuity (VA) before treatment was 6/5–6/6 in six patients, 6/8–6/9 in three and 6/18–6/38 in three. No tumour recurrence occurred during the follow-up period. Glaucoma treatment was required in 11 of 12 patients. The visual acuity at the last follow-up was 6/5–6/9 in five patients, 6/18–6/24 in three, 6/60–1/60 in two and no light perception in two. Four patients developed varying non-severe degrees of limbal stem cell deficiency, which was treatable with conservative measures. Conclusions Whole anterior segment PBR is a useful alternative to enucleation for diffuse iris melanoma. Most patients will need treatment for glaucoma and some may require treatment for tear-film instability and/or stem cell failure.

Long-term outcome of primary endoresection of choroidal melanoma

Background Endoresection of choroidal melanoma may offer the best hope of conserving vision in some patients but is controversial because of concerns regarding iatrogenic tumour dissemination. Methods Retrospective, non-randomised study of consecutive patients who underwent endoresection for choroidal melanoma at the Liverpool Ocular Oncology Centre between 1996 and 2010. Results The study included 71 patients with a mean age of 58.7 years. The tumour extended within 2 disc diameters of the optic disc in 46 (65%) eyes, involving the disc in 24 (34%) eyes. The mean largest basal tumour diameter and tumour thickness were 9.5 mm and 4.4 mm, respectively. The median follow-up was 4.1 years. The visual acuity at the latest follow-up was better than 6/30 in 31% eyes. The main causes of visual loss were foveal excision, rhegmatogenous retinal detachment (RD) and proliferative vitreo-retinopathy (PVR). Local recurrence developed in two patients (3%), who were treated by enucleation and proton beam radiotherapy, respectively. RD occurred in 16 cases (22%). Three (4%) eyes were enucleated, two because of PVR and one because of local tumour recurrence. Five patients died of metastatic disease. Conclusions Endoresection achieved high rates of local tumour control. This operation would seem to be a useful alternative to radiotherapy as a means of conserving vision in eyes with juxtapapillary melanoma.

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre

Background Uveal metastasis is the most common intraocular malignancy. Methods This was a retrospective study of all patients with uveal metastases referred to the Liverpool Ocular Oncology Centre between January 2007 and December 2012. Biopsy was performed as a primary investigation if the clinical examination suggested metastasis with no evidence of any extraocular metastases. Results Ninety-six patients (109 eyes) were included. Breast and lung carcinomas were the most common primary malignancies, affecting 41 and 27 patients, respectively. The median time interval between detection of primary cancer and uveal metastasis was 24 months (range 1–288 months). Thirty-nine patients underwent ocular biopsy, confirming the diagnosis in all patients. The biopsy indicated the site of origin in 24 out of the 27 without a known primary tumour. In 7 of these 27 cases, previous systemic investigations had failed to identify the primary tumour. Seventy-three patients received external beam irradiation; two patients received photodynamic therapy; and two patients had Ru-106 plaque radiotherapy. The visual acuity was stable or improved in 75.5% of the cases. Conclusions Immediate biopsy provides a quick diagnosis that may expedite treatment and improve any opportunities for conserving vision while facilitating the general oncologic management on these patients.

Trans-scleral local resection of toxic choroidal melanoma after proton beam radiotherapy

Aim To report on trans-scleral local resection of choroidal melanoma for exudative retinal detachment and neovascular glaucoma (toxic tumour syndrome) after proton beam radiotherapy (PBR). Methods A non-randomised, prospective study of secondary trans-scleral local resection of choroidal melanoma for exudative retinal detachment with or without neovascular glaucoma after PBR. The patients were treated at the Liverpool Ocular Oncology Centre between February 2000 and April 2008. The trans-scleral local resection was performed with a lamellar-scleral flap, using systemic hypotension to reduce haemorrhage. Results 12 patients (six women, six men) with a mean age of 51 years (range 20–75) were included in this study. The tumour margins extended anterior to ora serrata in six patients. On ultrasonography, the largest basal tumour dimension averaged 12.4 mm (range 6.8–18.1) and the tumour height averaged 7.1 mm (range 4.2–10.7). The retinal detachment was total in seven patients. Neovascular glaucoma was present in four patients. The time between PBR and local resection had a mean of 17.4 months (range 1–84). The ophthalmic follow-up time after the local resection had a mean of 46.2 months (range 14–99). At the latest known status, the eye was conserved in 10 patients, with a flat retina in all these patients and visual acuity equal or better than 6/30 in four patients. The reasons for enucleation were: patient request for enucleation when rhegmatogenous retinal detachment complicated the resection (one patient) and phthisis (one patient). Conclusions Exudative retinal detachment, rubeosis and neovascular glaucoma after PBR of a choroidal melanoma can resolve after trans-scleral local resection of the tumour. Our findings suggest that these complications are caused by the persistence of the irradiated tumour within the eye (‘toxic tumour syndrome’).

Intraocular Metastases--A Review.

Abstract: Intraocular metastases almost invariably arise in the uveal tract, mostly in the posterior choroid. They are the most common type of intraocular malignancy and often the first sign of tumor dissemination. Choroidal metastases generally appear as a creamy white or pale yellow mass associated with subretinal fluid and may be multifocal and bilateral. The most common primary sites are the breast and lung. Diagnosis is aided by a variety of tests, particularly ultrasonography and optical coherence tomography. Intraocular biopsy is useful in patients with clinical suspicion of uveal metastasis but no evidence of primary malignancy despite systemic evaluation. If systemic treatment fails to control the ocular tumor, a good response is usually achieved with local therapies such as external beam radiation therapy, photodynamic therapy, and transpupillary thermotherapy. The life expectancy of patients with choroidal metastases is generally poor but has been improving thanks to the therapeutic advances taking place.

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.

Transpalpebral proton beam radiotherapy of choroidal melanoma

Background Collateral damage to upper eyelid margin during proton beam radiotherapy (PBR) for choroidal melanoma may cause squamous metaplasia of the tarsal conjunctiva with keratinisation, corneal irritation, discomfort and, rarely, corneal perforation. We evaluated transpalpebral PBR as a means of avoiding collateral damage to the upper eyelid margin without increasing the risk of failure of local tumour control. Methods Retrospective study of consecutive patients who underwent PBR for choroidal melanoma between 1992 and 2007 at the Royal Liverpool University Hospital and the Douglas Cyclotron at Clatterbridge Cancer Centre, UK. Results Sixty-three patients were included in this study. Mean basal tumour diameter and tumour thickness were 11.8 mm and 3.6 mm, respectively. PBR mean beam range and modulation were 26.5 mm and 16.9 mm respectively. The eyelid margin was included in the radiation field in 15 (24%) eyes. The median follow-up was 2.5 years. Local tumour recurrence developed in 2 (3.2%) patients. In these two cases that developed tumour recurrence the transpalpebral treatment did not involve the eyelid margin. Six (9.5%) patients died of metastatic disease. No eyelid or ocular surface problems developed in any of the 48 patients who were treated without eyelid rim involvement, while 7 of the 15 patients with unavoidable irradiation of the eyelid rim developed some degree of madarosis. These seven patients all received more than 26.55 proton Gy to the eyelid margin. Symptoms, such as grittiness occurred in 12% of 48 patients without eyelid margin irradiation as compared with 53% of 15 patients whose lid margin was irradiated. Conclusions Transpalpebral PBR of choroidal melanoma avoids eyelid and ocular surface complications without increasing failure of local tumour control.

Choroidal schwannoma: a case series of five patients

Aim To report a case series of five patients diagnosed with choroidal schwannoma at the Liverpool Ocular Oncology Centre. Methods Patients with choroidal schwannoma were identified by searching the computerised database of the Liverpool Ocular Oncology Centre. Results The patients (3 males, 2 females) ranged in age from 15 years to 45 years. Three tumours were treated by enucleation, trans-scleral local resection, and combined bevacizumab and photodynamic therapy, respectively. Two were observed after confirmation of the diagnosis by biopsy. Conclusions Choroidal schwannoma has a variety of clinical manifestations. Associated features include hard exudates, retinal feeder vessels and serous retinal detachment. Biopsy with immunohistochemistry is required for diagnosis. Tumours not amenable to resection may respond to photodynamic therapy.