Primary Open Angle Glaucoma

La pression intraoculaire (PIO) fait partie des grandeurs biologiques variables. Les variations de la PIO sont tributaires de très nombreux facteurs. Certains ont une action sur le long terme (âge, saisons), d’autres assurent les variations à court et moyen terme. Parmi ces dernières, les variations nycthémérales suscitent des travaux de plus en plus nombreux. Leurs études chez l’homme se heurtent cependant à l’absence de méthode d’enregistrement continu de la PIO utilisable en clinique humaine et font donc appel à des mesures discontinues de la PIO, prises toutes les heures pendant 24 heures.Chez les sujets sains, les études récentes font état d’un rythme nycthéméral de la PIO avec une élévation de la PIO moyenne pendant la nuit et une acrophase durant la nuit. La démonstration de la reproductibilité des courbes nycthémérales de PIO dans le temps, pour un même sujet sain, qui conforte le caractère rythmique de cette grandeur, conduit à penser qu’un seul enregistrement de la PIO sur 24 h doit suffire pour caractériser le rythme propre d’un individu.Chez les patients porteurs de glaucome, il a été montré une modification du rythme nycthéméral de la PIO. Pour les glaucomes primitifs à angle ouvert (GPAO) pressionnels, il existe une inversion du rythme de la PIO avec une valeur moyenne de PIO plus élevée le jour que la nuit et une acrophase diurne. Les glaucomes à pression normale (GPN) se caractérisent par une perte totale de tout rythme nycthéméral.Dans le cadre du dépistage et de la prise en charge de la maladie glaucomateuse, les courbes de PIO (diurnes et si nécessaire nycthémérales) restent donc indispensables à des fins diagnostiques permettant de différencier GPAO, GPN, glaucome à pression nocturne élevée. Elles apportent des informations sur la sévérité du glaucome et sont d’une grande utilité dans la stratégie thérapeutique, représentant l’élément principal de la chronothérapeutique antiglaucomateuse.Intraocular pressure (IOP) varies and depends on many factors. These variations throughout the nycthemeron (the full 24-h period of a night and a day) are the most interesting to study. With the current techniques, it is impossible to measure continuously without waking the subject. Therefore, IOP must be measured hourly over 24 h with a portable tonometer, which provides short measurements in any posture, without requiring the subjects to rise during the night.Intraocular pressure depends on a nyctohemeral rhythm and in healthy subjects is higher at night than during the day, with a nocturnal peak value (acrophase). In the same normal individual, several 24-h measurements are identical. Each individual has his own 24-h IOP pattern.In glaucoma patients, however, the 24-h IOP rhythm was shown to be reversed, with values higher during the day (a midday peak in IOP) than during the night.The time course of the nyctohemeral curve of intraocular pressure is considered to play a role in the prognosis of glaucoma and can serve to classify the type of glaucoma (POAG, NTG). Lowering IOP is still the only option that is available for treating patients with glaucoma. Variations encountered in the individual's nyctohemeral IOP pattern must be taken into consideration to provide the most effective treatment.

PurposeTo investigate the involvement of stress-regulating genes, endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG).MethodsPOAG and PCAG patients recruited from different areas of Pakistan were diagnosed on the basis of clinical history, raised intraocular pressure (IOP), cup-to-disc ratio (CDR) and visual field defects. Their blood was collected and genomic DNA was extracted from it, followed by PCR amplification and VNTR typing of the eNOS gene, while the HSP70 SNP was analyzed with PCR-RFLP. For both of the polymorphisms, the genotype distribution of the POAG and PCAG patients was compared with unaffected controls.ResultsHSP70 polymorphism was found to be significantly associated with PCAG (χ2=15.29 [p<0.001], OR=2.63 [95% CI=1.55–4.48]), with p<0.001 for the dominant model and OR=2.09 (95% CI=1.10–3.96) , with p<0.01 for the recessive model, but not with POAG (χ2=2.96 [p>0.05]). As opposed to this significant eNOS association, was seen with PCAG (χ2=6.33 [p<0.05], OR=2.09 [95% CI=1.12–3.89]), with p<0.01 for the dominant model, as well as with POAG (χ2=8.89 [p<0.05], OR=2.23 [95% CI=1.26–3.39]), with p<0.01 for dominant model. For the eNOS case, we found a significant association with the risk allele “a” for POAG patients (χ2=9.29 [p<0.01], OR=2.02 [95% CI=1.25–3.28, p=0.001]) and PCAG patients (χ2=7.59 [p<0.01], OR=1.99 [95% CI=1.18–3.37, p<0.01]). Similarly, in the HSP70 case, there was a significant association with the risk allele “C” for POAG patients (χ2=3.57 [p=0.05], OR=1.38 [95% CI=0.97–1.94, p<0.05]) and PCAG patients (χ2=18.32 (p<0.001), OR=2.16 [95% CI=1.49–3.13, p<0.001]).ConclusionsThe intron 4 polymorphism of eNOS is associated with POAG, as well as PCAG, while the G+190C polymorphism in HSP70 is associated with PCAG, but not with POAG in the Pakistani population.

The lysyl oxidase-like protein 1 (LOXL1) gene is strongly associated with exfoliation glaucoma, which is very rare in the Chinese population. The implicated LOXL1 polymorphisms have not been associated with primary open-angle glaucoma (POAG). In this study, we investigated three of the LOXL1 polymorphisms in POAG in a southern Chinese population of Hong Kong and northern Chinese from Beijing. The Hong Kong group included 293 POAG patients and 250 controls, and the Beijing group included 169 POAG patients and 197 controls. LOXL1 single nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, were genotyped by direct DNA sequencing. Individual association was analyzed using the chi(2) test, and haplotype-based association analysis was performed in WHAP. Each of the candidate SNPs was not statistically associated with POAG in either group (p&gt;0.017, Bonferroni correction). Haplotype-based association analysis had identified a significant omnibus association (Omnibus chi(...

PURPOSE: To evaluate the initial medical decision regarding primary open-angle glaucoma (POAG) treatment in a referral center, and to assess the relationship between the persistence of treatment and the disease progression in cases managed exclusively with medication. METHODS: A retrospective chart review was performed for 65 patients with primary open-angle glaucoma referred to a tertiary hospital. The following clinical data were analyzed: initial medication, persistence of treatment, best corrected visual acuity, visual field mean deviation index, cup/disc ratio, and intraocular pressure. Patients were classified into four categories in order to verify the clinical evolution. RESULTS: The mean number of visits/ year was 4.4 ± 3.5, and the follow-up period was 40.7 ± 22.8 months. Mean persistence time was 12.9 ± 13.9 months. By six and twelve months, respectively, 39.1% and 62.5% of patients had discontinued the initially prescribed regimen, mainly by adding to (42%) or changing (26%) the course of treatment. Thirteen patients (21%) were reclassified to a worse category of primary open-angle glaucoma, however, despite this trend, no significant correlation was found between shorter persistence and primary open-angle glaucoma worsening. CONCLUSIONS: Persistence rates with initial therapy schemes were low, as measured by medical decisions to change the course of treatment. Therefore, improvement in the initial medical decision is crucial in order to offer a more stable and effective treatment for primary open-angle glaucoma.

The availability of the human genome sequence together with sequenced genomes of several model organisms provides an unprecedented opportunity to utilize comparative genomic approaches for the discovery of genes that contribute to human disease. We have used transgenic flies to establish an experimental paradigm for the discovery of genes that might be involved in the development of glaucoma, a prevalent disease affecting a large segment of the population. Inherited mutations in the trabecular meshwork-inducible glucocorticoid response protein/myocilin (TIGR/MYOC) are associated with juvenile glaucoma and some cases of adult primary open angle glaucoma. The interrelationships between TIGR/MYOC and the development of glaucoma, however, are not understood. We show that overexpression of human TIGR/MYOC in the eyes of Drosophila melanogaster results in distortion of ommatidia accompanied by fluid discharge. High-density oligonucleotide microarrays identified altered expression of 50 tr...

The purpose of this study was to investigate the effects of glaucoma surgery on retrobulbar hemodynamics and corneal surface temperature (CST). A total of 22 primary open-angle glaucoma eyes underwent deep sclerectomy, and 19 trabeculectomy. The follow-up was of 3 months. The peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) were evaluated in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs) by color Doppler imaging (CDI). CST was measured using infrared thermography. At 3 months, EDV was increased in OA (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 in deep sclerectomy, P=0.005 in trabeculectomy), CRA (P=0.044 and P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), and SPCAs (P=0.011 and P=0.003), and RI decreased in OA, CRA, and SPCAs (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 in both groups). CST values were augmented (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 in both groups). A negative correlation between the postoperative changes in RI-OA and CST was found (P=0.023 and P=0.032, respectively). Deep sclerectomy and trabeculectomy seem to be equally effective in improving retrobulbar hemodynamics. Color Doppler imaging and infrared thermography might be useful to evaluate the vascular outcome of glaucoma surgery.