From the Chief Editor

A future for imaging technology in glaucoma

R.N. Weinreb, MD, La Jolla, CA
David S. Greenfield, MD, Palm Beach Gardens, FL

The recent introduction of spectral domain optical coherence tomography (OCT) for glaucoma imaging offers extraordinary potential for improving glaucoma diagnosis and detection of glaucoma progression. However, utilization of current imaging technology by the clinician has taken considerable time, and it is reasonable to examine it to better understand the future of the spectral domain OCT in glaucoma. Although imaging to assess the optic nerve and parapapillary retinal nerve fiber layer (RNFL) began to emerge more than 20 years ago, the diffusion of this innovative technology has been slow.¹ In the course of this diffusion, a number of instruments have come and gone. Some technologies were introduced and never gained any traction with clinicians. Others were used in clinical practice, but were replaced by newer and, presumably, improved hardware that was not backwards comparable with the original instruments. Nevertheless, today we have several instruments that provide objective and quantitative measurements that are highly reproducible and show very good agreement with clinical estimates of optic disc and visual function. Yet, many clinicians continue to wonder how to use these in their clinical practice and clinical trials. Now, more than ever, it seems to be an appropriate time to assess the use of imaging in clinical practice.

There is general consensus¹ that examination and documentation of the optic disk and RNFL is essential for diagnosis and monitoring of glaucoma. Astute clinicians can observe well and document the characteristics of the glaucomatous optic nerve head and identify changes consistent with progression. Optic nerve head drawings are useful for documentation, but often are inaccurate, incomplete, and poorly reproducible even for skilled observers. Optic nerve head photography, particularly stereoscopic, provides a permanent record, but generally is not used because it is impractical and cameras generally are not available. Moreover, the differences among clinicians in their interpretation of photographs, either for diagnosis or progression, is remarkably large. The Glaucoma Diagnosis Consensus of the World Glaucoma Association² recommended digital imaging to facilitate assessment of the optic nerve head and RNFL. It recognized that different technologies may be complementary and may detect different abnormal features From the Chief Editor A future for imaging technology in glaucoma in the same patient. Moreover, it is suggested that the information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant clinical parameters, particularly functional measures.

For a variety of reasons, the use of imaging technology enhances clinical care. Firstly, imaging provides an effective means of establishing baseline documentation and quantifying structural damage in glaucoma. Secondly, imaging with certain instruments provides a means of quantifying optic nerve head size, a critical parameter for interpreting the meaning of the neuroretinal rim. Thirdly, imaging can provide important information for estimating risk of ocular hypertension. The Confocal Scanning Laser Ophthalmoscopy (CSLO) ancillary study to the Ocular Hypertension Treatment Study (OHTS)³ demonstrated the use of the CSLO for risk prediction, and provided the first evidenced-based validation for a glaucoma imaging technology. Similar studies demonstrating that certain structural changes can precede the observation of a glaucoma endpoint also have been performed with scanning laser polarimetry⁴ and time-domain optical coherence tomography.⁵ Undoubtedly, predictive models for glaucoma risk assessment will evolve that incorporate this imaging data.

Given the substantial advances in glaucoma imaging, it is important to remind clinicians that current glaucoma diagnosis cannot be solely instrument-based. Rather, the imaging information should be considered as being complementary to other clinical measures. Nevertheless, given the variability of drawings and subjective photographic interpretation, imaging may elevate the assessment of the optic nerve by the general clinician, perhaps to the level of a fellowship-trained glaucoma specialist. Moreover, imaging enables the clinician to objectively evaluate the parapapillary RNFL that changes early in the course of the disease, which cannot be readily measured by clinical examination. Finally, imaging enables a practical comparison of a patient with a population of age-matched normals, facilitating the ability to identify abnormal structural features. Optic nerve head hemorrhages, unfortunately, still cannot be detected reliably with any of the available imaging technologies.

After two decades of validation, particularly for glaucoma diagnosis, ocular imaging for detection of progression is finally at the verge of being implemented into clinical practice. Statistical methods for evaluating glaucomatous visual field progression have evolved considerably, yet criteria for defining progression remains inconsistent in the absence of established standards.⁶ Similar challenges exist with assessment of structural change. Imaging may serve as a useful adjunct to optic disc photography to provide complementary information that may facilitate progression detection using rate-based changes over time since the output data is quantitative, and highly reproducible at all stages of the glaucoma continuum. Still, there are few reported studies of imaging for glaucoma progression detection. It will be necessary to have long follow-up intervals to determine if the changes identified using only structural technologies predict the subsequent development of visual field progression.

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. However, the costs of replacing older technologies with improved ones has been detrimental to their gaining widespread acceptance. Established practice patterns are often a challenge to modify and, in this instance longitudinal studies are needed to validate the use of imaging for detection of glaucoma progression. Further, image quality that is dependent on operator skill, patient related factors such as pupil diameter and media clarity, and instrument dependent variables all still need to be addressed. In the final analysis, imaging may falsely identify glaucoma and its progression. Imaging also may fail to detect a glaucomatous optic nerve head or RNFL. Thus, clinicians should not make clinical decisions based solely on the results of one single test or technology.

Despite these limitations, there should be no question that imaging of the optic nerve head and RNFL in clinical practice today does facilitate glaucoma diagnosis and monitoring. However, the development and commercialization of high-speed Fourier-domain OCT provides both an opportunity and challenge for the busy clinician. Various instruments exist each of which offer higher speed and resolution as compared with time-domain OCT, along with the ability to perform three-dimensional imaging of posterior segment structures. Yet, obtaining technology that is not backwards compatible with previously collected data introduces uncertainty, along with other limitations that include evolving normative data sets and software that is neither optimized nor validated for clinical practice. Even as these limitations are addressed, it is likely that imaging will continue to complement the clinical examination and will not be used alone for clinical decision-making in the foreseeable future. One also should expect that imaging technologies will continue to evolve and new information will emerge that will enhance their use in clinical practice.

References

1. Greenfield DS, Weinreb RN. Role of optic nerve imaging in glaucoma clinical practice clinical trials. Am J Ophthalmol. 2008145:598-603.
2. Weinreb RN, Greve E (eds). Glaucoma Diagnosis. Amsterdam: Kugler Publications, 2004.
3. Zangwill LM, Weinreb RN, Berry CC, Smith AR, Dirkes KA, Liebmann JM, Brandt JD, Trick G, Cioffi GA, Coleman AL, Piltz-Seymour JR, Gordon MO, Kass MA, OHTS CSLO Ancillary Study Group. The confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study: study design and baseline factors. Am J Ophthalmol. 2004;137:219-27.
4. Mohammadi K, Bowd C, Weinreb RN, Medeiros FA, Sample PA, Zangwill LM. Retinal nerve fiber layer thickness measurements with scanning laser polarimetry predict glaucomatous visual field loss. Am J Ophthalmol 2004;138:592-601.
5. Lalezary M, Medeiros FA, Weinreb RN, Bowd C, Sample PA, Tavares IM, Tafreshi A, Zangwill LM. Baseline optical coherence tomography predicts the development of glaucomatous change in glaucoma suspects. Am J Ophthalmol. 2006;1442:576-82.
6. Heijl A, Bengtsson B, Chauhan BC, Lieberman MF, Cunliffe I, Hyman L, Leske MC. A comparison of visual field progression criteria of 3 major glaucoma trials in early manifest glaucoma trial patients. Ophthalmology 2008;115:1557-65