Advanced Glaucoma Progression Study (AGPS)

Detection of Glaucoma Progression Study With Macular OCT Imaging

Glaucoma is one of the leading causes of blindness in the world. The key to prevention of visual loss from glaucoma is early detection of the disease or its progression and timely treatment. The proposed study will investigate the role of various tests in improving detection of disease progression in advanced glaucoma. Evaluation of the peripheral field of vision (visual field examination) remains the current standard for detection of progression in glaucoma. However, there is a lot of variability or inconsistency in eyes with advanced glaucoma, which could make it difficult to detect worsening of glaucoma with visual fields. The optic nerve demonstrates significant damage in such eyes and hence oftentimes repeat imaging of the optic nerve head is not helpful for detection of change. Therefore, imaging of the central retina (the innermost sensitive tissue lining the inside of the eye), called macula, has been proposed to supplant imaging of the nerve in eyes with severe glaucoma. The macula aids in detailed central vision. Since the macular retinal neural cells are the last ones to be affected in glaucoma, measurement of macular retinal thickness could provide significant information with regard to the course of glaucoma. In the proposed study, glaucoma patients will be tested and followed with various measurements done with newer versions of optical coherence tomography (OCT) imaging and visual field machines. The patients will undergo repeat imaging and visual field testing every 6 months over the course of 5 years. Rates of change will be estimated. We will explore if changes in various outcome measures derived from imaging are correlated with the corresponding visual field changes in glaucoma, and whether the former can be used as an alternative method for detecting simultaneous or subsequent glaucoma progression. The hypothesis for this proposed research is that macular OCT parameters are valid structural measures that can be used especially in advanced disease to follow the course of glaucoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Open Angle Glaucoma; Chronic Angle Closure Glaucoma; Pseudoexfoliative Glaucoma

Detailed Description

Glaucoma is a major public health issue worldwide and manifests clinically as a chronic progressive optic neuropathy with concomitant visual field (VF) loss. Glaucoma can cause significant visual disability and decreased quality of life (1). Based on WHO's report in 2002, glaucoma is the second cause of blindness. The key to prevention of visual loss from glaucoma is early detection of the disease or its progression and timely treatment. Glaucoma can be quite advanced at the time of initial detection. The prevalence of advanced glaucoma at the time of diagnosis varies but can be quite high. For example, the average VF mean deviation (MD) in patients diagnosed with glaucoma in the Los Angeles Latino Eye Study was -9.6 dB (2), which represents moderately advanced to severe glaucoma. Detection of progression in advanced stages of glaucoma continues to be challenging. Visual field examination remains the gold standard for detection of progression in advanced glaucoma. However, long-term VF variability or noise in such eyes is significant, which could confound detection of change. The optic nerve head and peripapillary retinal nerve fiber layer (RNFL) demonstrate significant damage in such eyes and hence are not helpful for detection of change. About 50% of retinal ganglion cells (RGCs) are located within 4-5 mm of the macular center (3). Since the macular RGCs are the last ones to be affected in glaucoma, measurement of macular retinal thickness or retinal sublayers could provide significant information with regard to the course of advanced glaucoma.

The macular retinal sublayers can now be measured with reasonable accuracy with SD- OCTs. There is some evidence that measurement of the macular ganglion cell complex (GCC, combined thickness of RNFL, RGC and inner plexiform layer or IPL), or macular retinal thickness or volume may detect early glaucoma with a performance that approximates that of circumpapillary RNFL thickness measurements (4,5). In addition, such macular measurements have proved to be very reproducible (4,6). Given this excellent reproducibility, macular outcome measures would be the main candidates for following glaucoma eyes with advanced damage, in which the macular region is essentially the only retinal area with residual RGCs.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Jules Stein Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Advanced glaucoma patients

Description

Inclusion Criteria:

• Clinical diagnosis of primary open angle glaucoma, pseudoexfoliative glaucoma, and angle closure glaucoma
• Visual field MD of -6dB or worse OR visual field loss involvement at at least two points within the central 10 degrees of the field

Exclusion Criteria:

• Patient not within the ages of 40-80 years old
• Visual acuity worse than 20/50 at baseline
• Spherical refraction worse than 8D and cylindrical refraction worse than 3D
• Significant retinal or neurological diseases including diabetic retinopathy or age-related macular degeneration

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Advanced glaucoma; Patients with MD < -6 or visual field loss within the central 10 degrees of the visual field.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual field progression	Worsening of the MD and/or increased visual field loss within the central 10 degrees of the field.	5 years
Worsening of OCT measurements	Worsening of macular and retinal nerve fiber layer (RNFL) OCT measurements.	5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contrast sensitivity	Looking at any changes in contrast sensitivity using the Vector Vision CSV-1000 eye chart.	5 years

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Eye Institute (NEI)
• Investigators: Principal Investigator: Kouros Nouri-Mahdavi, MD, MSc, Jules Stein Eye Institute, UCLA

Publications and helpful links

General Publications

• Tan O, Chopra V, Lu AT, Schuman JS, Ishikawa H, Wollstein G, Varma R, Huang D. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009 Dec;116(12):2305-14.e1-2. doi: 10.1016/j.ophtha.2009.05.025. Epub 2009 Sep 10.
• McKean-Cowdin R, Wang Y, Wu J, Azen SP, Varma R; Los Angeles Latino Eye Study Group. Impact of visual field loss on health-related quality of life in glaucoma: the Los Angeles Latino Eye Study. Ophthalmology. 2008 Jun;115(6):941-948.e1. doi: 10.1016/j.ophtha.2007.08.037. Epub 2007 Nov 12.
• Mori S, Hangai M, Sakamoto A, Yoshimura N. Spectral-domain optical coherence tomography measurement of macular volume for diagnosing glaucoma. J Glaucoma. 2010 Oct-Nov;19(8):528-34. doi: 10.1097/IJG.0b013e3181ca7acf.
• Varma R, Ying-Lai M, Francis BA, Nguyen BB, Deneen J, Wilson MR, Azen SP; Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology. 2004 Aug;111(8):1439-48. doi: 10.1016/j.ophtha.2004.01.025.
• Curcio CA, Allen KA. Topography of ganglion cells in human retina. J Comp Neurol. 1990 Oct 1;300(1):5-25. doi: 10.1002/cne.903000103.
• Mwanza JC, Oakley JD, Budenz DL, Chang RT, Knight OJ, Feuer WJ. Macular ganglion cell-inner plexiform layer: automated detection and thickness reproducibility with spectral domain-optical coherence tomography in glaucoma. Invest Ophthalmol Vis Sci. 2011 Oct 21;52(11):8323-9. doi: 10.1167/iovs.11-7962.
• Lee JW, Morales E, Sharifipour F, Amini N, Yu F, Afifi AA, Coleman AL, Caprioli J, Nouri-Mahdavi K. The relationship between central visual field sensitivity and macular ganglion cell/inner plexiform layer thickness in glaucoma. Br J Ophthalmol. 2017 Aug;101(8):1052-1058. doi: 10.1136/bjophthalmol-2016-309208. Epub 2017 Jan 11.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimated): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Glaucoma, Optical Coherence Tomography, Progression
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Eye Diseases; Ocular Hypertension; Disease Progression; Glaucoma; Glaucoma, Open-Angle; Glaucoma, Angle-Closure
• Other Study ID Numbers: IRB# 11-003602; 1K23EY022659-01 (U.S. NIH Grant/Contract)