PMID- 29750734
OWN - NLM
STAT- MEDLINE
DCOM- 20190712
LR  - 20191210
IS  - 1536-5166 (Electronic)
IS  - 1070-8022 (Print)
IS  - 1070-8022 (Linking)
VI  - 38
IP  - 2
DP  - 2018 Jun
TI  - Evolution of Visual Outcomes in Clinical Trials for Multiple Sclerosis 
      Disease-Modifying Therapies.
PG  - 202-209
LID - 10.1097/WNO.0000000000000662 [doi]
AB  - : BACKGROUND:: The visual pathways are increasingly recognized as an ideal model 
      to study neurodegeneration in multiple sclerosis (MS). Low-contrast letter acuity 
      (LCLA) and optical coherence tomography (OCT) are validated measures of function 
      and structure in MS. In fact, LCLA was the topic of a recent review by the 
      Multiple Sclerosis Outcome Assessments Consortium (MSOAC) to qualify this visual 
      measure as a primary or secondary clinical trial endpoint with the Food and Drug 
      Administration (FDA) and other regulatory agencies. This review focuses on the 
      use of LCLA and OCT measures as outcomes in clinical trials to date of MS 
      disease-modifying therapies. METHODS: A Pubmed search using the specific key 
      words "optical coherence tomography," "low-contrast letter acuity," "multiple 
      sclerosis," and "clinical trials" was performed. An additional search on the 
      clinicaltrials.gov website with the same key words was used to find registered 
      clinical trials of MS therapies that included these visual outcome measures. 
      RESULTS: As demonstrated by multiple clinical trials, LCLA and OCT measures are 
      sensitive to treatment effects in MS. LCLA has been used in many clinical trials 
      to date, and findings suggest that 7 letters of LCLA at the 2.5% contrast level 
      are meaningful change. Few clinical trials using the benefits of OCT have been 
      performed, although results of observational studies have solidified the ability 
      of OCT to assess change in retinal structure. Continued accrual of clinical trial 
      and observational data is needed to validate the use of OCT in clinical trials, 
      but preliminary work suggests that an intereye difference in retinal nerve fiber 
      layer thickness of 5-6 mum is a clinically meaningful threshold that identifies an 
      optic nerve lesion in MS. CONCLUSIONS: Visual impairment represents a significant 
      component of overall disability in MS. LCLA and OCT enhance the detection of 
      visual pathway injury and can be used as measures of axonal and neuronal 
      integrity. Continued investigation is ongoing to further incorporate these 
      vision-based assessments into clinical trials of MS therapies.
FAU - Nolan, Rachel C
AU  - Nolan RC
AD  - Departments of Neurology (RCN, OA, JRR, SLG, LJB), Population Health (LJB), 
      Ophthalmology (SLG, LJB), and Physical Medicine and Rehabilitation (JRR), New 
      York University School of Medicine, New York, New York.
FAU - Akhand, Omar
AU  - Akhand O
FAU - Rizzo, John-Ross
AU  - Rizzo JR
FAU - Galetta, Steven L
AU  - Galetta SL
FAU - Balcer, Laura J
AU  - Balcer LJ
LA  - eng
GR  - K12 HD001097/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - J Neuroophthalmol
JT  - Journal of neuro-ophthalmology : the official journal of the North American 
      Neuro-Ophthalmology Society
JID - 9431308
SB  - IM
MH  - *Clinical Trials as Topic
MH  - Humans
MH  - Multiple Sclerosis/drug therapy/*physiopathology
MH  - Nerve Fibers/pathology
MH  - Optic Neuritis/drug therapy/physiopathology
MH  - Outcome Assessment, Health Care
MH  - Retinal Ganglion Cells/pathology
MH  - Sickness Impact Profile
MH  - Tomography, Optical Coherence
MH  - Vision Disorders/drug therapy/*physiopathology
MH  - Visual Acuity/*physiology
PMC - PMC6026328
MID - NIHMS976162
COIS- L. J. Balcer has received investigator-initiated research grant funding from 
      Biogen. The remaining authors report no conflicts of interest.
EDAT- 2018/05/12 06:00
MHDA- 2019/07/13 06:00
PMCR- 2019/06/01
CRDT- 2018/05/12 06:00
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2019/07/13 06:00 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - 00041327-201806000-00016 [pii]
AID - 10.1097/WNO.0000000000000662 [doi]
PST - ppublish
SO  - J Neuroophthalmol. 2018 Jun;38(2):202-209. doi: 10.1097/WNO.0000000000000662.