J.-P. Nordmann

Vision related quality of life and topical glaucoma treatment side effects

BackgroundLocal tolerance of topical glaucoma treatment is important to achieve a good compliance. The aim of this study was to evaluate the consequences of local anti-glaucoma drug side effects on the vision-related quality of life (QoL).MethodsA mail survey was sent to 20,000 homes of a panel representative of the French population asking whether one member of the family was suffering from ocular hypertension (OHT) or glaucoma. (POAG) A computer-assisted telephone interviewing system was used to confirm self-reported glaucoma, to describe the disease and its treatment, and medical item consumption. Vision-related QoL was assessed with the NEI-VFQ-25 (National Eye Institute Visual – Function Questionnaire) and local tolerance with the COMTOL (Comparison of Ophthalmic Medications for TOLerability).Results13,352 homes (66.7%) answered the mail. 581 people declared they were suffering from glaucoma or OHT. Prevalence was 1.8%, increasing with age. 204 patients were selected at random Their NEI-VFQ-25 global score showed an overall good QoL. Two domain scores showed some deterioration: general health and driving. 62.4% of the patients cited at least one local side effect. 25.4% had burning, 20.8% blurred vision and 20.2% tearing. Poor vision related QoL was associated with the presence of local side effects leading to poor perceived treatment satisfaction. Dissatisfied patients visited their ophthalmologist more frequently.ConclusionBased on a representative French sample, poor vision related QoL was associated with topical drug side effects that also impact patient satisfaction and compliance. Longitudinal data collection should be performed to confirm our findings.

Miniaturized high-intensity focused ultrasound device in patients with glaucoma: a clinical pilot study.

PURPOSE To evaluate the relative safety and potential efficacy of high-intensity focused ultrasound cyclocoagulation by a miniaturized annular device containing six piezoceramic transducers in patients with refractory glaucoma. METHODS This was a three-center prospective interventional pilot study. Twelve eyes of 12 patients with refractory glaucoma were insonified using a ring-shaped probe containing six miniaturized high-frequency transducers operating at 21 MHz. Ultrasound biomicroscopy (UBM) and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, 1 month, and 3 months after the procedure. Additional visits were performed 6 and 12 months after the procedure. RESULTS Intraocular pressure was significantly reduced (P < 0.01) from a mean preoperative value of 37.9 ± 10.7 mm Hg to a mean postoperative value of 27.3 ± 12.4, 25.2 ± 11.3, 25.2 ± 7.7, 24.8 ± 9.8, and 26.3 ± 5.1 mm Hg at 1 day, 1 week, 1 month, 3 months, and 6 months, respectively, and to a mean value of 24.7 ± 8.5 at the last follow-up visit. No major intraoperative or postoperative complications occurred. Minor postoperative corneal complications developed in four patients with previous corneal abnormalities: superficial punctate keratitis (n = 3) and central superficial corneal ulceration (n = 1). UBM showed cystic involution of the ciliary body in 9 of the 12 eyes and a suprachoroidal fluid space in 8 of the 12 eyes. CONCLUSIONS Ultrasonic circular cyclocoagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing six piezoceramic transducers seems to be an effective and well-tolerated method to reduce intraocular pressure in patients with refractory glaucoma.

Visual field loss in patients with refractory partial epilepsy treated with vigabatrin: final results from an open-label, observational, multicentre study.

Background: Use of the antiepileptic drug vigabatrin is associated with an elevated risk of visual field loss.Objective: To determine the frequency of, and risk factors for, vigabatrin-attributed visual field loss (VAVFL) in the setting of a large-scale, multinational, prospective, observational study.Study design: A comparative, open-label, parallel-group, multicentre study.Setting: Hospital outpatient clinics at 46 centres in five countries.Patients: 734 patients with refractory partial epilepsy, divided into three groups and stratified by age (8–12 years; >12 years) and exposure to vigabatrin. Group I comprised patients treated with vigabatrin for ≥6 months. Group II comprised patients previously treated with vigabatrin for ≥6 months who had withdrawn from the drug for ≥6 months. Group III comprised patients never treated with vigabatrin. Patients underwent perimetry at either 4- or 6-month intervals, for up to 36 months. Visual field outcome was evaluated masked to drug exposure.Intervention: Perimetry.Main outcome measure: The visual field outcome at each of four analysis points: (i) at enrolment (i.e. baseline, all patients); (ii) for patients exhibiting a conclusive outcome at the initial visual field examination; (iii) for patients exhibiting at least one conclusive outcome to the visual field examinations; and (iv) at the last conclusive outcome to the visual field examinations.Results: Of the 734 patients, 524 yielded one or more conclusive visual field examinations. For Group I, the frequency of VAVFL at the last conclusive examination was 10/38 (26.3%) for those aged 8–12 years and 65/150 (43.3%) for those aged >12 years. For Group II, the respective frequencies were 7/47 (14.9%) and 37/151 (24.5%). One case resembling VAVFL was present amongst the 186 patients in Group III at the last conclusive examination. The frequency of VAVFL in Groups I and II combined was 20.0% for those aged 8–12 years and 33.9% for those aged >12 years. VAVFL was associated with duration of vigabatrin therapy (odds ratio [OR] up to 15.2; 95% CI 4.4, 51.7), mean daily dose of vigabatrin (OR up to 26.4; 95% CI 2.4, 291.7) and male gender (OR 2.51; 95% CI 1.5, 4.1). VAVFL was more frequently detected with static than with kinetic perimetry (OR up to 0.43; 95% CI 0.24, 0.75).Conclusions: Since the probability of VAVFL is positively associated with treatment duration, careful assessment of the risk-benefit ratio of continuing treatment with vigabatrin is recommended in patients currently receiving this drug. All patients continuing to receive vigabatrin should undergo visual field examination at least every 6 months for the duration of treatment. We recommend two-level (three-zone), gradient-adapted, suprathreshold static perimetry of the peripheral field together with threshold perimetry of the central field out to 30° from fixation. The frequency of ophthalmological and perimetric examinations should be increased in the presence of VAVFL.

Autoradiographic localization of D1 and D2 dopamine binding sites in the human retina

The localization of dopamine binding sites was studied by in vitro autoradiography in the normal human retina using [125I]SCH 23982 for D1 receptor labelling and [125I]iodosulpride for D2 receptors. Results demonstrated that both types of binding sites were present in human retina. Binding of [125I]SCH 23982 to D1 dopamine receptor was blocked by 1 microM SKF 38393, SCH 23390 (D1 specific compounds) whereas bromocriptine and domperidone (D2 specific compounds) were inactive at the same concentration. On the contrary, binding of [125I]iodosulpride to D2 dopamine receptor was inhibited only by D2 drugs. Precise cellular distribution was given by microautoradiographic techniques and showed that binding sites were exclusively localized to the plexiform layers.

Nutritional, lifestyle and environmental factors in ocular hypertension and primary open‐angle glaucoma: an exploratory case–control study

Purpose:  To evaluate known and potential risk factors, including nutritional, lifestyle and environmental factors, differentiating patients with high‐tension primary open‐angle glaucoma (POAG) from control subjects with ocular hypertension (OHT).

Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension.

Purpose. To determine the prevalence of ocular surface diseases and identify risk factors in a population of patients receiving antiglaucomatous eyedrops over the long term. Methods. An observational cross-sectional study was designed to investigate ocular surface signs and symptoms using simple clinical tools. An ocular surface disease intensity score was calculated based on 10 questions regarding ocular surface symptoms and signs with a 4-grade scale. Patients were classified into 3 groups (A, B, and C) according to this total score. A multinomial logistic regression was performed in order to identify risk factors for surface disease. Results. In an overall population of 516 patients, 49% belonged to group A, 30% to group B, and 21% to group C. The multivariate analysis showed that the following factors were correlated with the severity of ocular surface disease: patient age, number of daily eyedrops, past topical treatment changes for ocular intolerance (found in the history of 40% of the patients), intraocular pressure (found to be significantly higher in patients with more severe ocular surface disease), and glaucoma severity. Conclusions. Patients treated for primary open-angle glaucoma or ocular hypertension often have ocular surface diseases, more often and more severely in older patients receiving more drugs and presenting with more severe glaucoma. These high prevalence values might therefore have consequences on the burden of the disease in terms of adherence to treatment and quality of life.

Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with β adrenergic antagonists

AIMS To compare the effect on intraocular pressure (IOP) of latanoprost monotherapy and timolol-pilocarpine in patients with glaucoma or ocular hypertension with inadequately controlled IOP on topical β adrenergic antagonists. METHODS This was a multicentre, randomised, observer masked, 6 week study performed in France and Sweden. 23 centres enrolled 237 patients with glaucoma or ocular hypertension and an IOP of at least 22 mm Hg on treatment with topical β adrenergic antagonists, alone or in combination. After a 21 day run in period on timolol 0.5% twice daily, patients were randomised either to latanoprost 0.005% once daily or to a fixed combination of timolol-pilocarpine twice daily. Changes in mean diurnal IOP from the baseline to the 6 week visit were determined with an analysis of covariance. RESULTS Mean diurnal IOP was statistically significantly decreased from baseline in both groups (p<0.001). Switching to latanoprost treatment reduced mean diurnal IOP by 5.4 (SEM 0.3) mm Hg (ANCOVA −22%) and switching to timolol-pilocarpine treatment reduced mean diurnal IOP by 4.9 (0.4) mm Hg (−20%). Blurred vision, decreased visual acuity, decreased twilight vision, and headache were statistically significantly more frequent in the timolol-pilocarpine group. CONCLUSIONS Latanoprost monotherapy was at least as effective as fixed combination timolol-pilocarpine twice daily treatment in reducing mean diurnal IOP in patients not adequately controlled on topical β adrenergic antagonists. Latanoprost was better tolerated than timolol-pilocarpine regarding side effects. These results indicate that a switch to latanoprost monotherapy can be attempted before combination therapy is initiated.

Autoradiographic characterization and localization of vasoactive intestinal peptide bindign sites in albino rat and rabbit eyes

Localization and pharmacological properties of vasoactive intestinal peptide (VIP) binding sites were investigated in eyes from albino rabbits and rats using an in vitro autoradiographic method. [125I]VIP was used as ligand, and various unlabelled peptides were studied to test the specificity of binding. Autoradiograms were generated by apposing 20-microns-thick cryostat eye sections to [3H]Hyperfilm or autoradiographic emulsion and quantified by means of image analysis procedures. Specific binding represented about 85% of total binding. Kinetic studies showed that equilibrium was reached after a 120-min incubation at room temperature. Biochemical investigations demonstrated that [125I-]VIP bound to a population of sites with high affinity (Kd = 2.27 +/- 0.25 nM). Inhibition of [125I]VIP binding with VIP and related peptides indicated the following rank order of potency: VIP greater than Peptide histidine isoleucine greater than secretin greater than human growth hormone-releasing factor, glucagon, VIP1-14, VIP14-28. In both species, specific binding was found in conjunctiva, iris, ciliary processes, choroid and retina. Moderate grain densities of VIP binding sites were also present in the rat cornea. Quantitative analysis of the autoradiograms revealed that the highest densities of [125I]VIP binding sites were located in the iris and ciliary epithelia in rabbits and in the inner retina in rats. Our findings suggest that VIP may play an important role in several ocular functions, especially in aqueous humor dynamics and retinal neuromodulation.

Cyclocoagulation of the Ciliary Bodies by High-Intensity Focused Ultrasound: A 12-Month Multicenter Study

PURPOSE To evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) cyclocoagulation in reducing intraocular pressure (IOP) in patients with refractory glaucoma by using a novel miniaturized delivery device (EyeOP1). METHODS We conducted a 12-month open-label multicenter prospective study (EyeMUST1 Study). Patients with primary (primary open-angle glaucoma [POAG]) or secondary refractory glaucoma were treated in two groups depending on the duration of each ultrasound shot (group 1: 4 seconds; group 2: 6 seconds). The primary efficacy outcome was based on IOP reduction at 6 and 12 months. RESULTS Fifty-two patients were enrolled: 36 (69%) had POAG and 16 (31%) had secondary glaucoma. Group 1 (n = 24) and group 2 (n = 28) had similar demographics and baseline characteristics. In group 1, IOP was reduced from a mean preoperative value of 29.7 ± 7.7 mm Hg (n = 3.5 glaucoma medications) to a mean postoperative value of 21.3 ± 6.7 mm Hg (n = 3.5 glaucoma medications) and 20.1 ± 6.7 mm Hg (n = 3.2 glaucoma medications) at 6 and 12 months, respectively. In group 2, IOP was reduced from a mean preoperative value of 29.0 ± 7.4 mm Hg (n = 3.3 glaucoma medications) to a mean postoperative value of 20.2 ± 7.4 mm Hg (n = 3.4 glaucoma medications) and 18.5 ± 6.6 mm Hg (n = 3.5 glaucoma medications) at 6 and 12 months, respectively. At 12 months, the IOP reduction was sustained in both groups (32% IOP reduction in group 1 and 36% IOP reduction in group 2). The overall tolerance of the technique was good, with no serious adverse events. CONCLUSIONS The new miniaturized HIFU EyeOP1 delivery device seems to be effective in decreasing IOP in patients with refractory glaucoma. The technology offers a good safety profile. (ClinicalTrials.gov number, NCT01338467.).

Measurement of treatment compliance using a medical device for glaucoma patients associated with intraocular pressure control: a survey.

Objective: To identify and characterize treatment compliance profiles of glaucoma patients and evaluate the association with intraocular pressure (IOP). Methods: A computerized device (Travalert®) that recorded daily instillation times and eye-drop counts was given for 3 months. Patients were declared compliant when at least 2 drops were instilled per day. Compliance rates were calculated for weekdays and weekends, separately, over 8 consecutive weeks. A principal components analysis (PCA) was followed by an ascendant hierarchical classification (AHC) to identify compliance groups. Results: 140 patients were recruited (mean age 65.5 years; 51.8% female) of whom 83.6% had primary open-angle glaucoma with mean IOP 23.9 mmHg before Travalert® use. 60.7% were treated with DuoTrav® (travoprost timolol fixed combination) and 39.3% with travoprost. The PCA identified two axes (compliance and treatment weeks). The AHC identified 3 compliance groups: ‘high’ (56.6%, approx. 80% compliance), ‘medium’ (21.2%, approx. 50% compliance), and ‘low’ (22.1%, approx. 20% compliance). Demographics and glaucoma parameters did not predict low compliance. Final mean IOP was 16.1 mmHg, but higher in the low compliance group (17.7 mmHg, P = 0.02). Conclusions: Compliance measurement by a medical device showed compliance rates <80% by 50% (approx.) of patients, significantly impacting IOP control. No demographic or glaucoma variable was associated with low compliance.