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## Complete Summary

#### GUIDELINE TITLE

Evidence report: the medical treatment of ocular myasthenia (an
evidence-based review). Report of the Quality Standards Subcommittee of
the American Academy of Neurology.

#### BIBLIOGRAPHIC SOURCE(S)

Benatar M, Kaminski HJ, Quality Standards Subcommittee of the American
Academy of Neurology. Evidence report: the medical treatment of ocular
myasthenia (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2007 Jun
12;68(24):2144-9. \[20 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Ocular myasthenia

#### GUIDELINE CATEGORY

Management\
Treatment

#### CLINICAL SPECIALTY

Neurology\
Ophthalmology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To perform a systematic review of the relevant literature and to
    provide evidence-based guidelines for the medical treatment of
    ocular myasthenia

-   To address two specific questions: 1) Does pharmacologic treatment
    lead to an improvement in ocular symptoms (diplopia and ptosis)?
    and 2) Is pharmacologic treatment associated with a reduced risk of
    progression from ocular to generalized myasthenia gravis (MG)?

#### TARGET POPULATION

Patients presenting with ocular myasthenia

#### INTERVENTIONS AND PRACTICES CONSIDERED

Corticosteroids and/or azathioprine were considered but could not be
recommended because of the absence of evidence

#### MAJOR OUTCOMES CONSIDERED

Effectiveness of therapy

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Two neurologists with experience in the evaluation and treatment of
patients with myasthenia gravis (MG) were appointed by the American
Academy of Neurology Quality Standards Subcommittee to prepare this
review. The Cochrane Neuromuscular Disease Group Register was searched
for randomized controlled trials; Medline (1966 to 2004) and EMBASE
(1980 to 2004) were also searched for randomized controlled trials,
case--control studies, and cohort studies. Search terms included
*myasthenia gravis*, *eye*, *ocular*, and *vision*, as well as a series
of terms describing specific therapies and specific types of clinical
studies. To be included in the review, studies had to meet three
criteria: 1) randomized (or quasi-randomized) controlled trial or
observational (cohort or case-- control) study design; 2) active
treatment compared with placebo, no treatment, or some other treatment;
and 3) results reported separately for patients with ocular myasthenia
(Grade 1) as defined by the Myasthenia Gravis Foundation of America.
Studies reporting outcome in children and adults were considered.

#### NUMBER OF SOURCE DOCUMENTS

Two randomized controlled trials (RCTs) and five observational studies
were identified.

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Classification of Therapeutic Evidence**

**Class I**: Prospective, randomized, controlled clinical trial with
masked outcome assessment, in a representative population. The following
are required: a) primary outcome(s) clearly defined; b)
exclusion/inclusion criteria clearly defined; c) adequate accounting for
dropouts and cross-overs with numbers sufficiently low to have minimal
potential for bias; d) relevant baseline characteristics are presented
and substantially equivalent among treatment groups or there is
appropriate statistical adjustment for differences.

**Class II**: Prospective matched group cohort study in a representative
population with masked outcome assessment that meets a--d above OR a
randomized controlled trial (RCT) in a representative population that
lacks one criteria a--d.

**Class III**: All other controlled trials (including well-defined
natural history controls or patients serving as own controls) in a
representative population, where outcome is independently assessed, or
independently derived by objective outcome measurement.\*

**Class IV**: Evidence from uncontrolled studies, case series, case
reports, or expert opinion.

\*Objective outcome measurement: an outcome measure that is unlikely to
be affected by an observer\'s (patient, treating physician,
investigator) expectation or bias (e.g., blood tests, administrative
outcome data).

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

The quality of randomized controlled trials was evaluated in six
domains---method of randomization, allocation concealment, patient
blinding, observer blinding, explicit inclusion/exclusion criteria, and
completeness of follow-up---using a set of predefined criteria. The
quality of observational studies was similarly evaluated in three
domains---control for confounding, completeness of follow-up, and
observer blinding---using predefined criteria. The method of
randomization was graded as adequate (computer-generated random numbers,
tables of random numbers, coin toss), unclear (statement made that trial
is randomized but method not described), or inadequate
(quasi-randomized).

Allocation concealment was graded as adequate (identical prenumbered
containers prepared by an independent pharmacy of central randomization
unit or sequentially numbered opaque sealed envelopes), unclear (no
details given of how the next assignment in the sequence was concealed),
inadequate (open allocation schedule, unsealed or nonopaque envelopes,
alternation, days of week, etc.), or not done. Patient and observer
blinding were graded as adequate (method of blinding described and
thought to be sufficient to ensure that the investigator was unaware of
the treatment received at the time outcome evaluation was performed),
unclear (authors state that study was blinded, but details not
provided), inadequate (some method used to blind investigators, but
technique was unreliable), or not done. Completeness of follow-up was
graded as adequate (analysis performed with \>80% of patients), unclear
(insufficient details provided on withdrawals, dropouts, etc.),
inadequate (\<80% of patients included in the analysis), or not done.
Finally, control for confounding was graded as adequate (multivariate
analysis that included at least two factors---age, duration of ocular
symptoms before initiation period of follow-up, concomitant
immunosuppressive therapy, duration of follow-up after entry into the
study, antibody status, presence of abnormalities on repetitive nerve
stimulation or single fiber electromyography---or data presented showing
that the treatment groups were comparable at baseline with respect to
this same set of factors), unclear (authors state that they controlled
for confounding, but details not given), inadequate (some effort made to
control for confounding, but insufficient number of relevant factors
were considered in the analysis), or not done.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Classification of Recommendations**

**A** = Established as effective, ineffective, or harmful for the given
condition in the specified population. (Level A rating requires at least
two consistent Class I studies.)

**B** = Probably effective, ineffective, or harmful for the given
condition in the specified population. (Level B rating requires at least
one Class I study or at least two consistent Class II studies.)

**C** = Possibly effective, ineffective, or harmful for the given
condition in the specified population. (Level C rating requires at least
one Class II study or two consistent Class III studies.)

**U** = Data inadequate or conflicting; given current knowledge,
treatment is unproven.

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Drafts of the guideline have been reviewed by at least three American
Academy of Neurology (AAN) committees, a network of neurologists,
Neurology peer reviewers, and representatives from related fields.

The guideline was approved by the Quality Standards Subcommittee on July
29, 2006; by the Practice Committee on March 15, 2007; and by the
American Academy of neurology Board of Directors on April 5, 2007.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

Definitions of the classification of therapeutic evidence (Class I--IV),
and strength of recommendations (A, B, C, U) are provided at the end of
the \"Major Recommendations\" field.

**Are Cholinesterase Inhibitors, Corticosteroids, or Other
Immunosuppressive Agents Effective in Improving Visual Symptoms in
Ocular Myasthenia?**

*Recommendations*

Given the absence of evidence, it is not possible to make any
evidence-based recommendations regarding the effects of cholinesterase
inhibitors, corticosteroids, or other immunosuppressive agents in
improving the symptoms of ocular myasthenia.

**Are Cholinesterase Inhibitors, Corticosteroids, or Other
Immunosuppressive Agents Effective in Reducing the Risk of Progression
from Ocular to Generalized Myasthenia Gravis (MG)?**

*Recommendations*

For patients with ocular myasthenia, the evidence does not support or
refute the use of corticosteroids and/or azathioprine to reduce the risk
of progression to generalized MG (**Level U**). The decision to use such
agents should be weighed against the potential for harmful side effects
of these medications. Furthermore, it is not possible to make any
evidence-based recommendations with regard to the question of whether
cholinesterase inhibitors have any effect in reducing the risk of
progression to generalized MG. Recommendations cannot be made because of
an absence of evidence.

**[Definitions]{.underline}**:

**Classification of Therapeutic Evidence**

**Class I**: Prospective, randomized, controlled clinical trial with
masked outcome assessment, in a representative population. The following
are required: a) primary outcome(s) clearly defined; b)
exclusion/inclusion criteria clearly defined; c) adequate accounting for
dropouts and cross-overs with numbers sufficiently low to have minimal
potential for bias; d) relevant baseline characteristics are presented
and substantially equivalent among treatment groups or there is
appropriate statistical adjustment for differences.

**Class II**: Prospective matched group cohort study in a representative
population with masked outcome assessment that meets a--d above OR a
randomized controlled trial (RCT) in a representative population that
lacks one criteria a--d.

**Class III**: All other controlled trials (including well-defined
natural history controls or patients serving as own controls) in a
representative population, where outcome is independently assessed, or
independently derived by objective outcome measurement.\*

**Class IV**: Evidence from uncontrolled studies, case series, case
reports, or expert opinion.

\*Objective outcome measurement: an outcome measure that is unlikely to
be affected by an observer\'s (patient, treating physician,
investigator) expectation or bias (e.g., blood tests, administrative
outcome data).

**Classification of Recommendations**

**A** = Established as effective, ineffective, or harmful for the given
condition in the specified population. (Level A rating requires at least
two consistent Class I studies.)

**B** = Probably effective, ineffective, or harmful for the given
condition in the specified population. (Level B rating requires at least
one Class I study or at least two consistent Class II studies.)

**C** = Possibly effective, ineffective, or harmful for the given
condition in the specified population. (Level C rating requires at least
one Class II study or two consistent Class III studies.)

**U** = Data inadequate or conflicting; given current knowledge,
treatment is unproven.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate treatment of ocular myasthenia

#### POTENTIAL HARMS

Not stated

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   This statement is provided as an educational service of the American
    Academy of Neurology (AAN). It is based on an assessment of current
    scientific and clinical information. It is not intended to include
    all possible proper methods of care for a particular neurologic
    problem or all legitimate criteria for choosing to use a specific
    procedure. Neither is it intended to exclude any reasonable
    alternative methodologies. The AAN recognizes that specific patient
    care decisions are the prerogative of the patient and the physician
    caring for the patient, based on all of the circumstances involved.

-   The absence of high-quality evidence means that it is not possible
    to make any evidence-based recommendations regarding the effects of
    cholinesterase inhibitors, corticosteroids, or other
    immunosuppressive agents with respect to improvement of ocular
    symptoms. There is similarly an absence of evidence regarding the
    effects of cholinesterase inhibitors on the risk of progression to
    generalized myasthenia gravis (MG).

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Benatar M, Kaminski HJ, Quality Standards Subcommittee of the American
Academy of Neurology. Evidence report: the medical treatment of ocular
myasthenia (an evidence-based review): report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2007 Jun
12;68(24):2144-9. \[20 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2007 Jun 12

#### GUIDELINE DEVELOPER(S)

American Academy of Neurology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

American Academy of Neurology (AAN)

#### GUIDELINE COMMITTEE

Quality Standards Subcommittee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Primary Authors*: Michael Benatar, MBChB, MS, DPhil; Henry J. Kaminski,
MD,FAAN

*Subcommittee Members*: Jacqueline French, MD, FAAN (*Co-Chair*); Gary
S. Gronseth, MD (*Co-Chair*); Charles E. Argoff, MD; Stephen Ashwal, MD,
FAAN (*ex-officio*); Christopher Bever Jr., MD, MBA, FAAN
(*facilitator*); John D. England, MD, FAAN; Gary M. Franklin, MD, MPH
(*ex-officio*); Gary H. Friday, MD, MPH, FAAN; Larry B. Goldstein, MD,
FAAN; Deborah Hirtz, MD (*ex-officio*); Robert G. Holloway, MD, MPH,
FAAN; Donald J. Iverson, MD, FAAN; Leslie A. Morrison, MD; Clifford J.
Schostal, MD; David J. Thurman, MD, MPH; William J. Weiner, MD, FAAN;
Samuel Wiebe, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

The American Academy of Neurology (AAN) is committed to producing
independent, critical and truthful clinical practice guidelines (CPGs).
Significant efforts are made to minimize the potential for conflicts of
interest to influence the recommendations of this CPG. To the extent
possible, the AAN keeps separate those who have a financial stake in the
success or failure of the products appraised in the CPGs and the
developers of the guidelines. Conflict of interest forms were obtained
from all authors and reviewed by an oversight committee prior to project
initiation. AAN limits the participation of authors with substantial
conflicts of interest. The AAN forbids commercial participation in, or
funding of, guideline projects. Drafts of the guideline have been
reviewed by at least three AAN committees, a network of neurologists,
Neurology peer reviewers, and representatives from related fields. The
AAN Guideline Author Conflict of Interest Policy can be viewed at
[www.aan.com](http://www.aan.com/). With regards to this specific
report, all authors have stated that they have nothing to disclose.

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: A list of American Academy of Neurology (AAN)
guidelines, along with a link to a Portable Document Format (PDF) file
for this guideline, is available at the [AAN Web
site](http://www.aan.com/go/practice/guidelines).

Print copies: Available from the AAN Member Services Center, (800)
879-1960, or from AAN, 1080 Montreal Avenue, St. Paul, MN 55116.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   AAN guideline development process \[online\]. St. Paul (MN):
    American Academy of Neurology. Available from the [American Academy
    of Neurology Web
    site](http://www.aan.com/go/practice/guidelines/development).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI Institute on October 9, 2007.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is
copyrighted by the American Academy of Neurology.

### DISCLAIMER

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Date Modified: 11/3/2008