Vision and vision-related outcome measures in multiple sclerosis

Abstract

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

Keywords: clinical trials methodology; multiple sclerosis; neuro-ophthalmology; optic neuritis; vision.

Figure 1

Low-contrast Sloan letter chart (Precision Vision). These charts have a standardized format based on Early Treatment Diabetic Retinopathy Study visual acuity charts, the standard used in ophthalmology clinical trials, and have several advantages over standard Snellen charts or near vision testing cards as traditionally used in multiple sclerosis trials: (i) letters (Sloan letters) are designed to be equally detectable for normal observers; (ii) each line has an equal number of letters (five per line); (iii) spacing between letters and lines is proportional to the letter size; (iv) change in visual acuity from one line to another occurs in equal logarithmic steps (change of three lines constitutes a doubling of the visual angle); and (v) visual acuity [for high-contrast (black letters on white) chart] may be specified by Snellen notation for descriptive purposes (i.e. 20/20), by the number of letters identified correctly. This figure shows the 25% contrast level for purposes of illustrating format; the actual contrast levels used in these trials, 2.5% and 1.25%, have substantially lighter grey letters. The charts measure 14 × 14 inches for easy use and portability in the multiple sclerosis clinical trial setting; charts may also be mounted on a retro-illuminated cabinet, thus eliminating the need for standardization of room lighting levels. Reprinted with permission (Balcer et al., 2007).

Figure 2

Single frame of spectral-domain OCT images through the fovea and macular region of the left eye with retinal layers labelled. (A) A 41-year-old female with relapsing-remitting multiple sclerosis. (B) Research study volunteer with no history of ocular or neurological disease. Note visible relative thinning of the macular GCL in the patient with multiple sclerosis (total macular volume = 7.52 mm³) compared to the disease-free control (total macular volume = 8.67 mm³). Similarly, the peripapillary RNFL was thinner in the patient with multiple sclerosis (85 μm) compared to the disease-free control (98 μm). Images are courtesy of Rachel Nolan and Lisena Hasanaj, Neurology Vision Research Laboratory, New York University School of Medicine.

Figure 3

Magnetic resonance optic nerve images acquired in a 30-year-old female with a 5-day history of acute right optic neuritis. (A) Axial post-contrast T₁-weighted image shows swelling and enhancement of the intraorbital and intracanalicular parts of the right optic nerve. (B) Coronal T₂-weighted image shows swollen hyperintense right optic nerve through posterior orbit. (C) Coronal post-contrast T₁-weighted image shows gadolinium-enhancement of right optic nerve in posterior orbit. Images are courtesy of Dr Ahmed Toosy, UCL Institute of Neurology, London, UK.