Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma

Francisco Otarola<sup>a</sup>; Gianni Virgili<sup>a</sup>; Anupa Shah; Kuang Hu; Catey Bunce; Gus Gazzard

doi:10.1002/14651858.CD012740.pub2

Cochrane Database of Systematic Reviews

Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma

Information

DOI:

https://doi.org/10.1002/14651858.CD012740.pub2 Copy DOI

Database:

Cochrane Database of Systematic Reviews

Version published:

09 March 2020see what's new

Type:

Intervention

Stage:

Review

Cochrane Editorial Group:

Cochrane Eyes and Vision Group

Copyright:

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

Francisco Otarola^a

Correspondence to: Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK

[email protected]

Centro de la Visión, Clínica las Condes, Santiago, Chile

These authors contributed equally to this work
Gianni Virgili^a

Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy

These authors contributed equally to this work
Anupa Shah

Cochrane Eyes and Vision, ICEH, London School of Hygiene & Tropical Medicine, London, UK
Kuang Hu

Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
Catey Bunce

School of Population Health & Environmental Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
Gus Gazzard

Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK

Institute of Ophthalmology UCL & NIHR Biomedical Research Centre, London, UK

Contributions of authors

Francisco Otarola, Kuang Hu and Catey Bunce wrote the protocol. All authors reviewed and approved the protocol.

Francisco Otarola, Gianni Virgili, Anupa Shah, and Kuang Hu screened the search results, extracted the data from the included studies, and wrote the review. All authors reviewed and approved the review.

Sources of support

Internal sources

National Institute for Health Research (NIHR), UK.

CB acknowledges financial support for her CEV research sessions from the Department of Health through the award made by the NIHR to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology

GG acknowledges support for this research by the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.

External sources

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
- This review was supported by the NIHR, via Cochrane Infrastructure funding to the CEV UK editorial base
The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS, or the Department of Health.

Declarations of interest

FO has no conflict of interest to declare.
GV has no conflict of interest to declare.
AS has no conflict of interest to declare.
KH performs minimally‐invasive glaucoma surgery. He has lectured on 'Constructing clinical trials for MIGS ‐ the lack of evidence and what to do about it' at the Moorfields International Glaucoma Symposium 2016, sponsored by Laboratoires Thea, which is contributing an educational grant to Moorfields Eye Hospital.
CB has no conflict of interest to declare.
GG: In the last five years, GG has received travel funding, and his host organisation has received both educational and unrestricted research funding from pharmaceutical and equipment manufacturers that are involved in the treatment of glaucoma, but none that are otherwise related to (or competing with) the subject of this review.

Acknowledgements

Cochrane Eyes and Vision (CEV) created and executed the electronic search strategies. We thank Nitin Anand and Jennifer Evans for their comments on the published protocol that forms the template for this one (Hu 2016).

We thank the members of the MIGS Consortium for their input in this review.

Version history

Published

Title

Stage

Authors

Version

2020 Mar 09

Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma

Review

Francisco Otarola, Gianni Virgili, Anupa Shah, Kuang Hu, Catey Bunce, Gus Gazzard

https://doi.org/10.1002/14651858.CD012740.pub2

2017 Aug 03

Ab interno trabecular bypass surgery with Schlemm´s Canal Microstent (Hydrus) for open angle glaucoma

Protocol

Francisco Otarola, Kuang Hu, Gus Gazzard, Catey Bunce

https://doi.org/10.1002/14651858.CD012740

Differences between protocol and review

The follow‐up times for the outcomes were decided after the protocol was published.
Two additional co‐authors, A Shah and G Virgili joined the review team.
The protocol included combination therapy with phacoemulsification as a separate comparison, and also for subgroup analysis. After discussion within the review team and MIGS Consortium, we opted to include it as a separate comparison, as this is likely to be a different indication.
We changed the objectives and removed the restriction to the inclusion of participants with medically uncontrolled glaucoma; explanations are given in the text as appropriate.
We added the secondary outcome: rate of visual field progression (DB/time) or proportion of participants whose field loss progressed in the follow‐up period.
In the 'Summary of findings' table, intraoperative and postoperative complications were pooled as a single outcome.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICOs

Population

Intervention

Comparison

Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

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 study

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Figure 3

Forest plot of comparison: 1 Cataract surgery with Hydrus microstent vs. cataract surgery (CS) alone, outcome: 1.1 Proportion drop‐free: short term

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Figure 4

Forest plot of comparison: 1 Cataract surgery with Hydrus microstent vs cataract surgery (CS) alone, outcome: 1.2 Proportion drop‐free: medium term

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Figure 5

Forest plot of comparison: 1 Cataract surgery with Hydrus microstent vs cataract surgery (CS) alone, outcome: 1.4 Mean change in IOP‐lowering drops taken per day: medium term

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Figure 6

Forest plot of comparison: 1 Cataract surgery with Hydrus microstent vs cataract surgery (CS) alone, outcome: 1.3 Mean change in IOP measured using Goldmann applanation tonometry: medium term

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Analysis 1.1

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 1 Proportion drop‐free: short‐term (6 to 18 months).

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Analysis 1.2

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 2 Proportion drop‐free: medium‐term (18 to 36 months).

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Analysis 1.3

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 3 Mean change in IOP measured using Goldmann applanation tonometry: medium‐term (18 to 36 months).

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Analysis 1.4

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 4 Mean change in IOP‐lowering drops instilled per day: medium‐term (18 to 36 months).

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Analysis 1.5

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 5 Proportion of participants requiring additional glaucoma surgery or laser.

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Analysis 1.6

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 6 Adverse events: loss of 2+ VA lines.

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Analysis 1.7

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 7 Adverse events: IOP spike > 10 mmHg.

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Analysis 1.8

Comparison 1 Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone, Outcome 8 Adverse events: bleeding.

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Analysis 2.1

Comparison 2 Hydrus microstent vs iStent trabecular micro‐bypass stent, Outcome 1 Proportion drop‐free: short‐term (6 to 18 months).

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Analysis 2.2

Comparison 2 Hydrus microstent vs iStent trabecular micro‐bypass stent, Outcome 2 Mean change in IOP measured using Goldmann applanation tonometry: short‐term (6 to 18 months).

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Analysis 2.3

Comparison 2 Hydrus microstent vs iStent trabecular micro‐bypass stent, Outcome 3 Mean change in IOP‐lowering drops instilled per day: short‐term (6 to 18 months).

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Analysis 2.4

Comparison 2 Hydrus microstent vs iStent trabecular micro‐bypass stent, Outcome 4 Proportion of participants with IOP < 21 mmHg.

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Summary of findings for the main comparison. Cataract surgery with Hydrus microstent compared to cataract surgery alone

Cataract surgery with Hydrus microstent compared to cataract surgery alone
Patient or population: people with cataracts and open angle glaucoma, many of whom had mild or moderate glaucoma, which was well‐controlled with medication Setting: eye clinics with surgical facilities Intervention: Hydrus microstent (Hydrus) plus cataract surgery Comparison: cataract surgery alone
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with cataract surgery alone	Risk with cataract surgery with Hydrus
Proportion of participants who were medication‐free (not using eye drops) medium‐term follow‐up at 24 months	Study population		RR 1.63 (1.40 to 1.88)	619 (2 RCTs)	⊕⊕⊕⊝ Moderate^a
	480 per 1000	782 per 1000 (671 to 902)
Mean change in unmedicated IOP (after washout) measured using Goldmann applanation tonometry medium‐term follow‐up at 24 months	The mean change in unmedicated IOP in the cataract surgery group was ‐5.95 mmHg	The MD in the cataract surgery plus Hydrus group was 2 mmHg lower (2.69 lower to 1.31 lower)	‐	619 (2 RCTs)	⊕⊕⊕⊝ Moderate^a
Mean change in the number of IOP‐lowering drops instilled per day medium‐term follow‐up at 24 months	The mean change in the number of IOP‐lowering drops instilled per day in the cataract surgery group was ‐0.76 drops	The MD in the cataract surgery plus Hydrus group was 0.41 drops lower (0.56 lower to 0.27 lower)	‐	619 (2 RCTs)	⊕⊕⊝⊝ Low^a,b
Proportion of participants who required further glaucoma surgery, including laser	Study population		RR 0.17 (0.03 to 0.86)	619 (2 RCTs)	⊕⊕⊝⊝ Low ^a,c
	25 per 1000	4 per 1000 (1 to 22)
Visual field progression	No data available
Mean change in health‐related quality of life	No data available
Proportion of participants experiencing intraoperative or postoperative complications medium‐term follow‐up at 24 months	Intraoperative: device malposition (1.6%) or hyphaema obscuring the surgeons view (1.1%) only occurred with Hydrus implantation Postoperative: Intraocular bleeding, loss of 2 or more VA lines, and IOP spikes of 10 mmHg or more were rare in both groups. There were no cases of endophthalmitis in either group				⊕⊕⊝⊝ Low^a,c
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; IOP: intraocular pressure; MD: Mean difference; RR: Risk ratio; OR: Odds ratio; VA: visual acuity
GRADE Working Group grades of evidence High‐certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate‐certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low‐certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low‐certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aUnclear or high risk of bias for most domains (‐1 for risk of bias) ^bMean change in number of drops was calculated on about half of participants using 2 to 4 medications in HORIZON 2018 (‐1 for indirectness) ^cSmall number of events with imprecision (‐1 for imprecision)

Summary of findings for the main comparison. Cataract surgery with Hydrus microstent compared to cataract surgery alone

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Summary of findings 2. Hydrus microstent compared to iStent trabecular micro‐bypass stent

Hydrus microstent compared to iStent trabecular micro‐bypass stent
Patient or population: people with open angle glaucoma, many of whom had mild or moderate glaucoma, which was well‐controlled with medication Setting: eye clinics with surgical facilities Intervention: Hydrus microstent (Hydrus) Comparison: iStent trabecular micro‐bypass stent (iStent) (n.2)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with iStent	Risk with Hydrus
Proportion of participants who were medication‐free (not using eye drops) short‐term follow‐up at 12 months	Study population		RR 1.94 (1.21 to 3.11)	148 (1 RCT)	⊕⊕⊝⊝ Low^a,b
	240 per 1000	466 per 1000 (290 to 746)
Mean change in unmedicated IOP (after washout) measured using Goldmann applanation tonometry short‐term follow‐up at 12 months	The mean change in unmedicated IOP in the iStent group was ‐5.1 mmHg	The MD in the Hydrus group was 3.1 lower (4.17 lower to 2.03 lower)	‐	148 (1 RCT)	⊕⊕⊕⊝ Moderate^a
Mean change in number of IOP‐lowering drops instilled per day short‐term follow‐up at 12 months	The mean change in the number of IOP‐lowering drops instilled per day in the iStent group was 0	The MD in the Hydrus group was 0.6 lower (0.99 lower to 0.21 lower)	‐	148 (1 RCT)	⊕⊕⊝⊝ Low^a,b
Proportion of participants who required further glaucoma surgery, including laser	Study population		not analysed	148 (1 RCT)	⊕⊝⊝⊝ Very low^a,c
	0/74	2/76
Visual field progression	No data available
Mean change in health‐related quality of life	No data available
Proportion of participants experiencing intraoperative or postoperative complications short‐term follow‐up at 12 months	No intraoperative complications reported. Postoperative: no cases of intraocular bleeding or endophthalmitis in either group. Hydrus: 2/74 cases of VA loss of 2 or more lines, 3/74 IOP spikes > 10 mmHg iStent: 1/76 cases of VA loss of 2 or more lines, 4/76 IOP spikes > 10 mmHg		not analysed	148 (1 RCT)	⊕⊕⊝⊝ Low^a,d
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; IOP: intraocular pressure; MD: Mean difference; RR: Risk ratio; OR: Odds ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
^aUnmasked investigator ^bLarge confidence intervals ^cSparse data with no events in one study arm and only two events overall (‐2 for imprecision) ^dSmall number of events with imprecision (‐1 for imprecision)

Summary of findings 2. Hydrus microstent compared to iStent trabecular micro‐bypass stent

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Comparison 1. Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Proportion drop‐free: short‐term (6 to 18 months) Show forest plot	2	639	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [1.39, 1.83]

2 Proportion drop‐free: medium‐term (18 to 36 months) Show forest plot	2	619	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [1.40, 1.88]

3 Mean change in IOP measured using Goldmann applanation tonometry: medium‐term (18 to 36 months) Show forest plot	2	619	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐2.69, ‐1.31]

4 Mean change in IOP‐lowering drops instilled per day: medium‐term (18 to 36 months) Show forest plot	2	619	Mean Difference (IV, Fixed, 95% CI)	‐0.41 [‐0.56, ‐0.27]

5 Proportion of participants requiring additional glaucoma surgery or laser Show forest plot	2	653	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.03, 0.86]

6 Adverse events: loss of 2+ VA lines Show forest plot	2	653	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.14, 1.50]

7 Adverse events: IOP spike > 10 mmHg Show forest plot	2	653	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.12, 1.24]

8 Adverse events: bleeding Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 1. Cataract surgery + Hydrus microstent vs cataract surgery (CS) alone

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Comparison 2. Hydrus microstent vs iStent trabecular micro‐bypass stent

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Proportion drop‐free: short‐term (6 to 18 months) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Mean change in IOP measured using Goldmann applanation tonometry: short‐term (6 to 18 months) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 Mean change in IOP‐lowering drops instilled per day: short‐term (6 to 18 months) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4 Proportion of participants with IOP < 21 mmHg Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Hydrus microstent vs iStent trabecular micro‐bypass stent

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Ab interno trabecular bypass surgery with Schlemm´s canal microstent (Hydrus) for open angle glaucoma

Information