High-tension Open-angle Glaucoma Research Articles

Comparing Perimetric Loss at Different Target Intraocular Pressures for Patients with High-Tension and Normal-Tension Glaucoma

To compare forecasted changes in mean deviation (MD) for patients with normal-tension glaucoma (NTG) and high-tension open-angle glaucoma (HTG) at different target intraocular pressures (IOPs) using Kalman filtering, a machine learning technique. Retrospective cohort study. From the Collaborative Initial Glaucoma Treatment Study or Advanced Glaucoma Intervention Study, 496 patients with HTG; from Japan, 262 patients with NTG. Using the first 5 sets of tonometry and perimetry measurements, each patient was classified as a fast progressor, slow progressor, or nonprogressor. Using Kalman filtering, personalized forecasts of MD changes over 2.5 years' follow-up were generated for fast and slow progressors with HTG and NTG with IOPs maintained at hypothetical IOP targets of 9 to 21 mmHg. Future MD loss with different percentage IOP reductions from baseline (0%-50%) were also assessed for the groups. Mean forecasted MD change at different target IOPs. The mean (± standard deviation) patient age was 63.5 ± 10.5 years for NTG and 66.5 ± 10.9 years for HTG. Over the 2.5-year follow-up, at target IOPs of 9, 15, and 21 mmHg, respectively, the mean forecasted MD losses for fast progressors with NTG were 2.3 ± 0.2, 4.0 ± 0.2, and 5.7 ± 0.2 dB; for slow progressors withNTG, losses were 0.63 ± 0.02, 1.02 ± 0.03, and 1.49 ± 0.07 dB; for fast progressors with HTG, losses were 1.8 ± 0.1, 3.4 ± 0.1, and 5.1 ± 0.1 dB; and for slow progressors with HTG, losses were 0.55 ± 0.06, 1.04±0.08, and 1.59 ± 0.10 dB. Fast progressors with NTG had greater MD decline than fast progressors with HTG at each target IOP (P≤0.007 for all). The MD decline for slow progressors with HTG and NTG were similar (P≥0.24 for all target IOPs). Fast progressors with HTG had greater MD loss than those with NTG with 0%-10% IOP reduction since baseline (P ≤ 0.01 for all), but not 25% (P= 0.07) or 50% (P= 0.76) reduction since baseline. Machine learning algorithms using Kalman filtering techniques demonstrate promise at forecasting future MD values at different target IOPs for patients with NTG and HTG.

Retinal Vasculometry Associations With Glaucoma: Findings From the European Prospective Investigation of Cancer–Norfolk Eye Study

PurposeTo examine retinal vasculometry associations with different glaucomas in older British people.DesignCross-sectional study.MethodsA total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined.ResultsA total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (−3.2 μm; 95% confidence interval [CI] −4.4 μm, −1.9 μm) and venules (−2.7 μm; 95% CI −4.9 μm, −0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (−0.2 mm2; 95% CI −0.3 mm2, −0.1 mm2) and NTG (−0.2 mm2; 95% CI −0.3 mm2, −0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (−3.9%; 95% CI −7.7%, −0.1% and −4.8%; 95% CI −7.4%, −2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses.ConclusionsRetinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma.

Differences in swept-source OCT angiography of the macular capillary network in high tension and normal tension glaucoma.

ABSTRACT Aim of the study The purpose of the present study was to determine if swept-source optical coherence tomography angiography (OCTA) of the superficial plexus in the macular region can detect differences between high-tension open-angle glaucoma (HTG) and normal-tension glaucoma (NTG). Materials and Methods In this prospective study 60 eyes from 60 patients (40 HTG; 20 NTG) underwent fovea centred 3 × 3 mm cube macula OCTA imaging by a swept-source OCTA device (Plex Elite, Zeiss, Jena, Germany). Quantitative analysis of the vasculature at the superficial plexus was performed by assessing the Perfusion Density (PD), defined as the total area of perfused vasculature per unit area in a region of measurement, for each group, respectively. Besides, macular ganglion cell layer thickness and mean deviation from visual field testing was assessed and correlated with PD. Results Average superficial PD of the measured 3 × 3 mm field was comparable between HTG and NTG (P = .567). In both groups a significant relation of PD and age (HTG: r = −0.48, p = .002; NTG: r = −0.615; p = .004) was shown, indicating reduced PD with increasing age. For both groups a positive correlation between PD and mean deviation (MD) (HTG: r = 0.492, p = .003; NTG: r = 0.530, p = .029) as well as PD and GCL thickness was shown (r = 0.486, p = .002 vs. r = 0.389; p = .09). However, the latter did not reach statistical significance in the NTG group. Conclusion PD at the central 3 mm around the fovea is comparable between HTG and NTG. Significant correlation with age and MD was shown in both groups.

Using Kalman Filtering to Forecast Disease Trajectory for Patients With Normal Tension Glaucoma

To determine whether a machine learning technique called Kalman filtering (KF) can accurately forecast future values of mean deviation (MD), pattern standard deviation, and intraocular pressure for patients with normal tension glaucoma (NTG). Development and testing of a forecasting model for glaucoma progression. We parameterized and validated a KF (KF-NTG) to forecast MD, pattern standard deviation, and intraocular pressure at 24months into the future using 263 eyes of 263 Japanese patients with NTG. We determined the proportion of patients with MD forecasts within 0.5, 1.0, and 2.5 dBs of the actual values and calculated the root mean squared error (RMSE) for each forecast. We compared KF-NTG with a previously published KF model calibrated using patients with high-tension open-angle glaucoma (KF-HTG) and to 3 conventional forecasting algorithms. The 263 patients with NTG had mean ± standard deviation age of 63.4 ± 10.5 years. KF-NTG forecasted MD values 24months ahead within 0.5, 1.0, and 2.5 dBs of the actual value for 78 eyes (32.2%), 122 eyes (50.4%), and 211 eyes (87.2%), respectively. The proportion of eyes with MD values forecasted within 2.5 dB of the actual value for the KF-NTG (87.2%) were similar to KF-HTG (86.0%) and the null model (86.4%), and much better than the 2 linear regression-based models (72.7-74.0%; P < .001). When forecasting MD, KF-NTG (RMSE= 2.71) and KF-HTG (RMSE= 2.68) achieved lower RMSE than the other 3 forecasting models (RMSE= 2.81-3.90), indicating better performance. As observed previously for patients with HTG, KF can also effectively forecast disease trajectory for many patients with NTG.

Phenotypic differences in normal vs high tension glaucoma.

Normal tension glaucoma (NTG) and high tension open angle glaucoma (HTG) are associated with characteristic patterns of optic nerve findings and corresponding patterns of visual field loss. In the past, clinicians viewed NTG and HTG as distinct entities, with separate underlying pathophysiologies and often different clinical presentations and courses. Literature review. Optic nerve and visual field findings in NTG have been reported to be dissimilar to those in HTG. In more recent years, however, there has been increasing recognition of the shared features NTG and HTG. There is now a trend to consider these two entities as part of a spectrum of glaucoma with overlapping pathophysiology and clinical characteristics.

Selected Abstracts From Other Journals

Objective: To investigate cross-sectional associations among blood pressures (BPs), arterial stiffness, and open-angle glaucoma (OAG). Methods: Study participants came from the population-based Rotterdam Study. The baseline examination phase took place after an extensive home interview from March 20, 1990, to June 17,1993, and the third phase between March 19,1997, and December 16,1999. Cases were classified into high-tension OAG (htOAG) and normal-tension OAG (ntOAG), according to an intraocular pressure greater than 21 mm Hg or 21 mm Hg or less. Pulse pressure was the difference between systolic and diastolic BP. Diastolic perfusion pressure was the difference between diastolic BP and the intraocular pressure; indicators of arterial stiffness were carotidfemoral pulse wave velocity and carotid distensibility. Associations were evaluated with logistic regression analysis, adjusted for age, sex, body mass index, smoking, diabetes mellitus, serum cholesterol level, and BPlowering treatment.

Blood Pressure, Arterial Stiffness, and Open-angle Glaucoma

To investigate cross-sectional associations among blood pressures (BPs), arterial stiffness, and open-angle glaucoma (OAG). Study participants came from the population-based Rotterdam Study. The baseline examination phase took place after an extensive home interview from March 20, 1990, to June 17, 1993, and the third phase between March 19, 1997, and December 16, 1999. Cases were classified into high-tension OAG (htOAG) and normal-tension OAG (ntOAG), according to an intraocular pressure greater than 21 mm Hg or 21 mm Hg or less. Pulse pressure was the difference between systolic and diastolic BP. Diastolic perfusion pressure was the difference between diastolic BP and the intraocular pressure; indicators of arterial stiffness were carotid-femoral pulse wave velocity and carotid distensibility. Associations were evaluated with logistic regression analysis, adjusted for age, sex, body mass index, smoking, diabetes mellitus, serum cholesterol level, and BP-lowering treatment. A total of 5317 participants were included in this study. In participants with a higher pulse pressure, the prevalence of htOAG was elevated (odds ratio [OR] per standard deviation, 1.32; 95% confidence interval [CI], 1.03-1.69). In persons treated for systemic hypertension, low diastolic perfusion pressure (<50 mm Hg) was inversely associated with ntOAG (OR, 0.25; 95% CI, 0.10-0.63) and positively associated with htOAG (OR, 4.68; 95% CI, 1.29-17.01). The lowest tertile of carotid distensibility compared with the highest had an OR for htOAG of 2.84 (95% CI, 0.99-8.10; P=.05). We found that htOAG was associated with high pulse pressure, possibly with increased carotid arterial stiffness, and, only in persons treated for systemic hypertension, with low diastolic perfusion pressure. In these persons, ntOAG was associated with high diastolic BP, whereas the association between ntOAG and low diastolic perfusion pressure was inverted.

Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma

Purpose To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open-angle glaucoma. Design Prospective case control study. Methods The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test. Results The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal-tension glaucoma was found to harbor the previously reported Glu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients. Conclusions This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease–causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.

Dopamine, dopaminergic drugs and ocular hypertension.

The study refers to the clinical experiences performed with several D1 and D2 dopaminergic receptors agonists in 20 patients with high tension open angle glaucoma. The substances were administered topically as eye drops as well as an ocular eye bath. The parameter examined was intraocular pressure (IOP). The substances taken in consideration were: Dopamine, Ibopamine (dopamine analog), Fenoldopam and 3B90 (D1-receptor agonists) and Bromocriptine (dopaminergic agonist with higher affinity for D2 than for D1-receptors). It has been shown that all selective D1-receptors agonists induce a significant increase in IOP only in eyes with hydrodynamic disorders (p < 0.001). Such hypertensive effects could not be antagonized either by topically administered dopaminergic antagonists (Sulpiride, D2-receptors antagonist, and Haloperidol, non-selective dopaminergic antagonist) or by the pretreatment with the commonly used topical antiglaucomatous drugs. The only substance which proved able to inhibit the IOP increase induced by the D1-receptors agonists was the D1-selective antagonist SCH-23390, suggesting that IOP increase may be a result of a stimulation of the D1-receptors. The authors hypothesize that dopaminergic system may play a role in the regulation of aqueous humor hydrodynamics.

Visual Field Change in Low-tension Glaucoma over a Five-year Follow-up

There is some evidence that the nature and progression of disease in low-tension glaucoma may be distinct from other open-angle glaucomas. The authors assessed visual field change by retrospective case review of all patients treated for low-tension glaucoma by the Glaucoma Service, Wills Eye Hospital, for at least 5 years. Sixty-two glaucomatous eyes of 36 patients were identified. All eyes were treated medically and 40 (65%) underwent at least one surgical procedure. Twenty-eight eyes (47%) had initial field loss confined to a single hemi-field and in the remainder both hemi·fields were involved. Thirty of 57 eyes (53%) showed progression at 3 years and 38 (62%) of 57 had progressed by 5 years. A dense scotoma extending from the nasal periphery toward fixation was the most common visual field defect. The rate of field change in this population is significantly greater than in a cohort of primary open-angle glaucoma patients also seen at Wills Eye Hospital, but who had elevated intraocular pressures. Patterns of field loss and rate of progression in this lowtension glaucoma population suggest that the natural history of low-tension glaucoma differs from high-tension open-angle glaucoma.