Comparisons of Medical, Laser, and Incisional Surgical Treatments for Open-Angle Glaucoma in Adults

1
Comparisons of Medical, Laser, and Incisional
Surgical Treatments forOpen-Angle Glaucoma in
Adults

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

2
Outline of Material

• This presentation covers
• The comparative effectiveness review (CER)
  process used by the Agency for Healthcare
  Research and Quality
• Background information
• Clinical questions addressed in the CER
• A summary of the CER results (Clinical Bottom
  Line) comparing medical, surgical, and medical
  versus surgical interventions for
• Lowering intraocular pressure
• Optic nerve damage and/or visual field loss
• Reducing visual impairment
• Reported adverse effects
• Gaps in knowledge
• Resources for shared decisionmaking

3
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development

• Topics are nominated through a public process,
  which includes submissions from health care
  professionals, professional organizations, the
  private sector, policymakers, the public, and
  others.
• A systematic review of all relevant clinical
  studies is conducted by independent researchers,
  funded by AHRQ, to synthesize the evidence in a
  report summarizing what is known and not known
  about the select clinical issue. The research
  questions and the results of the report are
  subject to expert input, peer review, and public
  comment.
• The results of these reviews are summarized into
  a Clinician Research Summary and a Consumer
  Research Summary for use in decisionmaking and in
  discussions with patients. The Research Summaries
  and the full report are available at
  www.effectivehealthcare.ahrq.gov/glaucomatreatment
  .cfm.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

4
Strength of Evidence Ratings

• The strength of evidence ratings only apply to
  the analysis of primary studies in this review
  and are classified into four broad ratings
• Systematic review data were included and were
  considered as the highest level of evidence for
  addressing questions of therapy, but it was not
  possible to adapt the evidence grading scheme to
  incorporate evidence from systematic reviews.

High High confidence that further research is very unlikely to change the confidence in the estimate of effect, meaning that the evidence reflects the true effect.
Moderate Moderate confidence that further research may change our confidence in the estimate of effect and may change the estimate.
Low Low confidence that further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimate, meaning there is low confidence that the evidence reflects the true effect.
Insufficient Evidence either is unavailable or does not permit a conclusion.

• AHRQ Methods Guide for Effectiveness and
  Comparative Effectiveness Reviews. Available at
  www.effectivehealthcare.ahrq.gov/methodsguide.cfm.
  
• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.Owens DK, Lohr KN, Atkins D,
  et al. J Clin Epidemiol 201063(5)513-23. PMID
  19595577.

5
Background Open-Angle Glaucoma

• Glaucoma is a leading cause of irreversible
  visual impairment and blindness worldwide.
• Glaucoma is an acquired disease of the optic
  nerve (neuropathy), characterized by a particular
  appearance of the optic nerve and by visual field
  defects that are usually midperipheral and in the
  nasal visual field.
• If optic nerve damage is associated with an open
  or closed appearance to the drainage channels for
  aqueous humor in the front of the eye, the
  glaucoma is referred to as open angle (the
  subject of this report) or closed-angle,
  respectively.

• Heijl A, Leske MC, Bengtsson B, et al. Arch
  Ophthalmol 2002120(10)1268-79. PMID 12365904.
• Kass MA, Heuer DK, Higginbotham EJ, et al. Arch
  Ophthalmol 2002120(6)701-13 discussion 829-30.
  PMID 12049575.
• Quigley HA, Boman AT. Br J Ophthalmol
  200690(3)262-7. PMID 16488940.
• Quigley HA, Flower RW, Addicks EM, et al. Invest
  Ophthalmol Vis Sci 198019(5)505-17. PMID
  6154668.
• Sommer A, Tielsch JM, Katz J, et al. Arch
  Ophthalmol 1991109(8)1090-5. PMID 1867550.

6
Pathophysiology of Glaucoma

• In mild glaucoma, damage to the optic nerve may
  be asymptomatic.
• If damage increases, patients may have difficulty
  with peripheral vision, contrast sensitivity,
  glare, adjustments between light and dark, and
  clear central vision.
• Severe glaucoma can result in total, irreversible
  blindness.

• Heijl A, Leske MC, Bengtsson B, et al. Arch
  Ophthalmol 2002120(10)1268-79. PMID 12365904.
• Kass MA, Heuer DK, Higginbotham EJ, et al. Arch
  Ophthalmol 2002120(6)701-13 discussion 829-30.
  PMID 12049575.
• Quigley HA, Boman AT. Br J Ophthalmol
  200690(3)262-7. PMID 16488940.
• Quigley HA, Flower RW, Addicks EM, et al. Invest
  Ophthalmol Vis Sci 198019(5)505-17. PMID
  6154668.
• Sommer A, Tielsch JM, Katz J, et al. Arch
  Ophthalmol 1991109(8)1090-5. PMID 1867550.

7
Treatments for Open-Angle Glaucoma

• Treatments focus on reducing intraocular pressure
  (IOP), which may prevent the secondary worsening
  of visual field loss, visual impairment, and
  blindness.
• Eye drops are currently the most common
  treatment, including prostaglandin analogs,
  beta-adrenergic antagonists, oral and topical
  carbonic anhydrase inhibitors, and
  alpha-adrenergic agonists.
• Laser trabeculoplasty is an outpatient procedure
  that lowers IOP by increasing the outflow of
  aqueous humor from the eye.
• Incisional surgeries include well-established
  techniques including trabeculectomy and aqueous
  drainage device surgery, as well as a host of
  newer procedures, such as nonpenetrating deep
  sclerectomy, canaloplasty, endoscopic
  cyclophotocoagulation, and alternative methods of
  trabecular bypass.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

8
Clinical Questions Addressed in the Comparative
Effectiveness Review

• What is the comparative effectiveness for
  medical, surgical, or medical versus surgical
  treatments for open-angle glaucoma in adults for
  these outcomes
• Lowering intraocular pressure?
• Preventing or slowing the progression of optic
  nerve damage and visual field loss?
• Reducing visual impairment?
• Patient-related quality of life?
• Adverse effects from treatments?

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

9
Clinical Bottom Line Lowering Intraocular
PressureMedical Interventions

• Overall, strong evidence from other systematic
  reviews (50 trials) found that
• As single agents, prostaglandin analogs are the
  most effective at lowering intraocular pressure
  (IOP).
• Prostaglandin analogs appear to be similar in
  their ability to lower IOP.
• Prostaglandin analogs lower IOP more than other
  agents, including
• Brimonidine (mean difference of 1.64 mmHg 4
  trials)
• Dorzolamide (mean difference of 2.64 mmHg 3
  trials)
• Timolol (5 greater at 6 months 4 trials)
• In combination, dorzolamide/timolol lowers IOP
  the same amount as a prostaglandin analog.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

10
Clinical Bottom Line Lowering Intraocular
PressureSurgical Interventions (1 of 3)

• Laser trabeculoplasty effectively lowers
  intraocular pressure (IOP) regardless of the type
  of laser used.
• Strength of Evidence Moderate
• With regard to incisional surgery, trabeculectomy
  more effectively reduces IOP than nonpenetrating
  surgeries such as viscocanalostomy and deep
  sclerectomy.
• Strength of Evidence Moderate
• Intraoperative mitomycin-C enhances IOP reduction
  when used with trabeculectomy but not when used
  with other surgical methods.
• Strength of Evidence Moderate

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

11
Clinical Bottom Line Lowering Intraocular
PressureSurgical Interventions (2 of 3)

• These surgical comparisons demonstrated similar
  lowering effects on intraocular pressure
  (Strength of Evidence Moderate)
• Trabeculectomy performed at nasal, superior, or
  temporal ocular sites
• Trabeculectomy with a fornix versus limbus
  conjunctival incision
• Laser suture lysis versus adjustable sutures
  after fornix-based trabeculectomy
• Fornix-based trabeculectomy plus either
  mitomycin-C (MMC) or an Ologen implant
• Limbus-based trabeculectomy with or without an
  intraoperative amniotic membrane graft
• Trabeculectomy plus MMC with or without an
  Ex-PRESS minishunt

Boland MV, Ervin AM, Friedman D, et al.
Comparative Effectiveness Review No. 60.
Available at www.effectivehealthcare.ahrq.gov/glau
comatreatment.cfm.
12
Clinical Bottom Line Lowering Intraocular
PressureSurgical Interventions (3 of 3)

• Two-site versus one-site phacotrabeculectomy may
  be associated with greater reductions in
  intraocular pressure (IOP).
• Strength of Evidence Moderate
• The IOP-lowering effect of phacotrabeculectomy is
  not affected by the location of the conjunctival
  incision or the presence or absence of a
  peripheral iridectomy.
• Strength of Evidence Moderate
• Evidence was insufficient to determine the
  comparative effectiveness of aqueous drainage
  devices in treating open-angle glaucoma.
• Strength of Evidence Insufficient

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

13
Clinical Bottom Line Lowering Intraocular
PressureMedical Versus Surgical Interventions

• Incisional surgery lowers intraocular pressure
  (IOP) more than laser surgery or medications.
• Strength of Evidence Low
• Initial treatment with lasers tends to reduce the
  need for medications to achieve the same IOP.
• Strength of Evidence Low

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

14
Clinical Bottom Line Lowering Circadian
Intraocular Pressure

• These medicines lower circadian intraocular
  pressure (IOP) throughout a 24-hour cycle
• Prostaglandin analogs (latanoprost, bimatoprost,
  travoprost)
• Beta-adrenergic blocker (timolol)
• Alpha-adrenergic agonist (brimonidine)
• Carbonic anhydrase inhibitor (dorzolamide)
• Strength of Evidence Low
• Over a 24-hour cycle, prostaglandin analogs
  (latanoprost, bimatoprost, and travoprost) appear
  to lower circadian IOP more than
• A beta-blocker (timolol)
• A topical carbonic anhydrase inhibitor
  (dorzolamide)
• An alpha-adrenergic agonist (brimonidine)
• Strength of Evidence Low
• Results for comparisons among prostaglandins were
  inconsistent however, the reported difference
  among prostaglandins in the magnitude of IOP
  lowering was about 1 mmHg.
• Strength of Evidence Low

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

15
Clinical Bottom Line Optic Nerve Damage and/or
Visual Field LossMedical Interventions
(Systematic Reviews)

• Overall, strong evidence from a Cochrane review
  (N 4,979 patients 26 trials) that included the
  Early Manifest Glaucoma Trial (n 255 patients)
  and the Ocular Hypertension Treatment Study (n
  1,636 patients) found that medical treatment
  decreased the rate of visual field loss and
  progressive optic nerve damage.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.
• Heijl A, Leske MC, Bengtsson B, et al. Arch
  Ophthalmol 2002120(10)1268-79. PMID 12365904.
• Kass MA, Heuer DK, Higginbotham EJ, et al. Arch
  Ophthalmol 2002120(6)701-13. PMID 12049574.
• Vass C, Him C, Sycha T, et al. Cochrane Database
  Syst Rev 2007 Oct 17(4)CD003167. PMID
  17943780.

16
Clinical Bottom Line Optic Nerve Damage and/or
Visual Field LossMedical Interventions (Primary
Studies)

• Treatment of ocular hypertension with medicines
  preserves visual fields better than no treatment.
• Strength of Evidence Low
• The Low-Pressure Glaucoma Treatment Study found
  that fewer patients treated with brimonidine
  (9.1) had progression of visual field loss than
  those treated with timolol (39.2 p 0.001).
• Strength of Evidence Low
• All other primary studies were of insufficient
  size or duration to provide additional evidence
  about the effects of medical treatments on the
  progression of optic nerve damage.
• Strength of Evidence Insufficient

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.
• Krupin T, Liebmann JN, Greenfield DS, et al. Am J
  Ophthamol 2011141(14)671-81. PMID 21257146.

17
Clinical Bottom Line Optic Nerve Damage and/or
Visual Field LossSurgical Interventions

• Studies comparing surgical interventions did not
  report outcomes related to optic nerve damage or
  visual field loss.
• Outcomes related to optic nerve damage and visual
  field loss are discussed in reference to the
  effectiveness of medical versus surgical
  interventions.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

18
Clinical Bottom Line Optic Nerve Damage and/or
Visual Field LossMedical Versus Surgical
Interventions (Systematic Reviews)

• Overall, strong evidence from three systematic
  reviews (10 trials) indicate
• Patients treated medically and/or surgically
  (trabeculoplasty or trabeculectomy) are less
  likely to experience progression of field loss
  and optic nerve damage versus those who received
  no treatment.
• The two systematic reviews comparing medical
  versus surgical interventions did not include
  contemporary medications (e.g., prostaglandin
  analogs).
• In four out of five trials, patients treated with
  older medications had more progression of visual
  field loss when compared with those randomized to
  laser trabeculoplasty or trabeculectomy.
• These results should be interpreted cautiously in
  light of the increased effectiveness of
  prostaglandin analogs when compared with these
  medications.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

19
Clinical Bottom Line Optic Nerve Damage and/or
Visual Field LossMedical Versus Surgical
Interventions (Primary Studies)

• Evidence from included primary studies was
  insufficient to distinguish a difference in
  visual field loss between surgical techniques and
  medications.
• Strength of Evidence Insufficient
• For advanced glaucoma, evidence from included
  primary studies was insufficient to guide
  clinical decisionmaking regarding initial
  trabeculectomy or medication.
• Strength of Evidence Insufficient

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

20
Clinical Bottom Line Reducing Visual Impairment

• Evidence was insufficient to determine any
  differences in the effects of medical, surgical,
  or medical versus surgical treatments on visual
  impairment.
• Strength of Evidence Insufficient
• Secondary outcomes of visual acuity were similar
  for all laser and other surgical interventions
  studied.
• Strength of Evidence Low

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm
• Burr J, Azuara-Blanco A, Avenell A. Cochrane
  Database Syst Rev 2004 Apr 18(2)CD004399. PMID
  15846712.
• de Jong LA. Adv Ther 200926(3)336-45. PMID
  19337705.
• Mielke C, Dawda VK, Anand N. Br J Ophthalmol
  200690(3)310-3. PMID 16488952.
• Russo V, Scott IU, Stella A, et al. Eur J
  Ophthalmol 200818(5)751-7. PMID 18850554.
• Shaarawy T, Mermoud A. Eye (Lond)
  200519(3)298-302. PMID 15258610.

21
Patient-Related Quality of Life

• Evidence from included studies did not address a
  direct link between treatments for open-angle
  glaucoma and relative changes in patient-reported
  outcomes such as vision-related quality of life
  due to the unavailability of studies with
  sufficiently long-term followup.
• Included studies did find that
• Patients preferred the medication that was
  administered less frequently.
• Fear of blindness in newly diagnosed patients
  (34) was significantly reduced 5 years after
  medical or surgical treatments (11) in the
  Collaborative Initial Glaucoma Treatment Study

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

22
Comparative Adverse Effects

• The evidence did not permit an analysis of the
  strength of evidence for comparative adverse
  effects across interventions.
• There were a number of issues with assessing
  adverse effects. For example, adverse effects
  were not the primary outcome for the studies,
  meaning that the studies were not powered to
  detect differences.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

23
Reported Adverse Effects Medical Interventions

• Conjunctival hyperemia (redness) is the most
  commonly reported adverse effect among the
  observational studies of medical treatment for
  open-angle glaucoma.
• Latanoprost is less likely to cause ocular
  redness among the prostaglandin analogs however,
  as a class, prostaglandins may produce more
  ocular redness than does timolol.
• Timolol is more likely to result in systemic side
  effects like shortness of breath or bradycardia.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

24
Reported Adverse Effects Surgical Interventions
(1 of 2)

• Trabeculectomy produces more hypotony, hyphema,
  shallow anterior chambers, cataracts, and
  choroidal detachment than the nonpenetrating
  procedures of deep sclerectomy or
  viscocanalostomy.
• The risk of epithelial toxicity was 5.85 times as
  great with the addition of postoperative
  5-fluorouracil in participants receiving primary
  trabeculectomy.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

25
Reported Adverse Effects Surgical Interventions
(2 of 2)

• There is no clear difference in adverse effects
  between one-site versus two-site
  phacotrabeculectomy.
• The adverse effects associated with glaucoma
  drainage devices have not been adequately
  compared with the adverse effects of other
  procedures used to treat open-angle glaucoma.
• Adverse effects reported from aqueous shunts
  include choroidal hemorrhage, choroidal
  complications, corneal complications, strabismus,
  no light perception, phthisis, tube exposure,
  retinal detachment, and infection.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

26
Reported Adverse Effects Medical Versus Surgical
Interventions

• Trabeculectomy is associated with worsening of
  cataracts and an increased need for cataract
  surgery over time when compared with medical
  treatments for glaucoma.
• Intraocular surgery rarely results in severe
  vision loss due to infection and/or bleeding.
  These risks are not associated with medical or
  laser treatments.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

27
Conclusions Outcomes

• Medications and laser and incisional surgeries
  are effective in lowering intraocular pressure
  (IOP).
• Prostaglandin analogs are consistently superior
  to the other drug classes in terms of their
  IOP-lowering ability and adverse effect profile.
• Laser trabeculoplasty lowers IOP regardless of
  the type of laser used.
• For incisional surgeries, trabeculectomy lowers
  IOP more than nonpenetrating surgical procedures,
  and this effect may be enhanced with mitomycin-C.
• Patients treated medically and/or surgically
  (trabeculoplasty or trabeculectomy) were less
  likely to experience progression of visual field
  loss and optic disc damage versus those who
  received no treatment.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

28
Conclusions Adverse Effects

• Harms from medications do not threaten vision and
  commonly consist of conjunctival hyperemia and
  ocular irritation.
• Complications of surgery are more significant
  than medications and may include infection,
  bleeding, cataract formation, choroidal
  effusions, hyphema, and flattening of the
  anterior chamber.
• Adverse effects are more common with
  trabeculectomy than with nonpenetrating surgeries
  and may be increased in the presence of
  mitomycin-C.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

29
Conclusions Glaucoma Treatment and Visual
Impairment or Vision-Related Quality of Life

• While at this time current evidence does not
  address a direct link between reductions in
  intraocular pressure (IOP), visual field loss, or
  optic nerve damage and reductions in visual
  impairment or vision-related quality of life,
  this should not be interpreted to mean that
  reductions in IOP, visual field loss, or optic
  nerve damage are not important for reducing
  visual impairment or maintaining vision-related
  quality of life, but rather that studies
  demonstrating this direct linkage are not
  available.
• Given the slow progression of glaucoma, even if
  left untreated, it is not surprising these
  studies were not identified.
• The time required to establish relative
  differences in patient outcomes requires studies
  with lengthy followup, which are not currently
  available.

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

30
Gaps in Knowledge

• The systematic review identified areas where more
  evidence is needed on
• A direct association between treatment for
  open-angle glaucoma (OAG) and visual impairment
  and/or patient-reported outcomes
• The relative risks and benefits of current
  medical and surgical treatments for OAG

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

31
Shared DecisionmakingWhat To Discuss With Your
Patients

• The severity of the patients glaucoma and need
  for treatment
• The different types of treatment for glaucoma
• The benefits and adverse effects of medicines,
  laser treatments, and surgeries for open-angle
  glaucoma
• Patient preferences regarding the types of
  treatment
• The importance of adherence to medicine regimens
• The importance of regular and consistent followup
  with an ophthalmologist or glaucoma specialist to
  monitor disease progression over time
• The cost of medicines and surgical treatments

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.

32
Resource for Patients

• Treatments for Open-Angle Glaucoma, A Review of
  the Research for Adults is a free resource for
  patients. It can help patients talk with their
  health care professionals about the many options
  for treating open-angle glaucoma. It provides
• Explanations of glaucoma and its causes
• Explanations of medical and surgical treatments
• Current evidence of effectiveness and adverse
  effects
• Questions for patients to ask their doctor

• Boland MV, Ervin AM, Friedman D, et al.
  Comparative Effectiveness Review No. 60.
  Available at www.effectivehealthcare.ahrq.gov/glau
  comatreatment.cfm.