Clinical evaluation of the optic disc in glaucoma remains a central method for diagnosis and follow-up, even with the widespread use of imaging devices such as OCT1). Morphological changes of the optic disc and retinal nerve fiber layer defects (RNFLD) may appear before visual field damage, making them important findings for early detection.
It is important to perform the examination systematically, and a “seven-step” approach covering the following observation points has been proposed.
Evaluation of cupping
Evaluation of color
Evaluation of contour
Confirmation of the ISNT rule
Measurement of disc size
Evaluation of vascular findings
Evaluation of peripapillary atrophy (PPA)
Morphological changes of the optic disc should be observed under magnified stereoscopic view 1)5). Observation under mydriasis is recommended, but prominent findings such as disc hemorrhage can be confirmed even without mydriasis1).
QWhy is clinical optic nerve evaluation necessary when imaging devices are available?
A
Imaging devices are only supplementary tools and are subject to limitations in measurement accuracy and artifacts 2). High myopia is not included in the normal database, and measurements cannot be compared between different devices 2). The final diagnosis must be made by integrating clinical findings, imaging analysis, and visual field testing 2).
In the early to middle stages of glaucomatous optic neuropathy, patients rarely report subjective symptoms. Visual acuity loss is often not noticed until visual field defects progress to involve the central visual field.
Physical findings suggestive of glaucomatous optic neuropathy include the following3).
Vertical elongation of the cup: Accompanied by reduction in neuroretinal rim width
Enlargement of the cup: Noted when disproportionately large relative to disc size
Focal or diffuse thinning of the rim: Most common at the superior and inferior poles
Optic disc hemorrhage: Occurs on the rim, peripapillary retinal nerve fiber layer, or lamina cribrosa
Nasal displacement of central retinal vessels: Vessels shift nasally as the cup enlarges
Baring of circumlinear vessels: Vessels previously on the rim move into the cup
Cup enlargement without rim pallor: Pallor exceeding the degree of cupping suggests non-glaucomatous etiology
Diffuse or localized thinning of the retinal nerve fiber layer: Slit-like or wedge-shaped defects wider than retinal vessels are highly suggestive of glaucomatous changes.
Beta-zone peripapillary atrophy: Observed in approximately 80% of glaucomatous eyes.
In normal eyes, the neuroretinal rim width is thickest in the order: Inferior > Superior > Nasal > Temporal 3)5). Deviation from this rule raises suspicion of glaucomatous changes. Approximately 80% of glaucoma patients show thinning of the inferior and superior rims, not following the ISNT rule 3). However, some reports indicate that fewer than 45% of normal eyes follow the ISNT rule 3).
Retinal nerve fiber layer defects may appear before optic disc cupping or visual field defects, making them important as early glaucomatous fundus changes. When slit-like or wedge-shaped defects wider than retinal vessels are observed, glaucomatous changes are highly likely.
Observation of the retinal nerve fiber layer is facilitated by using red-free light 1)3)5). With a slit-lamp microscope, use low-magnification red-free light or a high-magnification thin bright white beam within about 2 disc diameters around the optic disc5). Focusing slightly anterior to the major retinal vessels reveals the nerve fiber bundles as radial silvery-white striations.
The appearance of exposed pores of the lamina cribrosa within the cupping is called the lamina dot sign. This finding indicates deepening of the cup and reflects loss of nerve fibers due to glaucoma.
Many glaucoma patients exhibit optic disc hemorrhage at some point during the course of the disease 5). It commonly occurs at the superotemporal and inferotemporal rims. The duration is usually short, 2 to 4 months, and after resolution, localized rim notching appears. The risk is 3 to 5 times higher in normal-tension glaucoma. Optic disc hemorrhage is easily overlooked unless actively sought, so regular stereoscopic disc photography is a sensitive detection method.
QAt what C/D ratio should glaucoma be suspected?
A
The C/D ratio in normal eyes is within 0.3, and a ratio exceeding 0.7 is found in only about 5% of the population 2). A vertical C/D ratio of 0.7 or more, or an interocular difference of 0.2 or more, is suspicious for glaucoma2). However, since large optic discs have larger physiological cupping, it is necessary to consider disc size (DM/DD ratio) when making a judgment 2).
Sufficient magnification is necessary for observing the optic disc, and direct ophthalmoscopy is recommended 2). The direct ophthalmoscope provides excellent resolution and a 15x magnified upright image. However, the field of view is narrow and stereopsis is not obtained.
Using red-free light improves contrast and is useful for detecting disc hemorrhages and retinal nerve fiber layer defects 3)4). Indirect ophthalmoscopy with a 14D or 20D lens produces too small an image of the optic disc and is unsuitable for detailed observation 2).
This is the most suitable method for stereoscopic observation of the optic disc and retinal nerve fiber layer2).
Direct method: Performed under a slit lamp using the central part of a Goldmann-type three-mirror lens. The extent and depth of cupping are observed under high magnification with a slit beam 2).
Indirect method: Performed using a pre-corneal lens such as 78D or 90D. The image is inverted 2). Since it is non-contact and relatively easy to perform, it is widely used in daily clinical practice.
It is recommended to set the slit beam length to 1 mm or 2 mm and apply it to the optic disc, and to routinely familiarize oneself with the normal vertical diameter.
Advantages of Direct Ophthalmoscopy
High magnification: Allows detailed observation at 15x magnification.
High resolution: Easily captures fine findings.
Simplicity: Can be performed without special preparation.
Advantages of Pre-corneal Lens Method
Stereopsis: Enables three-dimensional assessment of cupping depth and retinal nerve fiber layer defects.
Wide field of view: Allows extensive evaluation of the peripapillary area.
Slit light: The morphology of the cupping can be directly evaluated with the beam.
Fundus photography is useful for recording and monitoring fundus changes, and stereoscopic photography is desirable 2). For recording the optic disc, a field of view of about 30° is suitable, and for recording the retinal nerve fiber layer, a field of view of 45° or more is appropriate 2). Color stereoscopic photography is also an excellent method for detecting optic disc hemorrhages 3)4).
For detecting retinal nerve fiber layer defects, fundus photography with red-free light is recommended 2). In Japanese fundi, observation of the retinal nerve fiber layer is relatively easy even with ordinary color photographs, but red-free light is useful for detecting subtle defects. Using a black-and-white converted image that extracts only the blue component allows evaluation of not only the presence but also the width of retinal nerve fiber layer defects. A filter with maximum transmittance around 495 nm is used 2).
OCT is currently the most widely used three-dimensional fundus analysis device and is widely applied in glaucoma diagnosis 2)3).
Peripapillary retinal nerve fiber layer thickness: Measured by a circular scan approximately 3.4 mm in diameter centered on the optic disc2). The average thickness of the entire circumference and each sector is compared with a built-in normal eye database.
Macular inner retinal layer thickness: There are programs that measure the retinal ganglion cell complex thickness or the ganglion cell layer + inner plexiform layer thickness 2).
Bruch’s membrane opening-minimum rim width (BMO-MRW): Attracting attention as a new quantitative method for optic disc morphology.
OCT results are affected by image quality and artifacts 2). High myopia is not included in the normal eye database, so caution is needed in interpreting results 2). Also note that direct comparison of measurements between different devices is not possible 2).
The diagnostic criteria based on the assessment of vertical cup-to-disc ratio and rim-to-disc ratio are shown below 2).
Judgment
Criteria
Condition
Glaucoma
Optic disc findings only
C/D ≥ 0.9, R/D ≤ 0.05, asymmetry ≥ 0.3
Suspected glaucoma
Requires further examination
C/D ≥ 0.7, R/D ≤ 0.1, asymmetry ≥ 0.2
In addition to the above quantitative assessment, the presence or absence of corresponding visual field abnormalities should be comprehensively evaluated 2). The final diagnosis should be made by combining qualitative and quantitative findings 2).
To improve inter- and intra-observer reproducibility, a quantitative evaluation system called DDLS has been proposed. It considers optic disc size (small < 1.50 mm, average 1.50–2.00 mm, large > 2.00 mm), the rim width-to-disc diameter ratio at the narrowest point, and the extent of rim loss (in degrees), aiming for objective assessment.
QIf OCT shows an "abnormal" result, does that confirm a diagnosis of glaucoma?
A
OCT is not a definitive diagnostic test for glaucoma1)2). Abnormal OCT findings can occur not only in glaucoma but also in other diseases 2). Artifacts and segmentation errors can also occur, so the final diagnosis must be made by integrating clinical findings, visual field tests, and OCT results 1)2).
In glaucoma, damage to retinal ganglion cells leads to loss of their axons, the retinal nerve fibers. This results in structural changes such as enlargement of the optic cup, thinning of the neuroretinal rim, nasal displacement of retinal blood vessels, and retinal nerve fiber layer defects.
Early abnormalities may appear as either diffuse thinning or localized defects 5). Glaucomatous changes typically begin at the superior and inferior poles of the rim and are recognized as vertical elongation of the cup. As the disease progresses, localized notching occurs, and with further progression, part of the rim disappears.
In glaucomatous optic neuropathy, enlargement of the cup precedes pallor of the rim. This is called “cup-pallor dissociation.” In non-glaucomatous optic atrophy, pallor of the rim precedes cup enlargement. This difference is the most useful point for distinguishing between the two.
Differentiation from non-glaucomatous optic neuropathy
Diseases requiring differentiation are as follows.
Myopic disc: Tilted disc, conus, and peripapillary atrophy make it difficult to determine glaucomatous changes. In myopia of -8D or less, there is no clear difference in disc shape from normal eyes, but beyond -12D, the vertical elongation becomes more pronounced.
Physiological large cupping: In large discs, physiological cupping also becomes large, so judgment is made after evaluating disc size using the DM/DD ratio.
Congenital anomalies: Optic disc hypoplasia, optic disc coloboma, optic disc pit, tilted disc syndrome. Carefully observe abnormalities in disc size and color, cupping/protrusion, and presence of peripapillary retinal atrophy.
Non-glaucomatous optic atrophy: The most useful distinguishing point is that pallor of the rim precedes rim loss. Cupping is shallow and relatively smooth, and the appearance or enlargement of peripapillary atrophy is usually not observed.
QHow do you distinguish between glaucomatous and non-glaucomatous optic atrophy?
A
The most useful distinguishing point is that in glaucoma, rim “loss” precedes, whereas in non-glaucomatous optic atrophy, rim “pallor” precedes. Non-glaucomatous cupping is shallow and smooth, and even with follow-up, the appearance or enlargement of peripapillary atrophy is rarely seen. Ultimately, judgment is made by combining visual field tests, fundus angiography, and longitudinal changes.
OCTA enables non-invasive and simple evaluation of blood flow in the superficial and deep retinal layers 2). It is known that retinal superficial blood flow decreases with advanced glaucoma, and blood flow evaluation may contribute to glaucoma diagnosis in addition to structural changes.
Research on automated glaucoma diagnosis using AI with fundus photographs is progressing. In the future, objective and automated progression assessment is expected to become possible. Conventional fundus photograph-based optic disc evaluation has the problem of relying on subjective judgment, but the introduction of AI is expected to overcome this issue.
In glaucomatous optic neuropathy before the appearance of clinically detectable visual field defects (preperimetric glaucoma), diagnosis is mainly based on imaging devices 2). OCT can detect changes in the inner retinal layers, particularly the macular retinal ganglion cell layer, which is one of the earliest sites of change in glaucoma, and the number of glaucoma cases first diagnosed by OCT is increasing 2).
OCT devices from various manufacturers are equipped with programs to evaluate changes over time, allowing trend analysis of peripapillary retinal nerve fiber layer thickness and macular inner layer thickness. Additionally, optic disc shape analysis software installed in stereo fundus cameras can automatically calculate optic disc shape parameters (cup volume, rim volume, eccentricity, tilt ratio, etc.) from stereoscopic photographs, enabling quantitative monitoring of changes over time.
