Optic nerve head and retinal nerve fiber layer analysis¹

Abstract

The purpose of the Committee on Ophthalmic Procedures Assessment is to evaluate on a scientific basis new and existing ophthalmic tests, devices, and procedures for their safety, efficacy, clinical effectiveness, and appropriate uses. Evaluations include examination of available literature, epidemiological analyses when appropriate, and compilation of opinions from recognized experts and other interested parties. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy’s Board of Trustees for consideration as official Academy policy.

Introduction

The field of ophthalmology has been evolving at a rapid pace as new technology continues to be integrated into everyday clinical practice. The process of integration is a long, complex one that involves scientific innovators, industry, clinical investigators, and regulatory agencies. In order for practicing ophthalmologists to evaluate new advances fairly, it is critical that information be disseminated accurately, promptly, and comprehensively.

The American Academy of Ophthalmology (AAO) implemented the Ophthalmic Procedure Preliminary Assessment (OPPA) in 1996 to evaluate new and rapidly evolving technology. The goal of the OPPA is to review the scientific literature to distill what is well established about the technology and to help define and refine the important questions to be answered by future investigations, recognizing that emerging technology is characterized by rapid change and expanding clinical indications.

The process for creating this assessment on optic nerve head analysis involved writing an outline, which was reviewed by the seven-member Ophthalmic Procedures Assessment (OPA) committee. The COPA Glaucoma Panel reviewed and analyzed the peer-reviewed literature and selected relevant articles. Ophthalmic organizations with interests in optic nerve head analysis also were contacted for their input. Members of the OPA committee and other AAO committees reviewed drafts of this assessment prior to formal approval by the Board of Trustees.

Glaucomatous optic neuropathy is defined by specific patterns of neuroretinal rim loss usually associated with visual field loss. However, clinical evaluation of the optic disc usually can identify early glaucoma damage before detectable visual field loss occurs as measured by standard automated perimetry.

Quigley and coworkers1 estimated the number of nerve fibers from histologic examinations of five optic nerves of normal subjects and in three optic nerves of glaucoma suspects. The glaucoma suspect patients had normal visual fields with the Goldmann perimeter. Estimates of axon numbers for these patients were smaller than the lower confidence boundary, and one value was only 60% of the normal average. Despite the multiple limitations of this study, several clinical studies support the idea that detectable damage to the optic nerve and nerve fiber layer (NFL) can generally be identified before currently detectable alteration in the visual field.2, 3, 4, 5 Sommer and coworkers3 showed progressive changes in the surface contour of the disc using serial stereophotographs in 10 of 12 eyes before the onset of glaucomatous visual field loss. Read and Spaeth6 noted also that cupping preceded visual field loss in 460 glaucomatous eyes. A retrospective longitudinal study showed that disc cupping generally preceded visual field loss, that serial photographs were necessary for the earliest detection of optic nerve damage in ocular hypertension, and that treatment is indicated for eyes exhibiting progressive disc cupping even without visual field defects.4

In a prospective study Odberg and Riise7 reported an increase in disc cupping by stereophotography in 19 of 46 eyes without a change in the visual field after 5 to 7 years, while only 1 eye showed a field abnormality in the absence of any discernible disc alteration. Other clinical studies have documented optic nerve abnormalities and defects in the retinal nerve fiber layer (RNFL) in advance of the appearance of visual field defects.5, 8 In a longitudinal study, Zeyen and Caprioli5 demonstrated that 40% of contralateral eyes of patients with unilateral visual field loss had progression of disc damage with normal visual fields during a 6-year follow-up period. It appears that the ratio of disc change to field change is high in the early stages of glaucomatous damage, as further demonstrated by Jonas and Grundler.9 It is generally appreciated by clinicians that the development of a reproducible glaucomatous visual field defect is characteristic of patients with moderate to well-established disease, but not with early disease.

Progressive optic nerve cupping is a manifestation of retinal ganglion cell death and loss of ganglion cell axons from the optic nerve, and it can be recognized by examination of the RNFL. In current practice, glaucomatous optic neuropathy is detected by evaluation of the optic nerve head, carried out by means of direct ophthalmoscopy or by indirect stereo biomicroscopy using the Goldmann, 90 diopter (D), or 78 D lenses, or directly with a Hruby lens. In addition, red-free ophthalmoscopy may be helpful in locating glaucomatous changes, including wedge-shaped defects and diffuse changes of the RNFL. The evaluation is usually combined with photographic documentation using stereoscopic color disc photography and monochromatic high-contrast photography of the NFL.

Interpretation of both ophthalmoscopy and photography is subjective in nature, however, and does not provide quantitative information. Therefore, the incorporation of appropriate outcome measures of structural optic nerve damage has been problematic. Cost-effective objective measures with high sensitivity, specificity, accuracy, and reproducibility are needed to identify early structural glaucoma damage as well as to detect early progression. These will ultimately define outcome measures for clinical trials of glaucoma treatment, as well as criteria for diagnosing and managing glaucoma.

Stereophotogrammetry has been used to make subjective measurements from disc photographs by outlining the neural rim on a transparency while viewing a superimposed stereoscopic disc photograph. However, it requires a highly trained technician and a fundus camera capable of simultaneous stereophotography.10 Computerized image analysis with digitized simultaneous stereoscopic videographic images has been used to quantify certain structural characteristics of the optic nerve head and peripapillary retina. The Rodenstock Optic Nerve Head Analyzer (Rodenstock Instruments GmBH, Munich, Germany) has probably had the most extensive evaluation within this group of instruments.11, 12, 13, 14, 15

These videographic techniques have been supplanted by confocal scanning laser imaging technology, which is used in the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany). Confocal laser imaging exploits the advantages of the confocal principle to produce an image of the optic nerve and NFL to develop quantitative structural information. Scanning laser polarimetry (e.g., NFA II [nerve fiber analyzer] with integrated GDx software, [Laser Diagnostic Technologies, San Diego, CA]) is a scanning laser ophthalmoscope that utilizes the birefringent properties of the NFL. Nerve fiber layer thickness can also be measured using optical coherence tomography, a technique that uses light to provide cross-sectional images of ocular tissue.

This OPPA examines the accuracy and clinical usefulness of the data obtained from optic nerve head and RFNL analysis techniques, and it raises further questions for future research.