Zhongshan angle-closure prevention (ZAP) study

ISRCTN	ISRCTN45213099
DOI	https://doi.org/10.1186/ISRCTN45213099
Protocol serial number	1
Sponsor	University College London (UK)
Funders	Fight for Sight UK, Sun Yat-sen University, Ministry of Education of the People's Republic of China, National Natural Science Foundation of China, Wilmer Eye Institute, The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center

Submission date: 16/01/2008
Registration date: 06/05/2008
Last edited: 30/05/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Current plain English summary as of 17/01/2022:
Background and study aims
Glaucoma is the leading cause of irreversible blindness. Primary angle closure glaucoma (PACG) is the more severe of the two major types of glaucoma. If you have healthy eyes, the fluid in your eye drains away through drainage channels. In some people the eye is shaped differently and the drainage area is very narrow (narrow drainage angles). Under certain circumstances the drain can completely close off, so your eye pressure increases, injuring your optic nerve and damaging your vision. This is considered an attack of angle closure glaucoma. Laser peripheral iridotomy (LPI) is the first-line treatment for PACG. LPI uses a laser beam to create a small hole in your iris, unblocking the drainage channels. LPI is also very effective at preventing symptoms developing in the unaffected eye of patients who have suffered the condition in the other eye. However, so far no conclusions can be drawn regarding the use of prophylactic (preventative) LPI in persons with narrow drainage angles and without any symptoms or signs of active glaucoma. To determine the case for performing prophylactic LPI for all people with narrow angles (1 in 5 Chinese women over the age of 60 fall into this category), it is important to identify how many people with narrow angles will eventually suffer acute symptoms or develop glaucoma. Equally, it is important to know if LPI will reduce this risk, and whether there is any significant adverse risk associated with early LPI treatment. This study aims to assess whether LPI is safe and effective at preventing the development of primary angle closure in high-risk angle-closure patients. The study also specifically aims to answer the question of whether there are any particular features that help to predict who will go on to develop angle closure.

Who can participate?
Guangzhou city residents aged 50 to 70 with narrow drainage angles.

What does the study involve?
The right and left eyes of each participant are randomly allocated to LPI treatment or current standard treatment only. Both treated and untreated eyes are examined on follow-up visits after 2 weeks, 6 months, 18 months, 36 months, 54 months and 72 months.

What are the possible benefits and risks of participating?
Participants will obtain regular and careful medical support from a qualified team of medical experts. There are no obvious risks in participating in this study.

Where is the study run from?
University College London (UK).

When is the study starting and how long is it expected to run for?
March 2008 to February 2017. Patient re-examination commencing 2022 (12+ year follow-up)

Who is funding the study?
1. Fight for Sight (UK)
2. Sun Yat-sen University (China)
3. Wilmer Eye Institute (USA).
4. Ministry of Education of the People's Republic of China (China)
5. National Natural Science Foundation of China (China)
6. The State Key Laboratory, Zhongshan Ophthalmic Center & SunYat-Sen University (China)

Who is the main contact?
1. Prof. Paul J Foster (p.foster@ucl.ac.uk)
2. Prof. Mingguang He (mingguang_he@yahoo.com)
3. Prof. David S Friedman (david_friedman@meei.harvard.edu)

Previous plain English summary:
Background and study aims
Glaucoma is the leading cause of irreversible blindness. Primary angle closure glaucoma (PACG) is the more severe of the two major types of glaucoma. If you have healthy eyes, the fluid in your eye drains away through drainage channels. In some people the eye is shaped differently and the drainage area is very narrow (narrow drainage angles). Under certain circumstances the drain can completely close off, so your eye pressure increases, injuring your optic nerve and damaging your vision. This is considered an attack of angle closure glaucoma. Laser peripheral iridotomy (LPI) is the first-line treatment for PACG. LPI uses a laser beam to create a small hole in your iris, unblocking the drainage channels. LPI is also very effective at preventing symptoms developing in the unaffected eye of patients who have suffered the condition in the other eye. However, so far no conclusions can be drawn regarding the use of prophylactic (preventative) LPI in persons with narrow drainage angles and without any symptoms or signs of active glaucoma. To determine the case for performing prophylactic LPI for all people with narrow angles (1 in 5 Chinese women over the age of 60 fall into this category), it is important to identify how many people with narrow angles will eventually suffer acute symptoms or develop glaucoma. Equally, it is important to know if LPI will reduce this risk, and whether there is any significant adverse risk associated with early LPI treatment. This study aims to assess whether LPI is safe and effective at preventing the development of primary angle closure in high-risk angle-closure patients. The study also specifically aims to answer the question of whether there are any particular features that help to predict who will go on to develop angle closure.

Who can participate?
Guangzhou city residents aged 50 to 70 with narrow drainage angles.

What does the study involve?
The right and left eyes of each participant are randomly allocated to LPI treatment or current standard treatment only. Both treated and untreated eyes are examined on follow-up visits after 2 weeks, 6 months, 18 months, 36 months, 54 months and 72 months.

What are the possible benefits and risks of participating?
Participants will obtain regular and careful medical support from a qualified team of medical experts. There are no obvious risks in participating in this study.

Where is the study run from?
University College London (UK).

When is the study starting and how long is it expected to run for?
March 2008 to February 2017

Who is funding the study?
1. Fight for Sight (UK)
2. Sun Yat-sen University (China)
3. Wilmer Eye Institute (USA).
4. Ministry of Education of the People's Republic of China (China)
5. National Natural Science Foundation of China (China)

Who is the main contact?
1. Prof. Paul J Foster (p.foster@ucl.ac.uk)
2. Prof. Mingguang He (mingguang_he@yahoo.com)
3. Prof. David S Friedman (david.friedman@jhu.edu)

Contact information

Dr Paul Foster
Scientific

University College London
Institute of Ophthalmology
11-43 Bath Street
London
EC1V 9EL
United Kingdom

Phone	+44 (0)20 7608 6899
Email	p.foster@ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Single-centre randomised controlled trial (not masked)
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised controlled trial of prevention of angle-closure glaucoma in China
Study acronym	ZAP
Study objectives	That laser iridotomy helps to prevent primary angle-closure (a major risk factor for glaucoma) in Chinese adults aged 50 years and older.
Ethics approval(s)	Current ethics approval as of 17/01/2022: 1. Ethical Review Board of Zhongshan Ophthalmic Centre (China), November 2002 2. London School of Hygiene and Tropical Medicine (UK), 17/03/2008, ref: 5267 Extension study: 1. Zhongshan Ophthalmic Centre (China), 28/01/2016, ref: Zhongshan Ophthalmic Center Medical Ethical Committee [2007] No.12 2. London School of Hygiene and Tropical Medicine (UK), 05/03/2011, ref: A240 5267 Extended Follow-up Study: Approved 01/11/2021, Zhongshan Ophthalmic Center Medical Ethical Committee (Zhongshan Ophthalmic Centre, China) Previous ethics approval: 1. Ethical Review Board of Zhongshan Ophthalmic Centre (China), November 2002 2. London School of Hygiene and Tropical Medicine (UK), 17/03/2008, ref: 5267 Extension study: 1. Zhongshan Ophthalmic Centre (China), 28/01/2016, ref: Zhongshan Ophthalmic Center Medical Ethical Committee [2007] No.12 2. London School of Hygiene and Tropical Medicine (UK), 05/03/2011, ref: A240 5267
Health condition(s) or problem(s) studied	Angle-closure glaucoma
Intervention	Current intervention as of 17/01/2022: The right and left eyes of each participant will be randomly allocated to the intervention treatment or no treatment (control). Intervention treatment: Laser peripheral iridotomy (LPI) by sequential argon then Nd:YAG laser. Duration of the laser treatment is about 5 minutes. Control: No intervention (current standard treatment only) Each participant will be examined at baseline, 2 weeks, 6, 18, 30 and 42 months. Each participant will be further examined at 54 and 72 months after LPI. Re-examination to assess visual function, supplementary surgery (i.e. cataract surgery), and to document any differences in risk factor profile for glaucomatous loss of vision (intraocular pressure, peripheral anterior synechiae) between treated and untreated eyes at 12+ from intervention. Previous intervention: The right and left eyes of each participant will be randomly allocated to the intervention treatment or no treatment (control). Intervention treatment: Laser peripheral iridotomy (LPI) by sequential argon then Nd:YAG laser. Duration of the laser treatment is about 5 minutes. Control: No intervention (current standard treatment only) Each participant will be examined at baseline, 2 weeks, 6, 18, 30 and 42 months. Added 20/09/2016: Each participant will be further examined at 54 and 72 months after LPI.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	The following will be assessed on each of the scheduled follow-up (6, 18, 30 and 42 months): 1. Raised intraocular pressure (either with or without symptoms). Intraocular pressure greater than 24 mmHg verified on two consecutive measurements on separate days. These patients will be further identified as having open, partially-closed or completely closed angles on dark room gonioscopy and anterior segment optical coherence tomography (AS-OCT). 2. Peripheral anterior synechiae 3. Glaucomatous optic neuropathy If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 6, 18, 30 or 42 months (end of the study). Added 20/09/2016: Outcomes will also be assessed at 54 and 72 months. If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 54 or 72 months (end of the study).
Key secondary outcome measure(s)	The following will be assessed on each of the scheduled follow-up (6, 18, 30 and 42 months): 1. Specular microscopy measures of corneal endothelial cell loss 2. Formation of lens opacity 3. Anterior segment optical coherence tomography measures (qualitative and quantitative) of ocular anterior segment anatomy 4. Digital iris photograph measures of iris 5. Ultrasound biomicroscopy measurements of ocular anterior segment anatomy If participants are felt to have met a failure criterion, we will re-assess (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 6, 18, 30 or 42 months (end of the study). Added 20/09/2016: Outcomes will also be assessed at 54 and 72 months. If participants are felt to have met a failure criterion, they are re-assessed (by examination with one of the senior investigators) within the next 2 weeks to confirm. The failure will then be classified as having occurred at 54 or 72 months (end of the study).
Completion date	28/02/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	50 Years
Sex	All
Target sample size at registration	1100
Key inclusion criteria	1. Anatomically narrow drainage angles in the anterior segment of the eye 2. No evidence of primary angle-closure (high pressure or peripheral anterior synechiae) 3. Aged greater than or equal to 50 years
Key exclusion criteria	1. Inability or unwillingness to give informed consent 2. Raised intraocular pressure, peripheral anterior synechiae or glaucomatous optic neuropathy 3. Previous intraocular surgery
Date of first enrolment	01/09/2008
Date of final enrolment	22/10/2010

Locations

Countries of recruitment

United Kingdom
England
Australia
China
United States of America

Study participating centres

UCL Institute of Ophthalmology & Moorfields Eye Hospital

11-43 Bath Street
London
EC1V 9EL
United Kingdom

Centre for Eye Research Australia (CERA)

Royal Victorian Eye and Ear Hospital
Peter Howson Wing
Level 7, 32 Gisborne Street
East Melbourne
Melbourne
3002
Australia

Massachusetts Eye and Ear Infirmary

243 Charles St
Boston
02114
United States of America

Zhongshan Ophthalmic Center

#54 Xian Lie South Road
State Key Laboratory of Ophthalmology
Clinical Research Center
Sun Yat-Sen University
Guangzhou
510080
China

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Current individual participant data (IPD) sharing statement as of 17/01/2022: The datasets generated and/or analysed during the current study are available from Prof. Paul Foster (p.foster@ucl.ac.uk), Prof Friedman (david_friedman@meei.harvard.edu), and Prof. Mingguang He (mingguang.he@unimelb.edu.au; mingguang_he@yahoo.com) on reasonable request. Previous individual participant data (IPD) sharing statement: The datasets generated and/or analysed during the current study are available from Prof. Paul Foster (p.foster@ucl.ac.uk) and Prof. Mingguang He (mingguang.he@unimelb.edu.au; mingguang_he@yahoo.com) on reasonable request.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Visual symptoms	01/07/2012		Yes	No
Results article	results	20/04/2019		Yes	No
Results article	Cataract progression	02/05/2022	03/05/2022	Yes	No
Results article	Iris volume change	26/05/2023	30/05/2023	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

30/05/2023: Publication reference added.
03/05/2022: Publication reference added.
17/01/2022: The following changes have been made:
1. The public title has been changed from "Zhongshan angle-closure prevention study" to "Zhongshan angle-closure prevention (ZAP) study".
2. The acronym has been changed from ZAAP to ZAP.
3. The ethics approval has been updated.
4. The intervention has been updated.
5. The trial participating centre "UCL Institute of Ophthalmology & Moorfields Eye Hospital", "Centre for Eye Research Australia (CERA)", "Massachusetts Eye and Ear Infirmary", and "Zhongshan Ophthalmic Center" have been added and the trial participating centre "University College London" has been removed.
6. The plain English summary has been updated.
7. The individual participant data (IPD) sharing statement has been updated.
8. The publication and dissemination plan has been updated.
9. The intention to publish date has been changed from 31/12/2017 to 13/03/2019.

10. The funder "The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center" has been added.
18/03/2019: Publication reference added.
20/09/2016: The overall trial end date was changed from 28/02/2011 to 28/02/2017.