Validation of a Prognostic Staging for Metastatic Uveal Melanoma: A Collaborative Study of the European Ophthalmic Oncology Group.

PURPOSE: To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting, and interpreting the results of clinical trials. DESIGN: Reliability and validity study. METHODS: The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc, which correspond to predicted survival times of ≥12, <12-6, and <6 months, respectively. The predictions were compared against observed survival. RESULTS: The 3 variables used to assign stage were independent predictors of survival in the validation dataset. Of the 249 patients, 110 (44%), 109 (44%), and 30 (12%) were classified to Working Formulation stages IVa, IVb, and IVc, respectively. Corresponding median observed survival times were 18.6, 10.7, and 4.6 months and worsened by increasing stage (P < .001). Of 201 patients managed without surgical resection of metastases, 83 (41%), 89 (44%), and 29 (15%) were classified to stages IVa, IVb, and IVc, respectively, and their median observed survival times were 17.2, 10.0, and 4.6 months (P < .001). Survival of 47 patients who underwent resection did not differ by working formulation stage (P = .69). CONCLUSIONS: This multicenter study confirms that the Working Formulation is a reliable and valid, repeatable system for dividing metastatic uveal melanoma into distinct prognostic subgroups, especially for stage-specific reporting of survival in prospective clinical trials.

Repeated intravitreal anti-vascular endothelial growth factor injections can induce iatrogenic ocular hypertension, especially in patients with open-angle glaucoma.

OBJECTIVE: To report the rate of intraocular pressure (IOP) elevation after repeated intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents and to determine the risk factors. METHODS: A total of 193 patients (217 eyes) undergoing ranibizumab (n = 196) or bevacizumab (n = 21) IVIs were prospectively examined. The incidence of ocular hypertension (OHT) after these injections was investigated with respect to the number of injections, pre-existing open-angle glaucoma, diabetes, YAG capsulotomy, age, and sex. RESULTS: A total of 1461 IVIs was performed. After a mean of 6.7 ± 7.1 IVIs (range, 1-49), 4.6% (n = 10) had IOP elevation more than 25 mm Hg and required medical treatment (1.4% of them spiked above 30 mm Hg). Patients with pre-existing glaucoma experienced higher prevalence of OHT (12.9%) and greater rates than the control group (19.6 ± 5.7 mm Hg vs 16.4 ± 3.9 mm Hg, p < 0.001). No significant difference was found in the diabetes subgroup (n = 66, p = 0.62) or in the YAG capsulotomy subgroup (n = 24, p = 0.51) compared with the control group. The IOP peak was significantly correlated with the total number of IVIs (p = 0.0002, r = 0.25). CONCLUSIONS: Serial IVIs may lead to persistent IOP elevation that requires IOP-lowering therapy. The risk is correlated with the number of injections and increases in the glaucoma population, and must be checked during follow-up.

Effect of topical pressure-lowering medication on prevention of intraocular pressure spikes after intravitreal injection.

Purpose. The aim of this study was to evaluate pressure increases after intravitreal injections (IVI) and the interest in using prophylactic pressure-lowering medications. 
Methods. This was a prospective study of 250 anti-vascular endothelial growth factor IVI (ranibizumab) divided into 5 groups of 50 IVI (group 1: no intraocular pressure [IOP]-lowering medication; group 2: apraclonidine 1%; group 3: acetazolamide; group 4: fixed association brimonidine + timolol; group 5: fixed association dorzolamide + timolol). The IOP was measured before, immediately after (T1), 15 minutes after (T15), and 45 minutes after (T45) the IVI using a tonometer. The data were analyzed by analysis of variance followed by a Bonferroni as post hoc test if necessary.
Results. The mean IOP peak in group 1 was 46.4±10 mmHg at T1, 21.7±10.2 mmHg at T15, and 15.4±8.6 mmHg at T45. It was not correlated with axial length (r=0.04, p=0.81) or lens status (phakic vs pseudophakic: p=0.88). A mild but significant correlation was found with age (r=0.36, p=0.006). Topical medications produced a significant reduction of IOP at every time point, of around 9 mmHg at T1. The reduction in IOP obtained with acetazolamide was not significant at T1 (-1.6 mmHg, p=0.12), but became significant at T15 and T45 (p=0.011 and p=0.015). 
Conclusions. Intraocular pressure spike was high but transient. Topical medications, however, produced a significant reduction in IOP spike as well as in the duration of the increased pressure. It would be advisable to prevent this IOP spike, especially when procedures are repeated, notably in patients with glaucoma.