Testing the Eligibility of Glaucoma Patients for Potential Gene Therapy Among a Clinic Population

Abstract Purpose Glaucoma patients who deteriorate despite standard treatment may benefit from novel gene therapies. Key inclusion criteria for a glaucoma gene therapy trial were devised. A retrospective chart review in a glaucoma clinic population was conducted. Feasibility of gene therapy inclusion criteria and factors associated with progression and fast progression < -1 decibels/year (dB/y) were evaluated. Methods 374 Primary Open Angle Glaucoma patients all of whom had performed at least 5 Swedish Interactive Threshold Algorithm Standard visual fields within a 58 months period. Two definitions were applied to characterise visual field progression rate using Guided Progression Analysis for an individual patient based on A, the eye with the greatest visual field loss, or B, the eye with the most rapid progression rate. Results Mean rate of visual field progression was − 0.50 dB/y (Definition A) and − 0.64 dB/y (Definition B). 19.0% (A) and 21.9% (B) of eyes, 71 (A) and 82 (B) eyes, were ‘fast progressors’ (< -1 dB/y). 37 (A) and 43 (B) eyes met the putative gene therapy inclusion criteria (≥ 50 years; mean deviation ≤ -4 to ≥ -12; ≤ -20 dB, progression rate between − 1 to -4 dB/y). Beta blockers (Odds ratio (OR) with 95% Confidence Intervals (CI): 2.84 (1.39–5.80); p = 0.004) (A), (OR (95%CI): 2.48 (1.30–4.75); p = 0.006) (B) and alpha agonists (OR (95%CI): 2.18 (1.14–4.17); p = 0.02) (A), (OR (95%CI) 2.00 (1.08–3.73); p = 0.028) (B) were significantly associated with fast progression. Conclusion A substantial proportion (10%) of patients in this clinic population would meet recommended gene therapy inclusion criteria.

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Long-Term Clinical Course of Normal-Tension Glaucoma: 20 Years of Experience

Journal of Ophthalmology ◽

10.1155/2017/2651645 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Sang Wook Jin ◽

Seung Yoon Noh

Keyword(s):

Visual Field ◽

Clinical Course ◽

Visual Fields ◽

Reduction Rate ◽

Normal Tension Glaucoma ◽

Mean Deviation ◽

Progression Rate ◽

Visual Field Progression ◽

The Mean

Purpose. The purpose of this study was to investigate the long-term clinical course of NTG patients who initiated intraocular pressure- (IOP-) lowering therapy.Methods. The present study included 72 normal-tension glaucoma (NTG) patients. The mean deviation (MD) was measured with visual fields. Nocturnal hypotension with weighted standard deviation (wSD) was determined by 24-hour ambulatory blood pressure monitoring. To identify risk factors for NTG progression, linear logistic regression analysis was employed.Results. The mean follow-up period was 21.2 ± 1.1 years. The mean MD progression rate was −0.28 ± 0.24 dB/year. The mean ocular perfusion pressure (OPP) was 52.1 ± 5.9 mmHg. The mean wSD was 14.5 ± 2.2. In the univariate model, disc hemorrhage (RR 7.12;P=0.004), IOP reduction rate (RR 2.12;P=0.045), and OPP (RR 1.94;P=0.027) were associated with glaucomatous visual field progression. However, in the multivariate model, the IOP reduction rate (RR 2.45;P=0.048) and OPP (RR 2.02;P=0.004) were detected to be significant factors associated with progression.Conclusions. The mean rate of visual field progression was −0.28 dB/year in NTG patients treated with medical therapy. The IOP reduction rate and OPP were associated with glaucomatous visual field progression.

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Comparison of Three Parametric Models for Glaucomatous Visual Field Progression Rate Distributions

Translational Vision Science & Technology ◽

10.1167/tvst.4.4.2 ◽

2015 ◽

Vol 4 (4) ◽

pp. 2 ◽

Cited By ~ 6

Author(s):

Andrew J. Anderson

Keyword(s):

Visual Field ◽

Parametric Models ◽

Progression Rate ◽

Visual Field Progression

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Role of Central Corneal Thickness on Baseline Parameters and Progression of Visual Fields in Open Angle Glaucoma

European Journal of Ophthalmology ◽

10.1177/112067210701700411 ◽

2007 ◽

Vol 17 (4) ◽

pp. 545-549 ◽

Cited By ~ 14

Author(s):

H. Shah ◽

C. Kniestedt ◽

A. Bostrom ◽

R. Stamper ◽

S. Lin

Keyword(s):

Visual Field ◽

Central Corneal Thickness ◽

Open Angle Glaucoma ◽

Corneal Thickness ◽

Visual Fields ◽

Negative Relationship ◽

Significant Risk ◽

Mean Deviation ◽

Open Angle ◽

Visual Field Progression

Purpose To evaluate the relationship of central corneal thickness (CCT) to baseline visual field parameters and visual field progression in patients with primary open-angle glaucoma (POAG). Methods Charts of consecutive patients with POAG were reviewed to obtain visual field data. Visual field was measured by standard threshold static perimetry. Variables analyzed included mean deviation (MD) and pattern standard deviation (PSD). Results A total of 121 eyes examined over 4 years were evaluated. A significant negative relationship between CCT and PSD (correlation coefficient: −0.02, p<0.05) was found. Analyses comparing CCT to change in PSD and MD (visual field progression) were statistically not significant. Conclusions Patients with thinner corneas initially present with a greater visual field defect, indicating that thin corneas may contribute to advanced glaucomatous damage at the time of diagnosis. However, CCT does not seem to be a significant risk factor for progression of the disease.

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Classification and Statistical Trend Analysis in Detecting Glaucomatous Visual Field Progression

Journal of Ophthalmology ◽

10.1155/2019/1583260 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Cristiana Valente ◽

Elisa D’Alessandro ◽

Michele Iester

Keyword(s):

Statistical Analysis ◽

Standard Deviation ◽

Visual Field ◽

Trend Analysis ◽

Open Angle Glaucoma ◽

Mean Deviation ◽

Threshold Strategy ◽

Visual Field Progression ◽

The Mean

Aim. To evaluate the agreement between different methods in detection of glaucomatous visual field progression using two classification-based methods and four statistical approaches based on trend analysis. Methods. This is a retrospective and longitudinal study. Twenty Caucasian patients (mean age 73.8 ± 13.43 years) with open-angle glaucoma were recruited in the study. Each visual field was assessed by Humphrey Field Analyzer, program SITA standard 30-2 or 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA). Full threshold strategy was also accepted for baseline tests. Progression was analyzed by using Hodapp–Parrish–Anderson classification and the Advanced Glaucoma Intervention Study visual field defect score. For the statistical analysis, linear regression (r2) was calculated for mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI), and when it was significant, each series of visual field was considered progressive. We also used Progressor to look for a significant progression of each visual field series. The agreement between methods, based on statistical analysis and classification, was evaluated using a weighted kappa statistic. Results. Thirty-eight visual field series were analyzed. The mean follow-up time was 6.2 ± 1.53 years (mean ± standard deviation). At baseline, the mean MD was −7.34 ± 7.18 dB; at the end of the follow-up, the mean MD was −9.25 ± 8.65 dB; this difference was statistically significant (p<0.001). The agreement to detect progression was fair between all methods based on statistical analysis and classification except for PSD r2. A substantial agreement (κ = 0.698 ± 0.126) was found between MD r2 and VFI r2. With the use of all the statistical analysis, there was a better time-saving. Conclusions. The best agreement to detect progression was found between MD r2 and VFI r2. VFI r2 showed the best agreement with all the other methods. GPA2 can help ophthalmologists to detect glaucoma progression and to help in treatment decisions. PSD r2 was the worse method to detect progression.

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Progression to blindness in 20 years among patients with glaucomatous visual field loss in a tertiary hospital in the Philippines

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2019-000424 ◽

2020 ◽

Vol 5 (1) ◽

pp. e000424

Author(s):

Cathleen Camille Cabrera ◽

Joseph Anthony Tumbocon ◽

John Mark de Leon

Keyword(s):

Visual Field ◽

Life Expectancy ◽

Residual Life ◽

Visual Field Loss ◽

Tertiary Hospital ◽

The Philippines ◽

Mean Deviation ◽

Factors Associated ◽

Early Disease Detection ◽

Fast Progression

ObjectiveTo determine visual field (VF) rates of change among patients with glaucomatous VF loss and proportion of those becoming blind based on residual life expectancy and factors associated with fast progression.Methods and analysisThis was a retrospective study of the VFs of patients with glaucomatous VF defects in at least one eye. Baseline and final VFs were reviewed. Rates of VF change (decibels (dB)/year) for each eye, together with the residual life expectancy based on age and sex, were used to predict mean deviation/defect (MD) at the end of expected lifetime. Blindness was defined if computed MD was 22 dB (Octopus) or −22 dB (Humphrey) or worse in the better eye. Factors associated with fast progression (>1 dB/year for Octopus or <−1 dB/year for Humphrey) and blindness were determined.ResultsThere were 1016 eyes of 583 patients eligible. There was decline in VF MD/year in 613/1016 (60.3%), 95% CI (57.3% to 63.3%) of eyes; however, only 98/1016 (9.7%), 95% CI (7.9% to 11.5%) of eyes showed fast progression. Among patients with bilateral VFs, 43/433 (9.9%), 95% CI (7.1 to 12.8) of eyes were predicted to progress to blindness. In multivariate analysis, factors associated with fast progression were baseline MD (p<0.001) and male sex (p=0.041). Factors associated with blindness were age <60 years (p=0.003), baseline MD (p=0.022), bilateral glaucomatous VF defects (p=<0.001) and fast progression (p<0.001).ConclusionPatients reaching blindness in a routine clinical setting was 10%. Because of association of age and baseline MD on blindness, early disease detection is important. VF progression rates and residual life expectancy must be incorporated in glaucoma care.

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Retrobulbar Hemodynamics and Visual Field Progression in Normal Tension Glaucoma: A Long-Term Follow-Up Study

BioMed Research International ◽

10.1155/2015/158097 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

D. Kuerten ◽

M. Fuest ◽

E. C. Koch ◽

A. Koutsonas ◽

N. Plange

Keyword(s):

Visual Field ◽

Normal Tension Glaucoma ◽

Doppler Imaging ◽

Progression Rate ◽

Visual Field Progression ◽

Follow Up Study ◽

Long Term Follow Up ◽

Retrobulbar Hemodynamics

Purpose. Vascular risk factors are important factors in the pathogenesis of glaucoma. The purpose of this research was to investigate retrobulbar hemodynamics and visual field progression in patients with normal tension glaucoma (NTG).Patients and Methods. 31 eyes of 16 patients with NTG were included in a retrospective long-term follow-up study. Colour Doppler imaging was performed at baseline to determine various CDI parameters in the different retrobulbar vessels. The rate of visual field progression was determined using the Visual Field Index (VFI) progression rate per year (in %). To be included in the analysis, patients had at least 4 visual field examinations with a follow-up of at least 2 years.Results. Mean follow-up was 7.6 ± 4.1 years with an average of 10 ± 5 visual field tests. The mean MD (mean defect) at baseline was −7.61 ± 7.49 dB. The overall VFI progression was −1.14 ± 1.40% per year. A statistical significant correlation between VFI progression and the RI of the NPCA and PSV of the CRA was found.Conclusion. Long-term visual field progression may be linked to impaired retrobulbar hemodynamics in patients with NTG only to a limited degree. Interpretation of the data for an individual patient seems to be limited due to the variability of parameters.

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