Cyclodestructive procedures for refractory glaucoma

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the relative effectiveness and safety of cyclodestructive procedures (cyclophotocoagulation (CPC), endocyclophotocoagulation (EPC), cryotherapy) compared with other procedures aimed to control intraocular pressure (IOP) (aqueous shunts, trabeculectomy) in people with refractory glaucoma of any type, and to assess the relative effectiveness and safety of cyclodestructive procedures compared with another cyclodestructive procedure.

Background

Description of the condition

Glaucoma is a chronic progressive optic neuropathy associated with structural damage to the optic nerve and associated visual field loss, which can lead to vision loss and blindness if left undiagnosed and untreated (Foster 2002). Glaucoma is a heterogeneous group of conditions with multiple etiologies. The two main types are open angle glaucoma (OAG) and angle-closure glaucoma (ACG). Neovascular glaucoma is a severe form of secondary glaucoma that results from occlusion of the trabecular meshwork and secondary closure of the angle by fibrovascular tissue proliferation.

Known risk factors that contribute to damage to the optic nerve include elevated intraocular pressure (IOP), older age, positive family history of glaucoma, African racial background, high myopia, high cup-to-optic disk ratios, exfoliation syndrome, and decreased central corneal thickness (Coleman 2008; Gordon 2002; Landers 2002; Medeiros 2003; Quigley 2011).

However, IOP remains the only modifiable risk factor for glaucoma and prognostic factor for glaucoma outcomes. Thus, therapies for glaucoma, regardless of disease mechanism, target IOP reduction (Coleman 2012). Normally, the rate of aqueous humor production by the ciliary body equals the rate of its outflow. IOP increases when there is excess aqueous humor production or when part or all of the aqueous humor drainage system is blocked (Pan 2011).

Randomized clinical trials (RCTs) of participants with glaucoma have shown that there is a clear benefit to lowering IOP with medications, laser procedures, and incisional surgery to prevent further optic nerve damage and visual field deterioration (Burr 2012; CNTGS 1998; Leske 2003; Lichter 2001; VanVeldhuisen 2000; Vass 2007).

Epidemiology

Glaucoma is an increasingly critical public health problem due to the aging world population. Glaucoma is the leading cause of irreversible blindness and the second leading cause of blindness worldwide (Quigley 2011). In 2006, Quigley projected that 60.5 million people worldwide would be diagnosed with glaucoma, and 8.4 million would be bilaterally blind from primary glaucoma in 2010 (Quigley 2006). Quigley 2006 also projected that by 2020 these would increase to 79.6 million and 11.2 million, respectively. OAG is the most common type of glaucoma and accounts for 74% of cases worldwide (Quigley 1996). Worldwide, of those over 40 years old, 2% are estimated to have OAG, 0.7% to have ACG, and 0.4% to have neovascular glaucoma (Quigley 1996; Quigley 2006). In OAG, incidence by gender is similar; however, black people have almost three times the age-adjusted prevalence than white people (Friedman 2004). In ACG, there are considerable difference in prevalence by ethnicity. The highest rates are reported in Chinese, Inuit, and other Asian populations (He 2006; Van Rens 1988).

Symptoms and diagnosis

OAG is often called the “silent thief of sight” because it progresses slowly and may cause irreversible damage before a person with glaucoma notices any vision loss. People with glaucoma typically do not notice visual field loss until central vision is affected in a late stage of the disease; 50% to 90% of people with glaucoma are unaware that they have glaucoma (Weinreb 2014).

ACG can be categorized into acute and chronic cases. Acute ACG requires immediate management to avoid blindness. People with acute ACG present with a painful red eye, blurred vision, headache, nausea, and vomiting (Weinreb 2014). People with chronic ACG present with similar symptoms as those with OAG. Glaucoma is diagnosed using tonometry, gonioscopy, optic nerve imaging, visual acuity, and visual field assessment.

Description of the intervention

Cyclodestructive procedures, first introduced by Vogt in the 1930s (Vogt 1936), are traditionally used in eyes with refractory glaucoma for whom filtration procedures have failed to lower IOP or slow progression, eyes with elevated IOP and limited useful vision on maximal medical therapy, and eyes with no visual potential in need of pain relief (Ansari 2007; Bloom 1997; Lin 2008; Pastor 2001). The goal of treatment is to reduce aqueous humor formation through ablation or destruction of the ciliary body epithelium. A number of different modalities have been used to achieve this aim including diathermy, cryotherapy, laser, ultrasound, and surgical excision (Beckman 1972; Bietti 1950; Coleman 1985; Shields 1985; Vogt 1936). Laser cyclophotocoagulation (CPC), first introduced in the 1970s by Beckman (Beckman 1973), has become the most common surgical method for reducing aqueous inflow. CPC can be performed using a neodymium:yttrium-aluminum-garnet (Nd:YAG) or diode laser (Lin 2004; Martin 2001) and laser energy can be delivered by either the contact or non-contact method (Lin 2002). Although CPC has been used to treat refractory glaucoma successfully, significant postoperative complications and discomfort have been reported by people undergoing this procedure (Lin 2004). Endoscopic cyclophotocoagulation (ECP), a newer method that specifically targets the ciliary epithelium under direct viewing, has become an increasingly popular treatment for refractory glaucoma. Since ECP can selectively ablate ciliary body tissue, ECP has a lower incidence of vision threatening complications (Lin 2002). However, ECP is an intraocular procedure and thus potential risks in order of frequency of occurrence post-treatment include fibrin exudate, hyphaema, cystoid macular edema, vision loss, and choroidal detachment (Lin 2002). Other potential complications that may occur but were not seen in Lin 2002 include endophthalmitis, choroidal hemorrhage, and retinal detachment.

Other glaucoma surgeries include trabeculectomy and aqueous shunts. Trabeculectomy is generally used in eyes where medications and laser therapy are insufficient to control disease (Prum 2016). Trabeculectomy is a filtering surgery where a full-thickness block of eye filtration tissue is removed to decrease resistance to the outflow filtration of aqueous. While trabeculectomy lowers eye pressure and is considered by many ophthalmologists to be the gold-standard glaucoma operation, it is associated with significant postoperative complications. Complications include hyphaema, shallow or flat anterior chamber, hypotony, choroidal detachment, and hypotony maculopathy (Eldaly 2014). Aqueous shunts are used to manage medically uncontrolled glaucoma when trabeculectomy has failed to control IOP or is unlikely to succeed (Prum 2016). Aqueous shunts consist of a tube that diverts aqueous humor to an end plate (Minckler 2006).

How the intervention might work

When there is excess aqueous humor production or when part or all of the aqueous humor drainage system is blocked, IOP increases (Pan 2011; Turkoski 2012). Aqueous humor is produced by the ciliary body epithelium. The laser energy that targets the ciliary body epithelium induces coagulative necrosis of these tissues and results in reduction of aqueous humor production and, thus, reduced IOP (Liu 1994). To achieve long term IOP reduction, multiple treatments are sometimes necessary because the ciliary epithelium can regenerate (Lin 2008).

Why it is important to do this review

While cyclodestructive procedures are not new, there is debate regarding which cyclodestructive method is best and how they compare to other glaucoma surgeries. Additionally, much of the literature reports only small non-comparative case series; such study designs cannot demonstrate a benefit of one therapy over another. A systematic review, ideally incorporating meta-analysis, would be beneficial to consolidate information across studies and to estimate the relative effects of different procedures on IOP control.

Objectives

To assess the relative effectiveness and safety of cyclodestructive procedures (cyclophotocoagulation (CPC), endocyclophotocoagulation (EPC), cryotherapy) compared with other procedures aimed to control intraocular pressure (IOP) (aqueous shunts, trabeculectomy) in people with refractory glaucoma of any type, and to assess the relative effectiveness and safety of cyclodestructive procedures compared with another cyclodestructive procedure.

Methods

Criteria for considering studies for this review

Types of studies

We will only include randomized controlled trials (RCTs).

Types of participants

We will include RCTs in which participants underwent a secondary procedure for refractory glaucoma (i.e. medically uncontrolled glaucoma for which other surgeries have failed). We will include all types of glaucoma (i.e. primary open angle glaucoma (OAG), angle-closure glaucoma (ACG), pigmentary glaucoma, exfoliation glaucoma, and secondary glaucoma such as neovascular glaucoma). There will be no restrictions based on participant age, gender, ethnicity, or co-morbidity.

Types of interventions

We will include all trials that compare cyclodestruction with aqueous shunts, trabeculectomy, or other cyclodestructive procedures. Also we will include trials with all types of lasers (i.e. ruby, Nd:YAG, diode), routes of administration (non-contact, contact), and laser settings. The primary comparison of interest will be any cyclodestructive procedure versus another glaucoma treatment (aqueous shunts, trabeculectomy) and the secondary comparison will be any cyclodestructive procedure versus another cyclodestructive procedure.

Types of outcome measures

Primary outcomes
  1. Change from baseline in pain control as reported by the participant or change in number of pain medications prescribed from baseline at 12 months post-intervention.

Secondary outcomes

Secondary outcomes for comparison of interventions will include the following.

  1. Mean change in intraocular pressure (IOP) from baseline (immediate preoperative IOP) in study eyes at one week, one month, three months, six months, 12 months, and last follow-up after the procedure, measured using Goldmann tonometry, TonoPen, or another standard device. If available from existing studies, we will examine IOP in time to event analysis.

  2. Mean change in best-corrected visual acuity in study eyes at 12 months post-intervention, measured by logarithm of the minimum angle of resolution (logMAR) chart or equivalent.

  3. Change in mean deviation in study eyes from baseline at 12 months post-intervention as measured by automated perimetry.

  4. Mean number of glaucoma medications, both topical and systemic, at 12 months post-intervention.

  5. Proportion of study eyes requiring additional glaucoma surgery by 12 months post-intervention.

Adverse outcomes

We will document adverse outcomes reported by the included studies (i.e. prolonged inflammation, hypotony, phthisis, fibrin exudates). Since these are intraocular procedures we also will document reports of endophthalmitis, retinal detachment, and choroidal hemorrhage.

Quality of life data

We will describe and compare quality of life outcomes by procedure whenever included trials report these data.

Search methods for identification of studies

Electronic searches

We will search CENTRAL (which contains the Cochrane Eyes and Vision (CEV) Trials Register) (latest issue), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to present), EMBASE (January 1980 to present), PubMed (January 1966 to present), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to present), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We will not use any date or language restrictions in the electronic search for trials.

In the Appendices we have provided the search strategy details for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), PubMed (Appendix 4), LILACS (Appendix 5), ClinicalTrials.gov (Appendix 6), and the ICTRP (Appendix 7).

Searching other resources

We will search the references of included studies for additional relevant studies without restrictions regarding language or date of publication.

Data collection and analysis

Selection of studies

Two review authors will independently review the titles and abstracts of all records identified through electronic and manual searches. Each review author will classify titles and abstracts as either ‘definitely relevant’, ‘possibly relevant’, or ‘definitely not relevant’. We will retrieve the full-text reports of all records classified as ‘definitely relevant’ or ‘possibly relevant’. The same two review authors will review full-text articles and classify the reporting studies as either ‘definitely include’ or ‘definitely exclude’. We will resolve any disagreements between the two review authors by discussion at each stage of selection. If a eligibility is unclear after discussion, we will consult a third review author. We will exclude those studies labeled as ‘definitely exclude’ and document the reasons for exclusion in the ‘Characteristics of excluded studies’ table. When information is unclear or unavailable from the study reports to include or exclude a study from the review, we will attempt to contact the study authors for clarification of eligibility.

Data extraction and management

Two review authors will independently extract data from the included studies using internet-based data abstraction forms developed in collaboration with Cochrane Eyes and Vision (CEV) in the Systematic Review Data Repository (srdr.ahrq.gov). We will abstract data from each study relevant to the study design and methods, participant characteristics, interventions, and outcomes (see Appendix 8). We will resolve any discrepancies between the two review authors by discussion and, if necessary, consult a third review author. One review author will enter data into Review Manager (RevMan) (RevMan 2014) and a second review author will verify the entered data.

Assessment of risk of bias in included studies

Two review authors will independently assess each included study for risk of bias using the tools described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We will assess the following 'Risk of bias' parameters.

  1. Sequence generation.

  2. Allocation concealment before randomization.

  3. Masking of participants, personnel, and outcome assessors.

  4. Incomplete outcome data reporting.

  5. Selective outcome reporting.

  6. Funding source.

We will assess each trial for each criterion and judge as being at either 'high', 'low', or 'unclear' risk of bias (lack of information or uncertainty over the potential for bias).

Measures of treatment effect

Dichotomous outcomes

We will analyze the need for additional glaucoma surgery using summary risk ratios (RRs) with 95% confidence intervals (CIs) when data are available.

Continuous outcomes

We will summarize mean reduction in IOP, mean change in logMAR visual acuity, mean deviations from visual field tests, number of glaucoma medications, and pain control as reported by the participant and amount of pain medications prescribed using summary mean differences with 95% CIs. Whenever the included studies have measured continuous outcomes using different scales, we will calculate standardized mean differences.

Unit of analysis issues

The participant will be the unit of analysis. The optimal study design will include one study eye per participant. If studies that used a paired-eye design meet the inclusion criteria of this Cochrane review, we will use the paired analysis when possible to keep the unit of analysis as the participant. We will record whether studies enrolled one or two study eyes per participant. If trials included both eyes per participant and followed them as study eyes, we will account, when possible, for intra-person correlation of outcomes as outlined in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Dealing with missing data

We will contact study authors to request missing details including but not limited to study methods, effect estimates, and standard deviations. If study authors do not respond within two weeks, we will use the data available. We also will refer to guidelines in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b) for further issues regarding how to account for missing data.

Assessment of heterogeneity

We will examine both clinical and methodological heterogeneity of included studies by examining variations in participant characteristics, inclusion/exclusion criteria, and assessments of primary and secondary outcomes. We will use the I² statistic (%) to determine the proportion of variation in outcomes attributable to heterogeneity, rather than chance. We will deem an I² statistic value of greater than 50% to reflect substantial heterogeneity. In addition, we will examine the overlap of effect estimates and CIs among individual studies, with poor overlap indicating heterogeneity.

Assessment of reporting biases

We will use funnel plots in RevMan (RevMan 2014) to examine signs of asymmetry to evaluate for publication bias when we include 10 or more studies in the meta-analysis. We will assess for potential selective outcome reporting as part of the 'Risk of bias' assessment.

Data synthesis

Our primary comparison for analysis will be any cyclodestructive procedure (cyclophotocoagulation (CPC), endocyclophotocoagulation (EPC), cryotherapy) versus standard glaucoma procedure (aqueous shunts, trabeculectomy). Secondary analyses will compare the relative effectiveness of cyclodestructive procedures.

When we do not detect any substantial heterogeneity, we will combine the results in a meta-analysis using a random-effects model. We will use a fixed-effect model when the number of studies that contribute outcome data to a meta-analysis is fewer than three. When clinical, methodological, and statistical (I² statistic value of greater than 50%) characteristics suggest substantial heterogeneity, we will present the results in a narrative summary and will not conduct a meta-analysis.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis will include comparisons between different types of procedures (CPC, EPC, cryotherapy), administration of procedures (non-contact versus contact), and underlying causes of glaucoma (open-angle, angle-closure, neovascular).

Sensitivity analysis

We will conduct sensitivity analyses to determine the impact of excluding studies with high risk of bias, industry funding, or without full-length reports.

'Summary of findings' table

We will follow the GRADE classification approach and use the effect estimate, measures of imprecision, indirectness, inconsistency, and risk of bias to grade the strength of evidence for each outcome (GRADEpro 2015). We will present the main outcomes in a 'Summary of findings' table when data are available.

Acknowledgements

We thank Lori Rosman, Trials Search Co-ordinator for Cochrane Eyes and Vision (CEV), who created the electronic search strategies.

We also acknowledge the CEV editorial team for their support and comments during protocol preparation. We thank Barbara Hawkins and Steve Mansberger for providing peer review comments to this protocol.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Glaucoma] explode all trees
#2 MeSH descriptor: [Intraocular Pressure] explode all trees
#3 MeSH descriptor: [Ocular Hypertension] explode all trees
#4 glaucom*
#5 (intra*ocular or ocular) near/3 (hypertension* or tension* or pressur*)
#6 IOP
#7 {or #1-#6}
#8 MeSH descriptor: [Lasers] explode all trees
#9 laser*
#10 MeSH descriptor: [Laser Coagulation] explode all trees
#11 MeSH descriptor: [Light Coagulation] explode all trees
#12 photocoagulat* or cyclocoagulat*
#13 coagulat* or argon* or diode*
#14 ND* YAG or Neodymium* YAG or ND*YAG or Neodymium*YAG or YAG*ND OR YAG*Neodymium
#15 cyclophotocoagulat* or cyclodestruct* or cycloablat* or endocyclophotocoagulat* or cryotherap*
#16 ciliary near/3 (destruct* or ablat
#17 MeSH descriptor: [Diathermy] explode all trees
#18 MeSH descriptor: [Electrolysis] explode all trees
#19 diatherm* or ultrasonic* or electrolys* or beta irradiat*
#20 {or #8-#19}
#21 #7 and #20

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.
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. exp glaucoma/
13. glaucom*.tw.
14. exp intraocular pressure/
15. ((intra?ocular or ocular) adj3 (hypertension* or tension* or pressur*)).tw.
16. Ocular Hypertension/
17. IOP.tw.
18. or/12-17
19. exp lasers/
20. laser*.tw.
21. laser coagulation/
22. exp Light Coagulation/
23. limit 22 to yr="1966 - 1992"
24. (photocoagulat* or cyclocoagulat*).tw.
25. (coagulat* or argon* or diode*).tw.
26. ((ND* adj1 YAG) or (Neodymium* adj1 YAG) or ND*YAG or Neodymium*YAG or YAG*ND or YAG*Neodymium).tw.
27. (cyclophotocoagulat* or cyclodestruct* or cycloablat* or endocyclophotocoagulat* or cryotherap*).tw.
28. (ciliary adj3 (destruct* or ablat*)).tw.
29. exp diathermy/
30. exp electrolysis/
31. (diatherm* or ultrasonic* or electrolys* or beta irradiat*).tw.
32. or/19-21,23-31
33. 18 and 32
34. 11 and 33

The search filter for trials at the beginning of the MEDLINE strategy is from Glanville 2006.

Appendix 3. EMBASE search strategy

#1 'randomized controlled trial'/exp
#2 'randomization'/exp
#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 'animal'/exp OR 'animal experiment'/exp
#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
#15 'placebo'/exp
#16 placebo*:ab,ti
#17 random*:ab,ti
#18 'experimental design'/exp
#19 'crossover procedure'/exp
#20 'control group'/exp
#21 'latin square design'/exp
#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 'evaluation'/exp
#27 'prospective study'/exp
#28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
#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'/exp
#34 'intraocular pressure'/exp
#35 'intraocular pressure abnormality'/de
#36 'ocular ischemic syndrome'/exp
#37 glaucom*:ab,ti
#38 ((intra*ocular OR ocular) NEAR/3 (hypertension* OR tension* OR pressur*)):ab,ti
#39 iop:ab,ti
#40 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39
#41 'lasers'/exp
#42 laser*:ab,ti
#43' laser coagulation'/exp
#44 photocoagulat*:ab,ti OR cyclocoagulat*:ab,ti
#45 coagulat*:ab,ti OR argon*:ab,ti OR diode*:ab,ti
#51 (nd* NEAR/1 yag):ab,ti OR (neodymium* NEAR/1 yag):ab,ti OR nd*yag:ab,ti OR neodymium*yag:ab,ti OR yag*nd:ab,ti OR yag*neodymium:ab,ti
#52 cyclophotocoagulat*:ab,ti OR cyclodestruct*:ab,ti OR cycloablat*:ab,ti OR endocyclophotocoagulat*:ab,ti OR cryotherap*:ab,ti
#53 ('ciliary body' NEAR/3 destruct*):ab,ti OR (ciliary NEAR/3 ablat*):ab,ti
#54 'diathermy'/exp
#55 'electrolysis'/exp
#56 diatherm*:ab,ti OR ultrasonic*:ab,ti OR electrolys*:ab,ti OR (beta NEXT/1 irradiat*):ab,ti
#57 #41 OR #42 OR #43 OR #44 OR #45 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56
#58 #40 AND #57
#59 #32 AND #58

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 glaucom*[tw]
#3 ((intraocular[tw] OR intracocular[tw] OR ocular[tw]) AND (hypertension*[tw] OR tension*[tw] OR pressur*[tw]))
#4 IOP[tw]
#5 #2 OR #3 OR #4
#6 laser*[tw]
#7 photocoagulat*[tw] OR cyclocoagulat*[tw]
#8 (coagulat*[tw] OR argon*[tw] OR diode*[tw])
#9 (ND YAG[tw] OR Neodymium YAG[tw] OR YAG ND[tw] OR YAG Neodymium[tw])
#10 (cyclophotocoagulat*[tw] OR cyclodestruct*[tw] OR cycloablat*[tw] OR endocyclophotocoagulat*[tw] cryotherap*[tw])
#11 ciliary[tw] AND (destruct*[tw] OR ablat*[tw])
#12 (diatherm*[tw] OR ultrasonic*[tw] OR electrolys*[tw] OR beta irradiat*[tw])
#13 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12
#14 #5 AND #13
#15 #1 AND #14
#16 Medline[sb]
#17 #15 NOT #16

Appendix 5. LILACS search strategy

(MH:C11.525$ OR glaucom$ OR MH:G14.440$ OR IOP OR (intraocular hypertension$) OR (intraocular tension$) OR (intraocular pressure$) OR (ocular hypertension$) OR (ocular tension$) OR (ocular pressure$)) AND (Laser$ 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$ OR MH:E02.520.745.410$ OR MH:E02.594.530$ OR MH:E04.014.520.530$ OR MH:E04.350.750.410$ OR MH:E04.540.630.410$ OR photocoagulat$ OR MH:E02.520.745$ OR MH:E04.350.750$ OR MH:E04.540.630$ OR Coagulat$ OR argon$ OR diode$ OR ND$YAG OR Neodymium$YAG OR Cyclophotocoagulat$ OR Cyclocoagulat$ OR cyclodestruct$ OR cycloablat$ OR endocyclophotocoagulat$ OR cryotherap$ OR Diatherm$ OR MH:E02.565.280$ OR MH:E02.779.496.280$ OR Electrolys$ OR MH:E05.301.250$ OR MH:SP4.011.097.057$ OR ultrasonic$ OR (ciliary destruct$) OR (ciliary ablat$) OR (beta irradiat$))

Appendix 6. ClinicalTrials.gov search strategy

(glaucoma OR hypertension OR intraocular pressure) AND (Laser OR cyclophotocoagulation OR cyclodestruction OR photocoagulation OR cryotherapy OR diathermy OR electrolysis OR cyclocoagulation OR coagulation OR argon OR diode OR ultrasonic)

(glaucoma OR hypertension OR intraocular pressure) AND (ciliary ablation OR ciliary destruction OR "beta irradiation")

Appendix 7. ICTRP search strategy

glaucoma AND laser OR glaucoma AND cyclophotocoagulation OR glaucoma AND cyclodestruction OR glaucoma AND photocoagulation OR glaucoma AND cryotherapy OR glaucoma AND diathermy OR glaucoma AND electrolysis OR glaucoma AND cyclocoagulation OR glaucoma AND coagulation OR glaucoma AND argon OR glaucoma AND diode OR glaucoma AND ultrasonic OR glaucoma AND ciliary ablation OR glaucoma AND ciliary destruction OR glaucoma AND beta irradiation OR hypertension AND laser OR hypertension AND cyclophotocoagulation OR hypertension AND cyclodestruction OR hypertension AND photocoagulation OR hypertension AND cryotherapy OR hypertension AND diathermy OR hypertension AND electrolysis OR hypertension AND cyclocoagulation OR hypertension AND coagulation OR hypertension AND argon OR hypertension AND diode OR hypertension AND ultrasonic OR hypertension AND ciliary ablation OR hypertension AND ciliary destruction OR hypertension AND beta irradiation OR intraocular pressure AND laser OR intraocular pressure AND cyclophotocoagulation OR intraocular pressure AND cyclodestruction OR intraocular pressure AND photocoagulation OR intraocular pressure AND cryotherapy OR intraocular pressure AND diathermy OR intraocular pressure AND electrolysis OR intraocular pressure AND cyclocoagulation OR intraocular pressure AND coagulation OR intraocular pressure AND argon OR intraocular pressure AND diode OR intraocular pressure AND ultrasonic intraocular pressure AND ciliary ablation OR intraocular pressure AND ciliary destruction OR intraocular pressure AND beta irradiation

Appendix 8. Data on study characteristics

Mandatory items Optional items
Methods
Study design
  • Parallel group RCT i.e. people randomized to treatment

  • Within-person RCT i.e. eyes randomized to treatment

  • Cluster RCT i.e. communities randomized to treatment

  • Cross-over RCT

  • Other, specify

Exclusions after randomization

Losses to follow-up

Number randomized/analyzed

How were missing data handled? e.g. available case analysis, imputation methods

Reported power calculation (Y/N), if yes, sample size and power

Unusual study design/issues

Eyes or unit of randomization/unit of analysis
  • One eye included in study, specify how the eye was selected

  • Two eyes included in study, both eyes received same treatment, briefly specify how analyzed (best/worst/average/both and adjusted for within person correlation/both and not adjusted for within person correlation) and specify if mixture one eye and two eye

  • Two eyes included in study, eyes received different treatments, specify if correct pair-matched analysis done

Participants
Country 

Setting

Ethnic group

Equivalence of baseline characteristics (Y/N)

Total number of participantsThis information should be collected for the total study population recruited into the study. If these data are only reported for the people who were followed up only, please indicate.
Number (%) of men and women
Average age and age range
Inclusion criteria 
Exclusion criteria 
Interventions

Intervention (N = )

Comparator (N = )

See MECIR 65 and 70

  • Number of people randomized to this group

  • Drug (or intervention) name

  • Dose

  • Frequency

  • Route of administration

 
Outcomes

Primary and secondary outcomes as defined in study reports

See MECIR R70

List outcomes

Adverse events reported (Y/N)

Length of follow-up and intervals at which outcomes assessed

Planned/actual length of follow-up

Contributions of authors

MC and AC conceived and designed the protocol. MC, CK, and AC wrote the protocol. All protocol authors approved the final protocol draft.

Declarations of interest

MC has no known conflicts of interest.
CK has no known conflicts of interest.
AC has no known conflicts of interest.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Methodological support provided by the Cochrane Eyes and Vision (CEV) US Project, supported by grant 1 U01 EY020522, National Eye Institute, National Institutes of Health, USA.

  • National Institute for Health Research (NIHR), UK.

    • Richard Wormald, Co-ordinating Editor for 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 protocol authors and not necessarily those of the NIHR, NHS, or the Department of Health.

Ancillary