Regulation of optic nerve head blood flow in normal tension glaucoma patients.

PURPOSE: To investigate the regulation of the optic nerve blood flow (Fonh) in response to an increase of the perfusion pressure (PPm) in normal tension glaucoma (NTG) patients and in age-matched normal volunteers. METHODS: Measurements were performed in 16 eyes of NTG patients and in 10 eyes of age-matched controls. Laser Doppler flowmetry (LDF) was applied to calculate the relative flux of red blood cells at the temporal rim of the optic nerve head (ONH) in response to increases in PPm. PPm was raised through an increase in systemic blood pressure induced by isometric exercise. Before being tested, all patients had 3 weeks of washout of any local medication. RESULTS: In the NTG group, mean ophthalmic arterial blood pressure increased during isometric exercise from 73 to 89 mmHg (22%), resulting in a 29% increase of the PPm. This increase did not induce any significant change in mean Fonh. For the control group, the 28% increase of PPm also did not significantly affect Fonh. There was a trend for a greater increase in vascular resistance during isometric exercise in the NTG than in the normal control group (47% versus 25%). CONCLUSIONS: The LDF parameters, measured in the ONH, did not indicate an abnormal Fonh regulation in response to an increase of the PPm in either normal subjects or NTG patients. The maintenance of constant blood flow is achieved by an increase in local vascular resistance. Our data show a greater percent increase in vascular resistance in the NTG patients compared to the normal subjects for a similar percent increase in PPm in both groups during squatting. This suggests some alteration of the vessel tone regulatory mechanisms in NTG patients.

[Glaucoma and quality of life]. / Glaucome et qualité de vie.

Glaucoma is a serious ocular disorder potentially leading to blindness. Measuring the quality of life of patients with glaucoma is important because it makes it possible to evaluate the impact of the disease and its treatment on the patient's everyday life. Hitherto, this was done using generic scales, or those developed for other diseases; but no scale suitable for glaucoma was available. The recently developed GlauQOL scale is now available. We present the short version of this questionnaire adapted to individual use within an ophthalmology consultation setting.

[Creating a specific quality-of-life questionnaire in patients with glaucoma: item generation]. / Création d'un questionnaire spécifique évaluant la qualité de vie chez les patients glaucomateux: la génération des items.

The methods for developing Health-Related Quality-of-Life (HRQoL) measures and their application in medical research have demonstrated their utility in various chronic, progressive, or life-threatening diseases. The efforts made to allow the patient's perspective to be included in the methodological framework of evidence-based medicine have been successful. The assumption of a strong relationship between clinical status and daily life is certainly valid in ophthalmology. However, there is a lack of specific HRQoL measures dedicated to ophthalmic diseases. Our work aimed at creating the first Glaucoma-specific Quality of Life scale - the Glau-QoL questionnaire - to provide researchers and physicians with a comprehensive, practical, and validated tool. This article describes the first stage of the process, which consisted in generating items and formatting them in order to create a questionnaire that exhaustively covers the relevant concepts. The whole process was conducted by an expert committee including clinicians and methodologists. The standard recommendations in the development of a HRQoL questionnaire were followed: we first identified existing tools and performed a preliminary collection of concepts from the published literature; we then designed an interview guide with the help of clinicians; a trained psychologist interviewed 22 patients at various disease severity stages (from isolated hypertonic to severely impaired); the interviews were tape-recorded and scripted; general domains and related detailed concepts were identified from the script; they were then analyzed and organized; the format of the questionnaire was set up; and questions were derived from the patient's verbatim to capture the identified detailed concepts. The test questionnaire was applied to seven patients for cognitive debriefing. We finally amended the test questionnaire and designed the pilot questionnaire according to the patients' tests and the clinician's review. The test questionnaire was well accepted by the patients, despite a completion duration ranging from 14 to 35 minutes. The pilot questionnaire contained 151 items, grouped into 5 sections: (1) vision problems, physicians, and daily treatment (49 items); (2) activities of daily living (37 items); (3) self-expression (37 items); (4) vision problems and mood (14 items); and (5) other questions (14 items). The next step of our work will be the item reduction process and the psychometric validation of the Glau-QoL questionnaire.

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.

[Correlation between Goldmann and non-contact tonometry based on corneal thickness]. / Correlation entre tonometrie de Goldmann et tonometrie non-contact en fonction de l'epaisseur corneenne.

In this transversal study, we measure the intra ocular pressure by means of the Goldmann tonometer and a Non-Contact tonometer along with the central cornea thickness in 136 eyes of 73 patients. The statistical analysis of the collected data doesn't allow us to establish a correlation between the variation of the corneal thickness and the difference between the Goldmann tonometer and Non-Contact tonometer measures. The relative precision of the Non-Contact tonometer compared with the Goldmann tonometer doesn't seem influenced by the central cornea thickness.

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

[Correlation between neuroretinal rim and optic disc areas in normal melanoderm and glaucoma patients]. / Corrélation entre les surfaces des anneaux rétiniens et des papilles, chez des sujets mélanodermes normaux et glaucomateux.

BACKGROUND: To evaluate optic disc size and its relationship with neuroretinal rim areas. MATERIAL AND METHODS: The study was prospective; 400 hundred patients with 292 glaucomatous and 108 non glaucomatous were enrolled in this study. Optic disc size quantification was assessed by the use of Goldmann 3 mirror contact lens; diameter reading were adjusted by the magnification factor of the lens, squares of the disc and the cupping were calculated using an ellipse formula, the neuroretinal rim area was then obtained by reducing the cupping area from the whole optic disc area. RESULTS: The mean age of the sample was 36.80 years (sd: 15.68 years).The average value of the vertical disc diameter was 2.045 mm (sd: 0.254) for glaucoma patients and 1.966 mm (sd: 0.237) in the control group; p<0.001. Neuroretinal rim area was 1.886 mm(2) (sd: 0.675) in the glaucoma group; and 2.165 mm(2) (sd: 0.425) in the control one; p<0. 004. In the glaucoma group, 72.97% of large optic disc were found (vertical diameter over 1.90 mm); and 63.80% in the control one. In the control group, neuroretinal rim area was wider in the large optic discs compared to the small discs, p<0.001, Anova test. Neuroretinal rim area was thinner in the glaucoma large disc compared to the control, p<0.005, Student test. Meanwhile, there was no difference in the medium and the small discs in the glaucoma and control groups; p > 0.005, Student Newmann test. CONCLUSION: Neuroretinal rim areas are thinner in the large glaucoma discs compared to the non glaucoma large discs. In Africa, this parameter could be helpful in the diagnosis and survey of glaucoma patients.

[Relevance of quality of life and treatment compliance measurement in patients with chronic open-angle glaucoma]. / Intérêt de la mesurede la qualité de vie (QDV) et de l'observance thérapeutiquechez les patients atteints de glaucome chronique à angleouvert. Groupe d'étude Glaucome et Qualité de Vie.

Chronic glaucoma is a severe disease that can induce blindness.Early diagnosis and symptomatic treatment reduce the risk of blindness. Treatment that will be started before the onset of clinical signs and will remain lifelong thereafter is troublesome, and therapeutic compliance is usually poor. Thus, quality of life (QOL) measurement in patients with chronic glaucoma has a particular purpose: to measure patients' perception of the disease and treatment in order to maintain good treatment compliance to ensure therapeutic management efficacy and to preserve visual function. No glaucoma-specific instrument is available in the medical and QOL literature. Various generic(SF-36, SF-20 and SIP) and specific(VAQ, VF-14, NEI-VFQ) QOL questionnaires,one glaucoma-specific symptomatic scale (GSS),and one treatment preference scale (COMTol) have been used to measure QOL in glaucoma patients. These instruments do not sufficiently measure the psychosocial dimension of the disease and the QOL impact of treatment. An instrument able to measure all dimensions needs to be developed in order to help ophthalmologists in the therapeutic management of their patients and to measure QOLin patients in the successive stages of the disease.

[Color Doppler ultrasonography of short para-optic ciliary arteries in vascular glaucoma]. / Echo-Doppler couleur des artères ciliaires courtes para-optiques dans le glaucome vasculaire.

PURPOSE: To study color Doppler imaging in orbital vessels, especially para-optic short ciliary arteries, in patients with vascular glaucoma. PATIENTS AND METHODS: Twenty vascular normal or moderate elevated pressure glaucoma patients (6 with bilateral glaucoma, 9 with unilateral glaucoma et 5 with asymmetric glaucoma) underwent a color Doppler imaging (Accusson 128XP) in orbital arteries: common carotid, ophthalmic artery, central retinal artery, short para-optic ciliary arteries. Systolic and diastolic blood flow velocities were measured, and resistance index of Pourcelot and ratios between different parameters were calculated. RESULTS: In patients with unilateral glaucoma, ratios of systolic velocities between para-optic ciliary artery and common carotid, and ratio of Pourcelot index between para-optic ciliary artery and ophthalmic artery were increased in glaucomatous eyes. And Pourcelot index were statistically significant increased in all glaucomatous patients of the study compared with normal subjects. DISCUSSION AND CONCLUSION: Comparison of Pourcelot index and ratios between parameters makes color Doppler imaging more reliable, especially when analyse short para-optic ciliary arteries, which vascularize optic nerve. In these arteries Pourcelot index was increased in vascular glaucoma patients. Vascular risk factor should be taken into consideration in this form of glaucoma.

Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies.

OBJECTIVES: To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol. STUDY DESIGN: Experimental animal and human tissue study. PARTICIPANTS: Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month. INTERVENTION: Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study. MAIN OUTCOME MEASURES: Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied. RESULTS: Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups. CONCLUSIONS: These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.

[Cytomegalovirus retinitis and ocular complications in AIDS patients in Togo]. / Rétinites à cytomégalovirus et complications oculaires du SIDA au Togo.

BACKGROUND: Cytomegalovirus retinitis seems to be an uncommon complication in African AIDS patients. This study was conducted in 200 patients in order to evaluate AIDS eye related complications with specific focus to cytomegalovirus retinitis. MATERIAL AND METHODS: During a period of 20 months, 200 patients (83 men and 117 women) presenting WHO AIDS case definition diagnosis were enrolled for a complete ocular examination comprising external, anterior segment and retinal fundus and fluorescein angiographic examination. RESULTS: For the whole, 200 patients underwent ocular examinations; of them 121 (60.5%) developed ocular complications. The most frequent complications were cotton wool spots (25.5%), cytomegalovirus (CMV) retinitis (21.5%), retinal hemorrhage (6%), papilloedema (3%), chorioretinal toxoplasmosis (3%), peripheral retinal vascularitis (2. 5%), herpes zoster ophthalmicus (2%). Among those with CMV retinitis, bilateral lesions were found in 30 cases, and unilateral ones in 13 cases. Poor vision was associated with the presence of CMV retinitis in 88% of cases. Death occurred in a mean range of 22 days after the "presumed" diagnosis of CMV retinitis. CONCLUSION: Cytomegalovirus retinitis represents the second ocular complication in AIDS patients in this study. Poor visual outcome was associated in 88% of cases. These results demonstrate that in some west African countries, CMV retinitis may be a common complication in AIDS patients.

[Asymmetrical forms of primary open angle glaucoma]. / Les formes asymétriques du glaucome primitif à angle ouvert.

PURPOSE: The goal of this study is to describe asymmetrical forms of primary open angle glaucomas in black african originated patients. MATERIAL AND METHOD: Data of 514 glaucomatous patients (1022 eyes) followed between 1993 and 1997, and attending our hospital eye department are retrospectively analysed. All the participants were diagnosed as primary open angle glaucomas; asymetry was defined as a difference of 0.2 at least between the vertical cup disc ratio of the same patient. RESULTS: The mean age of all 514 glaucoma patients was 34.52 +/- 15.55 years; 254 patients (49.40%) had no differences between cup disc values while 260 remaining others had asymmetric glaucomas (50.58%). Of them, 189 (72.69%) had a difference of 0.2 between both eyes; 49 (18.8%) had 0.3 difference; 7 (2.69%) had 0.4 difference; 4 (1.53%) had 0.5 difference, and 11 (4.23%) a difference of 0.6. Besides, 114 eyes (11.15%) had a vertical ratio of 0.9 at the first diagnosis. CONCLUSION: Carefully recognition of asymmetric cup disc ratios is of great diagnostic value in the the early stages of primary open angle glaucoma because 50% of all patients presented with this clinical form in our experience. This strategy would improve early diagnosis of glaucoma in our areas.

[Morphometry of the optic disc in Togolese patients with glaucoma or suspected glaucoma. Preliminary study]. / Morphométrie de la papille chez des sujets togolais glaucomateux et suspects de glaucome. Etude préliminaire.

PURPOSE: The aim of this study was to measure morphometric parameters of the optic disc in Togolese glaucoma patients and suspects by the mean of the millimetric scale of the slit lamp and the Goldmann contact lens. MATERIAL AND METHOD: We selected 202 patients (393 eyes) with a mean age of 36.69 years +/- 15.33 (standard deviation); they were divided into 2 subgroups A (162 glaucomatous) and B (40 glaucoma suspects); direct reading of the slit lamp millimetric scale and the Goldmann contact lens was used. RESULTS: In the group A, the optic disc vertical diameter was 1.792 +/- 0.21 mm; the horizontal diameter was 1.701 +/- 0.198 mm. In the group B, vertical disc diameter was 1.700 +/- 0.262 mm; the horizontal one was 1.662 +/- 0.190 mm. The vertical cup disc diameter was 1.147 +/- 0.274 mm in the group A and 0.708 mm +/- 0.274 mm in the group B. The neuroretinal area was 1.360 +/- 0.524 mm2 in group A and 1.786 +/- 0.467 mm2 in group B. CONCLUSION: This study using millimetric scale of the slit lamp and the three mirrors Goldmann contact lens was easy, simple and useful clinically. It could be helpful in conducting quantitative studies in countries with low resources because this method is costless compared with others.

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.

Genetic heterogeneity of primary open angle glaucoma and ocular hypertension: linkage to GLC1A associated with an increased risk of severe glaucomatous optic neuropathy.

The GLC1A locus for autosomal dominant juvenile and middle age onset primary open angle glaucoma (OAG) has been mapped to chromosome 1q21-q31. OAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT), a major risk factor for OAG, to GLC1A in eight French families with multiple cases of juvenile and middle age onset OAG. There was strong evidence of genetic heterogeneity, four families being linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT. Peak intraocular pressure (IOP) did not differ significantly between the two groups of families, while linkage to GLC1A conferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy. Testing linkage of familial OAG to GLC1A may therefore have prognostic value too.