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BackgroundEpiscleral brachytherapy is the most common eye-preserving treatment for medium-sized choroidal melanomas. γ-emitting iodine-125 (125I) and β-emitting ruthenium-106 (106Ru) are widely used. The latter is however generally reserved for thinner tumours (MethodsAll patients with ≥5.5 mm thick choroidal melanomas who were treated with plaque brachytherapy at a single institution between 1 November 1979 and 31 December 2015 were included (n=571). Size-controlled Cox regression HRs for postbrachytherapy enucleation, repeated brachytherapy and melanoma-related mortality were calculated, as well as Kaplan-Meier disease-specific survival and relative 10-year survival in matched subgroups.Results317 patients were treated with 106Ru and 254 with 125I. The rate of repeated brachytherapy was significantly higher among patients treated with 106Ru (8%) than with 125I (1%, p125I vs 106Ru 0.7, p=0.083) and melanoma-related mortality were not significant (125I vs 106Ru 1.1, p=0.63). Similarly, Kaplan-Meier disease-specific and relative 10-year survival was comparable in matched groups of 5.5–7.4 mm (relative survival 106Ru 59%, 125I 56%) and ≥7.5 mm thick tumours (relative survival 106Ru 46%, 125I 44%).ConclusionsRates of repeated brachytherapy were significantly higher among patients treated with 106Ru versus 125I for thick choroidal melanomas. There were, however, no significant differences in rates of enucleation or patient survival.

To compare the effect of combined low-dose transpupillary thermotherapy (TTT) and intravitreal ranibizumab with sham TTT and intravitreal ranibizumab in patients with neovascular age-related macular degeneration (AMD).A 24-month, double-masked, randomised, active-controlled clinical trial. 100 patients with primary neovascular AMD were randomly assigned (1:1) to receive intravitreal ranibizumab and sham TTT or intravitreal ranibizumab and low-dose TTT. After an initial loading phase of ranibizumab patients were assigned to receive quarterly low-dose TTT (136 mW/mm) or sham TTT for 24 months. Retreatment with ranibizumab was allowed in both treatment groups using a variable dosing regimen. The primary endpoint was the number of intravitreal injections with ranibizumab. Secondary endpoints included change in best corrected visual acuity (BCVA), central retinal thickness (CRT) and lesion area.In the per protocol (PP) population (78 patients) the mean number of ranibizumab injections was 8.0 in the sham TTT group versus 6.3 in the TTT group (p0.05). The mean number of injections between 0-12 months and 13-24 months was 4.8 versus 4.6 (p0.05) and 3.2 versus 1.7 (p0.01) in the sham TTT and TTT groups, respectively. There was no statistically significant difference in BCVA (+4.0 vs +0.9 ETDRS letters), CRT (-49.9% vs -36.4%) or lesion area (-0.3% vs -10.6%) between the treatment groups at the final examination. The results of the intent-to-treat population (92 patients) were similar to the PP population.Treatment with low-dose TTT significantly reduced the number or intravitreal injections of ranibizumab over 24 months. The results suggest that low-dose TTT can serve as an adjuvant in combination with intravitreal ranibizumab for neovascular AMD.The trial is registered at http://clinicaltrials.gov (no NCT00599222).

Although there are no randomised trials directly comparing topical chemotherapeutic agents mitomycin-C, 5-fluorouracil, and interferon-alpha2b, published studies indicate equal efficacy of these agents for treatment of non-invasive ocular surface squamous neoplasia (80%-88%). 5-Fluorouracil may be preferred, given low incidence of serious side effects and low cost to the patient.

AIM—To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS—Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 µm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS—The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS—The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.

Aim: To report symptoms and findings of lacrimal duct malfunction after topical mitomycin C (MMC) for conjunctival neoplasia. Methods: 14 consecutive patients treated with 1–6 cycles of topical 0.04% MMC four times daily for periods of 2 weeks were interviewed about symptoms of lacrimal duct malfunction. Patients who complained of tearing had examination of the puncta and canaliculi including probing and lacrimal duct irrigation. Results: Nine patients complained of epiphora after topical MMC. Three of these patients had normal puncta and canaliculi, patent to irrigation. In these patients epiphora ceased spontaneously after probing and irrigation. The additional six patients had stenosis of the punctum (n = 3), the common canaliculus (n = 1), both puncta and both canaliculi (n = 1) and complete occlusion of the lower canaliculus (n = 1). Conclusion: Obstruction of the puncta or canaliculi is not an infrequent event after topical 0.04% MMC.