Glaucoma is a neurodegenerative disease of the optic nerve that presents to the practitioner at various stages of a continuum that is characterized by accelerated retinal ganglion cell death, subsequent axonal loss and optic nerve damage, and eventual visual field loss.1
The initial changes in the optic nerve and retinal nerve fiber layer (RNFL) are often asymptomatic and undetectable with standard automated perimetry (SAP) and optic disc photography. Since glaucoma is a progressive disease, this suggests that awaiting overt signs of disease involves accepting some irreversible damage and probable progression.
Computerized imaging technologies provide objective and quantitative measures of the optic nerve and RNFL. Imaging provides an effective means of establishing baseline documentation, defining the stage of glaucoma severity, measurement of optic disc size, and assists the clinician with early glaucoma diagnosis and detection of progression.2 During the past several years, there has been an explosion of information that utilizes imaging technologies to differentiate normal from abnormal, improve precision, and increase resolution and image registration. The development and commercialization of high-speed Fourier-domain optical coherence tomography (OCT) offers higher speed and resolution than time-domain OCT, along with the ability
to perform three-dimensional imaging of posterior segment structures. This report highlights examples in which Fourier-domain OCT imaging (RTVue; Optovue, Inc., Fremont CA) adds to clinical care by providing adjunctive information that facilitates the early glaucoma diagnosis, risk assessment, and monitoring disease progression.
IMPACT OF EARLY GLAUCOMA DIAGNOSIS
Glaucoma produces irreversible optic nerve injury. As optic nerve damage progresses, severe visual dysfunction and blindness may ensue in a small group of patients. A study performed in Olmsted County, Minnesota, reported that ocular hypertensive patients under treatment followed for 20 years had a 14% cumulative probability of progression to unilateral blindness.3 Using a mathematical model for estimating the risk of glaucoma progression based upon randomized clinical trial data and population-based studies, data suggest that, in untreated patients, the estimated risk of progression from ocular hypertension to unilateral blindness is 1.5% to 10.5%.3 In treated patients, the estimated risk of progression is 0.3% to 2.4% over 15 years.1 The impact of delayed treatment upon the rate of progression of ocular hypertension to glaucoma is the subject of a follow-up study of the Ocular Hypertension Treatment Study (OHTS). This trial seeks to examine long-term differences between patients who received treatment early (medical group) compared with later (observation group).
RISK ASSESSMENT
Established risk factors for the progression of ocular hypertension to glaucoma include increased age, IOP, cup-to-disc ratio, optic disc hemorrhage, and reduced central corneal thickness.4 The Confocal Scanning Laser Ophthalmoscopy (CSLO) ancillary study to the OHTS reported that, when the optic disc is not classified by expert review of stereoscopic photographs as glaucomatous and the standard visual field is normal, certain optic disc features obtained using baseline CSLO imaging are associated with the development of primary open-angle glaucoma.5 Similar studies demonstrating that certain structural changes can precede the observation of a glaucoma endpoint have also been performed with scanning laser polarimetry6 and time-domain OCT.7
Figure 1 illustrates the left eye of a 60-year-old woman of African ancestry with ocular hypertension and a family history of glaucoma. Her untreated IOP is 28 mm Hg and the central corneal thickness is 571 µm. The optic disc is small but physiologic with an intact neural rim; however, there is a suggestion of reduced inferior RNFL reflectance on the color photograph. As illustrated in Figure 2, SAP and frequency doubling technology (FDT) perimetry are normal. Fourier-domain OCT demonstrates a significant reduction in inferior RNFL thickness on the nerve head map and RNFL thickness map (Figure 3). Despite an increased corneal thickness, this patient has a moderately advanced risk for progression to glaucoma based upon her elevated IOP, young age, family history, and baseline reduction in RNFL thickness. The patient was started on IOP-lowering therapy.
DETECTING EARLY GLAUCOMA
The significant advances in hardware and software platforms for glaucoma imaging should not mislead a clinician to think that glaucoma diagnosis can be solely machine-based at the current time. Rather, the imaging information should be considered complementary to other clinical measures. Yet, some data suggest that imaging and expert assessment of optic disc photographs are similar in their ability to identify early glaucoma,8 and it is clear that imaging does offer some very attractive advantages. Given the variability of clinician drawings and recordings of optic disc measures, imaging may elevate the assessment of the optic nerve by the general clinician to the level of a fellowship-trained expert. Fourier-domain OCT imaging enables the clinician to objectively evaluate the peripapillary RNFL, which, unlike the optic nerve, cannot be easily visualized or measured and has been demonstrated to change early in the course of the disease.9,10 RNFL abnormalities often exist in eyes with early glaucoma with normal SAP. Finally, Fourier-domain OCT enables the clinician to compare patients to a population of age-matched normals, thus facilitating one's ability to identify abnormal structural features.
Figure 4 illustrates a 54-year-old man with early open-angle glaucoma. The right optic nerve shows thinning of the inferior neural rim. Figure 5 demonstrates a normal SAP and a superior nasal defect on FDT perimetry. Fourier-domain OCT imaging of the RNFL and macular region was performed. The ganglion cell complex map demonstrates significant atrophy in the inferior macular region, and the nerve head map demonstrates thinning of the superior and inferior RNFL thickness (Figure 6).
DETECTING GLAUCOMA PROGRESSION
There are few studies involving the role of imaging in human glaucoma progression detection, hampered in part by rapidly evolving changes in technology that disrupt longitudinal studies. Progressive RNFL thinning measured with OCT11 and optic nerve cupping measured with CSLO12 have been reported in experimental models involving nonhuman primates. Many studies have identified greater changes in imaging-derived measures than SAP,13,14 but the specificity of such changes remains to be validated. Medeiros and colleagues have recently reported that the GDx VCC (Carl Zeiss Meditec, Inc., Dublin, CA) was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields.15 Given that Fourier-domain OCT is a relatively young technology, longer follow-up intervals are required in order to determine if the changes identified using this technology predict the subsequent development of visual field progression.
CONCLUSION
Fourier-domain OCT is an important tool for evaluating patients with ocular hypertension and early glaucoma. By quantifying glaucomatous structural changes in the optic nerve and the RNFL, this technology provides information that will enable the clinician to document and stage glaucomatous structural damage, facilitate risk assessment, and assist with early glaucoma diagnosis and monitoring.
