Historically, glaucoma progression was determined by evaluating the optic nerve in real-time and comparing it with previous fundus photography. The decision would then be made if the most recent picture indicated any change over time. Alternatively, practitioners would use visual field print-outs and inspect each field carefully to identify any flagged areas of field loss over time.
As the years went by, new developments came about to provide a better analysis of disease progression. Computer software has improved to where we can now identify clinical structural changes in microns long before the patient may experience any functional loss. The ZEISS CIRRUS RNFL OCT, Macula GCL/IPL OCT, and ZEISS HFA are clinical tools that provide a Guided Progression Analysis (GPA) report to highlight general and focal areas of progression in glaucoma patients over time.
Detecting change is important for patients diagnosed with glaucoma or as glaucoma suspects. This is a difficult task in itself, requiring periodic tests performed over years as change can occur anywhere in a patient’s lifetime. However, it becomes more difficult if you do not know how to appropriately interpret the analysis reports from these tools.
In this course we’ll review the common structural and functional tests by which glaucomatous progression can be identified at certain stages of the disease. We will also summarize the purpose of GPA and how to interpret the report, which will guide your clinical decision making on the treatment plan.
Disease Stage Matters
In the initial steps of glaucoma management, identify the stage of the disease. This will help to calculate their risk for progression, in addition to other factors1 such as:
- Intraocular pressure level
- Central corneal thickness
- Laterality of the disease
- Presence of disc hemorrhages
- Family history of glaucoma
- Comorbidities such as diabetes mellitus
Any glaucomatous progression may be measured by structural changes of the retinal nerve fiber layer (RNFL) at the optic nerve head and ganglion cell layer (GCL) at the macula using optical coherence tomography (OCT), or by functional changes noted as visual field deterioration using the Humphrey Field Analyzer (HFA). After you’ve established an appropriate baseline to be able to monitor for changes, the best method to detect progression will vary depending upon the disease stage.
Patients with mild to moderate stages of glaucoma at baseline are best monitored for progression in structural changes by RNFL OCT and GCL OCT. Patients with moderate to advanced stages of glaucoma at baseline are best monitored for progression in functional changes by HFA.
The Glaucoma Continuum, illustrated by Dr. Weinreb and colleagues,2 demonstrates that structural change often precedes functional change in the life span of the disease. Therefore, it makes sense that an OCT will detect structural changes to optic nerve head RNFL and macular GCL several years before visual field defects appear on the HFA. The average macular GCL thickness loss has shown to be detectable in all stages of glaucoma,3 therefore it may be beneficial to use GCL OCT longer than expected when compared to RNFL OCT.
Figure 1. The Glaucoma Continuum, presented in an article by Dr. Weinreb and colleagues in the American Journal of Ophthalmology (Vol 138, Issue 3, Sept. 2004), shows the progression of glaucoma from undetectable to asymptomatic to functional impairment.
Floor effect and tipping point
As the patient reaches the moderate to severe stages of glaucoma, they would have likely lost a significant amount of average RNFL thickness, leading to a “floor effect” on the OCT scan. Within the RNFL, the nerve fiber layers damaged from glaucoma comprise about 60% of the overall structure, while the remaining 40% include glial and other structural tissue that often remains.4
The average RNFL thickness will never reach zero, but rather halts to roughly 55-60um which is known as the floor effect. Structural changes on RNFL OCT scans will no longer be detectable on future imaging after this point.
As our patient transitions into the moderate stage of glaucoma, when should we expect visual field loss to develop? An article by Wollstein et al. performed a cross-sectional study5 to determine the average RNFL thickness at which VF damage becomes detectable and associated with structural loss. They identified a tipping point in which there is a statistically significant steeper decline in VF loss when the average RNFL thickness reaches 75um or less from age-matched normative value.
Substantial structural RNFL loss of 17%, or an average RNFL thickness of roughly 75um, appears to be the tipping point for functional visual field loss to be detectable.5,6
Figure 2. Plot showing healthy (H) and glaucoma (G) average RNFL thickness on the x-axis with corresponding visual field threshold values on the y-axis. The black line demonstrates the “broken stick” model, where the visual field declines at a slower rate with thicker average RNFL values. The tipping point is reached at 75um RNFL thickness where the visual field declines at a steeper rate.
Patient case: Demonstrating floor effect and tipping point
Here is an example of a patient with significant RNFL loss on an OCT scan in 2011. Focusing on the left eye, the average RNFL thickness falls below 60um and there are correlating VF defects on the 24-2.
As we monitor glaucomatous changes overtime between 2011 and 2016, notice that the average RNFL thickness in each quadrant plateaued as it reached the “floor effect”. We would not expect the RNFL thickness to decline any further, however, the patient’s visual field loss continued to decline significantly based on the 24-2 results.