Glaucoma

NOVEMBRO/DEZEMBRO 2010

Nguyen JV, Soto I, Kim KY, Bushong EA, Oglesby E, Valiente-Soriano FJ, Yang Z, Davis CH, Bedont JL, Son JL, Wei JO, Buchman VL, Zack DJ, Vidal-Sanz M, Ellisman MH, Marsh-Armstrong N.

Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma.
Proc Natl Acad Sci U S A. 2011 Jan 5. [Epub ahead of print]

Abstract
Optic nerve head (ONH) astrocytes have been proposed to play both protective and deleterious roles in glaucoma. We now show that, within the postlaminar ONH myelination transition zone (MTZ), there are astrocytes that normally express Mac-2 (also known as Lgals3 or galectin-3), a gene typically expressed only in phagocytic cells. Surprisingly, even in healthy mice, MTZ and other ONH astrocytes constitutive internalize large axonal evulsions that contain whole organelles. In mouse glaucoma models, MTZ astrocytes further up-regulate Mac-2 expression. During glaucomatous degeneration, there are dystrophic processes in the retina and optic nerve, including the MTZ, which contain protease resistant γ-synuclein. The increased Mac-2 expression by MTZ astrocytes during glaucoma likely depends on this γ-synuclein, as mice lacking γ-synuclein fail to up-regulate Mac-2 at the MTZ after elevation of intraocular pressure. These results suggest the possibility that a newly discovered normal degradative pathway for axons might contribute to glaucomatous neurodegeneration.

Bell NP, Ramos JL, Feldman RM

Safety, tolerability, and efficacy of fixed combination therapy with dorzolamide hydrochloride 2% and timolol maleate 0.5% in glaucoma and ocular hypertension
Clinical Ophthalmology 2010:4 1331–1346

Abstract: Glaucoma is a collection of diseases characterized by multifactorial progressive changes leading to visual field loss and optic neuropathy most frequently due to elevated intraocular pressure (IOP). The goal of treatment is the lowering of the IOP to prevent additional optic nerve damage. Treatment usually begins with topical pharmacological agents as monotherapy, progresses to combination therapy with agents from up to 4 different classes of IOP-lowering medications, and then proceeds to laser or incisional surgical modalities for refractory cases.
The fixed combination therapy with the carbonic anhydrase inhibitor dorzolamide hydrochloride 2% and the beta blocker timolol maleate 0.5% is now available in a generic formulation for the treatment of patients who have not responded sufficiently to monotherapy with beta adrenergic blockers. In pre- and postmarketing clinical studies, the fixed combination dorzolamide–timolol has been shown to be safe and efficacious, and well tolerated by patients. The fixed combination dorzolamide–timolol is convenient for patients, reduces their dosing regimen with the goal of increasing their compliance, reduces the effects of “washout” when instilling multiple drops, and reduces the preservative burden by reducing the number of drops administered per day.
Keywords: dorzolamide, timolol, glaucoma, ocular hypertension, elevated IOP, fixed combination
therapy.

Birt CM, Buys YM, Ahmed II, Trope GE; Toronto Area Glaucoma Society.

Prostaglandin efficacy and safety study undertaken by race (the PRESSURE study).
Glaucoma 2010; 19 (7): 460-467.

PURPOSE: Latanoprost, travoprost, and bimatoprost are prostaglandin or prostamide-type ocular hypotensive medications, all of which are effective and safe for lowering intraocular pressure (IOP). Most studies with these types of drugs have included patients mainly from European or white ethnic backgrounds; however, some reports have suggested that there is a difference in response between patients of white and African racial heritage. On account of the possibility that drugs may act differently in people of different ethnic background, we decided to study the effectiveness and safety of all 3 drugs in people from various ethnic heritages. Our hypothesis was that there might be a possible ethnic-based difference in IOP-lowering effectiveness between the 3 medications.
METHOD: This was a prospective randomized investigator-masked multicenter study. Patients newly diagnosed with open-angle glaucoma (primary, pseudoexfoliative, or pigmentary), or whose pressure became elevated after a washout period, were randomized to receive 1 of 3 prostaglandin/prostamide drugs. Assignment of drug was balanced by racial group and study site, and the investigator was masked to the drug used. The patients were requested to self-identify their racial group as White, African, East Indian, Asian, or Hispanic; to minimize the possibility of heterogeneity, all 4 grandparents had to be known to originate from the same group. However, for purposes of analysis, the patients were divided into 2 groups--White or Other. Patients were followed at 2, 6, 12, and 24 weeks; IOP and local side effects were assessed at each visit.
RESULTS: Eighty-three patients were recruited from 9 sites. The mean age of the patients was 61.5 ± 10.5 years. There were no differences in mean age or the distribution of sex between the patients whether examined by the 2 racial groups or the 3 drug groups. There was a highly statistically significant decrease in IOP from baseline to 12 weeks and from baseline to 24 weeks (F = 439.3, P<0.0001; F = 305.94, P<0.0001). There were no differences in treatment effect between the 3 drugs or between the 2 ethnic groups, (P > 0.05 for all comparisons) and there was no interaction between race and drug.
CONCLUSIONS: All 3 prostaglandin/amide drugs are highly effective at lowering IOP. No differences in effect between the drugs or between members of different racial groups were detected, although the study sample size was too small to be certain to detect differences, if they existed.

Pépin JL, Chiquet C, Tamisier R, Lévy P, Almanjoumi A, Romanet JP.

Frequent loss of nyctohemeral rhythm of intraocular pressure restored by nCPAP treatment in patients with severe apnea.
Arch Ophthalmol 2010; 128 (10): 1257-1263.

OBJECTIVE: To assess 24-hour intraocular pressure (IOP) and ocular perfusion pressure rhythms in newly diagnosed apneic patients before and after nasal continuous positive airway pressure (nCPAP) treatment.

METHODS: Intraocular pressure (using a Tonopen XL) and ambulatory blood pressure, measured hourly for 24 hours, were analyzed in 18 consecutive patients with obstructive sleep apnea for nyctohemeral rhythmicity (cosinor model). Twelve of 18 patients were reassessed after nCPAP use.

RESULTS: Before treatment, 28% of the patients with obstructive sleep apnea demonstrated a nocturnal acrophase, 22% a diurnal acrophase, and 50% absence of 24-hour rhythm of IOP. The ocular perfusion pressure rhythm was nocturnal in 78% of cases and absent in 22%. Using nCPAP, the mean (standard error of the mean) nocturnal IOP increased from 14.8 (0.8) to 18.3 (1.2) mm Hg (P < .03). Among patients with initial abnormal IOP rhythm (ie, rhythm with diurnal acrophase or absence of rhythm), 67% shifted to a normal 24-hour IOP profile after treatment.

CONCLUSIONS: Normal IOP nyctohemeral rhythm is lost in most patients with severe apnea. Nasal continuous positive airway pressure use restored a normal 24-hour IOP profile in most cases.

SETEMBRO/OUTUBRO 2010

Naka M, Kanamori A, Negi A, Nakamura M.

Elevated intraocular pressure reduces aquaporin-9 expression in rat optic nerve head and retina.
Invest Ophthalmol Vis Sci. 2010 Mar 31. [Epub ahead of print]

Abstract
Purpose. To investigate the effect of chronically elevated intraocular pressure (IOP) on expression of water channel aquaporins (AQPs) 1, 4 and 9 in the optic nerve and retina in rats. Methods. Three episcleral veins were cauterized to elevate IOP in left eyes of Sprague-Dawley rats. IOPs were monitored with a TonoLab rebound tonometer. At two and four weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and de-sheathed optic nerves were subjected to gene expression analyses. Results. IOP was significantly increased after surgery up to 4 weeks (p=0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and 9 immunoreactivities, which were co-labeled for glial fibrillary acidic protein, but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 in Müller cell end feet, and AQP9 mainly in NeuN positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1. Conclusions. AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Since AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy.

Aihara M.
Clinical appraisal of tafluprost in the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension.
Clin Ophthalmol 2010; 24 (4): 163-70.

Abstract
An elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which causes progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the treatment of glaucoma. Tafluprost, a novel prostaglandin analogue, was recently launched onto the market as an ocular hypotensive agent. Tafluprost is potent in its affinity for the prostanoid FP receptor and in its intraocular lowering efficacy. Moreover, it enhances the ocular hemodynamics and has neuroprotective effects. Clinical studies have demonstrated its efficacy at decreasing intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Figus M, Fogagnolo P, Lazzeri S, Capizzi F, Romagnoli M, Canovetti A, Iester M, Ferreras A, Rossetti L, Nardi M.
Treatment of allergic conjunctivitis: results of a 1-month, single-masked randomized study.
Eur J Ophthalmol 2010; 20 (5): 811-818.

Abstract
PURPOSE: To compare the effects of topical antiallergic eyedrops in relieving the signs and symptoms of patients with allergic conjunctival pathology.

METHODS: In this multicenter, single-masked, randomized study, 240 patients with signs and symptoms of allergic conjunctivitis were randomized to receive 1 of the following 8 treatments twice daily: cromolyn sodium/chlorpheniramine maleate, diclofenac, epinastine, fluorometholone, ketotifen, levocabastine, naphazoline/antazoline, and olopatadine. Clinical signs and symptoms were evaluated by a masked operator using a 10-point scale at the moment of enrollment (day 0) and at weeks 1, 2, and 4. The percentage of patients achieving at least a small (at least 50% reduction of the total scale score) or a good (at least 75%) improvement of signs and symptoms was calculated at each visit. Tolerability was also evaluated as the duration of discomfort after instillation.

RESULTS: All drugs gave some improvement in symptoms in more than 85% of cases. Epinastine and olopatadine obtained at least a good relief of symptoms in 37% and 33% of cases at week 1. At the end of the study, good improvement of symptoms was obtained in at least 70% of patients by epinastine, ketotifen, fluorometholone, and olopatadine, whereas a 75% improvement for signs was obtained only by fluorometholone and ketotifen. Naphazoline/antazoline induced higher discomfort compared to the other study treatments (p<0.0001).

CONCLUSIONS: The efficacy of epinastine, ketotifen, and olopatadine in the treatment of allergic conjunctivitis was comparable to fluorometholone. Naphazoline/antazoline had lower tolerability than the other study treatments.

Johnson TV, Fan S, Zhan G, Camras CB, Toris CB.

Efficacy and mechanisms of intraocular pressure reduction with latanoprost and timolol in par-ticipants with ocular hypertension: a comparison of 1 and 6 weeks of treatment.
J Glaucoma 2010; 19 (6): 356-364.

PURPOSE: To investigate whether the intraocular pressure (IOP) reduction and mechanism of action of timolol and latanoprost change between 1 and 6 weeks of treatment.
PATIENTS AND METHODS: Thirty participants on no ocular medications completed this double-masked, 6-visit, crossover study. At each visit IOP was determined by pneumatonometry, aqueous flow by fluorophotometry, and outflow facility by fluorophotometry and tonography. Separate values of uveoscleral outflow were calculated using the Goldmann equation, an episcleral venous pressure of 11 mm Hg, and each of the 2 outflow facility values. In a randomized fashion, both eyes were treated for 6 weeks with latanoprost 0.005% once daily or timolol 0.5% twice daily. Measurements were re-peated at 1 and 6 weeks of dosing. After 6 weeks of washout, the second drug was administered in a crossover manner. One and 6 weeks of treatment were compared with appropriate baselines using 1-way analyses of variance (ANOVA).
RESULTS: Timolol reduced aqueous flow by 27% at week 1 (P<0.001) and 16% at week 6 (P=0.03). Latanoprost increased uveoscleral outflow several fold at each visit (P<0.05). Neither drug altered out-flow facility. Neither drug showed a detectable change in aqueous humor dynamics at week 6 compa-red with week 1. Both drugs significantly (P<0.001) reduced IOP at 1 and 6 weeks of treatment.

CONCLUSIONS: Timolol and latanoprost significantly reduce IOP by different mechanisms. Timolol reduces aqueous flow whereas latanoprost increases uveoscleral outflow. Continued treatment with timolol or latanoprost for 6 weeks did not alter effects on aqueous humor dynamics. Outflow facility changes sometimes reported with prostaglandin analogues were not detected in this study.

Twa MD, Roberts CJ, Karol HJ, Mahmoud AM, Weber PA, Small RH.
Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.
J Glaucoma 2010; 19 (6): 382-390.

PURPOSE: To evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP).
METHODS: Repeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tono-meter: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated.
RESULTS: The sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to greater HH measu-rement variability.
CONCLUSIONS: The CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

JUNHO/JULHO/AGOSTO 2010

Kobelt G, Texier-Richard B; Buchholz P; Bron A; Renard JP; Rouland JF; Nordmann, JP.

Treatment of Glaucoma in Clinical Practice: Four-year Results From a Patient Registry in France
J Glaucoma 2010; 19 (3): 199-206.

Purpose: To investigate long-term resource consumption and clinical outcome of patients with early primary open-angle glaucoma or ocular hypertension treated with prostaglandins in clinical practice in France.
Methods: Thirty-four geographically spread specialized hospitals and private practices enrolled conse-cutive patients receiving, for the first time, a prostaglandin, alone or in combination. The study was based on routine practice and no consultations, examinations, or treatments were mandated by the pro-tocol. Treating physicians recorded each consultation, including all examinations performed, referrals, admissions, and prescriptions. Descriptive analysis of resource consumption and development of in-traocular pressure (IOP) and visual fields was performed, for all patients who completed the 4-year follow-up.
Results: The study enrolled 602 patients and 78% completed 4-year follow-up. Mean age was 65 years and mean time since diagnosis was 4 years. Mean IOP was reduced from a baseline of 21.2 mm Hg to 16.5 mm Hg during the first year and remained stable throughout the study. Mean visual fields at base-line were −4.2 mean deviation and stable during the follow-up. Total mean health care costs per patient were €1947, of which medication represented 50%. Over half of the patients (52%) remained on their initial medication during the 4 years. Drug changes were mostly because of inadequate IOP control and the number of treatment switches was significantly related to costs.
Conclusions: This is the first prospective study of treatment with prostaglandins in clinical practice. The results indicate that many patients with early glaucoma managed primarily with prostaglandins will show very little progression over 4 years. Compared with the mid-90s, costs have not increased despite the higher acquisition cost of prostaglandins, as surgical interventions and medical consultations have decreased.

Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC.

Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications.
Cornea 2010; 29 (6): 618-621.

PURPOSE: To determine the prevalence of ocular surface disease (OSD) in patients with glaucoma using topical intraocular pressure (IOP)-lowering therapy. METHODS: This prospective observational study enrolled patients with primary open-angle glaucoma or ocular hypertension who were on a topi-cal IOP-lowering medication regimen. Enrolled patients completed the ocular surface disease index (OSDI) and OSDI scores (0-100, with 0 representing no symptoms) were calculated for each patient. Medical history, demographics, and concomitant medication information were also collected. RE-SULTS: Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms. OSDI scores were significantly different between patients with and without a prior diagnosis of dry eye syndrome (25.2 +/- 15.4 vs 15.4 +/- 15.8, respectively; P = 0.0036) and between patients who did and did not use artificial tears at the time of study participation (23.0 +/- 15.6 vs 15.3 +/- 15.8, respectively; P = 0.0046). Mean OSDI scores varied significantly with the number of topical IOP-lowering medications used, with higher (more severe) OSDI scores in patients using multiple IOP-lowering medications. Specifically, patients on a single medication had a mean OSDI score of 12.9 +/- 13.1, which was significantly lower than those of patients on 2 (16.7 +/- 17.0; P = 0.007) or 3 medications (19.4 +/- 18.1; P = 0.0001). CONCLUSIONS: OSD is prevalent among medically treated patients with glaucoma. The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.

Tanna AP, Rademaker AW, Stewart WC, Feldman RM.

Meta-analysis of the efficacy and safety of alpha2-adrenergic agonists, beta-adrenergic antago-nists, and topical carbonic anhydrase inhibitors with prostaglandin analogs.
Arch Ophthalmol 2010; 128 (7): 825-833.

OBJECTIVE: To perform a meta-analysis to estimate the intraocular pressure (IOP)-lowering efficacy and safety of alpha(2)-adrenergic agonists (AAs), beta-adrenergic antagonists (BBs), and topical car-bonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA). METHODS: MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that re-ported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combina-tion therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test. RESULTS: Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group. CON-CLUSIONS: All 3 classes are similarly effective in lowering mean diurnal IOP when used in combina-tion with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.

Bailly D.
Pour mieux suivre le taux de progression du glaucome.
Basse Vision Infos 2010; 42: 12-13.

La société Allergan entame lA sixième saison de ses programmes Progress (PROgramme pour Gestion Rigoureuse et un Suivi Sérieux du glaucome).
Le programme 2010, qui s’intitule Progress Progression II, propose une mise au point sur la progression de l’atteinte structurale et de l’atteinte fonctionnelle du glaucome, ainsi que la présentation d’un nouveau logiciel simple et pratique permettant de la calculer.

Benoit A.

De nouveaux facteurs de risque pour le glaucome.
Basse Vision Infos 2010; 42: 28-29.

A l’occasion du congrès de la Société Française d’Ophtalmologie (SFO), le Pr Jean-Paul Renard, chef du service d’ophtalmologie à l’hôpital du Val de Grâce à Paris, a dévoilé les résultats de l’étude Pho-toGRAF. Celle-ci s’est attachée à déterminer les facteurs de risque de développer un glaucome chez les patients atteints d’une hypertonie intraoculaire. Parmi eux : l’hypercholestérolémie, un faible apport en précurseurs des acides gras oméga-3 et une catégorie socioprofessionnelle, celle des agriculteurs.

Sellem E.
Intérêt d’une bithérapie fixe dans le glaucome.
Basse Vision Infos 2010; 42: 30-31.

L’efficacité d’une seule molécule anti-glaucomateuse est souvent insuffisante pour atteindre la pres-sion-cible, c'est-à-dire la pression intraoculaire théorique, et très individuelle, à partir et en-deçà de laquelle l’ophtalmologiste peut espérer stabiliser le glaucome chez un patient donné. C’est une des raisons qui expliquent le succès des combinaisons fixes, devenues rapidement des traitements large-ment prescrits contre le glaucome depuis leur commercialisation au début des années 2000. A la fré-quente nécessité d’une plurithérapie, les combinaisons fixes présentent des avantages non contestables : efficacité, tolérance et diminution du nombre d’instillations imposées aux patients.

Nordmann JP, Baudouin C, Renard JP, Denis P, Lafuma A, Laurendeau C, Jeanbat V, Berdeau G
Measurement of treatment compliance using a medical device for glaucoma patients associated with intraocular pressure control: a survey.
Clinical Ophthalmology 2010; 4: 731–739.

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.
Keywords: glaucoma, compliance, efficacy, intraocular pressure control

Aptel F, Denis P.
Les clés d’une bonne observance.
Réalités Ophtalmol 2010; 174: 17-21.

De façon similaire à la plupart des pathologies chroniques cardio-vasculaires ou métaboliques, l’observance des patients glaucomateux aux traitements médicaux hypotonisants est un élément clé du succès de la prise en charge de leur pathologie.
De nombreuses études aux méthodologies diverses s’accordent pour montrer que l’observance des patients glaucomateux est très souvent médiocre, aussi bien en termes de respect des prescriptions (doses, horaires, précautions, etc…) que de qualité d’instillation des collyres ou de poursuite du traitement à moyen ou long terme. La compréhension des différents facteurs pouvant motiver un patient à prendre ou à ne pas prendre un traitement correctement et l’identification des patients à risque de mauvaise observance devraient conduire à la mise en place d’actions visant à réduire ces obstacles et à aider à la prise de conscience par le patient des enjeux du traitement.

Karmel M.
Surprising new treatment for glaucoma: Get the drops in the eye.
EyeNet 2010; 14 (4): 27-28.

Wester ST, Lee WW, Shi W.
Eyelash growth from application of bimatoprost in gel suspension to the base of the eyelashes.
Ophthalmology 2010; 117 (5): 1024-1031.

OBJECTIVE: To determine whether bimatoprost (Lumigan, Allergan Inc., Irvine, CA) causes increa-sed lash length when used in gel suspension applied to the base of the eyelashes. DESIGN: Randomi-zed controlled trial. PARTICIPANTS: Nineteen subjects were enrolled. METHODS: Subjects recrui-ted from the Bascom Palmer Eye Institute were screened, and those who met inclusion criteria were enrolled. Each participant received 2 vials of gel suspension, which contained bimatoprost and normal saline, respectively, each mixed 1:1 with Gonak gel (Akorn Inc., Lake Forest, IL) and labeled "right eye" and "left eye" according to randomization. The suspension was applied to the upper eyelid eye-lashes every evening on the designated eye for 6 weeks. MAIN OUTCOME MEASURES: Lash length was measured with a caliper at enrollment, at weekly intervals during the application of the gel, and at 1 and 3 months after discontinuation of its use. Visual acuity, ocular symptoms, intraocular pressure, and photographs were documented at these same intervals. RESULTS: The mean eyelash growth from baseline in the bimatoprost group was 2.0 mm versus a mean of 1.1 mm in the placebo group, which was a statistically significant difference (P=0.009). The average intraocular pressure decreased equally in both groups (2 mmHg). No change in visual acuity or iris discoloration was noted in any of the subjects. CONCLUSIONS: Our data showed an increase in eyelash length with the use of bimatoprost in gel suspension, suggesting the product's eyelash-lengthening properties. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Glaucome : de nouvelles perspectives de prise en charge grâce à la 1ère enquête française sur les facteurs de risques prédictifs (étude PhotoGRAF)

Réflexions Ophtalmol 2010; 15 (136): 65.

ABRIL/MAIO 2010

Katz LJ, Cohen JS, Batoosingh AL, Felix C, Shu V, Schiffman RM.
Twelve-month, randomized, controlled trial of bimatoprost 0.01%, 0.0125%, and 0.03% in patients with glaucoma or ocular hypertension.
Am J Ophthalmol 2010; 149 (4): 661-671.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of ophthalmic formulations of bimatoprost 0.01% and 0.0125% compared with bimatoprost 0.03%. DESIGN: Prospective, randomized, double-masked, multicenter clinical trial. METHODS: Patients with glaucoma or ocular hypertension were randomized to receive once-daily bimatoprost 0.01% (n = 186), bimatoprost 0.0125% (n = 188), or bimatoprost 0.03% (n = 187) for 12 months. The primary efficacy measure was IOP. Safety measures included adverse events and an objective assessment of conjunctival hyperemia. RESULTS: Baseline mean IOPs were similar among treatment groups. Differences in mean IOP between the bimatoprost 0.01% or 0.0125% groups and the bimatoprost 0.03% group were less than 0.9 mm Hg throughout follow-up. Bimatoprost 0.01%, but not bimatoprost 0.0125%, was equivalent in efficacy to bimatoprost 0.03% based on predetermined criteria (limits of the 95% confidence interval of the between-group difference in mean IOP within +/- 1.5 mm Hg at all time points and within +/- 1 mm Hg at most time points). The overall incidence of treatment-related adverse events was reduced significantly in the bimatoprost 0.01% and bimatoprost 0.0125% groups compared with the bimatoprost 0.03% group (P < or = .034). The percentage of patients with a moderate to severe increase from the baseline macroscopic hyperemia score was: bimatoprost 0.01%, 3.2%; bimatoprost 0.0125%, 9.0%; bimatoprost 0.03%, 9.1% (P = .019 for bimatoprost 0.01% vs 0.03%). CONCLUSIONS: Bimatoprost 0.01% was equivalent to bimatoprost 0.03% in lowering IOP throughout 12 months of treatment and demonstrated improved tolerability, including less frequent and severe conjunctival hyperemia. Bimatoprost 0.01% demonstrated a better benefit-to-risk ratio than bimatoprost 0.0125%. Copyright 2010 Elsevier Inc. All rights reserved.

MARÇO 2010

Panteleontidis V, Detorakis ET, Pallikaris IG, Tsilimbaris MK;

Latanoprost-Dependent Cystoid Macular Edema Following Uncomplicated Cataract Surgery in Pseudoexfoliative Eyes;
Ophthalmic Surg Lasers Imaging 2010: 1-5.

Cystoid macular edema (CME) following uncomplicated phacoemulcification associated with latanoprost is uncommon. OCT-proven CME associated with latanoprost in 3 eyes with pseudoexfoliation after uncomplicated phacoemulcification was reported. Latanoprost was discontinued whereas topical ketorolac was administered. In all cases, CME resolved completely within the following weeks. In one case the re-administration of latanoprost lead to CME recurrence, which was treated with permanent discontinuation of latanoprost. The correlation between latanoprost and CME and the complete resolution of CME following discontinuation of the drug suggest a causative association between latanoprost and CME.

Table ronde glaucome : Rouland UF, Payan J, Flores D, Diaz JL, Defreyn A, Baron P, Gracies H, Pellat B, Deriot JB, Conan S, Gabisson P, Cousin P, Chanseaume S.

Faut-il encore prescrire des bêtabloquants ?

Réalités Ophtalmol 2009; 168: 29-30.

FEVEREIRO 2010

Nordmann JP, Baudouin C, Bron A, Denis P, Rouland JF, Sellem E, Renard JP.

Xal-Ease: impact of an ocular hypotensive delivery device on ease of eyedrop administration, patient compliance, and satisfaction.
Eur J Ophthalmol 2009; 19 (6): 949-956.

PURPOSE: To measure the impact of the Xal-Ease delivery device on ease of eyedrop administration and on treatment compliance and satisfaction. METHODS: This prospective, multicenter, randomized, comparative, crossover study was conducted at 43 sites in France. Eligible subjects were >18 years of age, were diagnosed with primary open-angle glaucoma or ocular hypertension, had been treated with latanoprost or fixed-combination latanoprost/timolol for >or=3 months prior to enrollment, and did not require a therapy change. Subjects used either Xal-Ease or the dropper bottle for 4 weeks and then switched to the alternate delivery method for the next 4 weeks. Subjects completed questionnaires after 1 and 4 weeks in each treatment period. RESULTS: In all, 211 subjects were enrolled, 107 to the Xal-Ease/dropper bottle group and 104 to the dropper bottle/Xal-Ease group. Baseline demographic and ocular characteristics were similar. Use of Xal-Ease made it significantly less likely that the subject would need someone to help with drop instillation (6.9% vs 18.1%, respectively; p<0.001) and reduced the problem of the tip of the bottle touching the eye (3.2% vs 35.6%, respectively; p<0.001). Reported compliance rates were very high and similar across groups during both treatment periods. After 1 month of use during both treatment periods, more than 70% of subjects reported global satisfaction with Xal-Ease to their physicians. No adverse events associated with the use of Xal-Ease were noted. CONCLUSIONS: Xal-Ease generally makes administration of latanoprost or fixed-combination la-tanoprost/timolol easier compared with the dropper bottle.

Rolando M, Geerling G, Dua HS, Benítez-del-Castillo JM, Creuzot-Garcher C.

Emerging treatment paradigms of ocular surface disease: proceedings of the Ocular Surface Workshop. Br J Ophthalmol 2010; 94 (Suppl 1): 1-9.

The objective of the Ocular Surface Workshop in Rome, Italy, on 6 February 2009, was to enhance the understanding of ocular surface disease (OSD) through an exploration of the nature of its complexities and current treatment paradigms across Europe. It was hoped that the peer-to-peer discussions and updates regarding common knowledge, clinical practices and shared experiences at this workshop would subsequently shape future treatment approaches to OSD.

JANEIRO 2010

Cheng JW, Cai JP, Li Y, Wei RL.

A meta-analysis of topical prostaglandin analogs in the treatment of chronic angle-closure glau-coma.
J Glaucoma 2009; 18 (9): 652-657.

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering efficacy of prostaglandin analogs topical medications in patients with chronic angle-closure glaucoma (CACG). METHODS: Pertinent publications were identified through systematic searches of PubMed, EMBASE, KoreaMed, Chinese Biomedicine Database, and the Cochrane-Controlled Trials Register. Randomized clinical trials in-volving CACG patients treated with latanoprost, bimatoprost, or travoprost monotherapy were se-lected. Methodologic quality was assessed by a Delphi list with additions and scored out of a maxi-mum of 18. The outcome measures were absolute and relative reduction in IOP from baseline, for di-urnal curve, peak, and trough. The pooled effects were calculated using 2-step DerSimonian and Laird estimate method of the random effects model. RESULTS: Nine randomized clinical trials enrolling a total of 1,090 patients were included in the meta-analysis. Quality scores of included studies were gen-erally high, a mean of 14.9 (range, 12-18). The difference in absolute IOP reduction between pros-taglandin analogs and timolol varied from 0.4 to 1.6 mm Hg at diurnal curve, 0.9 to 2.3 mm Hg at peak, and 1.3 to 2.4 mm Hg at trough. Relative IOP reduction were diurnal curve, 31% (95% confi-dence interval, 27% to 34%), peak, 34% (31% to 37%), and trough 31% (28% to 35%) for latanoprost; diurnal curve, 26% (21% to 30%), peak, 28% (24% to 32%), and trough 27% (23% to 30%) for bima-toprost; diurnal curve, 28% (20% to 36%), peak, 32% (31% to 34%), and trough 31% (29% to 33%) for travoprost; and diurnal curve, 23% (19% to 27%), peak, 24% (20% to 29%), and trough 21% (19% to 24%) for timolol. CONCLUSIONS: Latanoprost, travoprost, and bimatoprost provide significant IOP-lowering efficacy in eyes with CACG; and the 3 prostaglandin analogs are associated with at least as effective as timolol.

Ozdemir G, Tolun FI, Gul M, Imrek S.

Retinal oxidative stress induced by intraocular hypertension in rats may be ameliorated by bri-monidine treatment and N-acetyl cysteine supplementation.
J Glaucoma 2009; 18 (9): 662-665.

PURPOSE: To investigate the effect of brimonidine and N-acetyl cysteine (NAC) on retinal oxidative status under ocular hypertension. MATERIALS AND METHODS: Ocular hypertension is produced in right eyes of 60 rats through intraocular injection of sodium hyaluronate. The left eyes received intracameral saline as sham. Twenty right eyes (brimonidine group) received topical brimonidine twice a day for a week. Other 20 eyes received intraperitoneal NAC (NAC group) once a day. Another group of 20 eyes were followed without any drugs but only intracameral sodium hyaluronate (sodium hyaluronate group) into right eyes. RESULTS: Intraocular injection of sodium hyaluronate increased intraocular pressure for a week and caused retinal peroxidation and decreased glutathione peroxidase and catalase levels. Brimonidine and NAC treatment reversed the retinal oxidative stress created by high intraocular pressure. CONCLUSIONS: Brimonidine and NAC supplementation provide antioxidative properties to retina and decrease retinal damage induced by ocular hypertension.

Table ronde glaucome : Rouland UF, Payan J, Flores D, Diaz JL, Defreyn A, Baron P, Gracies H, Pel-lat B, Deriot JB, Conan S, Gabisson P, Cousin P, Chanseaume S.

Faut-il encore prescrire des bêtabloquants ?
Réalités Ophtalmol 2009; 168: 29-30.

Anderson L, Lockwood AJ, Goverdhan S, Wormald R, Kirwan JF.
Cost effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandina-via and the United Kingdom using a decision-analytic health economic model.
Eye (Lond) 2009; 23 (12): 2264; author reply 2264.

C'est le commentaire et la réponse à l'auteur de l'article ci-dessous.

Stewart WC, Stewart JA, Mychaskiw MA.
Cost-effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandina-via and the United Kingdom, using a decision-analytic health economic model.
Eye (Lond) 2009; 23 (1): 132-140.

PURPOSE: To assess the cost-effectiveness of latanoprost or timolol in glaucoma treatment in Nor-way, Sweden, Denmark (Scandinavia) and the United Kingdom (UK). METHODS: A Markov model was constructed to perform a cost-effectiveness analysis. Health states were 'stable' and 'progressed' glaucoma, and transition probabilities for both primary open-angle and exfoliation glaucoma were de-rived from the medical literature. Practice patterns were obtained from surveys completed by 54 oph-thalmologists geographically dispersed throughout each country. Country specific unit costs were used for medications, patient visits, diagnostics, and therapeutic procedures. RESULTS: Over the life of the model latanoprost was less expensive than timolol by 5.3-7.6% (Scandinavia) and 2.1% (UK). Follow-ing adjustments, therapy in the original timolol-treated cohort was slightly more effective in each country with a difference in 0.003-0.015 years to progression of glaucoma existing between latano-prost. This may have resulted from the model design, which reflected that physicians ultimately control most patients' glaucoma over 5 years by adding or changing therapy. The associated incremental cost-effectiveness ratios for latanoprost vs timolol generated by the Scandinavian and the UK models, respectively, were: Norway 351,396 NOK; Sweden 988,985 SEK; Denmark 351,641; and the UK 4751 GBP. CONCLUSIONS: Over 5 years, in the UK timolol is the cost-effective option, whereas in Scandinavia latanoprost may be the cost-effective alternative to timolol.

Schmier JK, Covert DW

Characteristics of respondents with glaucoma and dry eye in a national panel survey
Clin Ophthalmol 2009; 3: 645-650.

BACKGROUND: There is an increasing body of evidence strongly suggesting that glaucoma medica-tions may contribute to ocular surface disease and development of dry eye. OBJECTIVE: To identify glaucoma patients with dry eye, using a nationally representative sample, and to compare clinical and treatment characteristics with controls without dry eye. METHODS: Patients taking intraocular pres-sure-lowering medications were identified from the Medical Expenditure Panel Survey. A matched cohort without glaucoma served as controls. Dry eye was identified by diagnosis or use of prescription or over-the-counter medications. Demographic and clinical characteristics and medication use patterns were compared. RESULTS: The analysis identified 629 respondents with glaucoma and 6,934 controls without glaucoma. Dry eye was more common among glaucoma respondents than nonglaucoma con-trols (16.5% vs 5.6%, P < 0.0001). There was a nonsignificant trend for respondents with dry eye to report higher rates of glaucoma adjunctive therapy use compared to those without dry eye (44.2% vs 35.0%, P < 0.076). Prostaglandin analogs were the most common glaucoma medication. CONCLU-SIONS: This analysis found that the rate of dry eye was higher in patients with glaucoma than in con-trols. The use of glaucoma adjunctive therapies may increase the rate of dry eye in glaucoma patients.

Stewart WC, Stewart JA, Mychaskiw MA.

Cost-effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandina-via and the United Kingdom, using a decision-analytic health economic model.
Eye (Lond) 2009; 23 (1): 132-140.

Lamirel C.

En direct de l'AAO 2009. Glaucome : « What's new, what's true ? »
Cahiers Ophtalmol 2009; 135: 8-9.

Quoi de neuf en sciences fondamentales ?
- pourquoi le nerf optique meurt-il ?
- pourquoi la pression intraoculaire est-elle élevée ?

La progression du glaucome en 2009
- examen de la papille
- CV et tendance évolutive
- hémorragies de la papille et progression du glaucome : cause ou effet ?

Améliorer la compliance des patients et leur habilité à instiller les collyres
- l'âge n'y fait rien
- un réservoir implanté

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