Optical coherence tomography (OCT) is an imaging diagnostic method that uses low-coherence beams to obtain cross-sectional images of the retina with micron-level resolution. In glaucoma diagnosis, three parameter groups are evaluated: ONH (optic nerve head), peripapillary RNFL (retinal nerve fiber layer), and macular inner layers 1)4).
Macular OCT imaging diagnosis is a method to quantitatively evaluate the thickness of the inner retinal layers in the macula, particularly the GCL (ganglion cell layer) and IPL (inner plexiform layer). Although approximately 50% of RGCs are concentrated within a 4.5 mm radius from the fovea (corresponding to the central ±8° visual field), this area accounts for only 7.3% of the total retinal area 2). Damage to the macula significantly affects quality of life 2).
Conventional glaucoma evaluation focused on the ONH, but in recent years, comprehensive evaluation combining optic disc analysis with macular inner layer analysis has been recommended. Glaucoma cannot be diagnosed by OCT alone; comprehensive judgment based on clinical findings and visual field tests is essential 1)4).
Glaucoma cannot be diagnosed with macular OCT alone. A result “outside normal limits” on OCT may be a false positive and does not necessarily indicate glaucoma. It is necessary to make a comprehensive judgment together with other test results such as clinical findings of the optic nerve head, visual field tests, and intraocular pressure measurements. On the other hand, macular OCT is a useful adjunctive tool for detecting early glaucoma that is not yet apparent on other tests.
In layer-by-layer analysis of the macular retina, the inner layers evaluated include the RNFL (retinal nerve fiber layer), GCL (ganglion cell layer), and IPL (inner plexiform layer). These layers contain the axons, cell bodies, and dendrites of RGCs, respectively 2).
| Name | Constituent Layers | Alternative Name |
|---|---|---|
| GCC | RNFL+GCL+IPL | GCL++ |
| GCIPL | GCL+IPL | — |
GCC (ganglion cell complex) is a three-layer complex of RNFL, GCL, and IPL. In some devices, it is called GCL++. Some devices use GCIPL (GCL+IPL) as a diagnostic parameter. The measurement range varies greatly depending on the device 3).
The main OCT modalities currently used are SD-OCT (spectral-domain OCT) and SS-OCT (swept-source OCT). Time-domain OCT (TD-OCT) is rarely used today due to insufficient resolution and speed. SD-OCT enables high-speed analysis of 26,000 A-scans/second or more, achieving rapid GCC analysis. SS-OCT has greater penetration depth and is also applied to analysis of the lamina cribrosa and choroid.
Macular OCT is particularly useful for detecting preperimetric glaucoma. In the stage before clinically detectable visual field defects appear, diagnosis relies mainly on imaging devices 3). Even in early glaucoma, approximately 50% of RGCs have already been lost, so measurement of macular RGC layer thickness is effective for early detection.
Up to 80% of patients with mild glaucoma have macular RGC damage, and early macular damage is more common than previously thought 2). Significant thinning of GCL and IPL has been reported even in patients classified as normal by standard visual field testing (HFA 24-2) 2).
There is a strong correlation between macular GCL+IPL thickness and RGC count 2). A study investigating structure-function relationships in the macula of 77 healthy eyes, 154 glaucoma suspect eyes, and 159 glaucoma eyes revealed that estimated macular RGC count was reduced by 41% in glaucoma eyes compared to healthy eyes 2). The correlation between estimated macular RGC count and macular GCL+IPL thickness was r²=0.65 (p<0.001) 2).
A significant correlation (r²=0.47, p<0.001) has been reported between macular thickness obtained from OCT and visual field defect (MD value)2). These findings support that thinning of the macular RGC layer is useful as a surrogate marker for RGC loss2).
Advantages of macular OCT
Detection of early changes: Macular changes may appear earlier and more consistently than RNFL changes
Ease of imaging: Does not require eye movement from the patient, making image acquisition easier and image quality generally higher
Correspondence with central visual field: The macula corresponds to the central visual field near the fixation point and is important for evaluating visual prognosis
Advantages of peripapillary RNFL analysis
Established diagnostic ability: Long track record in glaucoma diagnosis1)
Wide measurement dynamic range: Excellent for quantifying structural loss up to moderate glaucoma
Superiority in some studies: Some reports show RNFL thickness outperforms GCL thickness in direct comparisons
The combination of RNFL analysis and ganglion cell analysis is considered the best approach for OCT-based glaucoma evaluation1). All parameters can be used to differentiate mild to moderate glaucomatous eyes1).
Many quantitative images of the optic nerve head, RNFL, and inner macular layers based on structural changes are widely used for glaucoma diagnosis and progression detection, but they cannot replace clinical findings and visual field testing4).
Measurement of peripapillary RNFL thickness and macular inner retinal layer thickness by OCT allows quantitative recording of fundus findings, and programs for detecting changes over time are installed in OCT devices from various manufacturers3). The greatest advantage of OCT is that it is an objective test with low noise.
As a characteristic by disease stage, OCT detects changes early in mild glaucoma and shows a linear relationship with structural loss in moderate glaucoma 1). Since most commercial software does not correct for aging, a statistically significant slope does not necessarily indicate true glaucomatous progression 1).
In advanced glaucomatous eyes, there is a floor effect where OCT measurements can no longer detect further thinning 1)3). Macular inner retinal thickness shows little further change in glaucoma more advanced than −10 dB. Therefore, visual field testing is the main method for assessing progression in advanced glaucoma 3).
| Precaution | Details |
|---|---|
| Incompatibility between devices | Measurements cannot be compared between different OCT devices 1)3) |
| Artifacts | Segmentation errors, poor image quality |
| High myopia | Not included in the normative database 3) |
Different OCT devices have different measurement ranges and segmentation algorithms, so numerical values are not interchangeable between devices 1)3). However, glaucoma detection ability is considered to be roughly equivalent across manufacturers.
Yes. Different OCT devices have different measurement ranges and segmentation algorithms, so measurements are not interchangeable. It is important to continue using the same device for follow-up. However, glaucoma detection ability itself is reported to be roughly equivalent across manufacturers. Note that even different software versions may yield different results.
An OCT result outside the normal range may be a false positive and does not necessarily mean the subject has glaucoma 1). A diagnosis of glaucoma should not be made based solely on a single OCT result 1).
The sensitivity and specificity of automated diagnostic programs for glaucoma are reported to be around 80%. This is mainly due to individual differences in optic disc morphology and RNFL thickness, as well as numerical overlap between glaucomatous and normal eyes. Final judgment by an experienced ophthalmologist is essential for glaucoma diagnosis.
In advanced glaucoma, progression assessment using macular OCT becomes difficult due to the floor effect 3). Although structural (OCT) progression and visual field progression have been reported to be related, a definitive method for evaluating progression by OCT has not been established 3).
OCT is particularly useful in early to moderate glaucoma. It can detect structural changes at the pre-perimetric glaucoma stage before visual field defects appear, contributing to early diagnosis. In advanced glaucoma, however, the floor effect prevents detection of further thinning, so visual field testing becomes the main method for progression assessment.
Glaucoma has traditionally been characterized by ONH damage and peripheral visual field loss, with central vision thought to be preserved until the late stages 2). This view was based on HFA 24-2 testing and high-contrast visual acuity measurements, leading to overestimation of peripheral field loss and underestimation of central field loss 2).
Recent OCT studies have revealed that macular damage frequently occurs even in early stages of glaucoma 2). Studies using SD-OCT have reported that the thickness of the RGC+ layer in early to moderate glaucoma eyes is reduced by about 20% compared to healthy eyes 2).
RGC damage in the macula leads to decreased contrast sensitivity, changes in spatial summation, and increased visual crowding 2). Thinning of the GCL+IPL is significantly correlated with contrast sensitivity 2). These changes may not be adequately reflected by conventional high-contrast visual acuity tests 2).
OCTA can non-invasively assess blood flow in the superficial and deep retinal layers, and it is known that superficial retinal blood flow decreases as glaucoma progresses 3). Deep blood flow dropout around the optic nerve head is attracting attention as being related to glaucoma progression 3). OCTA is considered less susceptible to the floor effect than RNFL measurement and may be more advantageous than OCT for assessing progression in advanced glaucoma 3). However, standardized clinical applications have not yet been established 3).
Research is progressing on predicting glaucomatous visual field defects by evaluating macular OCT scans using deep learning. Advances in AI diagnosis using fundus photographs are also remarkable. In the future, it is expected that machine learning evaluation of objective macular OCT measurements will support early diagnosis of glaucoma based on structural changes before visual field defects appear.
A composite index including GCC volume loss, inferior RNFL thickness, age, and visual field defects has been reported to be superior to any single factor in predicting the development of glaucoma six years later. The construction of prediction models for detecting early-stage glaucoma using multivariate analysis is progressing.
OCTA is a technology that non-invasively visualizes microvessels in the retina and optic nerve head. Decreased superficial retinal blood flow associated with glaucoma progression has been reported, and it may be useful even in advanced glaucoma where conventional OCT shows a floor effect. However, standardized clinical applications have not yet been established, and further research is awaited.
