Assessment of the retinal ganglion cell layer (GCL) using automated quantitation of retinal ganglion cell–inner plexiform layer (IPL) thickness has become increasingly available with spectral domain optical coherence tomography (SD-OCT). Given the clinical benefits of using GCL thickness as an objective anatomic measure, there are now many reasons to incorporate GCL thickness into clinical practice. This is exemplified by 3 articles in this issue of Journal of Neuro-Ophthalmology (1–3).
Available SD-OCT algorithms provide GCL thickness measures in the macular region where the retinal ganglion cells are most numerous. Retinal ganglion cells are absent in the center of the fovea and increase dramatically to a peak of >10,000 cells per square degree at 0.6° eccentrically, followed by a decrease to <100 cells per square degree at 10° eccentricity (4). Meaningful measures of GCL thickness beyond the macular region are not available due to the resolution of the SD-OCT. Nevertheless, when permanent anatomic damage occurs as the result of optic neuropathy, reduction in GCL thickness is expected in the macula where the most of retinal ganglion cells reside.
There are several advantages of using SD-OCT macular GCL thickness as an objective measure of optic nerve injury compared with SD-OCT peripapillary retinal nerve fiber layer (RNFL) thickness. First, optic disc edema as a result of swollen axons increases RNFL thickness and may obscure retinal nerve fiber loss. GCL thickness detects optic nerve injury when optic disc edema is present and is helpful to predict prognosis and monitor treatment. However, when optic disc edema produces substantial peripapillary retinal edema, the SD-OCT GCL–IPL thickness algorithm may fail to provide proper segmentation resulting in falsely low values. Second, the RNFL thickness sector distribution for an anomalous optic nerve head may be altered and difficult to interpret, whereas macular GCL layer thickness is less likely to be affected. Third, macular GCL thickness may provide more precise topographical correlation with central visual field defects than peripapillary RNFL thickness. For instance, the corresponding optic nerve damage from homonymous hemianopia related to cerebral stroke is more apparent and correlates far better topographically with GCL thickness than RNFL thickness (5).
Macular GCL–IPL thickness is an additional clinical tool rather than a replacement for peripapillary RNFL thickness. The dynamic ranges of the 2 parameters in detecting an optic nerve abnormality are different in various clinical scenarios. The peripapillary RNFL thickness is sensitive in detecting optic disc edema. When optic disc edema is not present, RNFL thickness correlates reasonably well with visual field defects, particularly with sectoral or 2-dimensional en face analysis. Although macular GCL thickness may be sensitive in detecting early optic nerve damage, peripapillary RNFL thickness may be a better measure in more advanced optic neuropathies when macular GCL thickness has “bottomed out.” Because visual field defects may not occur until a considerable loss of axons has occurred, both GCL and RNFL thickness measures are especially helpful in scenarios where the visual field may be near normal (e.g., recovered optic neuritis, early compressive optic neuropathy). The GCL and RNFL measures also are useful when the patient cannot provide reliable visual fields. However, in advanced optic neuropathies, when both GCL and RNFL thickness have been maximally reduced, visual field testing remains the test of choice in following disease progression (e.g., severe optic nerve atrophy from idiopathic intracranial hypertension or from compressive optic neuropathy).
Macular GCL–IPL thickness analysis is obtained from typical macular SD-OCT without additional scanning time. Concurrent review of the retinal OCT is important because altered macular anatomy from conditions such as epiretinal membrane and cystoid macular edema may reduce the accuracy of segmentation of the GCL-IPL layer. On occasion, the automated GCL–IPL analysis may fail even without an obvious retinal abnormality. Available GCL–IPL analysis is designed to detect neuronal injury in disorders such as glaucoma and divides the macula into 6 sectors respecting the horizontal but not vertical meridian. Given the findings of GCL thickness changes respecting the vertical meridian in homonymous hemianopia from cerebral ischemic injury (5), modification of the GCL–IPL analysis into sectors respecting both the vertical and the horizontal meridians would be beneficial.
To advance the clinical relevance of GCL thickness, prospective longitudinal studies with adequate sample size are needed to determine the prevalence, variability, and time course of GCL thickness changes in neuro-ophthalmic conditions. Case reports, case series, and cross-sectional studies have offered intriguing GCL thickness observations. In this issue of the journal, Meier and associates (1) document a case of transsynaptic retrograde GCL thickness loss from a right occipital lobe abscess; Rebolleda and colleagues (2) report a case series of 4 patients with anterior optic neuritis (papillitis) with GCL thinning occurring before RNFL thinning; and Sari et al (3) found decreased GCL thickness in patients with Parkinson disease in a cross-sectional study. In all 3 reports, longitudinal studies of large cohorts of patients are needed to determine how to apply these observations in the clinic and in future research. For instance, what is the prevalence and time course of transsynaptic retrograde GCL thickness loss in patients with homonymous visual field defects from damage to the occipital cortex and would this be pertinent to the testing of potential treatment strategies? Can GCL thickness in the early stages of optic neuritis serve as a predictor of the final visual outcome? If it is a valid predictor, GCL thickness may be an important measure in selecting patients for evaluation of neuroprotective interventions. Longitudinal studies also would determine the prevalence, onset, and progression of GCL thinning in patients with Parkinson disease and help to assess the efficiency of various treatment modalities.
In conclusion, SD-OCT macular GCL thickness is a valuable objective clinical measure of optic nerve damage. Clinicians as well as researchers will increasingly integrate its use as evidence-based knowledge accumulates.
1. Meier PG, Maeder P, Kardon RH, Borruat FX. Homonymous ganglion cell layer thinning after isolated occipital lesion: macular OCT demonstrates transsynaptic retrograde retinal degeneration. J Neuroophthalmol. 2015;35:112–116.
2. Rebolleda G, de Dompablo E, Muñoz-Negrete FJ. Ganglion cell layer analysis unmasks axonal loss in anterior optic neuritis. J Neuroophthalmol. 2015;35:165–167.
3. Sari ES, Koc R, Yazici A, Sahin G, Ermis SS. Ganglion cell-inner plexiform layer thickness in patients with Parkinson disease and association with disease severity and duration. J Neuroophthalmol. 2015;35:117–121.
4. Wässle H, Grünert U, Röhrenbeck J, Boycott BB. Retinal ganglion cell density and cortical magnification factor in the primate. Vision Res. 1990;30:1897–1911.
5. Keller J, Sãnchez-Diamau BF, Villosiada P. Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells. PLoS One. 2014;9:e97444.