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Ganglion Cell Layer Analysis Unmasks Axonal Loss in Anterior Optic Neuritis

Rebolleda, Gema MD, PhD; de Dompablo, Elisabet MD; Muñoz-Negrete, Francisco J. MD, PhD

Journal of Neuro-Ophthalmology: June 2015 - Volume 35 - Issue 2 - p 165–167
doi: 10.1097/WNO.0000000000000204
Clinical Observation

Abstract: Optical coherence tomography is a valuable tool for evaluating patients with neuro-ophthalmic disorders. In the acute phase of anterior optic neuritis (ON), peripapillary retinal nerve fiber layer (pRNFL) measurements can underestimate the amount of damage as axonal swelling could mask the true degree of RNFL loss. Contrary to pRNFL evaluation, we hypothesize that macular ganglion cell layer analysis could detect true neuronal loss before swelling resolution in anterior ON. We describe 4 patients with anterior ON in whom ganglion cell layer and inner plexiform layer (GCIPL) thinning was detected earlier than pRNFL loss. GCIPL analysis may provide more accurate information than pRNFL thickness and serve as an early structural indicator of irreversible neuronal loss.

Supplemental Digital Content is Available in the Text.

Department of Ophthalmology, Hospital Universitario Ramón y Cajal, Madrid, Spain.

Address correspondence to Elisabet de Dompablo, MD, Department of Ophthalmology, Hospital Universitario Ramón y Cajal, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain; E-mail:

The authors report no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (

Spectral-domain optical coherence tomography (SD-OCT) has proven to be an essential imaging tool for neuro-ophthalmic pathologies. This technique evaluates neuronal integrity since it can demonstrate both retinal ganglion cell layer and peripapillary retinal nerve fiber layer (pRNFL) thinning in chronic optic nerve injury (1,2).

In anterior optic neuritis, pRNFL measurements obtained during the acute episode can underestimate axonal loss due to swelling that masks the true degree of pRNFL damage (3).

Macular thickness measurements have been reported to be useful to estimate and monitor the amount of ganglion cell loss in patients with papilledema (4). We hypothesize that macular ganglion cell layer and inner plexiform layer (GCIPL) analysis can detect structural changes masked within pRNFL analysis due to optic disc swelling. If correct, this analysis could help to establish a therapeutic window before irreversible neuronal loss occurs and identify patients needing more aggressive treatment.

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To assess this hypothesis, we prospectively evaluated 4 eyes of patients with anterior optic neuritis and collected the GCIPL macular thickness and pRNFL thickness with SD-OCT (Cirrus-OCT; Carl-Zeiss Meditec, Inc, Dublin, CA). We performed all examinations within 1 week of onset of optic neuritis. Visual fields were performed using standard automated perimetry (Humphrey Field Analyzer II 750; 24-2 Swedish interactive threshold algorithm; Carl-Zeiss Meditec).

All patients were evaluated and treated during the acute episode with intravenous steroids followed by a taper of oral steroids.

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Case 1

A 41-year-old woman, with no ocular history, complained of painful sudden vision loss in her left eye. Visual acuity was 20/20 in right eye and 20/30 in left eye. Funduscopy revealed a swollen left optic disc. She had a severe depression of her left visual field (mean deviation [MD]: −26.5 dB), and average left pRNFL was 129 μm and average left GCIPL was 78 μm eye (minimum: 75 μm). Two weeks later, average left pRNFL was 134 μm, whereas average GCIPL was decreased to 62 μm (minimum: 59 μm). This GCIPL thinning was detected while the left optic disc was still swollen. Left pRNFL analysis did not demonstrate axonal loss until 6 weeks later (pRNFL average: 69 μm) (See Supplemental Digital Content, Figure e1, At that time, acuity remained 20/30 in left eye, and MD of the left visual field was −23.57 dB.

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Case 2

A 44-year-old woman presented with pain and sudden vision loss in her right eye. Visual acuity was 20/200 in right eye and 20/30 in left eye. In the right eye, average pRNFL was thickened (169 μm), and average GCIPL was 90 μm (minimum: 89 μm). Three weeks later, right pRNFL average was 111 μm, but right GCIPL analysis revealed thinning (average: 71 μm; minimum: 66 μm). Six weeks after the acute episode, right optic disc edema had resolved, and average pRNFL thickness was still within normal limits (99 μm) while GCIPL showed thinning (average: 66 μm; minimum: 59 μm). Significant temporal pRNFL thinning was not apparent until 2 months later (See Supplemental Digital Content, Figure e2, Visual acuity improved to 20/20 in the affected eye, but the visual field did not improve during follow-up (MD: −27.75 dB).

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Case 3

A 35-year-old woman, diagnosed with relapsing–remitting multiple sclerosis, complained of blurred vision in her left eye. Visual acuity was 20/20 in right eye and 20/25 in left eye. The left optic disc was swollen, and pRNFL average was 109 μm. SD-OCT revealed abnormal color-coded GCIPL thinning. Left visual field testing showed a superior nerve fiber bundle defect (MD: −1.60 dB). Four months later, the left optic disc was no longer swollen, visual acuity was 20/20 and SD-OCT pRNFL analysis showed corresponding axonal loss. In this case, GCIPL was thinned at initial examination. Therefore, we could not assess if neuronal damage was due to the acute episode optic neuritis or a result of subclinical loss seen in some patients with multiple sclerosis.

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Case 4

A 36-year-old woman, with no previous visual complaints, was diagnosed with anterior optic neuritis in her left eye. Visual acuity was 20/20 in right eye and 20/25 in left eye. In the left eye, SD-OCT showed pRNFL thickening (average: 175 μm), but average GCIPL was within normal limits (average: 88 μm; minimum: 84 μm). A small paracentral scotoma was present in the left visual field (MD: −1.3 dB). Two weeks later, left pRNFL was 169 μm, and average GCIPL was 86 μm (minimum 81 μm), and at 8 weeks after onset, left optic edema persisted (average pRNFL thickness: 122 μm). Although GCIPL thickness was within normal limits, according to internal color-coded normative database, GCIPL thickness decreased in the superonasal and inferonasal sectors (by 9 μm and 10 μm, respectively). Three months later, GCIPL thinning (73 μm) in superonasal sector was color-coded as abnormally thinned (P < 0.5%), with reduced pRNFL thickness (average: 86 μm) (See Supplemental Digital Content, Figure e3, Visual acuity and visual field returned to normal in the left eye.

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Changes in RNFL and GCIPL measurements at baseline and at last follow-up and the percentage change in the involved eye vs uninvolved eye are shown in Table 1. During the acute episode, mean average RNFL was significantly thicker in the involved eye vs uninvolved eye (P = 0.033). At the last visit, all the parameters, average GCIPL, minimum GCIPL, and average RNFL were thinner in involved eyes than in uninvolved eyes (P = 0.05, P = 0.09, and P = 0.06, respectively).



The difference in the percentage of change between involved and uninvolved eye ranged from 12.5% to 30% of thinning for average GCIPL, 9.5%–35% for minimum GCIPL, and from 32.4% to 59.1% for average RNFL thickness. The mean percentage of change between thicknesses at baseline and last follow-up was statistically higher in involved than in uninvolved eye for average GCIPL and average RNFL thickness (P = 0.013 and P < 0.001, respectively).

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In our 4 patients with anterior optic neuritis, GCIPL thinning was detected within 1 month of presentation, several weeks earlier than pRNFL loss. During the acute phase, optic disc and axonal swelling obscured axonal damage using pRNFL analysis. As pRNFL thickness returned to normal, it was not possible to determine whether this is due to decreasing axonal edema or axonal loss. In all cases, GCIPL analysis predicted neuronal damage several weeks before pRNFL analysis demonstrated axonal loss.

In this study, patients having more severe GCIPL thinning at baseline (Cases 1 and 2) had greater visual field damage at last follow-up. However, in Cases 3 and 4, with milder GCIPL loss, there was less visual field damage and the fields returned to normal. Quantification of GCIPL changes during the acute phase is likely to enhance our knowledge of the pathophysiology and natural history of optic neuritis. GCIPL analysis seems to be more sensitive in detecting neuronal damage and may provide more accurate information than pRNFL analysis during the acute phase of optic disc edema. GCIPL should be considered as a biomarker of early structural damage in anterior optic neuritis.

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1. Rebolleda G, Gonzalez-Lopez JJ, Muñoz-Negrete FJ, Oblanca N, Costa- Frossard L, Alvarez-Cermeño JC. Color-code agreement among Stratus, Cirrus, and Spectralis optical coherence tomography in relapsing-remitting multiple sclerosis with and without prior optic neuritis. Am J Ophthalmol. 2013;5:890–897.
2. Syc SB, Saidha S, Newsome SD, Ratchford JN, Levy M, Ford E, Crainiceanu CM, Durbin MK, Oakley JD, Meyer SA, Frohman EM, Calabresi PA. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain. 2012;135:521–533.
3. Garas A, Simö M, Hollö G. Nerve fiber layer and macular thinning measured with different imaging methods during the course of acute optic neuritis. Eur J Ophthalmol. 2011;21:473–483.
4. Monteiro ML, Afonso CL. Macular thickness measurements with frequency domain-OCT for quantification of axonal loss in chronic papilledema from pseudotumor cerebri syndrome. Eye (Lond). 2014;28:390–398.

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© 2015 by North American Neuro-Ophthalmology Society