Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy and a major cause of irreversible blindness, with elevation of intraocular pressure (IOP) being a primary risk factor. The trabecular meshwork-inducible glucocorticoid response (TIGR)/MYOCILIN (MYOC) gene coding region is mutated in 3-4% of POAG patients. Here, in a retrospective study of 142 POAG patients, we evaluated the influence on glaucoma phenotype of a novel biallelic polymorphism (-1000C/G) located in the upstream region of the MYOC gene. Allele frequencies were similar among patients and controls. However, the G allele (frequency 17.6%), also designated as MYOC.mt1, was associated with an increased IOP (+4.9 mmHg, p=0.0004) and a more damaged visual field (p=0.02). Both effects were predominant in females. Moreover, whereas IOP in MYOC.mt1 noncarriers decreased very markedly to the normal range between diagnosis and inclusion in the study (p=3 x 10(-5) in both males and females), reflecting successful therapy, it decreased less noticeably in MYOC.mt1+ male patients (p=0.005) and not at all in MYOC.mt1+ female patients. MYOC.mt1 appears therefore to be an indicator of poor IOP control and greater visual field damage in diagnosed POAG patients, potentially due to a lack of response to therapeutic intervention. Its typing might help in the selection of treatment paradigms for the management of POAG patients.

High prevalence of sleep-disordered breathing in patients with primary open-angle glaucoma.

PURPOSE: Elevated intraocular pressure and systemic hemodynamic changes are main risk factors in primary open-angle glaucoma (POAG). Sleep-disordered breathing (SDB) characterized by snoring, excessive daytime sleepiness and insomnia is accompanied by large swings in blood pressure and repetitive hypoxic periods during sleep. The aim of this study was to evaluate whether there is any relationship between SDB and POAG. METHODS: Consecutively, 212 outpatients with POAG and 218 outpatients without POAG were recruited. Both eyes were examined. An interviewer-administered semi-structured questionnaire was used to collect SDB-related symptoms. RESULTS: After controlling for age, relative to control group, POAG patients showed a high prevalence of snoring (47.6%, p=0.04), snoring plus, excessive daytime sleepiness (27.3%, p=0.01) and snoring plus, excessive daytime sleepiness, plus insomnia (14.6%, p=0.01). CONCLUSION: We found a high prevalence of SDB in patients with POAG. Chronic hemodynamic changes and recurrent severe hypoxia resulting from SDB may contribute to anoxic optic nerve damage, implicated in glaucoma.

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.

Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23-q25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans . Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.

[Efficacy and tolerability of a combination of indomethacin and gentamicin for preventing inflammation after cataract surgery]. / Efficacité et tolérance d'une association d'indométacine et de gentamicine dans la prévention de l'inflammation consécutive à la chirurgie de la cataracte.

PURPOSE: The aim of the study was to compare 2 combinations of anti-inflammatory drug and antibiotic, in patients undergoing cataract surgery: 0.1% indomethacin/gentamicin or 0.1% dexamethasone/ neomycin. METHODS: Two hundred and two patients undergoing extra-capsular cataract extraction with posterior chamber lens implantation were included in a randomized, double-blinded multicentric study comparing 2 parallel groups of treatment. Treatment was administered the day before surgery, the day of surgery and for the following 7 days. On the 8th post-operative day, the antibiotic was stopped and the anti-inflammatory treatment continued alone until the 30th post-operative day. Post-operative ocular inflammation was assessed clinically on the 1st, 7th, 15th and 30th post-operative days. The main evaluation criterion of treatment efficacy was the assessment of anterior chamber flare and cells. RESULTS: No statistically significant difference-was observed between the 2 treatment groups concerning post-operative inflammation. Both treatments were well tolerated. CONCLUSION: Eye drops combining 0.1% indomethacin and gentamicin proved to be effective and well tolerated in preventing inflammation after cataract surgery.

[Hypotensive action of 0.5% carteolol versus 0.1% timolol in patients with intraocular hypertension]. / Action hypotensive du cartéolol 0.5% versus timolol 0.1% chez les patients porteurs d'une hypertonie intraoculaire.

PURPOSE: The aim of the study was to compare 2 beta-blocker eye drops at a low concentration: 0.5% carteolol and 0.1% timolol. METHODS: The study was designed as a random-order, double-blinded comparison of 2 parallel treatment groups. Fifty patients with early primary open angle glaucoma or high intraocular pressure were included. The treatment lasted 4 weeks, on the basis of 1 drop twice daily. Diurnal I.O.P. curve was assessed with 4 measurements from 8.30 a.m. to 4.30 p.m. before and after treatment. The 8.30 a.m. measure of the final assessment of I.O.P. curve was established prior to morning medication. The mean values of the 4 measures were compared. RESULTS: Both treatments reduced IOP by a comparable amount: 4.25 +/- 1.2 mmHg (mean +/- SD) for carteolol and 4.69 +/- 1.9 mmHg for timolol. The decrease of IOP was found at every time of assessment, without any significant difference between treatments. Both eye drops were very well tolerated. CONCLUSION: The results of this study show that the new beta-blocker eye drop solution 0.5% carteolol is effective for initial management of high intraocular pressure.

[Efficacy and tolerability of 2 presentations of eyedrops combining carteolol 2% and pilocarpine 2% in primary open-angle glaucoma and simple ocular hypertension]. / Efficacité et tolérance de 2 présentations de collyre associant le cartéolol 2% et la pilocarpine 2% dans le glaucome primitif à angle ouvert et l'hypertension oculaire simple.

PURPOSE: The aim of the study was to compare 2 combinations of eye drops containing 2% carteolol and 2% pilocarpine: LCM 1010: ready to use eye drops CBS 341A: eye drops to be reconstituted (freeze-dried powder + solvent). METHODS: Ninety-seven patients with primary open angle glaucoma or simple ocular hypertension were included in a randomized, double-blind multicentric study comparing 2 parallel groups of treatment. Intra-ocular pressure was greater than 21 mmHg with beta-blocker alone. One instillation of 2% carteolol-2% pilocarpine combination was given twice a day for one month. Before and after this treatment, intra-ocular pressure was measured at 9 am (12 hours after evening instillation) and at 11 am (2 hours after morning instillation). RESULTS: Both treatments reduced intra-ocular pressure by a comparable amount and there was no significant difference between groups at either measure: at 9 am: 2.11 +/- 2.39 mmHg (mean +/- SD) for LCM 1010 1.79 +/- 1.73 mmHg for CBS 341 A p = 0.25 at 11 am: 3.75 +/- 3.83 mmHg for LCM 1010 3.40 +/- 1.69 mmHg for CBS 341 A p = 0.42. Both eye drops were generally well tolerated. CONCLUSION: Efficacy and safety of ready to use eye drops 2% carteolol-2% pilocarpine combination proved to be comparable to that of eye drops to be reconstituted in the treatment of ocular hypertension poorly controlled by beta-blocker eye drops alone.

[Linkage between juvenile glaucoma and chromosome 1q in 2 French families]. / Liaison du glaucome juvénile au chromosome 1q dans deux familles françaises.

Primary open-angle glaucoma is a major cause of irreversible blindness in Western countries for which there is presently no curative treatment. Linkage of hereditary juvenile glaucoma with chromosome 1q21-q23 was recently described in 2 American families. Here we have studied two large French pedigrees with a similar form of familial autosomal dominant juvenile-onset glaucoma. Linkage of glaucoma with chromosome 1 was confirmed in these 2 families. Maximal lod-score of 7.60 was reached at the D1S212 marker for a recombination fraction of 4.4%. The typing of this marker should facilitate the screening of glaucoma families and the identification of individuals at risk for the disease. It will also provide a reference to evaluate the genetic heterogeneity of glaucoma.

[Surgical treatment of congenital glaucoma. Long-term results]. / Traitement chirurgical du glaucome congénital. Résultats à long terme.

We studied 317 eyes, operated on for congenital glaucoma by Elliot, iridencleisis, goniotomy and trabeculotomy with a follow up of 5 to 35 years. Elliot and iridencleisis gave 30 to 50% intraocular pressure stabilisation and 60% bad visual results. Goniotomy gave without treatment 60% pressure stabilisation and 37% good visual results. Trabeculectomy gave 74% pressure stabilisation and 53% good visual results. Trabeculotomy gave the best results and can be considered as the most efficient operation in congenital glaucoma.

[Long-term results of the treatment of glaucoma in children]. / Résultats à long terme du traitement chirurgical du glaucome infantile.

We have studied among 192 patients affected by congenital glaucoma the long term efficacy of 4 interventions. Elliot's trophination, iridencleisis, goniotomy, trabeculotomy. Trabeculotomy gives the best results and is the most suitable intervention in congenital glaucoma.

[Analysis of retinal fibers. Technics, preliminary results]. / Analyse des fibres rétiniennes. Techniques, resultats préliminaires.

Nerve fiber of 100 eyes were studied. The appearance of the nerve fiber layer was evaluated independently from black and white monochromatic photographs (440, 470, 500, 535, 590 nm) and by color photographs. The results are discussed according to the data of the literature.