Image from the Heidelberg Spectralis Glaucoma Module
Dr Rim Makhlouf
Nova Southeastern University College of Optometry, Florida USA
The irreversible nature of glaucoma makes prompt detection of progression crucial in order to preserve vision and prevent blindness.
Traditional ways of detecting glaucomatous progression include longitudinal stereoscopic analysis of the optic nerve, either ophthalmoscopically or by photography, as well as serial automated threshold perimetry.
The former method requires a trained eye to detect subtle morphologic changes in addition to the presence of observer-related subjectivity; the latter method can be difficult to use because patients are often poor visual-field-takers.
With poor visual-field takers, it may be especially challenging to distinguish between true glaucomatous changes and fluctuations that are due to inter-visit measurement variability or poor performance.
It is well established that evidence of structural changes may occur before any evidence of functional change is detected with automated perimetry.1,2 Therefore, assessment of structural parameters is crucial in determining glaucoma progression.
Optical coherence tomography (OCT) is an imaging technology that allows an in vivo cross-sectional view of the retina and optic nerve. It has emerged as a powerful tool in diagnosing and monitoring progression in glaucoma by measuring the thickness of the retinal nerve fibre layer (RNFL).
Time domain OCT
Two main generations of OCT are commercially available. Time domain OCT (TD-OCT) is the original version and measures progression based on event analysis. This type of analysis identifies progression when the amount of change in RNFL thickness from baseline exceeds a pre-established threshold considered to be indicative of true progression. Any amount of change below this threshold is assumed to be due to natural age-related loss and/or measurement variability.3 The disadvantages of this technique are the reduction of sensitivity if the threshold is set too low, or conversely, the reduction of specificity if the threshold is set too high.
Spectral domain OCT
Fortunately, technological advances have led to a new generation of OCT, spectral domain OCT (SD-OCT), which offers higher scanning rates and improved resolution, potentially decreasing the variability in RNFL thickness measurements.3 This allows the use of a trend-based approach for detecting progression by monitoring the behaviour of RNFL thickness over time, thus providing a rate of progression. This method is less sensitive to measurement variability because it is filtered out by the overall rate of change.3
It is important to note that there is often a poor agreement between functional and structural tests in the evaluation of glaucoma progression.4 Studies have shown that functional and structural tests may have different levels of sensitivity in detecting progression, depending on the stage of the disease.
In fact, in early glaucoma, progression by RNFL thickness is more noticeable than progression by visual field, whereas in advanced glaucoma, progression by visual field when expressed on a decibel scale is more noticeable than progression by RNFL thickness.4,5.6.7 Therefore, it may be less beneficial to use the OCT to detect progression in advanced glaucoma. Another reason is the ‘floor’ effect by which it becomes hard for the OCT to detect significant change and distinguish between true glaucomatous changes and measurement noise when the RNFL has become too thin.8
Ganglion cell complex
Another recent development is the use of SD-OCT to measure ganglion cell complex (GCC) thickness in order to detect glaucoma progression. As mentioned earlier, glaucoma involves loss of retinal ganglion cells. A retinal ganglion cell, like any other neuron, has a cell body, an axon and dendrites. The ganglion layer, RNFL and inner plexiform layer, respectively, represent the cell bodies, axons and dendrites of the retinal ganglion cells. Therefore, the GCC is the combination of all three of these layers.
The GCC thickness is measured at the level of the macula because retinal ganglion cell density is high in that area. As glaucoma progresses and ganglion cells continue to die, the GCC thickness decreases; therefore, progression is identified based on a trend analysis of GCC thickness over time. A recent study published by Bresciani-Battilana and colleagues found a strong correlation between GCC and RNFL parameters, suggesting that GCC is an additional structural parameter that can be used in the management of glaucoma.9
Because GCC is measured at the macula, it is important to rule out the presence of concurrent macular conditions that may affect results when taking GCC into consideration for glaucoma management.
Detecting progression remains one of the biggest challenges in glaucoma management even with the advent of recent technologies. OCT is a powerful tool in detecting structural changes but should not be used alone. It is important to look at both structure and function, due to the limited agreement between the two in regards to detection of progression.
1. Sommer A et al. Clinically detectable nerve fibre atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol 1991; 109: 1: 77-83.
2. Quigley HA et al. An evaluation of optic disc and nerve fiber layer examinations in monitoring progression of early glaucoma damage. Ophthalmology 1992; 99: 1: 19-28.
3. Kotowski J, Wollstein G, Folio L, Ishikawa H, Schuman J. Clinical use of OCT in assessing glaucoma progression. Ophthal Surg Laser Imag 2011; 42: 4: S6-S14.
4. Leung CK, Cheung CY et al. Evaluation of retinal nerve fiber layer progression in glaucoma: a study on optical coherence tomography guided progression analysis. Invest Ophthal Vis Sci 2010; 51: 1: 217-222.
5. Leung CK, Medeiros FA et al. American Chinese glaucoma imaging study: a comparison of the optic disc and retinal nerve fiber layer in detecting glaucomatous damage. Invest Ophthal Vis Sci 2007; 48: 6: 2644.
6. Schlottmann PG et al. Relationship between visual field sensitivity and retinal nerve fiber layer thickness as measured by scanning laser polarimetry. Invest Ophthal Vis Sci 2004; 45: 6: 1823-1829.
7. Leung CK et al. Comparative study of retinal nerve fiber layer measurement by StratusOCT and GDx VCC, I: correlation analysis in glaucoma. Invest Ophthal Vis Sci 2005; 46: 9: 3214.
8. Knight OJ, Chang RT et al. Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology 2009; 116: 7: 1271-1277.
9. Bresciani-Battilana E et al. Correlation between the ganglion cell complex and structural measures of the optic disc and retinal nerve fiber layer in glaucoma. Int Ophthalmol 2014; 35: 5: 645-650.
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