HHS Public Access: Peripheral Iridotomy For Pigmentary Glaucoma

HHS Public Access
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Cochrane Database Syst Rev. Author manuscript; available in PMC 2017 February 12.
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Published in final edited form as:

Cochrane Database Syst Rev. ; 2: CD005655. doi:10.1002/14651858.CD005655.pub2.
Peripheral iridotomy for pigmentary glaucoma

Manuele Michelessi1 and Kristina Lindsley2
1Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Rome,
Italy
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore,
Maryland, USA
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Abstract
BackgroundGlaucoma is a chronic optic neuropathy characterized by retinal ganglion cell
death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment
dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the
densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its
deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-
angle glaucoma found in patients with pigment dispersion syndrome.
Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has
been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in
the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and
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vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to
Contact address: Manuele Michelessi, Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Via
Livenza n 3, Rome, 00198, Italy. manuele_michelessi@yahoo.it.
CONTRIBUTIONS OF AUTHORS Conceiving of the review: Rajesh K Shetty (RKS).
Designing the review: MM, KL, RKS, SSV (Satyanarayana S Vedula).
Co-ordinating the review: KL.
Undertaking manual searches: KL, Andrew Law (AL).
Screening search results: KL, MM, SSV, RKS, AL, MA Tawfik (MAT).
Organizing retrieval of papers: KL, AL.
Screening retrieved papers against inclusion criteria: KL, MM, AL, MAT.
Appraising the quality of papers: KL, MM, AL, MAT.
Extracting data from papers: KL, MM, AL, MAT.
Writing to authors of papers to request additional information: KL, SSV, RKS.
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Obtaining and screening data from unpublished studies: MM, KL.

Managing data for the review: KL.
Entering data into RevMan: KL, AL, MM.
Analyzing data: MM, KL.
Interpreting data: MM, KL.
Writing the review: MM, KL.
DECLARATIONS OF INTEREST MM: none known.
KL: none known.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW In accordance with updates to Cochrane methods, we revised
assessment of methodological quality to assessment of risk of bias for included trials.
INDEX TERMS Medical Subject Headings (MeSH) Aluminum [therapeutic use]; Antihypertensive Agents [therapeutic use];
Glaucoma, Open-Angle [drug therapy; *surgery]; Intraocular Pressure; Iris [*surgery]; Laser Therapy [adverse effects; *methods];
Ophthalmologic Surgical Procedures; Randomized Controlled Trials as Topic; Visual Acuity; Yttrium [therapeutic use]
MeSH check words Humans
Michelessi and Lindsley Page 2
pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral
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laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown.
ObjectivesThe objective of this review was to assess the effects of peripheral laser iridotomy
compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or
no treatment, for pigment dispersion syndrome and pigmentary glaucoma.
Search methodsWe searched a number of electronic databases including CENTRAL,

MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We
last searched the electronic databases on 2 November 2015.
Selection criteriaWe included randomized controlled trials (RCTs) that had compared
peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion
syndrome and pigmentary glaucoma.
Data collection and analysisWe used standard methodological procedures for systematic
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reviews. Two review authors independently screened articles for eligibility, extracted data, and
assessed included trials for risk of bias. We did not perform a meta-analysis because of variability
in reporting and follow-up intervals for primary and secondary outcomes of interest.
Main resultsWe included five RCTs (260 eyes of 195 participants) comparing yttrium-
aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included
participants with pigmentary glaucoma at baseline, and two trials enrolled participants with
pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the
other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to
incomplete or missing data and selective outcome reporting.
Data on visual fields were available for one of three trials that included participants with
pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of
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visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio
(RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence).
The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the
proportion of participants with onset of glaucomatous visual field changes during the study period.
At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72
(95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial
reported that no eye showed visual field progression.
One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary
glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups
was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI 6.05 to 0.67;
14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber
depth at an average of nine months of follow-up and reported no meaningful differences between
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groups (mean difference 0.04 mm, 95% CI 0.07 to 0.15; 14 eyes; very low-quality evidence). No
other trial reported mean change in anterior chamber depth. Two trials reported greater flattening
of iris configuration in the laser iridotomy group than in the control group among eyes with
pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial
reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life
outcomes.
Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled
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participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group
required additional treatment between six and 23 months of follow-up than eyes in the control
group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with
pigment dispersion syndrome and indicated that the difference between groups at three-year
follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of
evidence for this outcome as very low.
Two trials reported that no serious adverse events were observed in either group among eyes with
pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two
participants required cataract surgery (at 18 and 34 months after baseline), and two participants
required a repeat iridotomy.
Authors' conclusionsWe found insufficient evidence of high quality on the effectiveness of

peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse
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events associated with peripheral iridotomy may be minimal, the long-term effects on visual
function and other patient-important outcomes have not been established. Future research on this
topic should focus on outcomes that are important to patients and the optimal timing of treatment
in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion
syndrome with established ocular hypertension, pigmentary glaucoma).
PLAIN LANGUAGE SUMMARY

Peripheral laser iridotomy for pigmentary glaucoma
Review questionWhat are the effects of peripheral laser iridotomy compared with other
treatments or no treatment for patients with pigment dispersion syndrome or pigmentary
glaucoma?
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BackgroundGlaucoma is a chronic eye condition associated with vision loss over time.
One of the major risk factors for glaucoma is increased pressure in the eye, known as ocular
hypertension. In eyes with pigment dispersion syndrome (PDS), particles from the iris
(colored part of the eye) break off from the iris and are deposited on other parts within the
eye. Sometimes, these particles block the flow of fluid out of the front portion of the eye,
leading to ocular hypertension. Pigmentary glaucoma is a specific form of glaucoma that
may be found in patients with PDS. Topcial medical therapy is usually the first-line
treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment.
Peripheral iridotomy is a procedure that is performed with a laser. A laser light beam is used
to burn a small hole in the iris to create an opening for free movement of fluid within the
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front portion of the eye. The goal of this procedure is to reduce pressure within the eye,
thereby reducing the chance of glaucoma and/or vision loss. However, it is unknown
whether peripheral iridotomy reduces the development or progression of pigmentary
glaucoma in practice.
Study detailsWe searched different electronic databases to identify randomized

controlled trials evaluating the effectiveness of peripheral iridotomy in people with PDS or
pigmentary glaucoma. We included five trials with a total of 260 eyes of 195 participants.
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Searches were up to date as of 2 November 2015.
Key resultsWe found no clear benefit for peripheral laser iridotomy versus no laser in
eyes with PDS or pigmentary glaucoma in terms of preventing loss of visual field. Very low-
quality evidence suggests that laser iridotomy may be more effective in lowering pressure
within the eye when compared with no laser iridotomy for up to 10 years after treatment.
Few adverse effects were reported among participants in these trials; the most commonly
reported adverse events were mild postoperative inflammation and cataract.
Quality of the evidenceWe graded the quality of evidence as very low as the result of
poor reporting of study methods, incomplete information for meaningful analysis of data,
and variation in outcomes assessed among trials. In conclusion, evidence is inadequate to
support the use of peripheral iridotomy as treatment for pigmentary glaucoma. Well-
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designed randomized controlled trials are needed to evaluate the effectiveness and safety of
peripheral iridotomy for PDS and pigmentary glaucoma.
BACKGROUND
Description of the condition
IntroductionGlaucoma is a chronic optic neuropathy characterized by retinal ganglion
cell death and consequent damage to the optic nerve head and the retinal nerve fiber layer.
Vision loss may occur with development of progressive visual field defects. Intraocular
pressure (IOP) higher than eye tissue susceptibility is the main risk factor for glaucoma;
elevation of IOP usually results from impairment of aqueous humor drainage. Aqueous
humor, a clear fluid that nourishes the eye, is secreted by the ciliary body into the posterior
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chamber of the eye, passes through the pupil into the anterior chamber, and is drained via the
trabecular meshwork.
Several origins have been proposed for elevated IOP associated with glaucoma. Blockage of
the aqueous fluid at the trabecular meshwork by the iris is known as angle closure.
Glaucoma consequent to angle closure is referred to as angle-closure glaucoma. Glaucoma
with no evidence of angle closure on gonioscopy is termed open-angle glaucoma.
Pigmentary glaucoma is a specific secondary form of open-angle glaucoma that occurs in
eyes with pigment dispersion syndrome. It was first described as a distinct clinical entity in
1949 by Sugar and Barbour (Sugar 1949).
Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment

epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of
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the iris pigment (melanin granules) and its deposition on various structures within the eye.
Friction between the iris and the lens zonules (suspending fibers of the lens) results in
mechanical disruption of the iris pigment epithelium (Campbell 1979; Farrar 1993). Loss of
integrity of the retinal pigment epithelial cell/photoreceptor complex in eyes with pigment
dispersion syndrome may contribute to pigment dispersion (Greenstein 2001). The liberated
pigment is deposited on lens zonules, anterior and posterior lens surfaces, iris, cornea, and
trabecular meshwork. The deposited pigment contributes to damage to the trabecular
meshwork over time, impeding the outflow of aqueous humor. This buildup of aqueous
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humor may lead to elevated IOP and associated glaucomatous optic neuropathy (Alvarado
1992; Grant 1963; Richardson 1977). This process usually occurs bilaterally.
EpidemiologyPigment dispersion syndrome and pigmentary glaucoma are prevalent in

many parts of the world, although they affect primarily white myopes (Farrar 1993). It is
estimated that pigmentary glaucoma affects 0.5% to 5% of people with glaucoma in the
Western world (Ritch 1997; Yang 2001). Pigmentary glaucoma was found in 0.6% of a
cohort of 176 people with glaucoma (95% confidence interval (CI) 0.01% to 3%) in the
Congo (Kaimbo Wa Kaimbo 1997). The prevalence of pigment dispersion syndrome is
higher; in a population screening study of 374 participants in Israel, 5.9% (95% CI 3.7% to
8.8%) had excessive corneal endothelial pigmentation (Gaton 1998).
Pigment dispersion syndrome affects men and women almost equally, with a slight
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predominance among men. Most people with pigmentary glaucoma are men, and the disease
tends to develop at an earlier age among men than among women (Migliazzo 1986; Scheie
1981; Sugar 1966; Yang 2001). Pigmentary glaucoma is diagnosed most commonly in the
third and fourth decades of life, although the average age of onset is uncertain (Speakman
1981). Young age, male gender, and myopia have been found to be significant risk factors
associated with the development of pigmentary glaucoma (Migliazzo 1986; Richter 1986).
In different retrospective studies, pigmentary glaucoma was reported to occur in 10% to 50%
of people with pigment dispersion syndrome within five years of follow-up, and in
approximately 15% by 15 years of follow-up (Farrar 1989; Migliazzo 1986; Siddiqui 2003).
One prospective study reported pigmentary glaucoma in 18% of participants with pigment
dispersion syndrome (Richter 1986).
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It is postulated that pigment dispersion syndrome is inherited in an autosomal dominant

fashion with incomplete penetration (Andersen 1997).
Presentation and diagnosisThe classic triad of clinical signs in pigment dispersion

syndrome consists of (1) a Krukenberg spindle (pigmented iris cells deposited on the
posterior surface of the cornea); (2) slit-like, radial, mid-peripheral iris transillumination
defects; and (3) pigment deposition on the trabecular meshwork (Sugar 1949).
In eyes with pigment dispersion syndrome, the iris tends to have a concave configuration and
often is inserted into the posterior ciliary body band. Mechanical friction between anterior
pockets of lens zonules and the peripheral iris during normal pupillary activity results in
pigment dispersion from the iris (Campbell 1979). The iris acts as a flap-valve, allowing
flow of aqueous from the posterior to the anterior chamber but not in the reverse direction,
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causing a reverse pupillary block, which results in posterior bowing of the iris, iris-zonular
touch, and consequent pigment release (Karickhoff 1992). The flow of aqueous humor from
the posterior chamber to the anterior chamber, against the pressure gradient, is assisted by
blinking (Liebmann 1995), exercise (Jensen 1995), and accommodation (Pavlin 1996).
Pigment dispersion syndrome associated with elevated IOP is usually defined as pigmentary
ocular hypertension (Niyadurupola 2008), whereas pigmentary glaucoma presents with
typical signs of pigment dispersion syndrome along with characteristics of glaucomatous
optic nerve damage (Alvarado 1992; Grant 1963; Richardson 1977). Patients usually have
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no subjective symptoms until the very late stages of optic atrophy and visual field loss.
Description of the intervention

First-line medical therapy for patients with elevated IOP, particularly in the face of
diminished trabecular meshwork drainage, consists of prostaglandin therapy. Prostaglandins
lower IOP by increasing uveo-scleral outflow, and offer the advantage of once-daily
administration. Another common therapy is aqueous suppression with a topical beta-blocker.
In theory, parasympathomimetics could decrease relative pupillary block, relieve irido-
zonular contact, and diminish pigment liberation; however, strong miotics rarely are
tolerated by young individuals because of the associated spasm of accommodation and
blurring of vision. Other medical interventions include alpha-agonists and topical carbonic
anhydrase inhibitors.
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Alternatives to medications for the management of pigmentary glaucoma include laser

procedures, such as argon laser trabeculoplasty and peripheral laser iridotomy. With
trabeculoplasty, a laser is used to burn selected areas of the trabecular meshwork to increase
aqueous outflow and lower IOP. Peripheral laser iridotomy involves creating an opening in
the iris tissue to serve as an alternate conduit for drainage of aqueous humor from the
posterior chamber to the anterior chamber and vice versa.
How the intervention might work

Effects of peripheral laser iridotomy are believed to be due to alleviation of the reverse
pupillary block mechanism following equalization of pressure between anterior and
posterior chambers. This equalization of pressure may allow the iris to flatten, thereby
decreasing irido-zonular contact and friction that lead to pigment dispersion syndrome
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(Laemmer 2008). Deposition of pigment on the trabecular meshwork would be eliminated or

minimized, and aqueous humor drainage could occur unimpeded.
Why it is important to do this review

The effectiveness of peripheral laser iridotomy in reducing the development or progression
of pigmentary glaucoma is unknown. Although alleviating the reverse pupillary block
mechanism may result in equalization of pressure between anterior and posterior chambers;
exercise and other factors may cause pigment dispersion. Peripheral laser iridotomy does not
directly correct underlying anatomical defects such as concavity of the iris or changes to the
trabecular meshwork from exposure to pigmentary deposition that occurred before the
procedure was performed. A systematic review of the evidence is needed to evaluate the
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usefulness of peripheral laser iridotomy in pigment dispersion syndrome and pigmentary

glaucoma.
OBJECTIVES
The objective of this review was to assess the effects of peripheral laser iridotomy compared
with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no
treatment, for pigment dispersion syndrome and pigmentary glaucoma.
METHODS
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Criteria for considering studies for this review

Types of studiesWe included randomized controlled trials (RCTs) in this review. We
excluded before-after studies in which changes in IOP with physical exercise before and
after treatment had been investigated because they do not address the objectives of this
review.
Types of participantsWe included trials that enrolled participants with documented

pigment dispersion syndrome and those with a diagnosis of pigmentary ocular hypertension
or pigmentary glaucoma. We applied no restrictions with respect to age, gender, ethnicity,
co-morbidities, use of adjunctive medications, or numbers of participants included in the
trials.
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Types of interventionsWe included trials that compared peripheral laser iridotomy

versus other modalities of treatment for pigment dispersion syndrome or pigmentary
glaucoma, such as medications, trabeculoplasty, trabeculectomy, or no treatment at all. We
imposed no restriction on the modalities of treatment that could be used for comparison.
Types of outcome measures

Primary outcomes: We included the following primary outcomes for comparison of
interventions.
Proportion of participants with pigmentary glaucoma and progression of

visual field loss. We assessed progression of visual field loss using
definitions specified in the included trials at six months and at one year of
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follow-up.
Proportion of participants with pigment dispersion syndrome with onset of

glaucomatous visual field changes as defined in included trials at six
months and at one year of follow-up.
Mean reduction in IOP from baseline as measured by any method at one

year of follow-up. We analyzed mean IOP values when included trials did
not report mean change in IOP.
We also assessed primary outcomes at other follow-up times as reported from the included
trials.
Secondary outcomes: We included the following secondary outcomes for comparison of

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interventions.
Mean visual acuity as measured on a logMAR chart (or equivalent) at six

months and at one year of follow-up.
Mean change in anterior chamber depth in millimeters measured by any

method at one year of follow-up.
Change in iris configuration as recorded by ultrasound bio-microscopy at

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one year of follow-up. Change in iris configuration may have been

reported in different ways including change in irido-corneal angle or loss
of convex shape of the iris as a consequence of peripheral iridotomy
relieving the relative pupillary block. We assessed this outcome as
reported in the included trials.
Mean change in aqueous melanin granules (i.e., pigment) using the laser
flare cell meter at one year of follow-up.
Pigment accumulation in the trabecular meshwork and on the iris as

documented using slit lamp photography, assessed by objective or
subjective criteria, at six months and at one year of follow-up.
Proportion of participants needing additional topical medication to control

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intraocular pressure at six months and at one year of follow-up.
We assessed secondary outcomes at other follow-up times as reported from the included
trials.
Adverse effects: We assessed the following adverse effects during the first year after trial
enrollment for comparison of interventions.
Halos.
Postoperative IOP spike.
Cataract.
Early postoperative ocular inflammation and persistent ocular

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inflammation following the procedure.
Posterior synechiae.
Retinal detachment.
We summarized other adverse effects reported from the included trials.
Quality of life measures: We planned to summarize data on quality of life measures

reported from the included trials.
Follow-up: We included in quantitative analyses outcomes with at least six months of

follow-up.
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Search methods for identification of studies

Electronic searchesWe searched the Cochrane Central Register of Controlled Trials
(CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10),
Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid
MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE
(January 1980 to November 2015), PubMed (January 1946 to November 2015), Latin
American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to
November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-

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trials.com) (last searched 7 May 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the

WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/
en). We did not use any date or language restrictions in the electronic searches for trials. We
last searched the electronic databases on 2 November 2015.
See Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE
(Appendix 2), EMBASE (Appendix 3), PubMed (Appendix 4), LILACS (Appendix 5),
mRCT (Appendix 6), ClinicalTrials.gov (Appendix 7), and the ICTRP (Appendix 8).
Searching other resourcesWe searched reference lists of identified trial reports to

find additional trials. We did not handsearch journal or conference proceedings specifically
for this review.
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Data collection and analysis

Selection of studiesTwo review authors independently assessed the titles and abstracts
of all records identified by electronic and manual searches. Each review author labeled each
record as A (definitely relevant), B (possibly relevant), or C (definitely not relevant). We
resolved differences through discussion and obtained full-text reports of records assessed as
A or B. Two review authors independently assessed the full-text reports and classified
each study as include, unsure, or exclude, according to the inclusion criteria for this
review. We resolved differences through discussion. For studies assessed as exclude, we
documented reasons for exclusion. For reports of studies published in languages not
understood by the review authors, we invited colleagues to assist with assessment for
eligibility. If any future study is assessed as unsure in updates to this review, we will
contact the trial investigators to request clarification.
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Data extraction and managementTwo review authors independently extracted and

recorded data related to study design and methods, participant characteristics, and primary
and secondary outcomes onto paper data collection forms developed and piloted for this
purpose. We adjudicated discrepancies through discussion. We planned to contact
investigators of included trials to request missing data. One review author entered all data
into Review Manager 5.3 (RevMan 2014), and a second review author verified the accuracy
of entered data.
Assessment of risk of bias in included studiesThe protocol for this review

described independent assessment of methodological quality by two review authors,
consistent with an earlier version of the Cochrane Handbook for Systematic Reviews of
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Interventions. When the Cochrane Handbook for Systematic Reviews of Interventions was
revised during the review process, we adapted our assessments according to corresponding
risk of bias domains. We followed criteria provided in Chapter 8 of the Cochrane Handbook
for Systematic Reviews of Interventions (Higgins 2011a) to determine high, low, and
unclear risk of bias within each included trial for each of the following domains: selection
bias (sequence generation and allocation concealment before randomization), detection bias
(masking of outcome assessors), attrition bias (rates of follow-up and handling of missing
data), and reporting bias (selective outcome reporting). Two review authors independently
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assessed the risk of bias for each trial and resolved disagreements through discussion.
We considered any method of allocation concealment (eg, centralized

randomization, use of sequentially numbered opaque envelopes) that
provided reasonable confidence that the allocation sequence had been
concealed from physicians enrolling patients to be adequate and at low
risk of bias. Whenever the adequacy of allocation concealment was
unclear from the trial report, we contacted the trial investigators to request
clarification. If they did not respond within two weeks, we categorized the
trial on the basis of available information.
We assessed masking of visual field and IOP outcome assessors in the

included trials. Masking of investigators and participants may not have
been possible with the interventions examined and was not assessed.
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We judged whether missing data had been handled appropriately in the

analysis of data from included trials. Our judgements considered rates of
follow-up, reasons for loss to follow-up, and analysis by the principle of
intention-to-treat (ITT). We assessed whether follow-up rates for treatment
and control arms were similar, and whether outcomes from all participants
were analyzed and with the group to which they had been randomly
assigned.
We assessed selective outcome reporting by comparing reported study

results versus outcomes specified in protocols, clinical trial registries,
and/or published design and methods papers. When no document
prespecifying study outcomes was available, we assessed risk of bias for
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selective outcome reporting as unclear.
Measures of treatment effectWe calculated risk ratios (RRs) with corresponding 95%
confidence intervals (CIs) for dichotomous outcomes, including onset of glaucomatous
visual field changes, progression in visual field loss, need for additional treatment, and
adverse events. We calculated mean differences (MDs) with corresponding 95% CIs for
continuous outcomes, including the mean change in IOP, mean change in anterior chamber
depth, and mean change in trabecular meshwork pigmentation.
Unit of analysis issuesWe planned to follow methods described in Chapter 16 of the

Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b) for trials with
multiple treatment groups, cross-over trials, and cluster-randomized trials. Because of
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limitations in data reporting, we analyzed outcomes on the basis of the unit of analysis
presented by trial reports. We documented unit of analysis issues (eg, paired-eye designs in
which the non-independence of eyes was not handled appropriately) and discussed the
potential impact of these issues on findings from individual trials and pooled estimates.
Dealing with missing dataWe contacted authors of included trials to request

additional information on issues that were categorized as unclear or missing from trial
reports. In cases when we were unable to communicate with primary investigators after two
or more attempts, or when primary investigators responded that no further information could
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be provided, we assessed the trial only on the basis of available information.
Assessment of heterogeneityWe assessed clinical and methodological heterogeneity

by comparing characteristics of participants, interventions, and outcomes across trials. We
planned to assess the inconsistency of effect estimates across trials by using the I2 statistic,
with a value of 50% or greater considered to indicate substantial statistical heterogeneity. We
also planned to examine the overlap of effect estimates and confidence intervals on a forest
plot, with poor overlap suggestive of heterogeneity.
Assessment of reporting biasesTo assess potential publication bias, we planned to

examine funnel plots whenever 10 or more trials were included in meta-analysis. We
assessed evidence of selective reporting as part of the Risk of bias' assessment. We did not
have access to protocols nor to clinical trial registration records for the included trials; thus,
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we compared outcomes specified in the methods sections of available reports with outcomes
for which results were reported.
Data synthesisAs a result of the variation in eligibility criteria among trials and
heterogeneity in measured and reported outcomes, we did not analyze outcome data in meta-
analyses. We planned to use a random-effects model when three or more trials were included
in the analysis, and a fixed-effect model when fewer than three trials were included.
Subgroup analysis and investigation of heterogeneityWe planned to conduct

subgroup analyses based on age and disease severity whenever sufficient data were
available.
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Sensitivity analysisWe planned to examine in sensitivity analyses the impact of

exclusion of trials with high risk of bias, changes in inclusion criteria cut-off points, and
exclusion of unpublished trials.
Summary of findingsTwo review authors independently graded the overall certainty

of evidence for each outcome using the GRADE (Grades of Recommendation, Assessment,
Development and Evaluation) classification (www.gradeworkinggroup.org/). We resolved
discrepancies by discussion and consensus within the review team. For each outcome, we
used the following criteria to grade the certainty of evidence as high, moderate, low, or very
low.
High risk of bias among included trials.

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Indirectness of evidence.
Unexplained heterogeneity or inconsistency of results.
Imprecision of results (i.e. wide confidence intervals).
High probability of publication bias.
We did not plan a priori to prepare a Summary of findings table consisting of relative and
absolute estimates of risk based on estimated risk across intervention groups in included
trials, as the protocol was published before this requirement was introduced (Shetty 2006).
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After conducting the systematic review, we did not prepare a Summary of findings table
because information needed to make such a table informative was not available.
RESULTS
Description of studies
Results of the searchElectronic searches conducted as of November 2, 2015, yielded
1544 records; after duplicates were removed, we screened 709 unique records (Figure 1). Of
these 709 records, we classified 16 as possibly relevant and reviewed the full-text reports.
These 16 reports represented 10 studies, five of which we included (11 reports) and five of
which we excluded (five reports). We identified no additional records upon searching other
sources.
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Included studiesWe included five RCTs (260 eyes of 195 participants) in this review
(Costa 1994; Gandolfi 1996; Georgopoulos 2001; Scott 2011; Uva 1996). All trials
compared laser iridotomy versus no laser treatment; three trials used a paired-eye design in
which one eye of each participant was randomized to the laser iridotomy group and the
fellow eye to the control group (Gandolfi 1996; Georgopoulos 2001; Uva 1996), and two
trials randomly selected one study eye per participant (Costa 1994; Scott 2011). For two
trials, the only available information was reported by a conference abstract, precluding the
usefulness of these trials in data synthesis (Georgopoulos 2001; Uva 1996).
Types of participants: Three trials included only participants with pigmentary glaucoma
(Costa 1994; Georgopoulos 2001; Uva 1996), and two trials enrolled only participants with
documented pigment dispersion syndrome (Gandolfi 1996; Scott 2011). Both Gandolfi 1996
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and Scott 2011 excluded participants with glaucomatous visual field defects; however, Scott
2011 included only participants with elevated IOP at baseline, whilst Gandolfi 1996
included participants with normal IOP at baseline and at high risk for succeeding IOP
decompensation due to a positive phenylephrine test result.
Two trials reported the country of enrollment: Italy (Gandolfi 1996) and the United
Kingdom (Scott 2011). Four trials included adult men and women (Costa 1994; Gandolfi
1996; Georgopoulos 2001; Scott 2011); Uva 1996 did not report participant characteristics.
Types of interventions: All trials used yttrium-aluminum-garnet (YAG) laser iridotomy in

the laser group versus no laser in the control group. The control group received no treatment
in three trials (Gandolfi 1996; Scott 2011; Uva 1996) and topical anti-glaucoma medication
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in two trials (Costa 1994; Georgopoulos 2001). In Gandolfi 1996, investigators controlled
postoperative inflammation by providing topical corticosteroids. In Scott 2011, eyes in the
iridotomy group received topical anti-glaucoma medication before and after laser treatment,
and researchers inserted an Abraham lens.
Types of outcomes: Follow-up times ranged from six months to 10 years across trials. Costa
1994 reported outcomes at two follow-up periods: one at a mean follow-up of eight months
in the laser group and 10 months in the control group, and the second with a minimum of
two years of follow-up. Georgopoulos 2001 reported that participants were followed for six
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to 23 months, and Uva 1996 for 12 to 37 months. Duration of follow-up was three years in
Scott 2011, and two years and 10 years in Gandolfi 1996.
Visual field: Three of the five trials measured outcomes related to visual field. Two trials
that included participants with pigment dispersion syndrome assessed visual field
deterioration using the Ocular Hypertension Treatment Study criteria or equivalent (Gandolfi
1996; Scott 2011). Additionally, Scott 2011 examined the time to visual field deterioration
when it occurred. Uva 1996 considered progression of visual field damage in eyes with
pigmentary glaucoma according to the need for trabeculectomy.
Intraocular pressure: Although IOP was measured and analyzed in all five trials, each trial
used a different metric or method of aggregation. Costa 1994 was the only trial that reported
mean reduction in IOP from baseline. Both Gandolfi 1996 and Georgopoulos 2001 assessed
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IOP control; however, these trials used different criteria to dichotomize IOP measures.
Gandolfi 1996 defined control as IOP that does not increase by more than 5 mmHg, and
Georgopoulos 2001 defined control as the need for additional treatment to control IOP if
greater than 21 mmHg. Scott 2011 measured IOP for safety and reported the proportion with
elevated IOP immediately after laser. Uva 1996 reported whether IOP changed significantly
from baseline within each group.
Visual acuity: No trial reported outcomes related to mean visual acuity; however, three
trials mentioned assessment of visual acuity. Costa 1994 reported only whether visual acuity
significantly changed from baseline; Gandolfi 1996 measured visual acuity as a safety
outcome but did not report results; and Scott 2011 reported recording visual acuity at each
follow-up visit but did not specify visual acuity as an outcome.
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Anterior segment measures: Only Costa 1994 reported mean change in anterior chamber
depth as an outcome. Additionally, Costa 1994 measured mean change in the anterior angle.
Both Georgopoulos 2001 and Uva 1996 reported changes in iris configuration measured by
ultrasound bio-microscopy. Neither Gandolfi 1996 nor Scott 2011 reported any anterior
segment measure.
No trial reported aqueous melanin granule outcomes.
Two trials assessed pigment accumulation in the trabecular meshwork as part of their
assessment of pigment dispersion indices (Costa 1994; Uva 1996); other signs of pigment
dispersion included iris transillumination and Krukenberg spindles.
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Need for additional topical medication: Two trials assessed the need for additional
treatment for control of IOP. Georgopoulos 2001 based the need solely on IOP values
(greater than 21 mmHg), whereas Scott 2011 considered both rise in IOP and increase in
AGIS (Advanced Glaucoma Intervention Study) scores from baseline. Additionally, Scott
2011 examined the time to start of medications whenever needed.
Adverse effects: Two trials reported adverse effects or safety outcomes. Gandolfi 1996
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defined deterioration in visual acuity, lens transparency, optic nerve head, and visual field as
safety outcomes in the trial. Scott 2011 specified transient hemorrhage, elevated IOP, and
iritis as immediate complications and reported the number needing repeat laser iridotomy,
retinal detachment, or cataract surgery. No trial reported halos or posterior synechiae as an
adverse event.
Quality of life measures: No trial reported cost or quality of life measures.
Excluded studiesWe excluded five studies after review of full-text reports; four studies
were not RCTs and one study included participants with angle-closure glaucoma only. We
have provided the reasons for exclusion in the Characteristics of excluded studies table.
Risk of bias in included studies

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A summary of risk of bias assessments for each trial is shown in Figure 2.
AllocationWe assessed two trials at low risk of bias for reporting random sequence
generation procedures (Scott 2011; Uva 1996) and one trial at low risk of bias for allocation
concealment before randomization (Scott 2011). No information on method of
randomization or allocation concealment was provided in the other three trial reports; thus
we assessed these trials to have had unclear risk of selection bias.
Masking (detection bias)Scott 2011 reported that visual field examiners were masked;
thus, we judged this trial at low risk of detection bias for visual field outcomes. The other
two of the three trials assessing visual field outcomes did not report whether outcome
assessors were masked (Gandolfi 1996; Uva 1996) and the other two trials did not report
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visual field outcomes (Costa 1994; Georgopoulos 2001). Visual field assessment is standard
in the care of glaucoma and is a core outcome measure of glaucoma. Therefore, we assessed
these four trials at unclear risk of bias with respect to visual field outcomes. IOP was
measured during follow-up by a masked observer in Gandolfi 1996, and by an unmasked
observer in Scott 2011; therefore, we judged these trials as having low risk and unclear risk
of detection bias, respectively. The remaining three trials did not report information about
masking; thus we judged them to have unclear risk of bias.
Incomplete outcome dataTwo trials reported that all study eyes randomly assigned
were followed and included in the analysis (ie, no loss to follow-up); therefore, we judged
these two as having low risk of attrition bias (Costa 1994; Uva 1996). We also assessed Scott
2011 as having low risk of attrition bias because fewer than 10% of participants were lost to
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follow-up, and reasons for and proportions of losses were balanced between groups. We
assessed the remaining two trials as having high risk of attrition bias. In Gandolfi 1996, 5/26
(19%) participants were excluded from the trial, four because they requested that both eyes
be treated with iridotomy. In Georgopoulos 2001, the number of participants included in the
main IOP analysis was not reported, and only 6/23 participants were included in the
ultrasound bio-microscopy assessment.
Selective reportingWe assessed four trials as having unclear risk of selective outcome
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reporting because no protocol or clinical trial registration was available, although all
outcomes mentioned in the Methods section had corresponding data in the Results section of
the trial reports (Costa 1994; Georgopoulos 2001; Scott 2011; Uva 1996). Gandolfi 1996
noted discrepancies in specified outcomes of interest versus outcomes for which data were
reported; thus we judged this trial as having high risk of selective outcome reporting.
Other potential sources of biasWe identified no other potential sources of bias.

Although none of the trials were registered prospectively, most predated this requirement by
sponsors and journal editors. No trials reported industry funding.
Effects of interventions
Because of differences in eligibility criteria and the outcomes measured and reported among
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trials, we did not analyze outcome data in meta-analyses.
Visual fieldOne of three trials that included participants with pigmentary glaucoma at
baseline reported the proportion of participants with progression of visual field loss (Uva
1996). At an average follow-up of 28 months (range 12 to 37), 2/16 eyes in the laser group
and 2/16 eyes in the control group showed progression of visual field damage and underwent
trabeculectomy (RR 1.00, 95% CI 0.16 to 6.25). We graded the certainty of the evidence for
this outcome as very low because of imprecision and potential risks of bias.
Both trials that enrolled participants with pigment dispersion syndrome at baseline reported
the proportion of participants with onset of glaucomatous visual field changes during the
study period (Gandolfi 1996; Scott 2011); however, we did not combine data in a meta-
analysis because of the difference in follow-up times. After three years of follow-up, Scott
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2011 reported that 8/52 (15%) eyes in the laser group and 3/53 (6%) eyes in the control
group converted to glaucoma (RR 2.72, 95% CI 0.76 to 9.68). After 10 years of follow-up,
Gandolfi 1996 reported that no eye in either group showed visual field progression. We
graded the certainty of the evidence for this outcome as very low as the result of imprecision
and potential risks of bias.
Intraocular pressureOnly one trial reported the mean change in IOP as an outcome
(Costa 1994). The mean change from baseline among nine eyes in the laser group at an
average of eight months of follow-up was 0.44 mmHg (SD 4.61), and among five eyes in
the control group at 10 months of follow-up was 2.25 mmHg (SD 1.70). Although the effect
estimate between groups favored laser, little to no difference was noted between the two
groups (MD 2.69 mmHg, 95% CI 6.05 to 0.67).
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In the Gandolfi 1996 trial, 1/21 (5%) eyes in the laser group and 11/21 (52%) eyes in the
control group had an increase in IOP of 5 mmHg or more from baseline (RR 0.09, 95% CI
0.01 to 0.64) at two years of follow-up. At 10 years, the effect was maintained with 3/21
(14%) eyes in the laser group, and 13/21 (62%) eyes in the control group had an increase in
IOP of 5 mmHg or more from baseline (RR 0.23, 95% CI 0.08 to 0.69).
Uva 1996 reported only that IOP was unchanged from baseline in each group. We graded the
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certainty of the evidence for this outcome as very low as a result of inconsistency,
imprecision, and potential risks of bias.
Visual acuityNo trial reported data related to mean visual acuity. Costa 1994 reported
only that visual acuity did not significantly differ between groups at an average of nine
months of follow-up.
Anterior segment measuresOne trial reported mean change in anterior chamber

depth as an outcome (Costa 1994). Mean change from baseline among nine eyes in the laser
group at an average of eight months of follow-up was 0 mm (SD 0.07), and among five eyes
in the control group at 10 months of follow-up 0.04 mm (SD 0.11). The effect estimate
between groups suggests little to no difference between groups (MD 0.04 mm, 95% CI
0.07 to 0.15). We graded the certainty of the evidence for this outcome as very low because
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of imprecision and potential risks of bias.
Two trials assessed iris configuration as measured by ultrasound bio-microscopy; however,

the information provided was not sufficient for inclusion in a meta-analysis. In
Georgopoulos 2001, six of 23 included participants underwent ultrasound bio-microscopy
for both eyes. The six eyes treated with laser showed flattening, and the six eyes in the
control group showed a more concave configuration compared with baseline. Uva 1996
reported that 14/16 eyes treated with laser showed flattening, and controls remained
unchanged.
Two trials reported pigment accumulation in the trabecular meshwork as an outcome. In

Costa 1994, mean change from baseline among nine eyes in the laser group at an average of
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eight months of follow-up was 0.22 (SD 0.44), and among five eyes in the control group at
10 months of follow-up 0.10 (SD 0.22). Although the effect estimate between groups
favored laser, little to no difference between groups (MD 0.32, 95% CI 0.67 to 0.03) was
reported. We graded the certainty of the evidence for this outcome as very low because of
imprecision and potential risks of bias.
Neither Gandolfi 1996 nor Scott 2011 reported any anterior segment measure. No trial
reported aqueous melanin granule outcomes.
Need for additional topical medicationTwo trials assessed the need for additional
treatment to control IOP; however, different criteria were used in determining whether
additional treatment was required. Georgopoulos 2001 reported that additional treatment
was needed for 19/23 (83%) eyes in the laser group and 11/23 (48%) eyes in the control
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group because IOP was greater than 21 mmHg at between six and 23 months of follow-up
(RR 1.73, 95% CI 1.08 to 2.75). Scott 2011 reported that 8/52 (15%) eyes in the laser group
and 9/53 (17%) eyes in the control group required topical anti-hypertensive medication as a
result of an unacceptable rise in IOP, increase in AGIS visual field score, or both, by three
years of follow-up (RR 0.91, 95% CI 0.38 to 2.17). We graded the certainty of the evidence
for this outcome as very low because of imprecision, inconsistency, and potential risks of
bias.
Adverse effectsTwo trials reported adverse effects or safety outcomes. Gandolfi 1996
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reported that no major side effects were encountered at two years of follow-up, and cases
of postoperative inflammation were mild and subsided within a few days with topical
steroids. At 10 years in the Gandolfi 1996 trial, lens transparency worsened in two eyes in
each group. Scott 2011 reported that cataract surgery was performed in one eye in each
group at 18 months for the laser group and at 34 months for the control group. No
immediate complication (transient hemorrhage, elevated IOP, and iritis) or retinal
detachment was reported by Scott 2011; two participants required a repeat iridotomy. No
trial reported halos or posterior synechiae as an adverse event.
Quality of life measuresNo trial reported cost or quality of life measures.
DISCUSSION
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Summary of main results

We found five trials (260 eyes of 195 participants) that had evaluated peripheral iridotomy
with yttrium-aluminum-garnet (YAG) laser compared with no laser iridotomy (Costa 1994;
Gandolfi 1996; Georgopoulos 2001; Scott 2011; Uva 1996). Data were sparse for outcomes
targeted for this systematic review, and too few trials reported outcomes in a similar manner
for meta-analysis. Among the included trials, no clear benefit was reported for laser
iridotomy compared with no laser in eyes with pigmentary glaucoma for visual field loss or
pigment dispersion syndrome in terms of preventing visual field progression. Very low-
quality evidence indicates that laser iridotomy may lower intraocular pressure (IOP) for up
to 10 years compared with no laser in eyes with pigmentary glaucoma or pigment dispersion
syndrome, and that eyes with pigmentary glaucoma treated with laser iridotomy may show a
flatter iris configuration than control eyes. Little to no clinical difference between groups
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was observed for change in anterior chamber depth or pigment accumulation in the
trabecular meshwork in eyes with pigmentary glaucoma. Differences between treatment
groups in the need for additional topical medication were inconsistent in the two trials that
reported this outcome. Few adverse effects were reported among participants in these trials;
the most commonly reported adverse events were mild postoperative inflammation and
cataract.
Overall completeness and applicability of evidence

For most outcomes specified for this review, sparse or no data were available for analysis.
Information for two of five trials was available only in conference abstracts (Georgopoulos
2001; Uva 1996), which provided limited details on study methods, participant
characteristics, and outcome measures. Follow-up times across trials ranged from six months
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to 10 years, and no two trials assessed the same outcome at the same follow-up time,
precluding meta-analysis.
A major issue in the applicability of evidence is the variation in participants' conditions at

baseline: Three trials included participants with pigmentary glaucoma (Costa 1994;
Georgopoulos 2001; Uva 1996), and two trials enrolled participants with documented
pigment dispersion syndrome with varying IOP criteria and different levels of risk at
baseline (Gandolfi 1996; Scott 2011). Such heterogeneity limits evidence synthesis and the
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ability to reach robust conclusions. Along the continuum that leads from pigment dispersion
syndrome to pigmentary glaucoma, different pathogenic stages can be recognized. In early
stages, dispersed pigment obstructs the trabecular meshwork, and pigment granules are
progressively phagocytized by trabecular endothelial cells. Outflow obstruction identified at
this early phase may be reversible. At late stages of disease, the trabecular endothelial cells
become overloaded with pigment and, subsequently, become necrotic and die. Loss of cells
causes trabecular meshwork beam collapse, which may result in a consequential increase in
IOP. Trabecular meshwork damage at this stage is probably irreversible. Thus, it is
reasonable to hypothesize that treatment with laser peripheral iridotomy may have different
success rates at different stages of disease. Such treatment may prevent progression of the
disease when pigment dispersion is still the main contributory factor (as at early stages of
pigment dispersion syndrome) and may be less effective at advanced stages, when trabecular
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damage as well as ocular hypertension is already established (as in individuals with pigment
dispersion syndrome with elevated IOP or pigmentary glaucoma).
Data also were not available to allow subgroup analyses to assess the effects of other
potentially important factors, such as participant age and disease severity at baseline. With
aging, pigment dispersion tends to be reduced as a consequence of increased axial length,
age-related miosis, and a general reduction in accommodation.
Quality of the evidence

We assessed the overall quality of the evidence as very low as a result of imprecision,
inconsistency, and potential risk of bias. No meta-analysis was possible because of
heterogeneous reporting of outcomes across trials, differences in trial duration, and the fact
that many study estimates had wide confidence intervals, yielding inconclusive results for
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most outcomes. Scott 2011 reported that a sample size of 43 eyes per group was needed to
detect a difference in visual field outcomes with 80% power at a 0.05 significance level.
Scott 2011 was the only trial that enrolled more than 30 eyes per group.
Potential biases in the review process

We followed standard Cochrane methods to minimize potential biases in the review process.
Agreements and disagreements with other studies or reviews

We found no other published systematic reviews on the effectiveness of peripheral iridotomy
for pigmentary glaucoma.
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AUTHORS' CONCLUSIONS
Implications for practice
Although risks of laser peripheral iridotomy may be minimal, this systematic review found
no high quality evidence for or against the usefulness of iridotomy for improving long-term
outcomes of visual field loss in pigmentary glaucoma and visual field progression in
pigment dispersion syndrome. Possible reduction in iris concavity and irido-zonular contact
with less pigment dispersion may not mitigate existing dysfunction of the trabecular
meshwork nor lead to a significant reduction in long-term visual function loss. However,
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laser peripheral iridotomy may have long-term beneficial effects on IOP in eyes with
pigment dispersion syndrome and in eyes at high risk of IOP decompensation.
Implications for research

Additional randomized controlled trials (RCTs) on laser peripheral iridotomy versus other
treatment or no treatment in eyes with pigmentary glaucoma are needed. Available data are
too sparse and scarcely representative of the whole disease continuum to allow for robust
conclusions. Improved understanding of the pathogenetic mechanisms involved in the
progression of this condition could help practitioners to identify which individuals would be
more likely to benefit from laser peripheral iridotomy, and could reveal when in the disease
process the procedure should be done. Careful differentiation of baseline characteristics (eg,
pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with
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established ocular hypertension, pigmentary glaucoma) seems essential when treatment

effects are assessed at different stages of the condition. Furthermore, trials should investigate
subgroup analysis for important co-variates such as age and iris concavity.
As with other forms of glaucoma, another important issue for future researchers to consider
is the outcome definition. IOP represents a surrogate outcome, which may be indicative of
the pathophysiological event occurring in the eye but may not reflect outcomes of greatest
importance to patients. Progression of visual field loss and incidence of glaucomatous visual
field damage may be outcomes most relevant to assessment of treatment effects with
iridotomy. Therefore, long-term follow-up (at least three years) would be important for
measuring visual field changes in future studies. Other outcomes associated with IOP
changes include the number of melanin granules in the aqueous humor (Mardin 2000).
Moreover, use of the opposite eye as a control for participants who have elevated IOP or
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pigmentary glaucoma in both eyes raises ethical issues. One would be ethically bound to
treat any eye with a very high IOP or signs of optic nerve damage. Pigmentary glaucoma,
like most glaucomas, tends to be asymmetrical, and so one eye (the worse eye) could be
more prone to damage than the other. It is thus more practical to randomly assigned
individuals instead of eyes.
DATA AND ANALYSES

This review has no analyses.
ACKNOWLEDGEMENTS
We gratefully acknowledge Rajesh K Shetty and Satyanarayana S Vedula, who conceived of and wrote the protocol
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for this review in 2006. We thank Karen Blackhall, who devised the original electronic search strategies, and Iris
Gordon and Lori Rosman, Trials Search Co-ordinators for CEV, who updated and ran the electronic search
strategies. We also thank MA Tawfik and Andrew Law for providing assistance with screening and abstracting data
for this review and Ahmad Aref, Daniel Maidana, Benjamin Rouse, Jimmy Le, and Barbara Hawkins for providing
comments on the review manuscript.
SOURCES OF SUPPORT Internal sources

Johns Hopkins University, USA.
External sources
The Cochrane Eyes and Vision US Project, supported by cooperative agreement 1 U01
EY020522, National Eye Institute, National Institutes of Health, USA.
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IRCCS Fondazione Bietti, supported by the Italian Ministry of Health and by Fondazione
Roma, Italy.
National Institute for Health Research (NIHR), UK.
Richard Wormald, Co-ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges
financial support for his CEV research sessions from the Department of Health through the
award made by the National Institute for Health Research to Moorfields Eye Hospital NHS
Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research
Centre for Ophthalmology.
The NIHR also funds the CEV Editorial Base in London.
The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the
Department of Health.
APPENDICES
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Appendix 1. CENTRAL search strategy

#1 ((glaucoma* or dispers* or deposit* or trabec*) near/3 pigment*)
#2 dispersion syndrome
#3 krukenberg spindle
#4 MeSH descriptor: [Exfoliation Syndrome] explode all trees
#5 (exfoliat* near/3 (syndrome* or glaucoma*))
#6 (Pseudoexfoliat* or Pseudo-exfoliat*)
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#7 (glaucoma capsulare or capsular glaucoma)
#8 #1 or #2 or #3 or #4 or #5 or #6 or #7
#9 MeSH descriptor: [Laser Therapy] explode all trees
#10 MeSH descriptor: [Lasers] explode all trees
#11 Laser*
#12 (iridotom* or LPI)
#13 #9 or #10 or #11 or #12

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#14 #8 and #13
Appendix 2. Medline (OVID) search strategy

1. Randomized Controlled Trial.pt.
2. Controlled Clinical Trial.pt.
3. (randomized or randomised).ab,ti.
4. placebo.ab,ti.
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5. drug therapy.fs.
6. randomly.ab,ti.
7. trial.ab,ti.
8. groups.ab,ti.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp animals/ not humans.sh.
11. 9 not 10
12. ((glaucoma* or dispers* or deposit* or trabec*) adj3 pigment*).tw.
13. dispersion syndrome.tw.

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14. krukenberg spindle.tw.
15. exp exfoliation syndrome/
16. (exfoliat* adj3 (syndrome* or glaucoma*)).tw.
17. (Pseudoexfoliat* or Pseudo-exfoliat*).tw.
18. (glaucoma capsulare or capsular glaucoma).tw.
19. or/1218
20. exp Laser Therapy/
21. exp Lasers/

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22. Laser*.tw.
23. (iridotom* or LPI).tw.
24. or/2023
25. 19 and 24
26. 11 and 25
Appendix 3. Embase.com search strategy

#1 `randomized controlled trial'/exp
#2 `randomization'/exp
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#3 `double blind procedure'/exp
#4 `single blind procedure'/exp
#5 random*:ab,ti
#6 #1 OR #2 OR #3 OR #4 OR #5
#7 ànimal'/exp OR ànimal experiment'/exp

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#8 `human'/exp
#9 #7 AND #8
#10 #7 NOT #9
#11 #6 NOT #10
#12 `clinical trial'/exp
#13 (clin* NEAR/3 trial*):ab,ti
#14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti

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#15 `placebo'/exp
#16 placebo*:ab,ti
#17 random*:ab,ti
#18 èxperimental design'/exp
#19 `crossover procedure'/exp
#20 `control group'/exp
#21 `latin square design'/exp

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#22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#23 #22 NOT #10
#24 #23 NOT #11
#25 `comparative study'/exp
#26 èvaluation'/exp
#27 `prospective study'/exp
#28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti

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#29 #25 OR #26 OR #27 OR #28
#30 #29 NOT #10
#31 #30 NOT (#11 OR #23)
#32 #11 OR #24 OR #31
#33 ((glaucoma* OR dispers* OR deposit* OR trabec*) NEAR/3 pigment*):ab,ti

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#34 `dispersion syndrome':ab,ti
#35 `krukenberg spindle':ab,ti
#36 `pseudoexfoliation'/exp
#37 (exfoliat* NEAR/3 (syndrome* OR glaucoma*)):ab,ti
#38 pseudoexfoliat*:ab,ti OR (pseudo NEXT/1 exfoliat*):ab,ti
#39 `glaucoma capsulare':ab,ti OR `capsular glaucoma':ab,ti
#40 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39

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#41 `low level laser therapy'/exp
#42 `laser'/exp
#43 laser*:ab,ti
#44 ìridotomy'/exp OR ìridotomy'
#45 iridotom*:ab,ti OR lpi:ab,ti
#46 #41 OR #42 OR #43 OR #44 OR #45
#47 #40 AND #46

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#48 #32 AND #47
Appendix 4. PubMed search strategy

#1 ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab]
OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR
(trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh])
#2 ((glaucoma*[tw] OR dispers*[tw] OR deposit*[tw] OR trabec*[tw]) AND pigment*[tw])

NOT Medline[sb]
#3 dispersion syndrome[tw] NOT Medline[sb]

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#4 krukenberg spindle[tw] NOT Medline[sb]
#5 (exfoliat*[tw] AND (syndrome*[tw] OR glaucoma*[tw])) NOT Medline[sb]
#6 (Pseudoexfoliat*[tw] OR Pseudo-exfoliat*[tw]) NOT Medline[sb]
#7 (glaucoma capsulare[tw] OR capsular glaucoma[tw]) NOT Medline[sb]
#8 #2 OR #3 OR #4 OR #5 OR #6 OR #7
#9 Laser*[tw] NOT Medline[sb]

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#10 (iridotom*[tw] OR LPI[tw]) NOT Medline[sb]
#11 #9 OR #10
#12 #8 AND #11
#13 #1 AND #12
Appendix 5. LILACS search strategy

(((glaucoma$ OR dispers$ OR deposit$ OR trabec$) AND pigment$) OR dispersion
syndrome OR krukenberg spindle OR Pseudoexfoliat$ OR Pseudo-exfoliat$ OR
glaucoma capsulare OR capsular glaucoma OR (exfoliat$ AND (syndrome$ or
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glaucoma$)) OR Sndrome de Exfoliacin OR Sndrome de Exfoliao OR

MH:C11.941.375.285$) AND (Laser$ OR iridotom$ or LPI OR MH:E02.594$ OR
MH:E04.014.520$ OR MH:E07.632.490$ OR MH:E07.710.520$ OR MH:
SP4.011.087.698.384.075.166.027$ OR MH:VS2.006.002.009$)
Appendix 6. metaRegister of Controlled Trials search strategy

(pigmentary glaucoma OR dispersion syndrome OR Pigment dispersion OR exfoliation
syndrome OR exfoliation glaucoma OR glaucoma capsulare OR capsular glaucoma OR
pseudoexfoliation OR Pseudo-Exfoliative) AND (Laser OR Lasers OR Iridotomy)
Appendix 7. ClinicalTrials.gov search strategy

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(pigmentary glaucoma OR dispersion syndrome OR Pigment dispersion OR exfoliation

syndrome OR exfoliation glaucoma OR glaucoma capsulare OR capsular glaucoma OR
pseudoexfoliation OR Pseudo-Exfoliative) AND (Laser OR Lasers OR Iridotomy)
Appendix 8. ICTRP search strategy

pigmentary glaucoma AND laser OR pigmentary glaucoma AND Iridotomy OR dispersion
syndrome AND laser OR dispersion syndrome AND Iridotomy OR Pigment dispersion
AND laser OR Pigment dispersion AND Iridotomy OR exfoliation syndrome AND laser OR
exfoliation syndrome AND Iridotomy OR exfoliation glaucoma AND laser OR exfoliation
glaucoma AND Iridotomy OR glaucoma capsulare AND laser OR glaucoma capsulare AND
Iridotomy OR capsular glaucoma AND laser OR capsular glaucoma AND Iridotomy OR
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pseudoexfoliation AND laser OR pseudoexfoliation AND Iridotomy OR Pseudo-Exfoliative

AND laser OR Pseudo-Exfoliative AND Iridotomy
REFERENCES
Costa VP, Gandham S, Smith M, Spaeth GL. The effects of peripheral iridectomy on pigmentary
glaucoma [O efeito da iridectomia perifrica em pacientes com glaucoma pigmentar]. Arquivos
Brasileiros De Oftalmologia. 1994; 57(1):3640.
Costa VP, Gandham S, Spaeth GL, Moster MR, Katz LJ, Wilson RP, et al. The effect of Nd:YAG laser
iridotomy on pigmentary glaucoma patients: a prospective study. Investigative Ophthalmology &
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Visual Science. 1994; 35 ARVO abstract 2760.

Spaeth GL, Moster MR, Mansukani S, Gandham S, Ruskovic D, Affel L, et al. The effect of peripheral
iridotomy on pigmentary glaucoma. Investigative Ophthalmology & Visual Science. 1995; 36
ARVO abstract 2616.
Gandolfi SA, Ungaro N, Tardini MG, Ghirardini S, Carta A, Mora P. A 10-year follow-up to determine
the effect of YAG laser iridotomy on the natural history of pigment dispersion syndrome. JAMA
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Figure 1.
Study flow diagram.
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Figure 2.
Risk of bias summary: review authors' judgements about each risk of bias item for each
included trial.
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CHARACTERISTICS OF STUDIES
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Characteristics of included studies [ordered by study ID]

Costa 1994
Methods Study design: parallel-group, randomized controlled trial

Number randomly assigned: 14 eyes of 14 participants: 9 eyes of 9 participants to laser group and 5 eyes of 5
participants to control group
Exclusions after randomization: none reported
Losses to follow-up: none reported
Number analyzed: 14 eyes of 14 participants: 9 eyes of 9 participants in laser group and 5 eyes of 5 participants in
control group
Unit of analysis: participant (1 eye per participant)
Handling of missing data: not applicable
Sample size and power calculation: not reported
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Participants Country: not reported

Mean age: 49 years (range not reported) in the laser group; 47 years (range not reported) in the control group
Gender: 7 (78%) men and 2 (22%) women in the laser group; 6 (86%) men and 1 (14%) woman in the control group
(potential error in reporting, control group does not add up to 5 participants)
Inclusion criteria: pigmentary glaucoma
Exclusion criteria: previous intraocular surgery
Equivalence of baseline characteristics: not reported
Interventions Laser: iridotomy using a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser

Control: anti-glaucoma medications in a predetermined order of pilocarpine 1%, beta blockers, and carbonic
anhydrase inhibitors
Length of follow-up:
Planned: up to 6 months, with extended follow-up at 2 years
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Actual: unclear; mean follow-up was 8 months in the laser group and 10 months in the control group
Outcomes Outcomes (primary and secondary outcomes not differentiated): visual acuity, mean change in IOP, mean changes
in graded pigment dispersion indices (iris transillumination, Krukenberg spindles, trabecular meshwork pigmentation),
and mean changes in anterior segment measures (chamber depth and angle)
Intervals at which outcomes assessed: 1, 3, 6 months, and 2 years
Information on cost of interventions or quality of life: none reported
Notes Study period: not reported

Trial registration: none reported
Source of funding: not reported
Disclosures of interest: not reported
Subgroup analyses: none reported
Risk of bias
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Bias Authors' judgement Support for judgement
Random sequence Unclear risk Method of randomization not reported.

generation (selection
bias)

Allocation Unclear risk Method of allocation concealment not reported.
concealment
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(selection bias)
Masking of outcome Unclear risk Visual field not reported as an outcome.

assessors (detection
bias)
Visual field
Masking of outcome Unclear risk Masking of IOP assessors not reported.

bias)
Intraocular pressure
Incomplete outcome Low risk Investigators reported no participants were lost to follow-up
data (attrition bias)
All outcomes
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Selective reporting Unclear risk No protocol or clinical trial registration record was available
(reporting bias) to assess selective outcome reporting. All outcomes
mentioned in the Methods section of the published paper
were reported in the Results section
Other bias Low risk None identified
Gandolfi 1996
Methods Study design: paired-eye, randomized controlled trial

Number randomly assigned: 52 eyes of 26 participants; the fellow eye of each participant was the control
Losses to follow-up: 5 participants; 1 participant died in a motor vehicle accident and 4 participants requested an
iridotomy in the fellow eye at an outside clinic
Number analyzed: 42 eyes of 21 participants
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Unit of analysis: eye (both eyes per participant)

Handling of missing data: excluded from analysis
Sample size and power calculation: Trial authors reported that the analyzed sample size was adequate to reveal a
difference of 45% in IOP with 95% power and type I error of 0.05. This seems to be post hoc power calculation, but
no clear information is available
Participants Country: Italy

Mean age: not reported (range 19 to 60 years); not reported by group
Gender: 14 (67%) men and 7 (33%) women; not reported by group
Inclusion criteria: referral to the authors' glaucoma service and diagnosed with pigment dispersion syndrome in both
eyes. Diagnosis was made if pigment was deposited on the corneal endothelium in both eyes, at least 1 slit-like mid-
peripheral transillumination defect was noted in the iris of both eyes, brownish pigment was deposited on the angle
structures at greater than 270 degrees for both eyes, IOP was less than 18 mmHg in both eyes, pigment was liberated
into the anterior chamber with topical phenylephrine in both eyes, visual field defects were absent in both eyes
Exclusion criteria: not reported
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Interventions Laser: iridotomy with an yttrium-aluminum-garnet (YAG) laser, after which each participant was administered 1 drop
of dexamethasone and 1 tablet of 250 mg acetazolamide
Control: no treatment

Planned: 2 years
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Actual: 2 years, with extended follow-up at 10 years
Outcomes Primary outcome, as denned by the trial: proportion with stable IOP, defined as IOP not increasing more than 5
mmHg; IOP calculated as an average of the 2 highest readings from the diurnal curve by Goldmann applanation
tonometry
Secondary outcomes, as denned by the trial: difference in IOP between treated eye and untreated fellow eye vs age;
difference in IOP between treated eye and untreated fellow eye vs refractive error; refraction measured after
cydoplegia (1% tropicamide, 1 drop every 5 minutes for 15 minutes)
Safety measures, as denned by the trial: loss of visual acuity, lens transparency, and visual field; progression of
optic nerve head damage
Intervals at which outcome assessed: every 6 months for 2 years, and at 10 years

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Source of funding: research grants from M. U. R. S. T., Rome, Italy

Disclosures of interest: The authors have no proprietary interest in any of the materials used in this study
Subgroup analyses: none reported; however, age and refractive error were plotted against IOP change for assessment
of correlation
Risk of bias
Random sequence Unclear risk Method of randomization not reported. An iridotomy was
generation (selection performed by the same investigator (SAG) in the randomly
bias) chosen eye after instillation of one drop of 0.2%
dexamethasone
Allocation Unclear risk Method of allocation concealment not reported

concealment
(selection bias)
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Masking of outcome Unclear risk Masking of visual field examiners not reported
bias)
Visual field
Masking of outcome Low risk The follow-up was performed by measuring (masked
assessors (detection observer) the daily IOP curve (from 8:00 AM to 6:00 PM, 6
bias) readings, 1 reading every 2 hours) every 6 months
Incomplete outcome High risk Excluded data from 5 of 26 (19%) participants, 4 of which
data (attrition bias) were based on treatment group
All outcomes
Selective reporting High risk The 10-year results paper specified safety outcomes (visual
(reporting bias) acuity, lens transparency, optic nerve head, and visual field)
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that were not reported in the 2-year results paper. Further,

visual acuity and optic nerve head outcomes were not
reported in the 10-year results paper
Georgopoulos 2001

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Exclusions after randomization: not reported
Losses to follow-up: not reported
Number analyzed: not reported, but in 6 patients UBM study was available for pre- and post-treatment evaluation
Handling of missing data: not reported
Sample size and power calculation: none reported

Mean age: 28 years (range 20 to 45 years); not reported by group
Gender: 17 (74%) men and 6 (26%) women; not reported by group
Inclusion criteria: clinically diagnosed pigmentary glaucoma in both eyes
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Equivalence of baseline characteristics: yes
Interventions Laser: iridotomy using a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser

Control: pilocarpine 2% drops 1 or 2 times daily
Planned: not reported
Actual: ranged from 6 to 23 months
Outcomes Outcomes (primary and secondary outcomes not differentiated): uncontrolled IOP, defined as the proportion of
participants who needed additional treatment for control of IOP (IOP > 21 mmHg), change in iris configuration
measured by UBM
Intervals at which outcome assessed: not reported
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Subgroup analyses: Changes in iris configuration were assessed in 12 eyes of 6 participants only; trial authors did
not report reasons for inclusion or exclusion in subgroup analysis
Risk of bias
Random sequence Unclear risk Method of randomization not reported

bias)
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concealment
(selection bias)
Masking of outcome Unclear risk Visual field not reported as an outcome

bias)

Visual field
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Masking of outcome Unclear risk Masking of IOP assessors not reported

bias)
Incomplete outcome High risk Number of participants analyzed not reported for IOP
data (attrition bias) outcomes. In 6 patients UBM study was available for pre-
and post-treatment evaluation; it was not clear why only
All outcomes 6/23 participants were part of the UBM study
Selective reporting Unclear risk All outcomes mentioned in the Methods section of the
(reporting bias) conference abstract were reported in the Results section
Scott 2011
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Methods Study design: parallel-group, randomized controlled trial

Number randomly assigned: 116 eyes of 116 participants: 57 eyes of 57 participants to laser group and 59 eyes of
59 participants to control group
Exclusions after randomization: 6 participants, 3 in each group, excluded after recruitment into the trial for not
meeting inclusion criteria
Losses to follow-up: 5 participants - 2 in the laser group and 3 in the control group - withdrew immediately after
randomization
Number analyzed: 116 eyes of 116 participants: 57 eyes of 57 participants to laser group and 59 eyes of 59
participants to control group
Unit of analysis: participant (1 eye per participant)
Handling of missing data: Primary analysis was an available case analysis; intent-to-treat analysis using last-
observation-carried-forward was done as secondary analysis
Sample size and power calculation: 43 eyes needed per group to detect difference with 80% power at the P value <
0.05 level
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Participants Country: United Kingdom

Mean age: 48 years (range 30 to 74 years) in the laser group; 49 years (range 24 to 86 years) in the control group
Gender: 39 (68%) men and 18 (32%) women in the laser group; 42 (71%) men and 17 (29%) women in the control
group
Inclusion criteria: ocular hypertension and pigment dispersion syndrome; pigmented angles with at least 1 other
feature of the following: Krukenberg's spindle, midperipheral iris, transillumination defects; backward-bowing iris
configuration; reliable, full visual field tested using the Humphrey Field Analyzer 242 full-threshold strategy ( 15%
false positives/negatives); 30% fixation losses; normal glaucoma hemifield test results; AGIS score 0; IOP >21
mmHg (off treatment); visual acuity of 20/40 or better
Exclusion criteria: other diseases leading to visual field loss; systemic medications that may alter IOP (ie,
glucocorticoids, cardiac glycosides, beta-adrenergic blockers); recent ocular trauma, infection, inflammation, or
surgery
Equivalence of baseline characteristics: the groups were similar at baseline with regard to age, gender, spherical
equivalent refraction, and baseline IOP
Interventions Laser: iridotomy using a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser; apraclonidine 1% instilled

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immediately before and after laser treatment; pilocarpine 2% and local anesthetic drops instilled before treatment;
Abraham lens inserted
Planned: 3 years

Actual: 3 years
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Outcomes Primary outcome, as denned by the trial: deterioration in visual field, first defined as an increase in AGIS score
from 0 to 1, then revised by trial investigators to Ocular Hypertension Treatment Study criteria because the AGIS
scoring system was developed for eyes with established glaucoma and may not be sensitive to detect changes in eyes
with ocular hypertension (visual field abnormalities defined as a point being flagged at the P value < 0.05 level in the
corrected pattern standard deviation, or having glaucoma hemifield test results outside normal limits on 3 consecutive
tests, with abnormalities of the same type, index, and location in each successive field and determined independently
by 2 readers)
Secondary outcomes, as denned by the trial: addition of topical anti-glaucoma medications over the study period;
time to start of medications if needed; and time of visual field conversion if it occurred
Safety outcomes, as denned by the trial: immediate complications (transient hemorrhage, elevated IOP, or iritis),
repeat laser iridotomy, retinal detachment, cataract surgery
Other measurements reported in the study: Snellen visual acuity recorded at each visit
Intervals at which outcome assessed: every 4 months for 3 years

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Source of funding: The Frost Charitable Trust, Surrey, UK; and the Special Trustees of Moorfields Eye Hospital
London, United Kingdom
Disclosures of interest: The author(s) have no proprietary or commercial interest in any materials discussed in this
article
Risk of bias
Random sequence Low risk Randomization was accomplished using a centralized

generation (selection computerized randomization system in the Research and
bias) Development office at Moorfields Eye Hospital using the
weighted coin method
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Allocation Low risk Patients were randomized after consent and were assigned
concealment study identification numbers to which only the Research and
(selection bias) Development office had unmasked access
Masking of outcome Low risk However, post hoc visual field analysis was performed by 2
assessors (detection readers masked to treatment
bias)
Visual field
Masking of outcome Unclear risk The IOP was measured by unmasked clinicians at each
assessors (detection visit
bias)
Incomplete outcome Low risk 11/116 (9%) participants with missing data included in the
data (attrition bias) final analyses
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All outcomes
Selective reporting Unclear risk No protocol or clinical trial registration record was available
(reporting bias) for assessment of selective outcome reporting. All outcomes
mentioned in the Methods section of the published paper
were reported in the Results section

Author Manuscript
Uva 1996

Losses to follow-up: none reported
Number analyzed: 32 eyes of 16 participants
Handling of missing data: none
Sample size and power calculation: none reported

Mean age: not reported
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Gender: not reported

Inclusion criteria: bilateral pigmentary glaucoma under medical therapy
Interventions Laser: iridotomy using a yttrium-aluminum-garnet (YAG) laser

Planned: not reported
Actual: mean 28 months (range 12 to 37 months)
Outcomes Outcomes (primary and secondary outcomes not differentiated): change in IOP, progression of visual field
damage, change in iris configuration measured by UBM, change in signs of pigmentary glaucoma (Krukenberg
spindle, iris transillumination, trabecular meshwork pigmentation)
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Intervals at which outcome assessed: not reported


Risk of bias
Random sequence Low risk Investigators used a randomization table

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bias)

concealment
(selection bias)

Masking of outcome Unclear risk Masking of visual field examiners not reported
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bias)
Visual field
Masking of outcome Unclear risk Masking of IOP assessors not reported

bias)
Incomplete outcome Low risk Investigators reported no participants lost to follow-up

data (attrition bias)
All outcomes
Selective reporting Unclear risk No protocol or clinical trial registration record was
(reporting bias) availablefor assessment of selective outcome reporting. All
outcomes mentioned in the Methods section of the
conference abstract were reported in the Results section
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AGIS: Advanced Glaucoma Intervention Study

IOP: intraocular pressure
mmHg: millimeter of mercury
UBM: ultrasound bio-microscopy
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Characteristics of excluded studies [ordered by study ID]

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Study Reason for exclusion
Birt 2004 Not a randomized trial; cohort study comparing effects of peripheral laser iridotomy in eyes with pigment dispersion vs
ocdudable angles
Jiang 2010 No participants of interest; paired-eye, randomized controlled trial comparing laser iridotomy vs no treatment in
primary angle-closure suspects
Kchle 2001 Not a randomized trial; case series assessing number of aqueous melanin granules in eyes with pigment dispersion
before vs after laser iridotomy
Newman-Casey 2011 Not a randomized trial; commentary discussing Scott 2011
Pillunat 2000 Not a randomized trial; case series assessing anatomical relationships of the iris in eyes with pigment dispersion before
vs after laser iridotomy
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Peripheral iridotomy for pigmentary glaucoma

Obtaining and screening data from unpublished studies: MM, KL.

laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown.

Search methodsWe searched a number of electronic databases including CENTRAL,

Authors' conclusionsWe found insufficient evidence of high quality on the effectiveness of

PLAIN LANGUAGE SUMMARY

Study detailsWe searched different electronic databases to identify randomized

Searches were up to date as of 2 November 2015.

Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment

EpidemiologyPigment dispersion syndrome and pigmentary glaucoma are prevalent in

It is postulated that pigment dispersion syndrome is inherited in an autosomal dominant

Presentation and diagnosisThe classic triad of clinical signs in pigment dispersion

Description of the intervention

Alternatives to medications for the management of pigmentary glaucoma include laser

How the intervention might work

(Laemmer 2008). Deposition of pigment on the trabecular meshwork would be eliminated or

Why it is important to do this review

usefulness of peripheral laser iridotomy in pigment dispersion syndrome and pigmentary

Criteria for considering studies for this review

Types of participantsWe included trials that enrolled participants with documented

Types of interventionsWe included trials that compared peripheral laser iridotomy

Types of outcome measures

Proportion of participants with pigmentary glaucoma and progression of

Proportion of participants with pigment dispersion syndrome with onset of

Mean reduction in IOP from baseline as measured by any method at one

Secondary outcomes: We included the following secondary outcomes for comparison of

Mean visual acuity as measured on a logMAR chart (or equivalent) at six

Mean change in anterior chamber depth in millimeters measured by any

Change in iris configuration as recorded by ultrasound bio-microscopy at

one year of follow-up. Change in iris configuration may have been

Pigment accumulation in the trabecular meshwork and on the iris as

Proportion of participants needing additional topical medication to control

intraocular pressure at six months and at one year of follow-up.

Postoperative IOP spike.

Early postoperative ocular inflammation and persistent ocular

inflammation following the procedure.

We summarized other adverse effects reported from the included trials.

Quality of life measures: We planned to summarize data on quality of life measures

Follow-up: We included in quantitative analyses outcomes with at least six months of

Search methods for identification of studies

November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-

trials.com) (last searched 7 May 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the

Searching other resourcesWe searched reference lists of identified trial reports to

Data collection and analysis

Data extraction and managementTwo review authors independently extracted and

Assessment of risk of bias in included studiesThe protocol for this review

We considered any method of allocation concealment (eg, centralized

We assessed masking of visual field and IOP outcome assessors in the

We judged whether missing data had been handled appropriately in the

We assessed selective outcome reporting by comparing reported study

selective outcome reporting as unclear.

Unit of analysis issuesWe planned to follow methods described in Chapter 16 of the

Dealing with missing dataWe contacted authors of included trials to request

be provided, we assessed the trial only on the basis of available information.

Assessment of heterogeneityWe assessed clinical and methodological heterogeneity

Assessment of reporting biasesTo assess potential publication bias, we planned to

Subgroup analysis and investigation of heterogeneityWe planned to conduct

Sensitivity analysisWe planned to examine in sensitivity analyses the impact of

Summary of findingsTwo review authors independently graded the overall certainty

High risk of bias among included trials.

12. ((glaucoma* or dispers* or deposit* or trabec) adj3 pigment).tw.

#14 ((singl* OR doubl* OR trebl* OR tripl) NEAR/3 (blind OR mask*)):ab,ti

#28 control:ab,ti OR prospectiv:ab,ti OR volunteer*:ab,ti

#33 ((glaucoma* OR dispers* OR deposit* OR trabec) NEAR/3 pigment):ab,ti