Objective To assess the ocular effects and safety profile of chronic sildenafil oral dosing in patients with pulmonary arterial hypertension.Design 12 week, double masked, randomised, placebo controlled, phase III trial with open label extension. Setting 53 institutions worldwide.Participants 277 adults with idiopathic pulmonary arterial hypertension or pulmonary arterial hypertension associated with connective tissue disease or after congenital heart disease repair (mean pulmonary artery pressure ≥25 mm Hg; pulmonary capillary wedge pressure ≤15 mm Hg at rest).Interventions During the double masked study, oral sildenafil 20 mg, 40 mg, or 80 mg or placebo (1:1:1:1) three times daily for 12 weeks was added to baseline drug treatment. In the extension study, the placebo, 20 mg and 40 mg groups received 40 mg three times daily titrated to 80 mg three times daily at week 6. After unmasking, the dose was titrated according to clinical need.Main outcome measure Ocular safety (ocular examinations, visual function tests, participants' reports of adverse events, and visual disturbance questionnaire completed by investigators) by treatment group at 12 weeks, 24 weeks, 18 months, and yearly.Results Findings of the objective assessments-that is, intraocular pressure and visual function tests (visual acuity, colour vision, and visual field)-were similar across groups (20 mg, n=69; 40 mg, n=67; 80 mg, n=71; placebo, n=70). No clinically significant changes occurred between baseline and 12 weeks, except for an efficacy signal in contrast sensitivity for the sildenafil 40 mg three times daily group. In right eyes, changes in intraocular pressure from baseline to week 12 ranged from a mean of −0.5 (95% confidence interval −1.3 to 0.2) mm Hg with placebo, −0.2 (−0.9 to 0.5) mm Hg with sildenafil 40 mg, and −0.1 (−0.7 to 0.5) mm Hg with 80 mg to 0.3 (−0.4 to 0.9) mm Hg with sildenafil 20 mg (the approved dose for pulmonary arterial hypertension). Mean changes from baseline to week 12 in contrast sensitivity in right eyes were −0.02 (SD 0.12) in the sildenafil 20 mg three times daily group compared with −0.05 (0.18) in the placebo group (P=0.044). Percentages of participants with deterioration in visual acuity (Snellen) from baseline to week 12 ranged from 10% (n=7) in the placebo group to 3% (n=2) in the sildenafil 20 mg three times daily group; the same percentages had visual field changes from normal to abnormal during the period in these two groups. The investigators did not deem any findings on colour vision assessment to be clinically significant. Findings of the objective assessments in the 40 mg and 80 mg three times daily sildenafil treatment groups and in left eyes were not substantially different, nor were any measures different throughout the open label extension compared with week 12. However, objective data were limited after month 18, as most participants had missing data or visual parameters were no longer collected by investigators. Incidence of ocular adverse events reported on the case report forms and a...

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BackgroundSeveral studies have investigated the effect of latanoprost on intraocular pressure (IOP). We compared the IOP-lowering effects of three higher concentrations of latanoprost with the commercially available concentration of 0.005% (50 μg/mL) in patients with primary open-angle glaucoma or ocular hypertension.MethodsTreatment-naive subjects or those receiving IOP-lowering medication with baseline IOP levels of ≥24 mmHg and ≤36 mmHg in at least one eye after washout were randomized to receive an evening dose of latanoprost 50, 75, 100, or 125 μg/mL for 4 weeks. At weeks 1, 2, 3, and 4, ocular examinations were performed and IOP was measured. Ocular symptoms and adverse events were monitored. The primary efficacy endpoint was the change in IOP from baseline to week 4 at 8 a.m. and 4 p.m. for the per protocol (PP) population using a "worse eye" analysis. Secondary efficacy endpoints were change in IOP at each time point from baseline across all visits, and percentage change in IOP from baseline to week 4 at 8 a.m.ResultsIn all, 282 patients were randomized and treated; 274 were included in the PP population. Treatment groups were similar at baseline; 68% were diagnosed with primary open-angle glaucoma. Mean baseline IOP levels were comparable across treatments. There were no statistically significant differences in IOP reductions from baseline to week 4 at either time point between those treated with higher concentrations of latanoprost versus those receiving 50 μg/mL. Least squares mean IOP changes at 8 a.m. were −10.13, -9.59, -10.02, and −9.06 mmHg for latanoprost 50, 75, 100, and 125 μg/mL, respectively, and at 4 p.m. were −8.90, -8.29, -8.81, and −8.34 mmHg, respectively. Results of secondary efficacy analyses supported those of the primary analysis. Conjunctival hyperemia, the most commonly reported adverse event, occurred in 16.9%, 18.6%, 20.8% and 15.9% of subjects receiving latanoprost 50, 75, 100, and 125 μg/mL, respectively.ConclusionsIOP reductions were observed in all treatment groups postbaseline, with no clinically relevant or statistically significant differences detected favoring any of the higher concentrations of latanoprost compared with latanoprost 50 μg/mL. All doses of latanoprost were well tolerated.Trial registrationClinical Trials.gov Identifier NCT01379144.

PurposeThis study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine.MethodsAs part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline.Results and discussionOf the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone–iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone–iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%).ConclusionThe results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT injections after they became a routine treatment procedure.

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