Section Editor

®

WriteClick Editor’s Choice

Robert C. Griggs, MD

Editors’ Note: In WriteClick this week, Dr. Fraser applies the Gullstrand equation and concludes that corneal thickness does not lead to significant magnification of the pupil when viewed from an eccentric angle. Authors Robert and Plant argue that the Gullstrand equation does not apply due to the relatively short object distance and the oblique angles of the considered rays. In response to Dr. Wright’s objections, authors Yadav et al. explain why the Guideline Development Subcommittee of the American Academy of Neurology concluded Sativex (nabiximols), a cannabisbased therapy, is considered to be a complementary and alternative medicine in multiple sclerosis. —Megan Alcauskas, MD, and Robert C. Griggs, MD

TOURNAY’S DESCRIPTION OF ANISOCORIA ON LATERAL GAZE: REACTION, MYTH, OR PHENOMENON?

J. Alexander Fraser, London, Canada: In their historical overview of the putative Tournay phenomenon, Drs. Robert and Plant1 argued that the pupil is selectively magnified by the cornea when it is observed at an eccentric angle. I do not think the mathematics of corneal optics support the authors’ conclusions. The refractive power (in diopters) of a patch of cornea, Pc, may be calculated by the Gullstrand equation2:

Author Response: Matthieu P. Robert, Gordon T. Plant, London, UK: The authors thank Dr. Fraser for his interest in our article. Using the Gullstrand equation, he concluded that the effects of corneal thickness on the possible magnification of the apparent pupil seen at an eccentric angle are negligible. The object distance here is much shorter than the focal length of the considered thick converging lens; therefore the virtual image of the pupil seen through the cornea is always—more or less—magnified. Physically modeling the optical distortion of the pupil seen through the cornea at eccentric angles is complex. Because of this eccentricity, the optical path of the rays through the cornea is significantly increased compared to the thickness of the cornea itself, which may result in a visible effect on the size of the virtual image of the pupil. In addition, we do not believe that using the Gullstrand equation here is relevant. This equation—as most of the common expressions in geometrical optics— is only valid in a paraxial approximation, while in the eccentric situation we discuss, the angles of the considered rays are oblique, accounting for maximal aberrations. © 2014 American Academy of Neurology 1.

Pc 5 ðP1 1 P2 Þ 2 ðt=nÞ 3 P1 3 P2

where P1 and P2 are the refractive powers of the outer and inner surfaces of the cornea, respectively; t is the thickness of the cornea; and n is the refractive index of the corneal stroma. By substituting in the empirically measured/calculated values: n 5 1.376, P1 5 47.959D, P2 5 26.23D2,3 we obtain the following: Pc 5 42 1 (217.2 3 t) Because t is on the order of 5 3 1024 m, its contribution to the overall refractive power of the cornea is miniscule (0.11 D), and variations in corneal thickness are an order of magnitude smaller still. Meanwhile, the (P1 1 P2) term may decrease to as low as 35 D in the peripheral cornea.4 Thus, the magnifying effect of increased corneal thickness is negligible relative to the minifying effect of a flattened curvature in the corneal periphery. 1484

Neurology 83

October 14, 2014

2.

3. 4.

Robert MP, Plant GT. Tournay’s description of anisocoria of lateral gaze: reaction, myth, or phenomenon? Neurology 2014;82:452–456. Vojnikovic B, Gabric N, Dekaris I, Juric B. Curvature analyses of the corneal front and back surface. Coll Antropol 2013;37(suppl 1):93–96. Olsen T. On the calculation of power from curvature of the cornea. Br J Ophthalmol 1986;70:152–154. Serrao S, Lombardo G, Lombardo M. Differences in nasal and temporal responses of the cornea after photorefractive keratectomy. J Cataract Refract Surg 2005;31:30–38.

SUMMARY OF EVIDENCE-BASED GUIDELINE: COMPLEMENTARY AND ALTERNATIVE MEDICINE IN MULTIPLE SCLEROSIS: REPORT OF THE GUIDELINE DEVELOPMENT SUBCOMMITTEE OF THE AMERICAN ACADEMY OF NEUROLOGY

Stephen Wright, Salisbury, UK: Yadav et al.1 described Sativex (nabiximols) as a complementary and

alternative medicine (CAM). This is incorrect. Nabiximols has been developed according to all relevant guidelines as a prescription medicine and is manufactured according to Good Manufacturing Practice. It has been tested in a preclinical and clinical development program, including more than 2,500 patients in randomized, placebo-controlled clinical trials (table e-1). Sativex has been authorized as a prescription medicine by more than 25 regulatory authorities around the world. It has a Summary of Product Characteristics and is not available anywhere in the world as an over-thecounter product. Our search revealed various definitions of CAMs and Sativex could not be defined as a CAM under any description. The comprehensive literature search performed by Yadav et al. missed key references, including several randomized controlled clinical studies and a meta-analysis.2–5 Notcutt et al.3 reported a randomized withdrawal study in those with spasticity due to multiple sclerosis (MS), which showed a highly significant difference between Sativex and placebo. This result prompted the UK regulatory authority (the Medicines and Healthcare Products Regulatory Agency) to state “Robust evidence of long-term efficacy of Sativex in the relief of spasticity in MS patients.is provided by the new placebo-controlled, parallel group, randomised withdrawal study GWSP0702.”6 Finally, we were disappointed that 2 of the double-blind, randomized, placebo-controlled studies were listed as Class 2 evidence. We would like further explanation on the classification determinations. We would respectfully suggest that Sativex be removed from a list of CAMs. Author Response: Vijayshree Yadav, Portland, OR; Christopher Bever, Jr, Baltimore; James Bowen, Seattle; Allen Bowling, Englewood, CO; Bianca Weinstock-Guttman, Buffalo, NY; Michelle Cameron, Dennis Bourdette, Portland, OR; Gary S. Gronseth, Kansas City, KS; Pushpa Narayanaswami, Boston: The authors thank Dr. Wright for outlining his concerns about the classification of Sativex as a CAM and the drug’s unavailability as an overthe-counter product anywhere in the world. However, in the United States, cannabis-based therapies for MS are currently considered CAM. We therefore found it appropriate for our guideline1 to include cannabis and all cannabis-based formulations, including the oromucosal form Sativex (nabiximols) and pill forms. We also included studies using Marinol (Food and Drug Administration [FDA]–approved for anorexia associated with weight loss in patients with AIDS and as secondary treatment for nausea

and vomiting associated with cancer chemotherapy).7 Moreover, the article was written by US authors using the United States as the reference point, an important factor for defining CAM. Sativex is not yet FDA-approved. The guideline is based on the review of the individual clinical studies (the full guideline, available as an online data supplement to the summary article, provides inclusion criteria for the studies) that did not include meta-analyses, such as Wade et al.1,5 Although this guideline did not include the additional 3 articles Dr. Wright mentioned,2–4 the American Academy of Neurology (AAN)’s recently published systematic review of medical marijuana included them and reached the same conclusions about efficacy of cannabis-based therapies in MS.1,8 We graded each study by following the AAN’s classification scheme for therapeutic studies (see full guideline) and the expert guidance of statisticians.1 The 2 randomized, controlled trials that Dr. Wright presumably references were graded Class II for lack of concealed allocation.9,10 © 2014 American Academy of Neurology 1.

2.

3.

4.

5.

6.

7.

Yadav V, Bever C Jr, Bowen J, et al. Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1083– 1092. Novotna A, Mares J, Ratcliffe S, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 2011;18: 1122–1131. Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex (nabiximols). Mult Scler 2012;18: 219–228. Langford RM, Mares J, Novotna A, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurology 2013;260:984–997. Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler 2010; 16:707–714. Medicines and Healthcare Products Regulatory Agency. Public Assessment Report, 2009, page 72. Available at: http://www.mhra.gov.uk/home/groups/ par/documents/websiteresources/con084961.pdf. Accessed September 11, 2014. US Food and Drug Administration. Drugs@FDA Database. Available at: http://www.accessdata.fda.gov/drugsatfda_ docs/label/2006/018651s025s026lbl.pdf. Accessed May 16, 2014.

Neurology 83

October 14, 2014

1485

8.

9.

Koppel BS, Brust JCM, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82:1556–1563. Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled

10.

trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol 2007;14:290–296. Collin C, Ehler E, Waberzinek G, et al. A doubleblind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 2010;32: 451–459.

WriteClick® rapid online correspondence The editors encourage comments about recent articles through WriteClick: Go to Neurology.org and click on the “WriteClick” tab at the top of the page. Responses will be posted within 72 hours of submission. Before using WriteClick, remember the following:

• WriteClick is restricted to comments about studies published in Neurology within the last eight weeks • Read previously posted comments; redundant comments will not be posted • Your submission must be 200 words or less and have a maximum of five references; reference one must be the article on which you are commenting • You can include a maximum of five authors (including yourself)

Enjoy Big Savings on NEW 2014 AAN Practice Management Webinars Subscriptions The American Academy of Neurology offers 14 cost-effective Practice Management Webinars you can attend live or listen to recordings posted online. AAN members can purchase one webinar for $149 or subscribe to the entire series for only $199. This is new pricing for 2014 and significantly less than 2013—and big savings from the new 2014 nonmember price of $199 per webinar or $649 for the subscription. Register today for these and other 2014 webinars at AAN.com/view/pmw14: Online Now – ICD-10: Are you Ready? Ensure Your Practice Does Not Receive Payment Interruptions Online Now – Protecting the Solo and Small Practice Neurologist Online Now – Accountable Care Organizations: The Role of Neurologists in New Health Care Models Online Now – E/M: Minimize Mistakes, Maximize Reimbursement Online Now – How Is Your Care Measuring Up?

Author disclosures are available upon request ([email protected]). 1486

Neurology 83

October 14, 2014

Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the Guideline Development Subcommittee of the American Academy of Neurology Stephen Wright, Vijayshree Yadav, Christopher Bever, Jr, et al. Neurology 2014;83;1484-1486 DOI 10.1212/01.wnl.0000455935.13606.91 This information is current as of October 13, 2014 Updated Information & Services

including high resolution figures, can be found at: http://www.neurology.org/content/83/16/1484.2.full.html

References

This article cites 8 articles, 4 of which you can access for free at: http://www.neurology.org/content/83/16/1484.2.full.html##ref-list-1

Permissions & Licensing

Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions

Reprints

Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus

Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.

Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology.

Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the Guideline Development Subcommittee of the American Academy of Neurology. - PDF Download Free
232KB Sizes 0 Downloads 7 Views

Recommend Documents