Objective-Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).Methods-Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at three centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed.Results-Among 299 patients (593 eyes) with ≥6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p<0.001; VA: p=0.005). RNFL thinning increased over time, with average losses of 2.9 μm at 2-3 years and 6.1 μm at 3-4.5 years (p<0.001 vs. 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (≥6.6 μm) increased from 11% at 0-1 year to 44% at 3-4.5 years (p<0.001).Interpretation-Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with sub-clinical axonal loss in the anterior visual pathway in MS and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.Address all correspondence to: Dr. Laura J. Balcer, Department of Neurology, 3 E. Gates, 3400 Spruce Street, Philadelphia, PA 19104, 215-349-8072, Fax 215-349-5579, lbalcer@mail.med.upenn.edu. NIH Public Access Author ManuscriptAnn Neurol. Author manuscript; available in PMC 2011 June 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptVisual dysfunction is a common cause of disability and reduced quality of life in multiple sclerosis (MS). 1 The anterior visual pathway is a frequent site for inflammation and demyelination, and axonal degeneration is likely to be a final common pathway to permanent visual loss. [2][3][4][5] Recognized by MS experts as a critical dimension for outcomes assessment, 6 vision has been an important area of investigation. The findings of many studies have supported low-contrast letter acuity as a candidate clinical trial outcome measure. It can capture subtle visual impairment, treatment effects, MRI lesion burden, prolonged visual evoked potential latencies, and quality of life. 1,[7][8][9][10][11][12][13] Many ongoing MS trials have incorporated low-contrast acuity as a tertiary outcome.The emergence of optical coherence tomography (OCT) in MS has brought the anterior visual pathway to the forefront as a model for measuring therapeutic efficacy, particularly for trials involving neuroprotection. 14-32 A reliable marker for axonal loss in MS, 24 retina...

Background Benign MS, traditionally defined as EDSS ≤3 and ≥15 years’ disease duration, is thought to follow a milder course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort, and examined the relation to vision and quality of life (QOL). Methods In this longitudinal study of vision in MS at three academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity were performed to assess visual function. RNFL thickness was determined using OCT-3. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and SF-36. Results Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS ≤3 and ≥15 years disease duration. Benign MS eyes had as much RNFL thinning (-3.6 μm, P=0.0008 vs. baseline, paired t-test) as typical MS eyes (-3.3 μm, P<0.0001). Both groups had significant low-contrast acuity loss. Prior history of optic neuritis (ON) was more frequent in benign MS (69% vs. 33% of eyes). History of ON distinguished benign vs. typical MS (P=0.002) and correlated with RNFL thickness at baseline (P=0.002) and disease duration (P=0.03), but not EDSS (P=0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75±21 vs. 88±11, P=0.005). Conclusions Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS, and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well-captured by the EDSS, accounts for a substantial degree of disability in benign MS.

The use of liquid nitrogen to treat skin and mucosal lesions is well understood in the dermatologic and gastrointestinal literature. Direct spray cryotherapy (SCT) in the airway has shown promising results in the treatment of esophageal premalignant and even invasive lesions. In the airway, several studies have shown it to be a safe, effective treatment for both benign and malignant disease. It is easily administered in the outpatient setting and can be repeated several times without undue side effects. In this article, we review the current literature on the use of SCT for the treatment of endobronchial lesions and also describe our own institutional experience of the use of SCT in the airway. The use of proper technique and airway venting is important in mitigating the complications of barotrauma from massive expansion of nitrogen upon conversion from the liquid to gaseous state. We also review some of the basic science principals behind the use of the cryotherapy to treat lesions in different tissues. We feel that SCT is a potential area for further research at both clinical and basic science level.

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