Optical Coherence Tomography for Detecting Glaucoma Progression
Perhaps the greatest value of optical coherence tomography imaging is in the longitudinal monitoring of structural damage. Several studies have shown that imaging parameters such as RNFL, neural rim, and macular thickness measurements can detect progressive glaucomatous damage. In addition, these parameters can provide quantitative assessment of rates of change in the disease, which are essential for establishing appropriate treatment. Although most glaucoma patients will show some evidence of progression if followed long enough, the rate of deterioration can be highly variable among them. While most patients progress relatively slowly, others have aggressive disease with fast deterioration, which can eventually cause blindness or substantial impairment unless treated appropriately. The use of imaging may assist in detection of patients who are fast progressors in need of more aggressive intervention.
Several studies have used SD-OCT to evaluate the role of RNFL, ONH, and macular measurements in assessing glaucoma progression. However, it is difficult to determine whether 1 parameter is better than another because of the lack of a perfect reference (“gold”) standard. Also, although glaucomatous changes reflect loss of RGCs, the temporal relationship between changes to the ONH, RNFL, and macula are still poorly understood. Overall, RNFL, ONH, and macular parameters show faster rates of loss in glaucomatous eyes compared with typical age-related changes observed in control eyes; however, there is considerable variation in reported rates of change. Figure 5-17 shows SD-OCT RNFL scans that were acquired over time in an eye that developed progressive RNFL loss in the inferior temporal region.
Detection of disease progression depends fundamentally on the ability to differentiate true change from the noise of test–retest variability and from changes attributable to a normal aging process. Several studies have shown that measurements of RNFL, ONH, and macular thickness obtained via SD-OCT have excellent short-term reproducibility. These reproducibility studies suggest that a change in global RNFL thickness of 5 μm between tests may indicate progression. However, it is important to exercise caution when interpreting such cutoffs. Most studies examining reproducibility excluded poor-quality scans and analyzed short-term rather than long-term reproducibility. In clinical practice, patients are followed over the course of many years, and long-term variability may be considerably greater than in the short term.
At present, there is no consensus on the best way to detect glaucoma progression using OCT. Although trend-based assessment of RNFL thickness over time has been commonly employed, it is also important to differentiate changes due to glaucoma from age-related changes. Previous longitudinal studies have found mean rates of change of approximately −0.50 μm/year in average RNFL thickness in healthy subjects. Accordingly, high rates of false-positive detection of progression occur when the only criterion required is a statistically significant negative slope of RNFL thickness change as a function of time (ie, a slope that is statistically significantly different from 0 with P < .05). For example, after 5 years of annual testing, up to 25% of nonglaucomatous eyes can be falsely identified as having progressed if this criterion is used for change in RNFL thickness. It has been suggested that trend-based analysis of RNFL thickness change should involve at least testing the statistical significance of the change relative to the mean estimate of age-related changes. Doing so would be analogous to evaluating visual field progression using mean deviation instead of mean sensitivity (with the former being an age-adjusted parameter) and could be described as an RNFL mean deviation trend analysis.
Detection of longitudinal changes with OCT is important not only for detecting progression in eyes with existing damage but also for detecting changes in eyes suspected of disease, which would then help confirm the diagnosis of glaucoma. Due to the wide range of normative values, significant changes in RNFL thickness or other parameters may be observed well before the measurements fall into the “outside normal limits” range (Fig 18-5).
Given the relative stability of the BMO as a point of reference for repeat scans, one might suppose that measurements taken relative to BMO would be more helpful than conventional structural measurements for detecting glaucoma progression. However, a recent study has suggested that it may be more difficult to detect changes using measurements of BMO-MRW and BMO–minimum rim area because of a relatively low longitudinal signal-to-noise ratio compared with peripapillary RNFL thickness measurements. This observation may have been the result of changes in the location of the BMO over time, possibly related to fluctuations in IOP or because of connective tissue remodeling as a result of glaucoma progression. One study suggested that BMO is located more posteriorly in older individuals versus younger individuals, suggesting that it may migrate posteriorly with age and is therefore a less stable landmark than previously hoped. Longer-duration studies are needed to determine whether BMO can be used as a long-term stable reference from which to measure glaucomatous changes.
Figure 5-17 SD-OCT images showing progressive RNFL loss. There is progressive loss of the RNFL in the inferotemporal sector. The plot at the bottom of the figure shows the rate of change in the parameter average RNFL thickness.
(Courtesy of Felipe A. Medeiros, MD, PhD.)
Figure 5-18 Series of SD-OCT RNFL scans of a patient followed from 2012 to 2016. The patient was suspected of having glaucoma at the beginning of follow-up due to the appearance of the optic disc. Note that the initial scan does not show any clear abnormality, and all parameters are within normal limits. There is progressive RNFL loss, initially in the inferior region, but subsequently also affecting the superior region over time. Note that the global and sectoral RNFL thickness parameters become clearly abnormal (flagged in red) only after 4 years.
(Courtesy of Felipe A. Medeiros, MD, PhD.)
Regardless of which measurement parameter is best, there is now a large body of evidence that progressive changes on OCT are clinically relevant. Faster rates of RNFL loss, visualized by OCT, are also associated with a higher risk for the future development of visual field defects. A study found that each 1-μm/year faster rate of RNFL loss in glaucoma suspects corresponded to a twofold-increased risk for the development of a visual field defect. Similar results have also been described in eyes with established glaucoma, in which progressive RNFL thinning on trend-based progression analysis was strongly predictive of visual field loss. Higher rates of RNFL loss have also been associated with a faster decline in quality of life in patients with glaucoma. Assessment of glaucoma progression on OCT should be combined with an assessment of functional changes in perimetry. The relationship between structural and functional changes in glaucoma is discussed in more detail in Chapter 6.
Since the introduction of OCT more than 25 years ago, our ability to detect and quantify glaucomatous structural changes has improved significantly. OCT provides a means to obtain reproducible measurements of the RNFL, ONH, and macula, each of which is of value in quantifying glaucoma progression. Although visual function is what matters most to patients, progressive structural changes can precede functional loss. In addition, patients who demonstrate a faster rate of change on OCT are at increased risk of worsening vision loss; OCT offers these patients the possibility of escalating treatment at an earlier stage to preserve more vision. The ability to assess glaucoma progression is likely to be improved further by novel approaches that incorporate information from OCT and visual fields, reducing the noise inherent in both tests (for further discussion, see Chapter 6).
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.