Download Comparative Effectiveness of Eye Drops vs. Laser Trabeculoplasty

October 2016
Comparative Effectiveness of Eye
Drops vs. Laser Trabeculoplasty
Final Report
Prepared for
Romana Hasnain-Wynia, PhD, MS
Ayodola Anise, MHS
Patient-Centered Outcomes Research Institute
Addressing Disparities Program
1919 M Street, NW Suite 250
Washington, DC 20036
Prepared by
Shivani Reddy, MD MSc
Meera Viswanathan, PhD MA
Andrew Kraska, BA
RTI International
3040 E. Cornwallis Road
Research Triangle Park, NC 27709
RTI Project Number 0214031.006.000.001
CONTENTS
Section
Page
1.
Contributors
1
2.
Introduction
1
3.
Patient Centeredness
2
4.
Burden of the Condition
2
5.
Evidence Gaps
3
5.1
Literature Review ........................................................................................ 3
5.1.1 Systematic Review: “Laser Trabeculoplasty for Open-Angle
Glaucoma” (Rolim de Moura et al., 2007)16 ........................................... 4
5.1.2 Systematic Review: “Treatment for Glaucoma: Comparative
Effectiveness” (Boland et al., 2012)48 ................................................... 4
5.1.3 Meta-analysis of SLT versus Topical Medication in the Treatment of
OAG (Li et al., 2015)49 ....................................................................... 5
5.1.4 Summary of Systematic Reviews ......................................................... 5
5.2
Limitations ................................................................................................. 5
5.2.1 Limitations in Comparative Effectiveness Research ................................ 5
5.2.2 Limited Research on Racial Disparities in Glaucoma Treatment ............... 5
5.2.3 Limited Reporting of Patient-Centered Outcomes................................... 6
6.
Guidelines
6
7.
Ongoing Research
6
8.
Likelihood of Implementation of Research Results in Practice
8
9.
Durability of Information
8
10. Potential Research Questions
9
11. Conclusion
9
References
10
Appendix A: Key Informant Information
A-1
Appendix B. Search Strategy
B-2
iii
TABLES
Number
Page
Table 1. Eligibility Criteria for Studies on the Comparative Effectiveness of Laser
Therapy versus Medical Therapy for Glaucoma ..................................................... 4
Table 2. Professional Health Organizations’ Guidelines for Treating OAG ........................... 6
Table 3. Ongoing Studies Comparing Laser Therapy with Medications ............................... 7
iv
Topic: Comparative Effectiveness of Eye Drops vs. Laser Trabeculoplasty
Overall Comparative Research Question: What is the comparative effectiveness of eye drops versus
laser trabeculoplasty to reduce excess morbidity from open-angle glaucoma in black and Hispanic
individuals?
1.
Contributors
PCORI Staff: Romana Hasnain-Wynia, PhD, MS; Ayodola Anise, MHS; Kaitlynn Robinson-Ector, MPH
RTI: Shivani Reddy, MD, MSc; Meera Viswanathan, PhD, MA; Andrew Kraska, BA
2.
Introduction
Glaucoma is a chronic, progressive eye disease characterized by optic nerve damage and visual
field loss. Glaucoma is classified into two broad categories: open-angle glaucoma (OAG) and angleclosure glaucoma; more than 80% of cases are OAG.1 Glaucoma can progress without causing symptoms
until the disease is quite advanced, leading to visual impairment and blindness. The second leading
cause of blindness worldwide after cataracts,2 glaucoma’s risk factors include older age, family history of
glaucoma, elevated intraocular pressure (IOP), type 2 diabetes mellitus, and black race or Hispanic
ethnicity.3-5 Several trials have shown that treatments reducing IOP—medications, laser therapy, and
incisional surgery—can slow the progression of glaucoma.6-9 This topic brief focuses on medications and
laser therapy, two treatments that physicians can deliver in an outpatient setting and that do not carry
the surgical risks of infection and bleeding. Medical therapy with eye drops typically has been the firstline treatment for glaucoma, although a growing body of evidence suggests that laser trabeculoplasty,
an office-based procedure that does not involve making an incision in the eye, can also be used as initial
therapy, particularly if a patient struggles with adherence to daily medications. Thus, glaucoma
treatment is a topic ripe for comparative effectiveness research—research that compares the benefits
and harms of two efficacious treatment options to help physicians and patients make clinical decisions
best suited for individual patients.
Glaucoma is characterized by a striking health disparity; black and Hispanic individuals are more
likely to have the disease than white individuals, and the onset of blindness starts 10 years earlier in
black individuals.10-12 In terms of the impact of health disparities on treatment, data on current
treatments of eye drops and laser trabeculoplasty are sparse. Older studies that compared surgery with
medications or laser therapy demonstrated that black and white individuals with medically uncontrolled
OAG have different outcomes.13,14 For example, in the Advanced Glaucoma Intervention Study, vision
was better preserved in black participants randomized to laser therapy compared with those
randomized to surgery; in contrast, white participants undergoing surgery had better visual outcomes.13
However, more recent comparative effectiveness research has not examined how the effectiveness of
current first-line treatment options used in practice—laser trabeculoplasty or eye drops—varies by
racial or ethnic subgroups. In this brief, we review the burden of glaucoma, the current evidence base
for glaucoma treatment, ongoing studies, and opportunities for new comparative effectiveness
research.
1
3.
Patient Centeredness
In the face of clinical uncertainty, patient-centered care becomes essential to the management
of disease.15 Both medical and laser therapy are associated with slowing progression of disease.16,17
However, some patients may not opt for medical therapy because of the side effects and costs of daily
medication.18,19 The need for retreatment 5 to 10 years after laser therapy may pose a concern for other
patients.20 Patients can also find lifelong adherence to a chronic medication burdensome for several
reasons. Patients with deteriorating vision from glaucoma may be unable to self-administer
medications, or patients may struggle to comply with complex dosing schedules.21 Accordingly, some
experts suggest laser therapy as first-line treatment for patients who have difficulties with
adherence.22,23 Strong patient–provider communication and patient education can support decision
making about a therapy that promotes improved patient outcomes and takes into consideration
patients’ preferences.24 Patients and doctors should make treatment decisions in the context of the
patient’s age, preferences, and degree of ocular damage.22,25 Furthermore, as discussed in the sections
below, the impact of the disease and effect of treatment may vary by racial and ethnic subgroups,
emphasizing the importance of patient-centered care.
4.
Burden of the Condition
Glaucoma affects an estimated 2.9 million individuals in the United States; over half (54.3%) are
unaware that they have the disease.10 The projected prevalence of OAG is expected to rise to 7.32
million by 2050.26 Glaucoma is the second leading cause of blindness worldwide.2 Furthermore,
glaucoma can have a profound effect on a patient’s quality of life (QOL). As visual loss progresses,
glaucoma patients can struggle with activities of daily living like walking, reading, and driving,27-29
although even patients early in disease can report reduced QOL.30
As noted above, glaucoma disproportionately affects black and Hispanic individuals. Studies
using the National Health and Nutrition Survey (NHANES) estimate the prevalence of glaucoma in black
individuals at 3.7% compared with 2% for white individuals.10 Black individuals have roughly 4.4 times
greater odds of having undiagnosed and untreated glaucoma than white individuals.11 Although rates of
blindness increase with age for all individuals, studies show that the onset of blindness starts 10 years
earlier for black individuals.12 Glaucoma is the leading cause of blindness in black individuals in the
United States,31 whereas age-related macular degeneration is the leading cause for white individuals.32
Estimates for glaucoma prevalence in Hispanic individuals range from 1.9% to 4.7%, and some
studies report prevalence comparable with blacks.10,33,34 Hispanic individuals have 2.5 times greater odds
of undiagnosed and untreated glaucoma than non-Hispanic whites in an NHANES study.11 In a study of
the National Health Interview Survey, Dominicans and Central and South Americans were among the
understudied racial and ethnic groups with high rates of self-reported visual impairment.35 Accounting
for future demographic shifts, Hispanic men are predicted to be the largest demographic group with
OAG in 2050.26
Few studies compare prevalence of glaucoma across racial and ethnic groups.36 Furthermore,
we do not have a clear understanding of the factors that underlie these observed health disparities; the
reasons are likely multifactorial and include biologic and social determinants of health.
2
Advances in genetics research have led to the identification of several genetic variants
associated with glaucoma.37 The African Descent and Glaucoma Evaluation Study (ADAGES) has
identified anatomic differences in the eyes of black and white participants38 and was the first study
powered to assess performance on several visual field-test variables.39 Whether these findings are
associated with early onset of disease or more rapidly progressive disease remains to be seen.
Some studies have shown that black and Hispanic patients are less likely to be seen by an eye
care provider40,41 and are less likely to undergo monitoring once diagnosed with glaucoma even when
they have insurance.42 These patients also have lower rates of medical and surgical treatment than
white patients.43,44 Patient factors such as poor understanding of disease, mistrust of the medical
community, limited financial resources, and poor adherence to therapy also serve as barriers to
diagnosis and treatment of glaucoma.45-48 Studies of patient–physician communication found that
although patient education could improve adherence to medical therapy for glaucoma,49 providers were
less likely to educate black patients about glaucoma than white patients.50
5.
Evidence Gaps
We identified evidence gaps primarily through a review of peer-reviewed primary studies and
systematic reviews and supplemented our understanding through conversations with three key
informants. Our key informants are clinical investigators and practicing ophthalmologists with
appointments at major academic centers in the United States. They have led glaucoma studies with
funding from multiple sources, including the Centers for Disease Control and Prevention, the National
Eye Institute, and industry. (Appendix A lists our key informants.)
5.1
Literature Review
The mainstay of glaucoma treatment is reducing IOP, which can be achieved through
medications (eye drops), laser therapy, or incisional surgery. Eye drops and laser therapy are provided in
outpatient settings. The major classes of eye drops are prostaglandin analogues (e.g., latanoprost,
travoprost), beta adrenergic antagonists (e.g., timolol, betaxolol), carbonic anhydrase inhibitors (e.g.,
acetazolamide, dorzolamide), alpha2 adrenergic agonists, and combination treatments. Prostaglandins
lower IOP more than other classes of medications and are currently used as first-line therapy.51 Laser
therapies include argon laser trabeculoplasty (ALT) and more recently selective laser trabeculoplasty
(SLT). The effectiveness of laser therapy decreases over 5 years of follow-up.20 Incisional surgeries, such
as trabeculectomy, achieve the greatest reduction of IOP with longer lasting results compared with
medical or laser therapy.51 However, incisional surgery carries the rare risk of intraocular infection and
bleeding not present with medical or laser therapy51 and is outside the scope of the literature review for
this topic brief.
We performed a systematic search using the populations, interventions, comparators,
outcomes, timing, and setting (PICOTS) framework in Table 1 (Appendix B lists the search strategy). We
identified five comparative effectiveness systematic reviews.17,51-54 Three reviews included the same
primary studies,52-54 so we selected the review that included a meta-analysis to discuss below.52 The
remaining primary studies we identified from title and abstract review were (1) included in one of the
aforementioned systematic reviews, (2) protocols for ongoing studies discussed in Section 7, or (3)
exclusions for wrong comparator, primarily older eye drops that are no longer used in clinical practice or
no active comparator. We describe two major trials excluded for no active comparator below.
3
The Collaborative Normal Tension Glaucoma Study compared any treatment to reduce IOP (eye
drops, laser therapy, or incisional surgery) with observation; likewise, the Early Manifest Glaucoma Trial
compared a combination of laser therapy and eye drops with observation only. Both of these studies
reported a 50% reduction in the progression of glaucoma, finding that even small changes in IOP can
slow the progression of glaucoma.8,9 According to one key informant, the striking benefit of treatment
observed in these seminal studies shifted the treatment paradigm away from observation to providing
some form of IOP-lowering treatment when glaucoma is diagnosed. Thus, we did not include studies
with an inactive comparator in our literature review.
Table 1. Eligibility Criteria for Studies on the Comparative Effectiveness of Laser Therapy versus
Medical Therapy for Glaucoma
PICOTS
Population
Intervention
Comparator
Outcomes
Time frames
Setting
Study designs
Population: Adults >40 years with OAG
Laser trabeculoplasty or combination laser and medical therapy
Medical therapy (eye drops)
Final health outcomes: Reduced visual impairment, patient-reported outcomes
Intermediate health outcomes: Reduced IOP, visual field loss, optic nerve damage
Harms: Adverse effects of eye drops or laser trabeculoplasty
All
Outpatient settings
Randomized controlled trials (RCTs)
IOP= intraocular pressure; OAG = open-angle glaucoma; RCT = randomized controlled trial.
5.1.1
Systematic Review: “Laser Trabeculoplasty for Open-Angle Glaucoma” (Rolim de Moura et al.,
2007)17
A Cochrane meta-analysis of three trials comparing ALT with medications reported that ALT
reduced the chance of uncontrolled IOP at 6 months and 24 months (pooled relative risk [RR] 0.80, 95%
confidence interval [CI] 0.71 to 0.91, I2=0%). The review found a lower but not statistically significant
difference in the risk of visual field progression for ALT when compared with medications at the 2-year
follow-up (RR 0.70, 95% CI 0.42 to 1.16, I2 0%). The review also reported no differences in optic nerve
deterioration. Two older studies from the 1980s evaluated the effectiveness of ALT combined with
medications in patients already using medications; patients receiving combined ALT and medications
were less likely to fail therapy than those on medications alone.55,56 The review did not pool results
because of the underlying heterogeneity of interventions. In terms of harms, two studies reported
adverse effects of peripheral anterior synechiae in the ALT-treated patients (pooled RR 11.15, 95%CI
5.63 to 22.09, I2=0%) compared with medications. The primary outcomes of this review were all
intermediate visual outcomes (failure to control IOP, failure to stabilize visual field progression, and
failure to stabilize optic disc deterioration); authors found no evidence for outcomes related to visual
impairment or vision-related QOL.
5.1.2
Systematic Review: “Treatment for Glaucoma: Comparative Effectiveness” (Boland et al., 2012)51
Boland and associates,51 in a review for the Agency of Healthcare Research and Quality,
examined the effect of medical, laser, and surgical treatments for OAG on intermediate and final visual
health outcomes including harms. They report intermediate visual outcomes from Rolim de Moura et
al.17 and three additional primary studies in which laser therapy and medication groups did not differ
significantly in the change in IOP, visual field loss, and optic nerve deterioration.57-59 Regarding harms,
4
laser therapy did not carry the risk of ocular discomfort associated with medications. The reviewers
identified no evidence regarding visual impairment outcomes.
5.1.3
Meta-analysis of SLT versus Topical Medication in the Treatment of OAG (Li et al., 2015)52
A systematic review and meta-analysis by Li and associates52 included five studies comparing SLT
with medications. Of these, three studies compared SLT with prostaglandin eye drops (current first-line
therapy),60-62 and two studies compared SLT with medications from several classes.59,63 In the four
studies that reported percent IOP reduction (IOPR%) between the SLT and medication groups, the
pooled results showed no significant difference between the two groups (weighted mean difference in
IOPR%=-1.90, 95% CI -5% to 1.1%, I2=0%). The results were robust to sensitivity analyses of study type
(RCT only) and medication comparator (prostaglandin only). Li and associates also found no significant
difference in success rates between the two therapies, although the definition of success varied by
study. Three studies reported adverse events, but the review did not pool the results. The reviewers did
not report on visual impairment outcomes.
5.1.4
Summary of Systematic Reviews
In summary, the studies reviewed by Rolim de Moura and associates17 show that ALT or ALT in
combination with medications reduces the risk of some intermediate visual health outcomes in
glaucoma compared with medications alone. In comparison, results from Boland et al.51 and Li et al.52
show no significant differences in outcomes between medications and laser therapy. This difference
may be due to the use of older eye drops in the studies of the Cochrane Review by Rolim de Moura et
al.,17 which are not as effective as first-line medical therapy typically used today (e.g., prostaglandins).16
None of the reviews reported race or ethnicity subgroup analyses for studies comparing laser therapy
with medications.
5.2
Limitations
The authors of these reviews and our key informants highlighted several limitations in the body
of evidence for glaucoma treatments.
5.2.1
Limitations in Comparative Effectiveness Research
Reviewers and key informants agreed that the number of studies that adequately compare two
or more treatments over time is insufficient to draw conclusions about the comparative effectiveness of
most currently used therapies. Much of the evidence comparing laser therapy with medical therapy
relies on trials that used older medication therapies that do not have the improved clinical effectiveness
or milder side effect profile of current first-line treatment with prostaglandins.16 Glaucoma research
would also benefit from more rigorous study design, standardized diagnostic criteria for glaucoma and
severity of disease, and standardized reporting of outcomes using the World Glaucoma Association
guidelines.51,52,64
5.2.2
Limited Research on Racial Disparities in Glaucoma Treatment
Evidence for racial disparities in glaucoma treatment comes from older studies that were
excluded from our review for wrong intervention (e.g. surgery). The Advanced Glaucoma Study (2000–
2004) and the Collaborative Initial Glaucoma Treatment Study (CIGTS) (2001) compared incisional
surgery with laser therapy and medications, respectively. Both studies found that black participants had
5
worse outcomes than white participants who had surgery first.6,14 No studies on the differential impact
of treatment on racial subgroups have been published since these two studies. Key informants and
reviewers proposed additional RCTs to understand racial differences in response to laser therapy
compared with medications.17
5.2.3
Limited Reporting of Patient-Centered Outcomes
Most studies report intermediate outcomes but are not long enough to measure outcomes that
ultimately matter to patients—visual impairment, vision-related QOL, or pragmatic outcomes like
delaying the need for surgery.17,51 The minimal QOL data from treatment trials come from the CIGTS and
Early Manifest Glaucoma trials, which were excluded from our review because they used surgery as a
major intervention. Although ophthalmologic examination may show optic nerve deterioration, the
patient may not have any disability in activities of daily living for years,65 thus emphasizing the need for
data on patients’ experience of treatment to better tailor glaucoma management.
The challenges of measuring QOL in glaucoma lie in the chronic, indolent nature of the disease.
The most commonly used measure is the National Eye Institute Visual Function Questionnaire (NEI-VFQ25), which is not specific to glaucoma and may not capture the slow progressive changes in function in
glaucoma as compared with, say, cataract disease. Some have suggested modifying the NEI-VFQ-25 to
make it more glaucoma specific.66 Two key informants recommended developing better glaucomasensitive QOL measures.
6.
Guidelines
Table 2 lists professional health organizations that offer guidelines for glaucoma management.
In general, these guidelines recommend medications as first-line therapy, but none give a definitive
recommendation.
Table 2. Professional Health Organizations’ Guidelines for Treating OAG
Organization, Year
American Academy of
Ophthalmology, 201622
American Academy of
Family Physicians, 201667
American Glaucoma
Society, 201668
Canadian
Ophthalmological Society,
200969
American Optometric
Association, 201070
Recommendations
Medical treatment is the most common initial intervention. Laser trabeculoplasty can be
considered as initial therapy in some specific patients or as an alternative for patients for
whom adherence will be difficult.
Early treatment of patients with glaucoma is recommended to reduce the risk of visual
field progression.
Treatment should be based on the therapy with the best chance of lowering the patient’s
IOP.
The overarching aims of glaucoma management are to preserve visual function and
maintain or enhance overall health-related QOL. This is achieved through a careful
process of observing and monitoring visual function and providing patient education and
support and medical, laser, or surgical intervention, as appropriate.
In the choice of a specific form of treatment or the decision to alter or provide additional
therapy, the overriding consideration must be the risk or benefit to the patient. All forms of
treatment for glaucoma have potential harms for the patient. The clinician must evaluate
the possible impact of the treatment from a social, psychological, financial, and
convenience standpoint.
IOP = intraocular pressure; OAG = open-angle glaucoma; QOL = quality of life.
7.
Ongoing Research
We captured ongoing glaucoma research in our primary literature search and by searching
ClinicalTrials.gov,71 NIHRePORTER,72 and HRSProj,73 and National Institutes of Health funding.74 We
6
found four active comparative effectiveness treatment trials for glaucoma, summarized in Table 3. All of
these studies compare SLT to eye drops, specifically first-line medical therapy of prostaglandins or any
topical medication. All studies assess intermediate ocular outcomes, including IOP reduction, visual field
progression, and optic nerve deterioration; two are powered to examine health-related QOL as primary
outcomes. The first study is conducted in an African population, although study protocols or
descriptions did not include a subgroup analysis by race or ethnicity for any of the studies in Table 3.
Additionally, we identified a number of projects funded by the National Eye Institute aiming to
identify genetic markers associated with OAG in blacks and Mexican Americans,75-78 as well as a few
studies on aspects of glaucoma management in these subgroups (i.e., adherence in blacks with
glaucoma).79,80
Table 3. Ongoing Studies Comparing Laser Therapy with Medications
Study
(Clinical Trial
Identifier)
Primary Glaucoma
Treatment Trial in
Kenya and South
Africa—SLT vs.
Medication
(NCT02774811)80
A Comparison of
Bimatoprost SR to
Selective Laser
Trabeculoplasty in
Patients With OpenAngle Glaucoma or
Ocular Hypertension
(NCT02636946)81
Laser-1st versus
Drops-1st for
Glaucoma and
Ocular Hypertension
Trial (LiGHT)82
(ISRCTN32038223)83
The Glaucoma Initial
Treatment Study
(GITS)84
(ACTRN1261100072
0910)85
Funding
Agency
Location
Population;
Size
Investigations
Outcomes
Duration
Status as
of 2016
University
UK, South 18 years or
College, London Africa,
older, men and
Kenya
women,
glaucoma,
black African;
400
Allergan
US
18 years or
older, men and
women with
OAG; 160
Multicenter RCT IOP reduction
of SLT versus
prostaglandin
12 months
analogue
therapy
Recruiting
RCT of SLT
IOP reduction
versus
Bimatoprost SR 24 weeks
Recruiting
National
UK
Institutes of
Health,
Research Health
Technology
Assessment
Panel
18 years or
older, men and
women newly
diagnosed with
OAG; 718
Multicenter RCT
of SLT versus
eye drops (any
drug)
Australian
National Health
and Medical
Research
Council
18 years or
older, newly
diagnosed
men and
women,
primary OAG
or pseudoexfoliation
glaucoma; 400
Multicenter RCT
of SLT versus
eye drops (any
drug)
Australia
Health-related QOL
Complete,
Glaucoma-specific QOL results not
measures
published
IOP reduction
Visual field progression
Optic nerve progression
Adverse effects
Adherence
Cost-effectiveness
36 months
Health-related QOL
Recruiting
Glaucoma-specific QOL
measures
IOP reduction
Visual field progression
Optic nerve
progression, Adverse
effects
Cost-effectiveness
24 months
IOP = intraocular pressure; OAG = open-angle glaucoma; QOL = quality of life; RCT = randomized controlled trial;
SLT = selective laser trabeculoplasty; UK = United Kingdom; US = United States.
7
8.
Likelihood of Implementation of Research Results in Practice
Our key informants did not identify practice-level barriers to implementation of comparative
effectiveness research on laser therapy versus eye drops. Although laser therapy is widely available in
ophthalmologic practices, provider-level and patient-level factors are barriers to its implementation.
One key informant noted that even after the trials of the 1980s and 1990s suggested comparable
efficacy of medications and laser therapy, laser therapy experienced limited uptake, even among
patients who may struggle with adherence to chronic treatment with eye drops. Another key informant
noted general clinical inertia to adopting new research.86 However, as discussed above, comparative
effectiveness research on laser trabeculoplasty and currently used eye drops is limited. Additionally,
comparative effectiveness research on racial differences in treatment is nearly nonexistent. Further
research in these areas can support provider–patient medical decision making.
Our key informants indicated a need for broader research into the contextual factors influencing
racial disparities. One informant noted the multiple ongoing glaucoma genetics studies funded by the
National Eye Institute, but he also pointed to the limited research in understanding and overcoming
barriers to accessing glaucoma care for black and Hispanic populations. Studies examining the reasons
for racial disparities could facilitate implementation of comparative effectiveness research and help
reduce health disparities. For example, the Philadelphia Glaucoma Detection and Treatment study is a
community-based intervention where educational workshops, screening, and treatment are offered on
site in underserved communities, in settings like churches and community centers. Twenty percent of
participants had suspected OAG and 9% received a diagnosis.87 Among newly diagnosed OAG patients
who attended a workshop that presented laser therapy and medications as first-line therapies, 20%
chose laser therapy over medications for initial treatment.87 This uptake was much higher than
expected, according to one of our key informants, indicating the role for improved patient education.
Project EQUALITY (Eye Care Quality and Accessibility Improvement in the Community), another
community-based intervention offering educational workshops, showed some improvement in
knowledge88 and offers glaucoma screening and treatment through community-based optometrists with
ophthalmology telemedicine support (results not yet available).
All key informants also noted the importance of patient-reported outcomes in supporting
implementation of research findings: information about patient experience and QOL with different
procedures could better guide medical decision making and facilitate implementation of comparative
effectiveness research.
9.
Durability of Information
In the last few decades, research advances have solidified the practice paradigm of lowering IOP
to slow the progression of visual loss in glaucoma, using medical therapy, laser trabeculoplasty, or
incisional surgery. Our key informants did not anticipate new medical therapies that would make the
use of laser therapy or surgery obsolete. Even if a new medication came to market with better efficacy
and fewer side effects, adherence to medications for a chronic condition would remain an issue.
Minimally invasive glaucoma surgeries (MIGS) is an umbrella term applied to newly developed
surgical techniques using micro devices that aim to achieve the same IOP-lowering effects of surgery
without the less-than-ideal risk profile. Most studies of MIGS are of limited quality and duration and lack
8
study standardization, cost-effectiveness data, and information on ideal patient selection.89
Furthermore, many of these surgeries have been performed in patients with concurrent cataract
surgery; MIGS may be the more appropriate procedure in patients already undergoing surgery.89 Our
key informants had differing views on the future role of MIGS, particularly in racial and ethnic subgroup
populations. One downside of laser therapy is that the IOP-lowering effects generally dissipate after 5
years.20 One key informant suggested that if the promise of MIGS were realized—lower risk compared
with surgery and more durable reduction in IOP compared with laser therapy—then it would be
important to incorporate MIGS into future comparative effectiveness research. However, two other key
informants emphasized that incisional surgery, even minimally invasive surgery, still carries the risk of
intraocular infection, bleeding, and possible blindness that medical and laser therapy do not and that
the latter two will remain mainstays of initial treatment for glaucoma. Moreover, even if MIGS do show
comparable efficacy to laser or medical therapy, black patients may not benefit compared with white
patients as observed with past comparative effectiveness research on surgical treatment of
glaucoma.6,14
10.
Potential Research Questions
The evidence gaps identified by our evidence review (Section 5) are not adequately addressed
by ongoing research (Section 7). We highlight comparative effectiveness research areas in which PCORI
can offer funding opportunities for impactful research for glaucoma treatments.
1) What is the comparative effectiveness of laser therapy versus eye drops on patient-centered
outcomes of visual impairment and quality of life?
Longer studies are required to study visual impairment, and further work in patientreported outcomes for glaucoma could help address this question. Studies will need to
address patient-level, provider-level, and system-level barriers to treatment that may help
facilitate implementation of comparative effectiveness research for high-risk populations.
2) What is the comparative effectiveness of laser therapy versus eye drops for black and
Hispanic individuals?
More comparative effectiveness studies are needed for all patients, but future studies
should be powered to measure differences in racial and ethnic subgroups. Studies will need
to address patient-level, provider-level, and system-level barriers to treatment that may
help facilitate implementation of comparative effectiveness research for high-risk
populations
11.
Conclusion
Untreated, glaucoma silently leads to visual impairment and blindness. Black and Hispanic
individuals are disproportionately affected. Future comparative effectiveness research in glaucoma may
fill evidence gaps by focusing on patient-centered outcomes, outcomes by racial and ethnic subgroups,
and strategies for addressing barriers to treatment that can lead to a reduction in disparities.
9
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17
Appendix A: Key Informant Information
Michael Boland, MD, PhD
Associate Professor of Ophthalmology
Wilmer Eye Institute at Johns Hopkins University School of Medicine
600 N. Wolfe Street
Baltimore, MD 21287
L. Jay Katz, MD
Glaucoma Service Director
Wills Eye Hospital
840 Walnut Street, Suite 1110
Philadelphia, PA 19107
Paul R. Lichter, MD, MS
Professor
Kellogg Eye Center at University of Michigan
1000 Wall Street
Ann Arbor, MI 48105
A-1
Appendix B. Search Strategy
B1. Search strategy for primary literature review.
PubMed – 232 records
#1 (glaucoma*[Title] OR "Glaucoma"[Mesh:NoExp] OR "Glaucoma, Open-Angle"[Mesh]) AND
(laser*[Title] OR "Laser Therapy"[Mesh] OR "Lasers"[Mesh] OR ("Trabeculectomy"[Mesh] AND
laser*[Text Word]) OR "trabeculoplasty"[Title]) AND (eye drop*[Title] OR eyedrop*[Title] OR ophthalmic
drop*[Title] OR eye solution*[Title] OR ophthalmic solution*[Title] OR ((topical*[Title] OR
ophthalmic*[Title]) AND (drop*[Title] OR solution*[Title] OR administ*[Title])) OR "Administration,
Ophthalmic"[Mesh] OR "Administration, Topical"[Mesh:NoExp] OR "Ophthalmic Solutions"[Mesh] OR
"Ophthalmic Solutions"[Pharmacological Action] OR "Prostaglandins, Synthetic"[Mesh] OR prostaglandin
analog*[Title] OR synthetic prostaglandin*[Title] OR Latanoprost[Title] OR Travoprost[Title] OR
Tafluprost[Title] OR Unoprostone[Title] OR bimatoprost[Title] OR "latanoprost"[Supplementary
Concept] OR "Travoprost"[Mesh] OR "tafluprost"[Supplementary Concept] OR "isopropyl
unoprostone"[Supplementary Concept] OR "Bimatoprost"[Mesh] OR "Adrenergic betaAntagonists"[Mesh] OR "Adrenergic beta-Antagonists"[Pharmacological Action] OR β-Adrenergic
blocker*[Title] OR beta adrenergic blocker*[Title] OR Adrenergic beta-Antagonist*[Title] OR
"Timolol"[Mesh] OR "Levobunolol"[Mesh] OR "Carteolol"[Mesh] OR "Metipranolol"[Mesh] OR
"Betaxolol"[Mesh] OR Timolol[Title] OR Levobunolol[Title] OR Carteolol[Title] OR Metipranolol[Title] OR
betaxolol[Title] OR "Adrenergic alpha-Agonists"[Mesh] OR "Adrenergic alpha-Agonists"[Pharmacological
Action] OR Adrenergic alpha-Agonist*[Title] OR α-Adrenergic agonist*[Title] OR alpha Adrenergic
agonist*[Title] OR Brimonidine[Title] OR apraclonidine[Title] OR "Brimonidine Tartrate"[Mesh] OR
"apraclonidine"[Supplementary Concept] OR "Carbonic Anhydrase Inhibitors"[Mesh] OR "Carbonic
Anhydrase Inhibitors"[Pharmacological Action] OR Carbonic anhydrase Inhibitor*[Title] OR
Dorzolamide[Title] OR Brinzolamide[Title] OR acetazolamide[Title] OR "dorzolamide"[Supplementary
Concept] OR "brinzolamide"[Supplementary Concept] OR "Acetazolamide"[Mesh] OR "Cholinergic
Agonists"[Mesh] OR "Cholinergic Agonists"[Pharmacological Action] OR Cholinergic agonist*[Title] OR
Pilocarpine[Title] OR carbachol[Title] OR "Pilocarpine"[Mesh] OR "Carbachol"[Mesh]) Filters: Publication
date from 1990/01/01; English – 232
Embase – 58 records (29 records with duplicates removed)
#1 (glaucoma*:ti OR ‘glaucoma’/mj OR ‘open angle glaucoma’/mj) AND (laser*:ti OR ‘laser’/mj OR
‘ophthalmic laser’/exp/mj OR ‘low level laser therapy’/mj OR (‘trabeculectomy’/mj AND laser*:ti,ab) OR
trabeculoplasty:ti) AND ((eye NEXT/1 drop*):ti OR eyedrop*:ti OR (ophthalmic NEXT/1 drop*):ti OR (eye
NEXT/1 solution*):ti OR (ophthalmic NEXT/1 solution*):ti OR ((topical* OR ophthalmic*) AND (drop* OR
solution* OR administ*)):ti OR ‘intraocular drug administration’/exp/mj OR ‘prostaglandin
derivative’/exp/mj OR (prostaglandin NEXT/1 analog*):ti OR (synthetic NEXT/1 prostaglandin*):ti OR
Latanoprost:ti OR Travoprost:ti OR Tafluprost:ti OR Unoprostone:ti OR bimatoprost:ti OR ‘beta
adrenergic receptor blocking agent’/exp/mj OR (‘β-Adrenergic’ NEXT/1 blocker*):ti OR (‘beta adrenergic’
NEXT/1 blocker*):ti OR (‘Adrenergic beta’ NEXT/1 Antagonist*):ti OR Timolol:ti OR Levobunolol:ti OR
Carteolol:ti OR Metipranolol:ti OR betaxolol:ti OR ‘alpha adrenergic receptor stimulating agent’/exp/mj
OR (‘Adrenergic alpha’ NEXT/1 Agonist*):ti OR (‘α-Adrenergic’ NEXT/1 agonist*):ti OR (‘alpha Adrenergic’
NEXT/1 agonist*):ti OR Brimonidine:ti OR apraclonidine:ti OR ‘carbonate dehydratase inhibitor’/exp/mj
OR (‘Carbonic anhydrase’ NEXT/1 Inhibitor*):ti OR Dorzolamide:ti OR Brinzolamide:ti OR
acetazolamide:ti OR ‘cholinergic receptor stimulating agent’/exp/mj OR (Cholinergic NEXT/1 agonist*):ti
OR Pilocarpine:ti OR carbachol:ti) AND [english]/lim AND [1990-2016]/py 58
B-2
Web of Science - 122 records (93 records with duplicates removed)
#3 122 #2 OR #1
#2 72 TITLE: (glaucoma* AND ("eye drop*" OR eyedrop* OR "ophthalmic drop*" OR "eye solution*" OR
"ophthalmic solution*" OR ((topical* OR ophthalmic*) AND (drop* OR solution* OR administ*)) OR
"prostaglandin analog*" OR "synthetic prostaglandin*" OR Latanoprost OR Travoprost OR Tafluprost OR
Unoprostone OR bimatoprost OR "β-Adrenergic blocker*" OR "beta adrenergic blocker*" OR
"Adrenergic beta-Antagonist*" OR Timolol OR Levobunolol OR Carteolol OR Metipranolol OR betaxolol
OR "Adrenergic alpha-Agonist*" OR "α-Adrenergic agonist*" OR "alpha Adrenergic agonist*" OR
Brimonidine OR apraclonidine OR "Carbonic anhydrase Inhibitor*" OR Dorzolamide OR Brinzolamide OR
acetazolamide OR "Cholinergic agonist*" OR Pilocarpine OR carbachol)) AND TOPIC: ((laser* OR
trabeculoplasty)) AND LANGUAGE: (English) Indexes=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH
Timespan=1990-2016
#1 59 TITLE: (glaucoma* AND (laser* OR trabeculoplasty)) AND TOPIC: (("eye drop*" OR eyedrop* OR
"ophthalmic drop*" OR "eye solution*" OR "ophthalmic solution*" OR ((topical* OR ophthalmic*)
NEAR/2 (drop* OR solution* OR administ*)) OR "prostaglandin analog*" OR "synthetic prostaglandin*"
OR Latanoprost OR Travoprost OR Tafluprost OR Unoprostone OR bimatoprost OR "β-Adrenergic
blocker*" OR "beta adrenergic blocker*" OR "Adrenergic beta-Antagonist*" OR Timolol OR Levobunolol
OR Carteolol OR Metipranolol OR betaxolol OR "Adrenergic alpha-Agonist*" OR "α-Adrenergic agonist*"
OR "alpha Adrenergic agonist*" OR Brimonidine OR apraclonidine OR "Carbonic anhydrase Inhibitor*"
OR Dorzolamide OR Brinzolamide OR acetazolamide OR "Cholinergic agonist*" OR Pilocarpine OR
carbachol)) AND LANGUAGE: (English) Indexes=SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH Timespan=19902016
Cochrane Library - 123 records (42 records with duplicates removed)
#1 glaucoma*:ti or glaucoma*:kw Publication Year from 1990 to 2016 3627
#2 laser* or trabeculoplasty:ti or laser* or trabeculoplasty:kw Publication Year from 1990 to 2016 8752
#3 "eye drop*" or eyedrop* or "ophthalmic drop*" or "eye solution*" or "ophthalmic solution*" or
((topical* or ophthalmic*) and (drop* or solution* or administ*)) or "prostaglandin analog*" or
"synthetic prostaglandin*" or Latanoprost or Travoprost or Tafluprost or Unoprostone or bimatoprost or
"β-Adrenergic blocker*" or "beta adrenergic blocker*" or "Adrenergic beta-Antagonist*" or Timolol or
Levobunolol or Carteolol or Metipranolol or betaxolol or "Adrenergic alpha-Agonist*" or "α-Adrenergic
agonist*" or "alpha Adrenergic agonist*" or Brimonidine or apraclonidine or "Carbonic anhydrase
Inhibitor*" or Dorzolamide or Brinzolamide or acetazolamide or "Cholinergic agonist*" or Pilocarpine or
carbachol:ti or "eye drop*" or eyedrop* or "ophthalmic drop*" or "eye solution*" or "ophthalmic
solution*" or ((topical* or ophthalmic*) and (drop* or solution* or administ*)) or "prostaglandin
analog*" or "synthetic prostaglandin*" or Latanoprost or Travoprost or Tafluprost or Unoprostone or
bimatoprost or "β-Adrenergic blocker*" or "beta adrenergic blocker*" or "Adrenergic beta-Antagonist*"
or Timolol or Levobunolol or Carteolol or Metipranolol or betaxolol or "Adrenergic alpha-Agonist*" or
"α-Adrenergic agonist*" or "alpha Adrenergic agonist*" or Brimonidine or apraclonidine or "Carbonic
anhydrase Inhibitor*" or Dorzolamide or Brinzolamide or acetazolamide or "Cholinergic agonist*" or
Pilocarpine or carbachol:kw Publication Year from 1990 to 2016 16108
#4 #1 and #2 and #3 123
B2. Search strategy for ongoing research studies.
Search terms: “trabeculoplasty” WITH Condition: glaucoma; “Medical therapy AND trabeculoplasty”
WITH Condition: Glaucoma
B-3