Retinal thinning in amyotrophic lateral sclerosis patients without ophthalmic disease

Abstract

Importance: Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that primarily affects motor neurons. Recently, three causative genes have been implicated in both ALS and glaucoma. However, it is still uncertain whether patients with ALS have neurodegeneration in their retinas. If so, retinal thickness measurements might be a useful biomarker for ALS progression. Previous work in this area has been inconclusive, as it has not taken into account the effect of ophthalmic diseases on retinal thinning.

Objective: To determine whether there are differences in retinal neurons in ALS patients utilizing spectral-domain optical coherence tomography (SD-OCT). We tested the hypothesis that ALS patients exhibit retinal neurodegeneration that is not associated with ophthalmic diseases.

Design, settings and participants: Observational, comparative, cross-sectional study performed on patients recruited from the Duke University Medical Center ALS clinic. Patients underwent a comprehensive ophthalmologic examination to rule out ocular pathology. 21 patients met inclusion criteria. Two eyes with ocular pathology were excluded, leading to a total of 40 eyes of 21 patients included in the study. Retinal neurodegeneration was assessed by retinal nerve fiber layer (RNFL) thickness measurement using SD-OCT (Spectralis; Heidelberg Engineering).

Main outcomes and measures: ALS disease severity, determined through the ALS Functional Rating Scale (ALSFRS-R); mean and six sector RNFL thickness values compared to age-adjusted values in the normative database provided by Heidelberg Engineering; RNFL thickness correlation with ALSFRS-R, ALSFRS-R progression rate, forced vital capacity (FVC), and visual acuity.

Results: ALSFRS-R mean score was 30+/-10. Mean RNFL thickness in ALS patients was 88.95 +/- 10.8 microns, significantly thinner than values in the normative database (95.81 +/- 0.8). These RNFL thickness values did not demonstrate correlation to ALSFRS-R score, ALSFRS-R progression rate, FVC, intraocular pressure, or visual acuity.

Conclusions: Using SD-OCT, our study shows that ALS patients without ocular pathology exhibit thinned retinal layers. Future studies are warranted to clarify the clinical relationship between retinal thinning and motor neuron loss in ALS.

Fig 1. Representative clinical findings, SD-OCT and macular map from an ALS subject.

OCT results were compared to the age-adjusted normative database by the integrated SD-OCT analysis software. Thin retinal areas are presented in a report format used in a typical clinic visit for ophthalmic examinations.

Fig 2. Mean and sectorial RNFL thickness comparison between ALS subjects and age-adjusted normal values.

Total and six sector RNFL values were compared to the age-adjusted normal value utilized by the Spectralis SD-OCT system. The data presented here include mean ± standard error of the mean. Data for the right eye is indicated by OD and the left eye by OS. The right eye group showed significant thinning in total RNFL thickness, temporal sector RNFL thickness, and superonasal sector RNFL thickness. The left eye group had significant thinning in total RNFL thickness, temporal sector RNFL thickness, and superotemporal sector RNFL thickness.

Fig 3. Bivariate fit for RNFL thickness and ALFRS-R score.

No significant correlation between mean RNFL thickness and ALSFRS-R score was found. Please note that most ALSFRS-R scores were relatively high, indicating mild ALS disease severity. Data shown are from right eyes only, but we obtained the same result from left eyes: there was no correlation observed between ALSFRS-R and RNFL thinning.

Fig 4. Bivariate fit for RNFL thickness and ALFRS-R progression rate.

No significant correlation between mean RNFL thickness and ALSFRS-R progression rate was found. Again, data shown are from right eyes only, but the same result was obtained from left eyes.

Fig 5. Bivariate fit for RNFL thickness and FVC.

No significant correlation between mean RNFL thickness and FVC was found. The data shown are from right eyes only; the same result was found in left eyes.

Fig 6

Bivariate fit for ALFRS-R score and intraocular pressure (A), and ALFRS-R score and visual acuity (B). (A) No significant correlation between ALSFRS-R score and intraocular pressure (IOP) were found. (B) Similarly, there was no correlation between ALSFRS-R score and visual acuity (VA). Data shown are from right eyes only, but analyses with left eye data were comparable.