[Assessment of a pupillometric method for the screening of glaucoma]. / Évaluation d'une méthode pupillométrique pour la détection du glaucome.

BACKGROUND: Glaucoma is a progressive optic neuropathy, remaining asymptomatic for a long time, which makes its early diagnosis difficult. Visual field testing is still the gold standard but is less than ideal. The goal of this study is to assess a pupillometric test, administered passively to the subject for one minute, to measure its sensitivity and specificity in the classification of healthy eyes and glaucomatous eyes, and to evaluate its tolerability compared to visual field testing. METHODS: Forty-five participants were included in this single-center, interventional, prospective study. They underwent 3 monocular pupillometric tests with light stimulation: 6 pupillary responses were recorded during full-field multifocal stimulation (performed twice) and pupillary hippus cycle study. RESULTS: Analysis of spectral power and pupillary measurements with full-field multifocal stimulation provides a 0.94 sensitivity and a 0.88 specificity, a virtually perfect discrimination for early stages of glaucoma. Analysis of pupil cycle time provides a 0.92 sensitivity and a 0.88 specificity for early stages. Acceptability of this test by patients is superior to visual field testing. CONCLUSION: These results show that data from our pupillometric recordings provide a good classification of healthy and glaucomatous eyes and must be confirmed on a larger population.

Posterior segment Intra-Ocular Implant (IOL) dislocation: Predisposing factors, surgical management, outcome analysis.

PURPOSE: To evaluate the predisposing factors, management and visual prognosis of intraocular Lens (IOL) dislocation into the posterior segment. METHODS: The cases of posterior IOL dislocation from January 2012 to May 2017 at 2 centers were reviewed. Only eyes with dislocations requiring IOL explantation or repositioning were included. Predisposing factors, interval between cataract surgery and IOL dislocation, circumstances of onset, management, and postoperative complications are reported. RESULTS: 72 eyes of 72 patients were included. The mean age was 67.6 years. 47 patients (68%) were men. The mean time interval from cataract surgery to IOL dislocation was significantly shorter in the out-of-the bag group than the in-the-bag IOL dislocation group (3.8 months vs 132 months, P=0.002). Predisposing factors for out-of-the-bag IOL dislocation were mainly capsular rupture and/or zonular dehiscence (83%) after complicated cataract surgery. The predisposing factors for in-the-bag IOL dislocation were high myopia (40%), pseudoexfoliation syndrome (40%), previous vitrectomy (38%), or Marfan syndrome (3%) with uneventful cataract surgery. The type of luxated implant was mainly a 3-piece foldable IOL (50%), followed by foldable one-piece IOL (28%) and a rigid one-piece IOL (17%). Most cases of posterior chamber IOL dislocation occurred spontaneously (80%) without a trigger event. Management consisted of a posterior approach in 24 cases (33%) or an anterior approach in 48 cases (67%), associated with IOL repositioning in 20 eyes (28%), and IOL replacement in 34 eyes (47%). Finally, 18 eyes (25%) were left aphakic. Postoperative complications occurred in 7 cases (9.7%). CONCLUSIONS: Predisposing factors and time from cataract surgery to IOL dislocation were different for out-of-the bag versus in-the-bag IOL dislocation. Management of IOL dislocation varied considerably, depending on surgeon preference and experience. Surgery for IOL dislocation significantly improved best corrected visual acuity and was associated with a low complication rate.

Comparison of a non-preserved 0.1% T-Gel eye gel (single dose unit) with a preserved 0.1% T-Gel eye gel (multidose) in ocular hypertension and glaucomatous patients.

AIM: This comparative, open design, phase III study was to assess the non-inferiority of the non-preserved T-Gel 0.1% single dose unit (SDU) versus its preserved multidose (MD) reference. METHODS: 175 patients with bilateral POAG or OHT were randomised: 87 patients were to receive one drop daily of T-Gel 0.1% MD and 88 patients were to receive one drop daily of T-Gel 0.1% SDU, for a treatment period of 12 weeks. The primary efficacy variable was the change in intraocular pressure (IOP) in the worse eye between the baseline and the last assessment. Subjective and objective ocular signs as well as adverse events were recorded for safety. Global tolerance was assessed by the investigator and by the patient. RESULTS: The mean percentage reduction from baseline IOP was 24% for both treatments groups, which was consistent with previous studies. The safety results were comparable in both treatment groups. Because of gel formulation, mild short lasting episodes of blurred vision occurred for about 20% of patients. The global tolerance assessment reported that both treatments were well tolerated. CONCLUSION: The overall study results demonstrated that T-Gel 0.1% SDU is not inferior to T-Gel 0.1% MD.

Naturalistic, prospective study of glaucoma and ocular hypertension treatment in France: Strategies, clinical outcomes, and costs at 2 years.

PURPOSE: To prospectively observe second-line treatment strategies, their clinical outcomes, and treatment costs in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) in France. METHODS: Second-line patients were recruited from September 14, 1998, to December 20, 2000, in 37 centers and were followed for up to 2 years. Outcomes were numbers of and reasons for treatment changes, changes in clinical parameters (intraocular pressure (IOP) levels, visual field defects, and optic nerve excavation), and direct medical costs associated with glaucoma management. This article reports results of the final analysis of 2-year follow-up data for patients with at least two contacts with a study ophthalmologist. RESULTS: Data were analyzed for 346 patients and 672 treated eyes. Monotherapy was used as first-line therapy in 92.0% of eyes. Second-line treatment was initiated an average of 2.8+/-0.2 years after diagnosis, primarily due to insufficient IOP control (60.3%) and adverse drug reactions (18.3%). Relative risk (RR) (95% CI) for adverse drug reactions (ADR) under monotherapy was 1.00 (1.00-1.00) under beta blockers (n = 116) versus 0.40 (0.16-0.64) under latanoprost (n = 21), 2.30 under carbonic anhydrase inhibitors (n = 29), and 2.90 under adrenergics (n = 38); RR for ADR under combination therapy was 1.00 (1.00-1.00) for unfixed combinations without latanoprost (n = 66) versus 0.11 (0.00-0.22) for unfixed combinations of latanoprost + timolol (n = 3). Cardiac or pulmonary problems have been reported in 26.9% of patients. Persistency on initial therapy was 62.5% (95% CI 53.0-72.0) for latanoprost monotherapy versus 41.1% (34.8-47.4) for beta-blocker monotherapy and 43.6% (26.6-60.6) for the latanoprost + timolol combination versus 29.8% (15.2-44.4) for combination therapies that did not include latanoprost. Average daily cost for latanoprost monotherapy was similar to that for patients who failed beta-blocker monotherapy: latanoprost + timolol did not cost more than therapeutic combinations without latanoprost. CONCLUSIONS: Insufficient IOP control and adverse drug reactions are the two main reasons for changing first-line treatment in patients with POAG or OH. After 2 years, second-line treatment with latanoprost, as monotherapy or combined with timolol, provides superior safety and persistency to treatment at an acceptable cost.

[Hypothesis on the role of nutritional factors in ocular hypertension and glaucoma]. / Hypothèses sur le rôle des facteurs nutritionnels au cours des hypertonies oculaires et du glaucome.

Recent notions in connection with oxidative stress and the fat balance of long chain polyunsaturated fatty acids (PUFA) families have brought new insight to a probable role of nutritional factors in glaucoma and intraocular hypertony. The modifications of the extracellular matrix of the trabecula could be influenced by oxidative stress. On the one hand, collagen apoptosis and remodeling (associated with an increase in intraocular pressure) are mainly influenced by hydrosoluble antioxidants such as glutathione. On the other hand, elastin apoptosis and remodeling (correlated with the occurrence of optic atrophy) are particularly influenced by liposoluble antioxidants such as vitamin E. In addition, the dietary ratio of omega3/omega6PUFA intake could influence the balance of intraocular pressure. Omega-3 PUFA could influence cyclooxygenase competition. A diet with increased omega-3 and decreased omega-6 could thus favor an increase in intraocular pressure reducing synthesis of PG-F2, leading to a decrease in uveoscleral outflow. The true importance of these factors has not yet been solidly determined and studies are in progress to clarify the real implication of these nutritional factors.

[Vitreous hemorrhage in a neonate with galactosemia. A case report]. / Hémorragie intra-vitréenne du nouveau-né et galactosémie. A propos d'un cas.

Galactosemia is an inherited metabolic disorder due to a defect in one of the three enzymes required to fully metabolize the galactose in glucose: the galactose 1-phosphate uridyltransferase. Because this enzyme is present in the normal foetal liver since the tenth week of gestation, its defect cause congenital abnormality due to galactose accumulation, when the mother had taken milk during the pregnancy. It is mainly a liver pathology whereas the foetal cataract is rare. This latter is usually considered as the sole ophthalmic consequence of this disorder but exceptional ocular haemorrhages have also been described. We report the case of a neonate with galactosemia free from foetal cataract but presenting an unilateral vitreous haemorrhage. Retinal anomalies seen after vitrectomy are probably the source of the vitreous blood favoured by the coagulopathy associated with the neonatal disease. The causes of infant vitreous haemorrhages are often debated and their complications, especially severe amblyopia, require vitrectomy within the month following their discovery. In galactosemia, vitreous haemorrhage can be prevented by an early diagnosis and an appropriate treatment of the liver pathology.

[Clinical pilot study to evaluate the efficacy of a preservative-free hypertonic ophthalmic solution for patients with symptomatic corneal edema]. / Étude clinique pilote évaluant l'efficacité d'une solution ophtalmique hyperosmolaire sans conservateur chez des patients présentant un œdème cornéen symptomatique.

This exploratory clinical trial aims to assess the effect on visual acuity and central corneal thickness of an unpreserved hypertonic ophthalmic solution containing sodium chloride (5%) and sodium hyaluronate, in patients with chronic corneal edema caused by endothelial disease reducing their visual acuity. Twenty patients were enrolled and treated with the hypertonic solution (1 to 2 drops per eye, 4 times a day over 28 days). Progression of visual acuity (ETDRS score) and corneal thickness (ultrasonic pachymetry) was measured from baseline (without treatment) through the treatment period (Day 7 and Day 28). The analyses were performed on 18 patients (Full Analysis Set [FAS] population). The causes of corneal edema were Fuchs endothelial dystrophy in 10 cases and post-cataract surgery endothelial decompensation in 8 patients. The mean visual acuity values for the FAS population compared between baseline (Day-7) and one week of treatment (Day+7) show a significant 5-point VA improvement (P<0.001 paired Wilcoxon test). For corneal thickness, there was also a significant decrease (P=0.033 paired Wilcoxon test). Functional improvement was observed at 28 days of instillation. No adverse events were recorded during the clinical study. In conclusion, the unpreserved hyperosmolar solution containing sodium chloride and sodium hyaluronate significantly improved ETDRS visual acuity after one week of use. In this clinical trial, the solution also showed excellent tolerability results.

Founder effect in GLC1A-linked familial open-angle glaucoma in Northern France.

Open-angle glaucoma (POAG) is a highly prevalent cause of visual impairment. Six families grouping 71 living patients affected with juvenile-onset and middle-age POAG (age at diagnosis ranging from 10 to 65 years) were linked to the GLC1A locus. All patients carried a mutation of an evolutionarily conserved asparagine residue to a lysine at position 480 (N480K) in the olfactomedin-homology domain, which is encoded by the third exon of the GLC1A gene. The N480K mutation was also identified in 14 unaffected carriers who are at high risk of developing POAG. Although four of the families had ancestors identified in Northern France, the pedigrees could not be interconnected by genealogical investigation. However, haplotype analysis indicated that all the carriers had inherited the N480K mutation from the same founder. Screening of a selected set of 67 POAG patients who originated from Northern France and underwent trabeculectomy before the age of 50, detected one patient with the N480K mutation associated with the same disease haplotype already characterized in the 6 families. This group of 72 POAG patients is the largest one having a GLC1A mutation in common and provides a unique tool to investigate the factors influencing the variable expressivity of the GLC1A gene.

The efficacy and safety of unfixed and fixed combinations of latanoprost and other antiglaucoma medications.

Adjunctive therapy for the management of glaucoma is commonly used. Unfixed combinations of the prostaglandin analog latanoprost and other glaucoma medications have been demonstrated to effectively lower intraocular pressure (IOP). The range of reported additional reductions in IOP compared to a monotherapy baseline are as follows: latanoprost-timolol (13-37%), latanoprost-pilocarpine 2% (7-14%), latanoprost and carbonic anhydrase inhibitors (15-24.1%), and latanoprost and dipivefrin (15-28%). There is a fixed combination of latanoprost (0.005%) and timolol (0.5%) that has been investigated in Phase III trials in Europe and the United States. In these trials, it was noted that the efficacy of the fixed combination was superior to either of the monotherapy components. After 12 months of follow-up of patients on fixed combination, there was no evidence of long-term drift. The new formulation appears to be safe and does not demonstrate any more side effects than either of the components. The convenience of a fixed combination may enhance patient compliance. Unfixed combination therapy with latanoprost and other antiglaucoma medications and the fixed combination formulation of latanoprost and timolol provide an effective and safe option for lowering IOP in glaucoma patients.

A comparison of the intraocular pressure-lowering effect of 0.5% timolol maleate and the docosanoid derivative of a PGF2 alpha metabolite, 0.12% unoprostone, in subjects with chronic open-angle glaucoma or ocular hypertension.

The efficacy of 0.5% timolol was compared with that of the prostaglandin derivative unoprostone in maintaining control of intraocular pressure (IOP) in subjects with chronic open angle glaucoma (COAG) or ocular hypertension (OH) already responding satisfactorily to beta-blocker monotherapy. In a two-centre, double-masked, randomised parallel group study, 40 subjects were placed on 0.5% timolol eyedrops twice daily for two weeks. They were then randomised either to continue with 0.5% timolol or to switch to 0.12% unoprostone, applied twice daily for six weeks. IOP was measured at two-weekly intervals. The status of the conjunctiva, iris, cornea and anterior chamber was kept under observation. Ocular safety was monitored by measurements of visual acuity, and any systemic adverse events were recorded. After six weeks' treatment, there were no statistically significant differences in mean change from baseline IOP within or between treatment groups. For the subjects treated with unoprostone, mean IOP increased by 0.69 mm Hg (p = 0.368) while that of the timolol-treated subjects fell by 0.47 mm Hg (p = 0.287). The difference in mean IOP between groups was 1.16 mm Hg (p = 0.211, 95% confidence interval [CI] -0.69 to 3.02). The most common complaint was a mild and transient burning sensation on instillation which occurred more frequently in the unoprostone group. In conclusion, an aqueous solution of 0.12% unoprostone isopropyl, applied topically to the eye twice daily for six weeks, was as effective as 0.5% timolol in maintaining control of IOP in subjects with chronic open angle glaucoma or ocular hypertension. Both treatments were safe and well tolerated.

Comparison of the intraocular pressure lowering effect of latanoprost and a fixed combination of timolol-pilocarpine eye drops in patients insufficiently controlled with beta adrenergic antagonists. French Latanoprost Study Group, and the Swedish Latanoprost Study Group.

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 beta 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 beta 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 beta 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.

A comparison of the fixed combination of latanoprost and timolol with the unfixed combination of brimonidine and timolol in patients with elevated intraocular pressure. A six month, evaluator masked, multicentre study in Europe.

PURPOSE: To compare the intraocular pressure (IOP) reducing effect and safety of fixed combination (FC) latanoprost/timolol with unfixed combination (UFC) brimonidine/timolol in patients with increased IOP. METHODS: In this 6 month, randomised, evaluator masked, parallel group European study, patients with glaucoma or ocular hypertension and IOP > or =21 mm Hg on monotherapy or >16 mm Hg on dual therapy received either FC latanoprost/timolol at 8:00AM or UFC brimonidine/timolol at 8:00AM and 8:00PM. The primary outcome was the difference from baseline to month 6 in mean diurnal IOP reduction. RESULTS: 325 of 334 randomised patients were included in intent to treat analyses (FC latanoprost/timolol, 163; UFC brimonidine/timolol, 162). Baseline diurnal IOP levels were similar: FC latanoprost/timolol, 26.4 (SD 2.7) mm Hg; UFC brimonidine/timolol, 26.5 (SD 2.8) mm Hg (p = 0.851). At month 6, levels were 16.9 (SD 2.8) mm Hg in FC latanoprost/timolol patients and 18.2 (SD 3.1) mm Hg in UFC brimonidine/timolol patients (p<0.001). No adverse events were reported by 76.4% and 75.5% of patients receiving FC latanoprost/timolol versus UFC brimonidine/timolol, respectively. Larger proportions of brimonidine/timolol treated patients reported study medication related adverse events (18.6% v 7.3%) and discontinued study participation because of this (10.8% v 1.8%). CONCLUSION: Fixed combination latanoprost/timolol administered once daily is both more effective and better tolerated than twice daily dosing with UFC brimonidine/timolol.

Simulator for laser photocoagulation in ophthalmology.

The practice of laser photocoagulation plays a major role in the ocular therapy, but the persistence of many postoperative complications denotes genuine difficulty in mastering the technique. The authors present a device which, thanks to the use of simulation, enables actual practice to be dissociated from apprenticeship. While complying with the constraints of realism with regard to habitual conditions of laser use, the device offers access to a wide variety of clinical situations. The apparatus is built around the traditional instrument. A virtual image of the fundus is produced in real time from the sensors which detect the actual gestures used. The calculations make use of textured geometrical models. Digitized color photographs are organized to form a database which reflects the diversity of pigmentations and pathologies. A software interface has been developed to facilitate the use of the device. The prototype is operated using a PC-compatible computer; it displays the images at the rate of at least seven per second on a miniature CGA screen incorporated in the slit-lamp. It is currently being validated for clinical applications. Above and beyond apprenticeship in laser photocoagulation, its potential applications extend to the entire field of ophthalmogical symptomatology and, more broadly, to the simulation of any examination conducted with the help of binocular or endoscopic optics.

Naturalistic, prospective study of glaucoma and ocular hypertension treatment in France: strategies, clinical outcomes, and costs at 1 year.

PURPOSE: To prospectively observe second-line treatment strategies, their clinical outcomes, and treatment costs in patients with glaucoma or ocular hypertension (OH) in France. METHODS: Patients were recruited between 1998 and 2000 in 37 centers and were followed for up to 2 years. Outcomes were numbers of and reasons for treatment changes, changes in clinical parameters (intraocular pressure [IOP] levels, visual field defects, and optic nerve excavation), and direct medical costs associated with glaucoma management in patients receiving monotherapy or combination therapy. This article reports results of an interim analysis of 1-year follow-up data for patients having at least two contacts with a study ophthalmologist. RESULTS: Data were analyzed for 283 patients and 549 treated eyes. Ocular hypotensive monotherapy was used as first-line therapy in 92.0% of eyes. Second-line treatment was initiated an average of 3.4 +/- 0.5 years after diagnosis, primarily due to insufficient IOP control (62.8%). Mean IOP reductions after 1 year of second-line therapy were 3.0 mmHg in eyes treated with latanoprost monotherapy versus 2. 1 mmHg in those receiving beta-blocker monotherapy (p = 0.02) and 5.4 mmHg in eyes treated with the latanoprost + timolol combination versus 4.1 mmHg in those receiving combination therapies that did not include latanoprost (p = 0.01). Although second-line treatment with latanoprost was more costly than treatment with beta blockers, the average daily cost for latanoprost monotherapy was similar to that for patients who failed beta-blocker monotherapy, and latanoprost + timolol was less costly than therapeutic combinations without latanoprost. CONCLUSIONS: Insufficient IOP control is the main reason for changing first-line treatment in patients with glaucoma or OH. After 1 year, second-line treatment with latanoprost, as monotherapy or combined with timolol, provides superior IOP control at an acceptable cost.

Changes in medical and surgical treatments of glaucoma between 1997 and 2000 in France.

PURPOSE: To analyze quantitative changes in glaucoma treatment strategies between 1997 and 2000 in France. METHODS: Numbers of ab externo trabeculectomies and other glaucoma surgeries were extracted from the national database of the French Diagnosis Related Group system, which includes data for both public and private hospitals. Mean lengths of stay and hospital costs were estimated using national cost scales published by the French Ministry of Health. Numbers of patients treated per year with latanoprost, brimonidine, or the fixed combination of dorzolamide + timolol were estimated from drug unit sales using defined daily doses for each drug. RESULTS: Between 1997 and 2000, the number of patients treated with a glaucoma drug increased from 410,000 to 734,000 patients per year. This increase was associated with the introduction of three new glaucoma drugs: 245,000 patients received latanoprost (71.0%), brimonidine (28.8%), or the fixed combination of dorzolamide + timolol (0.2%). During the same period, the surgery rate in patients receiving medical treatment declined by 47%, from 5.9% to 3.1% . The total number of glaucoma interventions declined by 4.6% (-12% in public hospitals and 0% in private hospitals). This relative stability resulted mostly from a shift from trabeculectomies to other procedures, mainly to new filtering procedures in private hospitals. CONCLUSIONS: Between 1997 and 2000, new glaucoma drugs, primarily latanoprost and brimonidine, improved intraocular pressure control and delayed surgery, reducing the glaucoma procedure rate in patients receiving glaucoma-related medical treatment by 47%.