Family history in primary open-angle glaucoma

A family history of glaucoma was found in 50% of patients with primary open-angle glaucoma (POAG) and 43% of patients with ocular hypertension (OH). Positive family history was twice as prevalent in those with OH and either HLA-B7 or B12 antigens than in OH with neither antigen (P less than .01). Although POAG occurred equally in men and women, the prevalence of a positive family history of glaucoma on the maternal side of the family in POAG patients was six to seven times greater than on the paternal side (P less than .0005). However, in patients with OH, but no glaucomatous field loss, there was no difference in prevalence of maternal and paternal family history. Even in OH with HLA-B7 or B12 antigens, there was no predominance of maternal family history. The implication that offspring were more likely to develop POAG when their mother's side of the family rather than their father's side had the disease has provided an additional potentially useful risk factor in patients with OH. In addition, it has raised interesting questions as to possible maternal cytoplasmic factors in the transmission and pathogenesis of POAG.     

Novel trabecular meshwork inducible glucocorticoid response mutation in an eight-generation juvenile-onset primary open-angle glaucoma pedigree

OBJECTIVE: This study aimed to update a large kindred with juvenile-onset primary open-angle glaucoma (POAG) first described in 1940 and to identify the underlying genetic cause of the disease. DESIGN: Molecular genetic study of a single kindred, including clinical examination, retrospective review of clinical and family history records, linkage analysis, and mutation screening. PARTICIPANTS: The retrospective review included 957 members of a single large family. The linkage study included 40 members of 1 branch of the family in which juvenile-onset POAG is segregating in an autosomal-dominant pattern. Mutation screening included 15 at-risk family members with juvenile-onset POAG, probands of 40 families with adult-onset POAG, probands of 11 additional unrelated juvenile-onset POAG families, and 43 unrelated normal control subjects. INTERVENTION: Clinical and family history records were obtained, ophthalmologic examinations were performed, and blood samples were drawn for use in genotyping. MAIN OUTCOME MEASURES: Allele sizes of microsatellite repeat genetic markers from the vicinity of the GLC1A glaucoma gene on chromosome 1q were assigned based on size fractionation of DNA fragments generated by polymerase chain reaction (PCR). Linkage was established by the method of lod scores. Mutations were identified by determination of the DNA sequence of PCR products amplified from the trabecular meshwork inducible glucocorticoid response (TIGR) gene. Glaucoma status for purposes of linkage and mutation analysis was based on a combination of ophthalmologic examination, clinical records, family history, and previously published information. For some individuals reported in the pedigree, but not included in the genotyping studies, less information was available as presented in the text and tables. RESULTS: Autosomal-dominant POAG was confirmed or reported for 78 members of an 8-generation family. Linkage analysis showed significant evidence for linkage of juvenile-onset POAG in one branch of the family to D1S452 (maximum lod score of 6.42 at a recombination fraction of 0.00) and other markers in the vicinity of the GLC1A gene on chromosome 1q. Screening of the TIGR gene identified a mutation that results in substitution of asparagine for isoleucine at codon 477 near the carboxyterminal end of the protein. CONCLUSIONS: The authors' findings strongly suggest that the juvenile-onset POAG locus in this family is the GLC1A locus and that the underlying cause of the disease is the IIe477Asn TIGR mutation that cosegregates with juvenile-onset POAG in one branch of this large family. Lack of samples from deceased individuals prevented the authors from determining whether reported adult-onset cases in this family could also be attributed to the IIe477Asn TIGR mutation. Absence of the IIe477Asn TIGR mutation from other juvenile- and adult-onset POAG families implies that this TIGR mutation is not a common cause of glaucoma.     

Diabetes in primary open-angle glaucoma patients with inferior visual field defects

We reviewed the charts of 144 randomly selected patients with primary open-angle glaucoma who had Aulhorn's stage 1, 2, or 3 visual field defects to investigate whether primary open-angle glaucoma patients with predominantly inferior visual field defects had a higher prevalence of diabetes mellitus than primary open-angle glaucoma patients without such visual field defects. Of the 59 patients with mainly inferior visual field defects in one or both eyes, 19 (32%) had diabetes mellitus, while 11 of 85 (13%) patients without such defects had diabetes mellitus. This difference was statistically significant (P = 0.0096). These results suggest that primary open-angle glaucoma patients with predominantly inferior visual field defects in one or both eyes are more likely to have diabetes and that such patients with no known history of diabetes may benefit from glucose tolerance testing to detect occult impaired glucose tolerance or diabetes mellitus.     

HLA antigens and primary open-angle glaucoma in black Americans

Black patients with primary open-angle glaucoma, when compared to nonglaucomatous individuals, demonstrate significantly increased prevalences of the HLA antigens B7 and B12 and significantly decreased frequencies of A1 and A11. White patients with primary open-angle glaucoma have in common with blacks the increases in B7 and B12 and the decrease in A11, but present no deficit of A1. In addition, white patients with primary open-angle glaucoma demonstrate a significant increase of A3 and a decrease of Bw35, both of which are not found in blacks.     

Immunohemostatic mechanisms in the development of primary open-angle glaucoma

The charts of 247 allergic patients (all ages) who were receiving immunotherapy were studied retrospectively. They belong to a private setting at the city of Santa Ana Chiautempan, Tlax (Mexico). We looked at whether they were compliant or noncompliance. Compliance was considered as those who did not stop immunotherapy during a 18-month period, and shorter periods s noncompliance. One hundred and fifty two (62%) were compliant and 95 (38%) were not. Noncompliance causes were: 29 patients felt better soon, 19 claimed high costs, 8 changed to alternative medicine. 6 felt worse because of immunotherapy, 6 moved to other cities, 2 preferred other allergists and 25 did not answer the questionnaire. Forty six per cent stopped during the first 2 to 6 months and 56% within 8 and 14 with a median of 5.4. Eighty per cent from those who were compliant claimed they felt much better and 18% only slightly better. The average length-compliance was 29.7 months.     

Prevalence of primary chronic open-angle glaucoma in Ivory Coast

BACKGROUND: The aim of this study was to determine and analyze the rate of chronic open-angle glaucoma in C?te d'Ivoire. METHODS: The prevalence of chronic glaucoma (POAG) was retrospectively evaluated in a population of 33,000 patients attending a private clinic including 24,751 black subjects and 8,249 white subjects. Patients with a cup/disc superior to 0.5 and an abnormal Goldmann's kinetic perimetry, associated with (POAG with "elevated" pressure or not (POAG with normal pressure) with an intraocular hypertension (intra ocular pressure superior to 21 mmHg) were distinguished. RESULTS: Prevalence was from 2.1% for the black subjects and 0.75% for the white subjects. Mean age was 46.4 +/- 12.5 years for blacks subjects versus 52.8 +/- 12.2 years for white subjects. This prevalence increased with age in both populations. Out of 571 cases of POAG, 465 (81.4%) were previously known and 450 of them were treated; 38.5% of the POAG cases had normal pressure. CONCLUSION: Primary open-angle glaucoma is a major health care problem emphasizing the need for detection and prevention in C?te d'Ivoire.     

Histocompatibility (HL-A) antigens and primary open-angle glaucoma

For the diagnosis of lumbar P.I.D. discography is much superior to myelography. The risks of both techniques are the same, but the side-effects of discography are clearly less. Higher lesions remain a problem if they do not show up neurologically (s. the prolapsed disc at L 2/3). Here segmental blocking, posterior gaping of the intervertebral space and displacement of the dural sac show clearly the posterior prolapse. In the standard discogram of the lower 3 discs it would have been missed. In spite of this our present experience with lumbar discography is so positive, that we are about to test a long term series, whether and to which extend discography could replace myelography in cases where there is no hint at a space-occupying lesion, other than a disc or whether the order of these investigations should be reversed.     

A novel Asp380Ala mutation in the GLC1A/myocilin gene in a family with juvenile onset primary open angle glaucoma

Glaucoma describes a clinically and genetically heterogeneous group of diseases that result in optic neuropathy and progressive loss of visual fields. A gene for juvenile onset primary open angle glaucoma JOAG) has recently been mapped to 1q21-31. Mutations in the trabecular meshwork induced glucocorticoid response gene (TIGR, also known as myocilin or the GLC1A locus) have been found to cause both juvenile and later onset primary open angle glaucoma. Family TCD-POAG1 is a Spanish kindred, which segregates JOAG in an autosomal dominant fashion. This family was found to be linked to the previously identified GLC1A locus on chromosome 1q. Direct sequencing of the TIGR/myocilin gene showed a heterozygous A to C transition in codon 380, resulting in the substitution of alanine for aspartic acid (Asp380Ala). This substitution created a StyI restriction site, which segregated with the JOAG phenotype and permitted rapid screening of all members of the family. This restriction site was not present in 60 controls.     

Understanding the new primary open-angle glaucoma preferred practice pattern

Recent developments in our knowledge of the renin-angiotensin system (RAS) necessitate an update of the classical view on this system. These developments pertain to the pathways leading to formation of angiotensin II and other active metabolites, their receptors, biological functions and the presence of renin-angiotensin systems in tissues. The implications of the above new developments for the current interest in tissue renin-angiotensin systems as potential targets for drug therapy in cardiovascular disease are discussed in this review.     

Analysis of the systemic corticosteroid sensitivity of patients with primary open-angle glaucoma

Patients with primary open-angle glaucoma have an ocular and systemic sensitivity to corticosteroids. We adapted a cellular assay that used peripheral blood lymphocytes to detect this corticosteroid sensitivity in vitro in a microtiter assay. It reduced the time, cost, and amount of blood required to examine a patient. We examined ten subjects on three separate days and demonstrated that the reliability of one 50% inhibitory concentration was about 76%. We then studied 25 patients with primary open-angle glaucoma and 25 control subjects using this in vitro assay. The patients with primary open-angle glaucoma were significantly more sensitive to corticosteroids than the control subjects (P less than .001).     

Influence of axial length on visual field defects in primary open-angle glaucoma

With the high frequency of myopia in Taiwan, potential complications or associated conditions, such as glaucoma, are of great concern. To investigate the role of axial length in glaucoma, we enrolled 307 primary open-angle glaucoma (POAG) patients from 1986 through 1996. For the control group, 124 persons were recruited from a survey of a non-glaucoma population and the Ophthalmology Out-patient Department of the National Taiwan University Hospital. Routine eye examination, stereophotography of the optic disc, automated visual field tests, and A-scan ultrasonography were performed on each patient. The Glaucoma Hemifield test was used for analysis of visual field results. The mean axial length was longer in the POAG group than in the control group, especially in the younger age groups (40-59 yr). The POAG group was divided into a short-axial-length (SAL, axial length < 26 mm) group and a long-axial-length (LAL, axial length > or = 26 mm) group. Both subgroups had the deepest visual field defects in the upper and lower nasal areas. The LAL group had deeper visual field defects and the defects were more frequently involved in all sectors analyzed than the SAL group defects. The upper visual field had deteriorated more in the SAL group, whereas the depth of scotoma was similar in the upper and lower hemifields in the LAL group. Our results support the idea that glaucoma patients have a longer axial length than people without glaucoma, and that visual field defects are more pronounced in patients with LAL than in those with SAL.     

Malignant glaucoma induced by miotics postoperatively in open-angle glaucoma

A case of malignant glaucoma that developed in a patient with primary open-angle glaucoma is described. The malignant course was induced during the immediate postoperative period by the inadvertent use of miotics. The malignant course was successfully managed by osmotic agents, acetazolamide, cycloplegics, mydriatics, and topical steroids.     

Genetic mapping of autosomal dominant primary open-angle glaucoma (POAG) in Sardinia

Primary open-angle glaucoma (POAG) can be subdivided into two groups according to age of onset: (1) the more prevalent middle to late-age-onset chronic open-angle glaucoma (COAG) diagnosed after age 40, and (2) the less common form, juvenile open-angle glaucoma (JOAG), which occurs between 3 years of age and early adulthood. Susceptibility to either COAG or JOAG has been found to be inherited. The discovery of several genetic markers spanning the region 1q21-q24 in genetic linkage with autosomal dominant juvenile open-angle glaucoma (adJOAG) represents a major breakthrough towards the localisation of gene(s) responsible for the disease. Linkage analysis is a powerful means of distinguishing disease loci in large families with dominant disease. However the size of the group of families may represent a crucial factor for the linkage analysis. Sardinia is an island with a relatively isolated ethnic group showing a relatively high frequency of ad JOAG and COAG (Fossarello et al, 1994) and it is genetically more homogeneous than most Western populations. Therefore it represents an ideal ethnic group to search for linkage. We identified 18 families affected by POAG in which the disease appears to be inherited as autosomic dominant trait. In all families but two, occurrence of both JOAG and COAG in the same kindred was observed. Identification of adPOAG locus was performed by linkage analysis using 9 microsatellite markers spanning the region 1q21-q24. No significant linkage was observed. Our findings provide further evidence for genetic heterogeneity in autosomal dominant primary open angle glaucoma, even in a geographic area where a relatively homogeneous genetic background exists.     

Non-penetrating deep sclerectomy combined with a collagen implant in primary open-angle glaucoma. Medium-term retrospective results

PURPOSE: To evaluate the middle term tonometric results of a new filtering procedure, the non penetrating deep sclerectomy with collagen device, in primary open-angle glaucoma. This technique aims to eliminate or minimize the complications of classical trabeculectomy. MATERIAL AND METHOD: This procedure has been developed by Koslov et al. Under a limbal-base conjunctival flap and a superficial scleral flap, the ablation of a deep scleral flap takes away the external wall of Schlemm's canal, leaving only the Descemet membrane. A visible filtration across the opened Schlemm's canal and Descemet membrane is obtained. To improve the aqueous filtration, a cylindric collagen device, made from biocompatible porcine scleral tissue, known for its high water content, is fixed in the deep scleral bed with a 10/0 nylon suture. This device provides a support for the elimination route of aqueous humor and acts like a sponge, carrying the liquid by capillary action. It is sterilized by irradiation. Full guarantee against viral contamination is provided. This procedure ends in one suture (40/0 nylon) of superficial scleral flap and conjunctival closing suture. We conducted a retrospective study. Our material included 159 patients (92 males, 65 females), 2/9 eyes. The mean age was 65 years (11-91). The mean follow-up : 8 months (3-20). The types of glaucoma were: POAG: 183 eyes; juvenile POAG: 18 eyes: pigmentary glaucoma: 11 eyes; capsular glaucoma: 7 eyes, 58 eyes (40 patients) presented one or several risk factors of failure for filtering surgery. RESULTS: The mean pre-operative IOP was 24 mmHg +/- 6.60; 15.7 +/- 5.30 at the end of the follow-up (delta average IOP: 9.1 +/- 7.1). The probability success rate (IOP < or = 20 mmHg), according to the Kaplan-Meier Method, was 89% at six months, 75.6% at 16 months. With monotherapy with beta blockers, 79% at 16 months. It was better in the without risk factors group. The mean change in visual acuity was inferior to 0.1 at the end of the follow-up. Except several hyphemas, no complications of the trabeculectomy were observed. The reelevation of IOP was due to an internal obstruction (goniosynechiae or bad filtration), it was treated with Nd-Yag laser with a 2/3 of success rate. External obstruction was treated by 5FU injections into the bleb. CONCLUSION: Non penetrating deep sclerectomy with collagen device can be an excellent alternative to trabeculectomy in open and wide angles. It does not modify visual actuity. It carries less complications than trabeculectomy and the use of antimitotic agents is safer.     

A comparative study of visual field damage in low-tension and primary open-angle glaucoma

Methods to encapsulate biological materials are now widely used. Sometimes bioencapsulation is considered as a universal technique conducting to identical results independently on the biological material used. For instance, a similar behavior is frequently waited for different strains of immobilized microorganisms without taking into account substantial differences in its physiological and morphological characteristics. Often interactions with the matrix support are also neglected. Thus, some concepts developed throughout all these years working in bioencapsulation merits to be revisited.     

Plasma cortisol suppression test used to predict the development of primary open-angle glaucoma

Forty patients classified as high responders (GG) to dexamethasone testing (intraocular pressure greater than 31 mm Hg) without visual field loss were subjected to plasma cortisol suppression testing. After a five-year follow-up adequate data were available on 35 patients. Eighteen responded to 1.0 mg of dexamethasone-diphenylhydantoin suppression testing in a similar fashion to patients with primary open-angle glaucoma while 17 responded in a similar fashion to subjects classified as low (NN, intraocular pressure less than 20 mm Hg) and intermediate (NG, intraocular pressure 20 to 31 mm Hg) responders to dexamethasone testing. Eight of the 35 patients developed glaucomatous visual field loss during the follow-up period. These eight patients were not more sensitive to suppression of plasma cortisol than the 27 patients maintaining normal visual fields. Thus, plasma cortisol suppression testing failed to predict the development of primary open-angle glaucoma in GG responders.     

Molecular basis of open-angle glaucoma in Italy

Glaucoma is a group of ocular diseases characterized by an optic neuropathy in which degeneration of retinal ganglion cells leads to a characteristic excavation of the optic nerve head. Primary open-angle glaucoma (POAG) can be subdivided into two groups according to age of onset:- 1. the more common middle- to late-age onset, chronic open-angle glaucoma (COAG) diagnosed after the age of 40 years; 2. the rarer juvenile open-angle glaucoma (JOAG), which is diagnosed between the age of 3 years and early adulthood. Recently, the gene coding for the trabecular meshwork-induced glucocorticoid response protein (TIGR), located in chromosome 1 (1q23-25), was found mutated in patients affected by POAG. In this work we describe the clinical and molecular genetic features of several Italian families affected by autosomal dominant POAG, collected in various regions of Italy.