Progression Of Open-angle Glaucoma Research Articles

Risk factors for primary open angle glaucoma progression: what we know and what we need to know

Recent literature is reviewed in order to identify possible risk factors leading to primary open angle glaucoma progression and blindness. Several risk factors have been suggested to be important for progression of open angle glaucoma. Intraocular pressure appears to be an important risk factor for progression of glaucoma. It is still not clear if intraocular pressure fluctuation and central corneal thickness are related to progression. Myopia might be related to glaucoma progression as well as optic disc hemorrhages. Vascular factors appear to be related to progression also. Genetics seem to play an important role in open angle glaucoma. Identifying risk factors associated with progression of patients with primary open angle glaucoma is essential to our clinical practices. The level of understanding regarding those risks is suboptimal at this point. Prospective long-term studies are needed if we wish to better understand the disease and help those patients at greater risk of progression and blindness.

Estimating the Rate of Progressive Visual Field Damage in Those with Open-Angle Glaucoma, from Cross-Sectional Data

To estimate the rate of visual field progression in open-angle glaucoma (OAG) subjects, by using data from population-based cross-sectional studies. Subjects with OAG were identified in nine surveys of randomly sampled populations using standard criteria for glaucomatous optic neuropathy. Subjects were of European, African, Chinese, and Hispanic ethnicity. The measure of OAG damage was the mean deviation (MD) of an automated visual field test (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA). The rate of progression was the mean of all subjects' damage in the worse eye divided by an average time since onset. Time since onset was estimated from age-specific prevalence rates. A total of 1066 subjects with OAG contributed visual field data. The mean worsening in decibels per year was: European-derived, -1.12; Hispanic, -1.26; African-derived, -1.33; and Chinese -1.56 (difference among ethnicities, P = 0.16). The mean duration of disease was lowest among Chinese persons at 10.5 years (95% CI: 8.8-12.6) and was highest in African-derived subjects at 15.4 years (95% CI: 14.6-15.9). The progression rate was not consistently related to age or gender. By combining disease duration and progression rate, the model predicted that 15% or fewer of the worse eyes would reach the end of the field damage scale in the patient's lifetime. The estimates of typical worsening per year in the worse eye among subjects with OAG suggested slightly more rapid progression than in some clinic-based studies. The rate did not differ significantly by ethnicity or gender, but was worse in those with known, treated OAG and in pseudophakic subjects.

Canadian Glaucoma Study: 1. Study design, baseline characteristics, and preliminary analyses

Background: The Canadian Glaucoma Study is a multicentred, prospective longitudinal study designed to study a variety of systemic risk factors for the progression of open-angle glaucoma under a standardised interventional protocol for intraocular pressure (IOP) control. Methods: Newly or previously diagnosed patients with early to moderate open-angle glaucoma were recruited consecutively from 5 hospital-based university departments. Baseline parameters, including an assessment of peripheral vasospasm, haematologic, coagulation, and immunopathologic variables were obtained. Newly diagnosed patients were targeted for a ≥30% reduction in IOP, whereas previously diagnosed patients entered the study at a physician-defined target IOP. After baseline examinations, patients were followed at 4-month intervals with standard automated perimetry, short-wavelength automated perimetry, and confocal scanning laser tomography, and at 28–32-month intervals with stereo disc photography. If the patient had visual field progression with standard automated perimetry, a further ≥20% reduction in IOP was mandated. A standardized IOP treatment protocol, ranging from topical monotherapy to filtration surgery, was implemented. Results: A total of 258 patients (130 men and 128 women, median age 65.0 years) were enrolled. Baseline median values for visual acuity, visual field mean deviation, untreated IOP, and refractive error were 0.10 logMAR, −4.04 dB, 25.0 mm Hg, and 0.00 D, respectively. Approximately 30% of the patients were hypertensive, 16% had cardiovascular disease, 9% thyroid disease, 9% diabetes, 14% migraine, and 19% were smokers.The median follow-up was 5.3 years, with 148 (57.0%) and 51 (19.8%) patients completing ≥5 and ≥7 years follow-up, respectively. The cumulative visual field progression rate at 2,4,6, and 8 years was 11.3%, 21.5%, 33.1%, and 43.5%, respectively. Interpretation: We describe the study design and baseline patient characteristics of the Canadian Glaucoma Study and present some preliminary results. This long and close followup of a large group of patients will reveal the importance of several systemic factors for the progression of glaucoma.

Canadian Glaucoma Study: 1. Study design, baseline characteristics, and preliminary analyses.

The Canadian Glaucoma Study is a multicentered, prospective longitudinal study designed to study a variety of systemic risk factors for the progression of open-angle glaucoma under a standardised interventional protocol for intraocular pressure (IOP) control. Newly or previously diagnosed patients with early to moderate open-angle glaucoma were recruited consecutively from 5 hospital-based university departments. Baseline parameters, including an assessment of peripheral vasospasm, haematologic, coagulation, and immunopathologic variables were obtained. Newly diagnosed patients were targeted for a >or=30% reduction in IOP, whereas previously diagnosed patients entered the study at a physician-defined target IOP. After baseline examinations, patients were followed at 4-month intervals with standard automated perimetry, short-wavelength automated perimetry, and confocal scanning laser tomography, and at 28-32-month intervals with stereo disc photography. If the patient had visual field progression with standard automated perimetry, a further >or=20% reduction in IOP was mandated. A standardized IOP treatment protocol, ranging from topical monotherapy to filtration surgery, was implemented. A total of 258 patients (131 [corrected] men and 127 [corrected] women, median age 65.0 years) were enrolled. Baseline median values for visual acuity, visual field mean deviation, untreated IOP, and refractive error were 0.10 logMAR, -4.04 dB, 25.0 mm Hg, and 0.00 D, respectively. Approximately 30% of the patients were hypertensive, 16% had cardiovascular disease, 9% thyroid disease, 9% diabetes, 14% migraine, and 19% were smokers. The median follow-up was 5.3 years, with 148 (57.0%) and 51 (19.8%) patients completing >or=5 and >or=7 years follow-up, respectively. The cumulative visual field progression rate at 2, 4, 6, and 8 years was 11.3%, 21.5%, 33.1%, and 43.5%, respectively. We describe the study design and baseline patient characteristics of the Canadian Glaucoma Study and present some preliminary results. This long and close follow-up of a large group of patients will reveal the importance of several systemic factors for the progression of glaucoma.

Longitudinal changes in the visual field and optic disc in glaucoma

The nature and mode of functional and structural progression in open-angle glaucoma is a subject of considerable debate in the literature. While there is a traditionally held viewpoint that optic disc and/or nerve fibre layer changes precede visual field changes, there is surprisingly little published evidence from well-controlled prospective studies in this area, specifically with modern perimetric and imaging techniques. In this paper, we report on clinical data from both glaucoma patients and normal controls collected prospectively over several years, to address the relationship between visual field and optic disc changes in glaucoma using standard automated perimetry (SAP), high-pass resolution perimetry (HRP) and confocal scanning laser tomography (CSLT). We use several methods of analysis of longitudinal data and describe a new technique called "evidence of change" analysis which facilitates comparison between different tests. We demonstrate that current clinical indicators of visual function (SAP and HRP) and measures of optic disc structure (CSLT) provide largely independent measures of progression. We discuss the reasons for these findings as well as several methodological issues that pose challenges to elucidating the true structure-function relationship in glaucoma.

Clinical relevance of optineurin sequence alterations in Japanese glaucoma patients

Purpose:To study the clinical relevance of sequence alterations in the optineurin gene (OPTN) among Japanese patients with open-angle glaucoma, including both primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Methods:Genomic DNA was isolated from 83 patients with open-angle glaucoma (55 with POAG and 28 with NTG) and 58 control subjects. The 13 exons of OPTN corresponding to the coding region were amplified by polymerase chain reaction and directly sequenced. Clinical factors were compared between glaucoma patients with and without a certain nucleotide change. Results:The reported heterozygous mutations, c.458G > A(Glu50Lys) in exon 4 and c.691_692insAG in exon 6, were not found in any glaucoma patients or control subjects. The reported c.603T > A(Met98Lys) in exon 5 was significantly more prevalent in the POAG (8/55, 14.5%, p = 0.0147) and NTG (4/28, 14.2%, p = 0.0369) patients, and even in both the POAG and NTG patients combined (12/83, 14.4%, p = 0.0149, Fisher exact probability test), than in the control subjects (1/58, 1.7%). The rates of the reported c.1944G > A(Arg545Gln) in exon 16 were not significantly different between open-angle glaucoma patients (3/83, 3.6%) and control subjects (4/58, 6.8%). In addition, a heterozygous change, c.412G > A(Thr34Thr) in exon 4 was found in 18 (21.6%) open-angle glaucoma patients and seven (12.0%) control subjects. Another heterozygous change, c.457C > T(Thr49Thr), in exon 4 was found only in three POAG patients. The 18 open-angle glaucoma patients with c.412G > A showed significantly larger cup-to-disc ratios (p = 0.0178, Mann-Whitney U test), significantly more deteriorated mean deviations of the visual field in the left eye at the final visit (p = 0.0076), and a significantly higher rate of surgery and/or laser history (p = 0.0321, Fisher exact probability test) than the 65 open-angle glaucoma patients without the nucleotide change. Conclusions:Met98Lys is a risk-associated alteration for open-angle glaucoma, including POAG and NTG, in the Japanese population as initially reported. The amino acid-preserving polymorphism, c.412G > A, may be a genetic risk factor for the progression of open-angle glaucoma in this Japanese population.

Using the arteriolar Pressure Attenuation Index to predict ocular hypertension progression to open-angle glaucoma.

Vascular phenomena are considered important to optic nerve and visual field progression in open-angle glaucoma (OAG). A recently described formulation, the Pressure Attenuation Index (PAI), links arteriolar caliber variations to pressure loss along the retinal arteriolar system. To examine whether the PAI could predict ocular hypertension (OHT) progression to OAG. The PAI was calculated for 27 eyes of 14 patients with OHT using initial and final digitized optic disc photographs taken during a follow-up interval of 5 to 18 years. Serial stereo color disc photographs and visual fields were analyzed to determine progression. At baseline, the arteriolar tree of 8 subjects with OHT that progressed to OAG (n = 8 eyes) demonstrated a 45.8% greater mean PAI value than that of 7 subjects who did not progress (n = 7 eyes) (mean +/- SEM, 5.31 +/- 0.93 vs 3.64 +/- 0.34; r = 0.83). Progression was independent of baseline cup-disc ratio. The PAI values of subjects with stable OHT remained stable after a median follow-up interval of 12.0 years. The PAI values of subjects with OHT that progressed demonstrated a further increase of 19.97% +/- 11.24% during a median follow-up period of 6.0 years. The results support the hypothesis that low end-arteriolar pressure predicts the progression from OHT to OAG. The PAI provides a new, early, reproducible, and physiological method to study vascular phenomena in glaucoma.

Correlation of visual field progression between eyes in patients with open-angle glaucoma

Purpose To investigate the correlation of visual field progression between eyes in patients with chronic forms of open-angle glaucoma (OAG) and to determine risk factors for progression. Design Retrospective observational case series. Participants One hundred fifty-two patients seen between April and November 2000 undergoing bilateral treatment for at least 2 years for OAG and who were followed with standard automated perimetry at the University of Washington Medical Center Eye Clinic. Methods Visual field progression was defined using criteria modified from Anderson and Advanced Glaucoma Intervention Study (AGIS) scoring. Progression from a normal to an abnormal visual field required abnormality of two of three criteria (glaucoma hemifield test, corrected pattern standard deviation, and total deviation plot abnormality) on at least two consecutive fields. For abnormal visual fields, criteria for progression were modified from Anderson and were based on worsening observed at three adjacent points on the total deviation plot on at least two consecutive fields. Another definition of progression was a change in AGIS score of four or more points. Main outcome measures Visual field progression. Results The mean follow-up period was 7.5 ± 3.6 years. Fifty-four patients (35.5%) showed progression of the more severely affected of the two eyes (worse eye), and 37 patients (24.3%) had progression in the less affected fellow (better) eye. Among these patients, 24 (15.8%) had bilateral progression (44% and 65% of worse and better eyes with progression, respectively). The between-eye correlation for progression was statistically significant (chi-square with Yates’ continuity correction; χ = 16.7, P = 0.00004; R = 0.348, P = 0.00001). The Kaplan-Meier estimates at 10 years for progression in the worse eye, the better eye, and both eyes was 44%, 33%, and 21%, respectively. Conclusions Between-eye correlation of visual field progression in patients with chronic OAG was statistically and clinically significant. Patient-specific factors may play an important role in visual field progression in OAG. Documented progression of visual field loss in one eye may prompt the physician to consider reducing the target intraocular pressure in both eyes.

Rate of Progression in Open-angle Glaucoma Estimated From Cross-sectional Prevalence of Visual Field Damage

To estimate the rate of visual field loss in persons with open-angle glaucoma. The visual field data obtained by Goldmann perimetry from 151 persons with open-angle glaucoma from the Baltimore Eye Survey were graded on a nine-level severity scale. Approximately one half of these persons had previously diagnosed glaucoma and were being treated. Using regression analysis, their scores were compared to other features, including age, vertical cup/disk ratio, treatment status, gender, race, and intraocular pressure. These data were used to estimate the average rate of progressive field loss and blindness in glaucoma. Among 112 black subjects, the severity of visual field damage was significantly associated with age (P < .02), history of glaucoma treatment (P < .04), and intraocular pressure (P < .0001). Using the relationship between age and damage, we estimated that the rate of deterioration of black glaucoma subjects was two grading levels per decade, which is consistent with previous reports. For 39 white subjects, the inclusion of age improved the model relationship between damage score and other variables. The best estimate of individual damage rate for whites was similar to that in blacks. However, the statistical association of age and damage in whites was less strong than in blacks, possibly because of fewer white subjects in the sample. While glaucoma is a frequent cause of visual disability, rate of progressive visual field loss is not sufficient to lead to bilateral blindness in the majority of those affected. Aggressiveness of glaucoma therapy should be related to the rate of visual field loss stressing confirmation of field progression.

Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma

The content of the fibronectin, an extracellular glycoprotein in the drainage outflow system of human eyes was determined by the indirect immunoperoxidase staining technique. The degree of fibronectin accumulation in ocular tissues was evaluated by quantitative morphometric analysis. It was shown that the fibronectin level was elevated in the ocular drainage outflow system of humans in ageing and was rapidly increased at different stages of primary open-angle glaucoma development. Increased deposit of fibronectin in trabecular tissues, mainly, in the inner wall of Schlemm's canal and juxtacanalicular, or cribriform part of trabecular meshwork, was demonstrated along with ageing and glaucoma disease progression. A hypothesis underlying the glaucomatous process as an adhesive impairment was proposed