A Single Center, Randomized and Controlled Clinical Study of Inverted Internal Limiting Membrane Insertion Combined With Air Tamponade in the Treatment of Macular Hole Retinal Detachment in High Myopia
Phase: NA
Conditions: Macular Holes, Retinal Detachment, High Myopia
Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

 
Version number: Version 2     Version date: April 2, 2017 
 
 
 
 
A Single Center, Randomized and Controlled Clinical Study of 
Inverted Internal Limiting Membrane Insertion Combined 
with Air Tamponade in the Treatment of Macular Hole Retinal 
Detachment in High Myopia   
 
Study Protocol 
 
Version number: 2.0 
Version date: April 2, 2017 
 
 
 
 
Principal Investigator: Fenghua Wang 
Department of Ophthalmology  
Shanghai General Hospital 
 
 
 

 
Version number: Version 2     Version date: April 2, 2017 
Summary 
1. Purpose  
To evaluate the surgical outcomes of inverted internal limiting membrane insertion combined 
with air tamponade in the treatment of macular hole retinal detachment (MHRD) in high myopia, 
and also to compare the treatment efficacy between different surgical approaches of MHRD.  
 
2. Design 
Design: a prospective, single-centered, randomized, controlled clinical trial 
 
3. Target 
Patients with high myopia complicated by macular hole associated-retinal detachment. 
 
4. Inclusion Criteria 
Inclusion Criteria 
1) Prior written informed consent should be obtained before any assessment is carried out; 
2) Participants are more than 18 years of age, and less than 75 years of age, male or female 
Chinese patients; 
3) Visual impairment is caused by macular hole associated with retinal detachment secondary 
to high myopia; 
4) Axial length ≥ 26mm, or the refractive error ≥ -6.0D 
 
5. Exclusion criteria 
Exclusion Criteria 
1) Failure to comply with research or follow-up procedures; 
2) Diabetes with uncontrolled blood glucose (defined as fasting plasma glucose more than 
7.0mmol/L or blood glucose more than 11.1mmol/ L 2 hours postprandial), and / or with diabetic 
retinopathy; 
3) Poor control of blood pressure in hypertensive patients (defined as blood 
pressure >150/95mmHg, including antihypertensive medication); 

 
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4) With surgical contraindication due to other local or systemic conditions at screening or 
baseline; 
5) With any active ocular or periocular infection or inflammation (e.g., blepharitis, 
conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at screening or baseline; 
6) With uncontrolled glaucoma at screening or baseline (IOP ≥ 30mmHg when receiving 
medical treatment or as judged by the researchers); 
7) With the presence of iris neovascularization or neovascular glaucoma at screening or baseline; 
8) With ocular diseases which may interfere the study results at screening or baseline, including 
severe vitreous hemorrhage, peripheral retinal hole, proliferative diabetic retinopathy, 
proliferative vitreoretinopathy (≥ Level C ), choroidal detachment; 
9) With other causes which may result in macular hole associated-retinal detachment at 
screening or baseline, except high myopia; 
10) Previously underwent scleral buckling surgery; 
11) With current or planned medication known to have toxic effects on the lens, retina or optic 
nerve, 
including 
hydroxychloroquine, 
chloroquine, 
hydroxychloroquine, 
tamoxifen, 
phenothiazine and ethambutol; 
12) With laboratory abnormalities, such as ALT, AST, TB, GGT, LDH, exceeded the normal 
limit by more than 2 times, and CREA or blood urea nitrogen exceeded 1.2 times the normal 
limit; 
13) With abnormal coagulation function (defined as more than normal prothrombin time for 3 
seconds or more, more than 1.5 of the international standard ratio (INR), activated partial 
thromboplastin time of 10 seconds or longer than the upper limit of normal time); 
14) Patients who participated in any clinical study of medication within 3 months prior to 
screening (excluding vitamins and minerals) 
 
6. Exit criteria 
Exit criteria 

 
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1) Due to adverse events, especially severe adverse events, the researchers consider 
withdrawal of patients based on concerns of safety and ethics; 
2) Drop out; 
3) The patients voluntarily withdraw the informed consent; 
4) Serious violation of the study protocol due to the subjects or investigators' reasons; 
    5) Other reasons that the researchers believe for quitting the study 
 
7. Treatment 
Group 1: The patients in Group 1 are treated by the surgical method of standard 3-port 23 gauge 
pars plana vitrectomy + internal limiting membrane peeling + air-fluid exchange + silicone oil 
infusion 
Group 2: The patients in Group 2 are treated by the surgical method of standard 3-port 23 gauge 
pars plana vitrectomy + internal limiting membrane peeling + inverted internal limiting membrane 
insertion + air-fluid exchange. 
  
8. Inspection and observation schedule 
     
Period 
    
Project 
Screen
ing 
period 
Randomiz
ation 
period 
Follow up period1 
Baseli
ne 
Treatment 
V
1 
V
2 
V
3 
V
4 
V
5 
V
6 
V
7 
Termina
tion 
Unsched
uled visit 
Visiting 
time 
-7~0d 
0d 
1
d 
1
w 
2
w 
4
w 
8
w 
12
w 
6
m 
12m 
— 
 
Informed 
consent 
× 
 
 
 
 
 
 
 
 
 
 
 Inclusion 
and 
exclusion 
criteria 
× 
×2 
 
 
 
 
 
 
 
 
 

 
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Demograp
hic data 
× 
 
 
 
 
 
 
 
 
 
 
Chief 
complaint 
and 
current 
medical 
history 
× 
 
 
 
 
 
 
 
 
 
 
Medical 
history 
× 
 
 
 
 
 
 
 
 
 
 
Previous 
surgery/ 
trauma 
history 
and ocular 
surgery 
history 
× 
 
 
 
 
 
 
 
 
 
 
Diagnosis 
× 
 
 
 
 
 
 
 
 
 
 
Vital signs 
3 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
General 
physical 
examinati
on 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Slit lamp 
examinati
on 4 
(binocular
) 
× 
 
 
 
 
 
 
 
 
 
 

 
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Slit lamp 
examinati
on 5 
(study 
eye) 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
ECG and 
chest 
radiograp
hy6 
× 
 
 
 
 
 
 
 
 
 
 
Laborator
y 
examinati
on 7 
× 
 
 
 
 
 
 
 
 
 
 
Auxiliary 
examinati
on8 
× 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Low 
vision 
quality of 
life 
questionn
aire 9 
× 
 
 
 
 
 
× 
× 
× 
× 
 
History 
change 
 
× 
 
 
 
 
 
 
 
 
 
Randomiz
ation 
 
× 
 
 
 
 
 
 
 
 
 
Surgical 
treatment 
 
× 
 
 
 
 
 
 
 
 
 

 
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Subject 
files 
× 
 
 
 
 
 
 
 
 
 
 
Adverse 
events 10 
 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Previous / 
combined 
medicatio
n 11 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
× 
Quit 
in 
advance 
 
 
× 
× 
× 
× 
× 
× 
× 
× 
 
Statistical 
summary 
of 
major 
endpoints 
 
 
 
 
 
 
 
 
× 
 
 
Summary 
of 
the 
study 
 
 
 
 
 
 
 
 
 
× 
 
Unschedul
ed visits 
 
 
 
 
 
 
 
 
 
 
× 
Research 
statistics 
summary 
 
 
 
 
 
 
 
 
 
× 
 
Remarks 
(1) Visit Window: Visit 2 to visit 6; each visit has a window period of ±3 days; visit 7 and end visit allow a 
window period of ±7 days. 
(2) If both the eyes meet the requirements in the screening, the eye with the poorer BCVA should be selected as the 
study eye, unless for medical reasons, the researchers believe that the other eye is more suitable for the research. 
The study eye will undergo surgical treatment according to the protocol. If the BCVA damage of the contralateral 
eye is caused by macular hole associated with retinal detachment secondary to high myopia, according to the 

 
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judgment of the researchers, the contralateral eye can also be recommended for surgical treatment. The 
contralateral eye was labeled as the contralateral eye for treatment. The treatment of bilateral eyes should not be 
performed on the same day. 
(3) Vital signs, including blood pressure, pulse, respiration, armpit temperature, should be measured after sitting 
for 5 minutes. 
(4) Slit lamp examination: Use “Slit Lamp Examination Form-I” (Attachment 1). Accept the examination results 
carried out before the informed consent signature during the same hospitalization. 
(5) Slit lamp examination: Use “Slit Lamp Examination Form-II” (Attachment 2). 
(6) ECG, chest radiography: Accept the examination results carried out before the informed consent signature 
during the same hospitalization. 
(7) Laboratory examination includes routine blood test, blood biochemistry, routine blood coagulation, hepatitis B 
quantification, HCV antibody, TPPA+RPR and HIV antibody. Accept the examination results carried out before the 
informed consent signature during the same hospitalization. 
(a) Routine blood test: white blood cell, neutrophil, lymphocyte, neutrophil ratio, lymphocyte ratio, red blood cell, 
hemoglobin, platelet. 
(b) Blood biochemistry: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate 
dehydrogenase, gamma glutamyltransferase, total bilirubin, direct bilirubin, total protein, albumin, urea, creatinine, 
uric acid, glucose, triglyceride, total cholesterol, potassium, sodium, chloride, calcium, phosphorus. 
(c) Routine blood coagulation: prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, 
prothrombin time -INR. 
(8) Auxiliary examinations:  
(a) Auxiliary examinations in the screening period include: BCVA OU, IOP OU, OCT of study eye, wide angle CP 
of study eye, the multifocal electroretinogram of study eye, microperimetry analysis of study eye, ocular axis 
measurement of study eye, B-scan ultrasound of study eye. Accept the examination results carried out before the 
informed consent signature during the same hospitalization. 
(b) Auxiliary examinations in V1 and 2 include: BCVA OU, IOP OU, OCT of study eye, wide angle CP of study 
ocular axial measurement of study eye; 
(c) Auxiliary examinations in V3 include: BCVA OU, IOP OU, OCT of study eye, wide angle CP of study eye, B-
scan ultrasound of study eye; 
(d) Auxiliary examinations in V4 include: BCVA OU, IOP OU, OCT of study eye, wide angle CP of study eye; 

 
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(e) Auxiliary examinations in V5, 6, 7, end visits, and unscheduled visits include: BCVA OU, IOP OU, OCT of 
study eye, wide angle CP of study eye, the multifocal electroretinogram of study eye, microperimetry analysis of 
study eye and B-scan ultrasound of study eye . 
(9) The low vision quality of life questionnaire: Subjects were asked to self-rate according to the low vision quality 
of life questionnaire (Attachment 3); 
(10) Adverse events: Adverse events were collected from the time the subjects sign informed consent until the end 
of the study. 
(11) Previous/ combined medication: Collect relevant information from the time the subjects sign informed 
consent until the end of the study, including all the medication used for the treatment of AE or SAE. 
 
9. Outcome Assessment 
1) Primary Outcome Assessment: 
Macular hole closure rate: Fundus examination combined with optical coherence tomography 
(OCT) are performed 3 months after surgery. 
2) Secondary Outcome Assessment: 
Best corrected visual acuity (LogMAR): 6 months after the surgery 
Reattachment rate of retinal detachment: Use fundus examination combined with B-scan 
ultrasound, optical coherence tomography (OCT) to observe the reattachment rate of retinal 
detachment within 12 months after the surgery.(The reattachment rate assessment is performed 12 
months after the first surgery among the patients with air tamponade. The reattachment rate 
assessment is performed 12 months after the first surgery among the patients with silicone oil 
tamponade, and the silicone oil removal is performed 6 months after the previous surgery.) 
Postoperative complication rate 
 
10. Adverse event 
(1) Adverse events (AE) refer to any adverse event that occurs during clinical studies, but do 
not necessarily have causal relationship with the surgery. 
Safety evaluation should be carried out from the signature of the informed consent until the 
end of the study, according to management requirements (Adverse events or serious adverse events 
should be reported). 
(2) Severe adverse events (SAE) refer to the occurrence of hospitalization, prolonged 

 
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hospitalization, disability, incapacity, life-threatening or death, congenital malformations during the 
clinical trials. 
(3) Record of adverse events 
During the study, all adverse events should be recorded. Records should include the name of 
AE (using the standard medical terminology), the date of AE occurrence and disappearance / 
stablization, severity, impact on the surgery, relationship with the surgery, treatment measures and 
outcomes. 
(4) Reports of serious adverse events 
If serious adverse events occur, researchers must fill in the report of serious adverse events. 
The report should be signed and dated, and be reported to the ethics committee within 24 hours. 
 
11. Target case load and sample size calculation  
Target case load: 38 
The study uses the superiority design. According to the references and the professional 
judgment, macular hole closure rate is 25% in the control group (group 1), while in the experimental 
group (group 2), macular hole closure rate is 65%. The significant level αis 0.05, and test 
performance (1- beta) is 0.80. The software of NCSS PASS 14 is used, and each group has 17 cases 
with the loss rate of 10%. The final sample size is 38. 
 
12. Randomization 
Stratified randomization is conducted according to the extent of retinal detachment [type 1 
(within the arcade area), type 2 (beyond the arcade area)]. The software of NCSS PASS 14 will be 
used. The study includes 2 groups. 
13. Masking method  
In this study, the third party independent evaluation method is used to evaluate the results of 
the study. The analyzer is in the masking state, and the patients and the surgeons are in the non-
masking state. 
14. Statistical data processing  
(1) Validity analysis: Descriptive statistical method is used to describe the research indicators. 
Univariate analysis of continuous variables is performed using ANOVA, and univariate analysis of 
categorical variables is performed using chi square test. The repeated measurement data are 

 
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analyzed by mixed effect model. The population of effectiveness analysis is the population of people 
with intention to be treated. 
(2) Safety analysis: The safety assessment of clinical parameters (including adverse events, 
laboratory tests, vital signs, etc.) will be carried out. Descriptive statistics method is adopted. The 
safety analysis of the population is the population of all groups received treatment. 
(3) Subgroup analysis: To determine whether the therapeutic effects of different subgroups are 
consistent, the component outcomes (and 95% confidence interval (CI)) are estimated for the major 
endpoints within the subgroup of the following categorical variables: 
The type of retinal detachment [type 1 (within the arcade area), type 2 (beyond the arcade area)] 
Gender (male and female) 
 
15. Study implementation period (Anticipated) 
April 7th, 2017 to April 6th, 2020 
 
16. Quality Control  
The researcher and laboratory personnel involved in this project must have the professional 
knowledge and experience required in the study protocol; 
The researchers and other staff involved in the study perform their duties, and strictly follow the 
clinical trial plan and adopt standard operating procedures to ensure the implementation of the 
quality control and quality assurance system; 
To ensure that the data is complete, accurate, authentic and reliable, all the relevant observation 
results and findings need to be verified in each phase of the clinical trials; 
The researchers and other staff who participated in the study have sufficient time and reliable 
sources of subjects for the study; 
For all examinations, examination room conditions must meet the requirements: clean, quiet, 
and no pollution; Pipeline arranged neatly; Safety management measures, emergency and first-aid 
facilities are all required; Instruments placed properly; Dustproof, shockproof, appropriate special 
ventilation and exhaust facilities are required; For the instruments sensitive with the change of 
temperature and humidity, there is a constant temperature and dehumidification device; The 
examination room responsible personnel with corresponding professional theory and practical 

 
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experience, can effectively organize, guide and carry out business, and be responsible for the study 
results; Different inspection instruments are operated by specially-assigned staff, and regular 
verification is required. 
The specimen involved in the study are collected by specially-assigned staff; 
The procedure is checked according to the standard operating procedures; 
When the study protocol needs to be modified, ethical committees should be convened 
according to standard operating procedures, and the functions of the ethics committee should be 
fully applied to ensure the interests of the subjects to be protected; 
Set up data files and keep all the original data according to the requirements of the scheme in 
chronological order for verification; 
The inspectors regularly check the related activities and documents, to evaluate whether the 
study is operated according to the study protocol, standard procedures and relevant laws and 
regulations, and whether the test data is recorded timely, truly, accurately and completely. The 
inspection should be carried out by personnel not involved in the study, and the audit report shall be 
written. Meetings should be held with relevant personnel to discuss the problems found in the audit. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Specific Study Protocol 
Overall objective 
To evaluate the surgical outcomes of inverted internal limiting membrane insertion combined 
with air tamponade in the treatment of macular hole retinal detachment (MHRD) in high myopia, 
and also to compare the treatment efficacy between different surgical approaches of MHRD. 
 
Main study contents 
This study uses a new surgical method (vitrectomy combined with inverted internal limiting 
membrane insertion) to evaluate its effect on the prognosis of macular hole retinal detachment 
secondary to high myopia. 
This study uses a new surgical method (intraocular sterilized air tamponade) to assess its effect 
on the prognosis of macular hole retinal detachment secondary to high myopia. 
This study compares this new type of surgery with the current commonly used surgery 
(vitrectomy combined with internal limiting membrane peeling + silicone oil infusion) on the 
prognosis of macular hole retinal detachment secondary to high myopia. 
 
Study protocol 
Title: 
A Single Center, Randomized and Controlled Clinical Study of Inverted Internal Limiting 
Membrane Insertion Combined with Air Tamponade in the Treatment of Macular Hole Retinal 
Detachment in High Myopia 
 
Key word: 
Surgical procedures, air tamponade, high myopia, macular hole retinal detachment 
 
Study design: 
Single center, randomized, controlled, interventional, prospective 
 

 
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Aim: 
The aim of this study is to evaluate the effectiveness and safety of different surgical procedures for 
patients with macular hole retinal detachment secondary to high myopia. 
 
Primary Outcome Measure: 
To evaluate the effectiveness of different surgical procedures by evaluating the following 
indicators: 
Macular hole closure rate: Fundus examination combined with optical coherence tomography 
(OCT) are performed 3 months after surgery. 
 
Secondary Outcome Measure: 
To evaluate the effectiveness and safety of different surgical procedures by evaluating the 
following indicators: 
Best corrected visual acuity (LogMAR): 6 months after the surgery 
Reattachment rate of retinal detachment: Use fundus examination combined with B-scan 
ultrasound, optical coherence tomography (OCT) to observe the reattachment rate of retinal 
detachment within 12 months after the operation.(The reattachment rate assessment is performed 
12 months after the first surgery among the patients with air tamponade. The reattachment rate 
assessment is performed 12 months after the first surgery among the patients with silicone oil 
tamponade, and the silicone oil removal is performed 6 months after the previous surgery.) 
Postoperative complication rate of ocular adverse events 
Postoperative complication rate of the non ocular adverse events 
Postoperative complication rate of severe adverse events 
 
 
Key inclusion criteria 
Prior written consent is required before any assessment. 
Study eye selection criteria: 
Age: ≥18 years old, ≤75 years old 

 
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Visual impairment is caused by macular hole associated with retinal detachment secondary to 
high myopia 
Axial length ≥ 26mm, or the refractive error ≥ -6.0D 
 
Key exclusion criteria 
Exclusion criteria for general medical history: 
Local or systemic surgical contraindications at screening or baseline 
For both eyes: 
With any ocular eye or periocular infection or inflammation (e.g., blepharitis, conjunctivitis, 
keratitis, scleritis, uveitis, endophthalmitis) at screening or baseline; 
With uncontrolled glaucoma at screening or baseline (IOP ≥ 30mmHg when receiving medical 
treatment or as judged by the researchers); 
With the presence of iris neovascularization or neovascular glaucoma at screening or baseline. 
For research eye: 
With ocular diseases which may interfere the study results at screening or baseline , including 
severe vitreous hemorrhage, peripheral retinal hole, proliferative diabetic retinopathy, proliferative 
vitreoretinopathy ( ≥ Level C ), choroidal detachment; 
With other causes which may result in macular hole associated-retinal detachment at screening 
or baseline, except high myopia; 
Previously underwent scleral buckling surgery. 
Exclusion criteria for past or current systemic drug use: 
With current or planned medication known to have toxic effects on the lens, retina or optic nerve, 
including hydroxychloroquine, chloroquine, hydroxychloroquine, tamoxifen, phenothiazine and 
ethambutol. 
 
Study design 
This study is a prospective, randomized, controlled study, involving multiple visits within 12 
months. The patients with macular hole retinal detachment secondary to hign myopia are randomly 

 
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divided into 2 treatment groups: 
Group 1: The patients in Group 1 are treated by the surgical method of standard 3-port 23 gauge 
pars plana vitrectomy + internal limiting membrane peeling + air-fluid exchange + silicone oil 
infusion 
Group 2: The patients in Group 2 are treated by the surgical method of standard 3-port 23 gauge 
pars plana vitrectomy + internal limiting membrane peeling + inverted internal limiting membrane 
insertion + air-fluid exchange 
 
Sample size calculation 
The study uses the superiority design. According to the references and the professional 
judgment, macular hole closure rate is 25% in the control group (group 1), while in the experimental 
group (group 2), macular hole closure rate is 65%. The significant level αis 0.05, and test 
performance (1- beta) is 0.80. The software of NCSS PASS 14 is used, and each group has 17 cases 
with the loss rate of 10%. The final sample size is 38. 
 
Grouping method 
Patients are assessed whether they meet the inclusion/exclusion criteria before inclusion. The 
clinical research center completes the compliance assessment form, preoperative consents and 
informed consent. Informed consent is a qualified standard, since it is agreed by the subjects to be 
selected, randomly assigned, and agreed to complete the regular follow-up after the surgery. 
1) Informed consent of the subjects 
In this study, researchers must explain the research purpose, process, possible profit and risk 
to the subjects (or the legal representative, or witnesses). Only when the subjects (or the legal 
representative, or witnesses) fully understand the study, and sign informed consent, can they be 
selected. 
The informed consent form should be signed by the subjects (or their legal representatives or 
witnesses) and the researcher who executed the informed consent procedure in two copies, each of 
which has one copy. 
2) Allocation of screening number of subjects 

 
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The subjects who signed the informed consent will be assigned to a screening number. The 
center will assign a number of 4 Arabia numbers to each subject, with individual uniqueness. Among 
them, the first number represents the clinical center number, and the second, third, fourth number is 
the ordinal number, which is assigned to each subject according to the chronological order of the 
informed consent agreement. The subjects name writing rules: When the name is consisted with two 
characters, fill in the first two letters of each phonetic alphabet; When the name is consisted with 
three characters, fill in the first letters of each phonetic alphabet and the second letter of the third 
phonetic alphabet; When the name is consisted with four characters, fill in the first letters of each 
phonetic alphabet; When the name is consisted with five or more than five characters, fill in the first 
letters of the first four phonetic alphabets. 
Randomized controlled clinical trial design is used in this study. 
Randomization: Stratified randomization is conducted according to the type of retinal 
detachment [type 1 (within the arcade area), type 2 (beyond the arcade area)]. The software of NCSS 
PASS 14 will be used. The study includes 2 treatment groups. 
 According to randomization procedures, the researchers assign ID numbers to patients. The 
ID number of the randomization group must be recorded together with the patient screening number 
in a random directory. Completed random directory should be signed and hand over to the data 
center by the researcher.  
     
Masking method  
In this study, the third party independent evaluation method is used to evaluate the results of 
the study. The analyzer is in the masking state, and the subjects and the surgeons are in the non-
masking state. 
 
Outcome evaluation 
1) Primary Outcome Measures: 
To evaluate the effectiveness of different surgical procedures by evaluating the following 

 
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indicators: 
The difference between macular hole closure rate, closed type in each group from baseline to 
the 3rd month 
2) Secondary Outcome Measures: 
To evaluate the effectiveness and safety of different surgical procedures by evaluating the 
following indicators: 
The difference of the reattachment rate of retinal detachment between each group from baseline 
to the 6th month 
The difference of the reattachment rate of retinal detachment between each group from baseline 
to the 12th month 
The change of BCVA relative to baseline and the difference between groups from baseline to 
the 6th month 
The change of BCVA relative to baseline and the difference between groups from baseline to 
the 12th month 
The number of people whose BCVA result improves by more than 1 row, 2 rows and 3 rows 
comparing to the baseline at a time. 
The number of people whose BCVA result decreases by 3 rows comparing to the baseline at a 
time  
The difference of multifocal ERG results between each group from 1 week to the 6th month 
after surgery 
The difference of multifocal ERG results between each group from 1 week to the 12th month 
after surgery 
The change of microperimetry analysis results from 1 week to the 6th month after surgery 
relative to baseline, and the difference between each group 
The change of microperimetry analysis results from 1 week to the 12th month after surgery 
relative to baseline, and the difference between each group 
The change of the extent of foveal ellipsoid zone damage from baseline to the 6th month after 
the surgery relative to baseline, and the difference between each group 
The change of the external limiting membrane integrity of fovea from baseline to the 6th month 
after the surgery relative to baseline, and the difference between each group 

 
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The change of the extent of foveal ellipsoid zone damage from baseline to the 12th month after 
the surgery relative to baseline, and the difference between each group 
The change of the external limiting membrane integrity of fovea from baseline to the 12th 
month after the surgery relative to baseline, and the difference between each group 
Describe the number of retreatment and retreatment modalities for patients with different 
surgical procedures over a period of 12 months 
Evaluate the safety of different surgical procedures by assessing the type, frequency and 
severity of ocular adverse events and non-ocular adverse events or severe adverse events during 12 
months 
 
Data analysis 
(1) Validity analysis: Descriptive statistical method is used to describe the research indicators. 
Univariate analysis of continuous variables is performed using ANOVA, and univariate analysis of 
categorical variables is performed using chi square test. The repeated measurement data are 
analyzed by mixed effect model. The population of effectiveness analysis is the population of people 
with intention to be treated. 
(2) Safety analysis: The safety assessment of clinical parameters (including adverse events, 
laboratory tests, vital signs, etc.) will be carried out. Descriptive statistics method is adopted. The 
safety analysis of the population is the population of all groups received treatment. 
(3) Subgroup analysis: To determine whether the therapeutic effects of different subgroups are 
consistent, the component outcomes (and 95% confidence interval (CI)) are estimated for the major 
endpoints within the subgroup of the following categorical variables: 
The type of retinal detachment [type 1 (within the arcade area), type 2 (beyond the arcade area)] 
Gender (male and female) 
 
CRC assistance 
The study requires one to two clinical research coordinator (CRC) 
Responsiblities: 

 
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(1) Contact the subjects before 3-7 days before a follow-up; 
(2) Communicate with the director in advance, and make appointments for patient follow-ups; 
(3) Arrange the relevant examination for the patients; 
(4) Have good communication skills; 
(5) Fill in Case Report Form. 
 
Benefit status of subjects 
The therapy in this study may help to further control the patient's condition, to optimize the 
treatment of the disease, to provide the necessary advice for the future treatment of patients, to 
provide useful information for treatment or disease; 
If the subjects quit the study, the doctors will still perform the related examinations and 
treatments to ensure the safety of the subjects. 
 
Risk supervision 
The principal investigator and researchers should make full use of the informed consent when 
asking the patient to participate in the clinical trial. They should confirm that the patients fully 
understand its content, participate in this study based on the their free will, and sign the informed 
consent. The principal investigator, researchers and participants should sign on the informed consent 
form respectively. 
During the implementation process of the clinical trials, if serious adverse events (including 
the events such as the occurrence of hospitalization, prolonged hospitalization, disability, incapacity, 
life-threatenning or death, congenital malformation during the process of the clinical trial) occur, 
the events must be promptly reported to the center of clinical trials and the principal investigator. 
When the subjects suffer any health impairment caused by the study, researchers undertake the 
cost of treatment and the corresponding economic compensation for clinical trial-related injury or 
death, except the impairment caused by medical accidents. 

 
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Research schedule 
Time 
Schedule 
2017.4~2018.3 
Enroll patients, observe patients, collect clinical data, complete 
international clinical trial registration (clinicaltrial.gov), and complete 
midterm summary of patients who completed the first year visit  
2018.4~2019.3 
Follow patients up and collect clinical data  
2019.4~2020.4 
Complete the visit of all patients, complete the analysis of clinical data, 
subject summary, and prepare acceptance. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Technology Roadmap 
 

 
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Attachment 1  
Slit Lamp Examination Form (right eye)-I 
Whether to have slit lamp examination (right eye)?: 1□Yes→Please record as follows, 0□No 
Other lesions of 
eyelid 
0□No 
1□Yes, Please describe: _________________________________ 
1. Conjunctiva (right eye) 
Congestion 
0□Normal. It may appear white or reddish pink, without peripheral congestion. 
The conjunctival or bulbar conjunctival vessels are easily 
observed 
1□Slight redness, reddish color, mainly confined to the palpebral conjunctiva 
or bulbar conjunctiva 
2□Mild redness, reddish color, mainly confined to the conjunctiva or bulbar 
conjunctiva 
3□Moderate, palpebral conjunctiva or bulbar conjunctiva is bright red 
4□Severe, palpebral conjunctiva or bulbar conjunctiva is deep diffuse bright 
red 
Edema 
0□Normal, no swelling 
1□Slight, beyond normal and regional 
2□Mild, mild conjunctival swelling, beyond normal, regional 
3□Moderate, conjunctival swelling moderately 
4□Severe, large conjunctival swelling 
Subconjunctival 
hemorrhage 
0□Nil, no bleeding 
1□Slight, flat and less than 1 quadrant 
2□Mild, bulging, and 1 quadrant, or flat and more than 1 quadrants 
3□Moderate, bulging and >1 quadrant, but less than 2 quadrants 
4□Severe, bulging and more than 2 quadrants 

 
Version number: Version 2     Version date: April 2, 2017 
Other 
conjunctival 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
2. Cornea (right eye) 
Edema 
0□Nil, transparent and clear 
1□Slight, micro and local epithelial haze 
2□Mild, turbid vitreous appearance and may contain tiny droplets 
3□Moderate, turbid vitreous appearance with a large number of vacuoles 
4□Severe, bullous and / or stromal edema, localized or diffuse, with or without 
matrix streaks 
Other 
corneal 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
 
Slit Lamp Examination Form (right eye)-I 
3. Anterior chamber (right eye) 
Cell number 
0□Nil, no cells 
1□Slight, 1-5 cells  
2□Mild, 6-25 cells 
3□Moderate, 26-50 cells 
4□Severe, the number of cells is too large to count 
Anterior chamber flare 
0□Nil, no Tyndall effect 
1□Slight, almost cannot distinguish the Tyndall effect 
2□Mild, slight brightness 
3□Moderate, strong brightness 
4□Severe, very strong and aqueous humor is white or milky 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
4. Iris / pupil (right eye) 
Iris / pupil (right eye) 
Clinically significant abnormality: 0□No1□Yes, Please describe: 

 
Version number: Version 2     Version date: April 2, 2017 
_____________ 
5. Lens (right eye) 
Lens (right eye) 
1□Complete 
2□Artificial 
3□Nil 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Transparency 
Cortex  
0□Nil 
1□There are turbidity, but below standard pictures 
 
2□There are turbidity, and the severity of the standard picture is the 
same or more serious 
 
3□Not applicable 
Nucleus 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
Posterior capsule 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
 
Slit Lamp Examination Form (right eye)-I 
6. Vitreum (right eye) 

 
Version number: Version 2     Version date: April 2, 2017 
Anterior vitreous cell 
count 
0□Nil, no cells 
1□Slight, 1-10 cells  
2□Mild, 11-30 cells 
3□Moderate, 30-50 cells 
4□Severe, >50 cells 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Vitreous 
/ 
anterior 
retinal hemorrhage 
0□Nil 
1□Slight 
2□Mild 
3□Moderate 
4□Severe 
7. Macular and retina (right eye) 
Macular hole 
0□Nil 
1□Hole diameter≤1/3PD 
2□Hole diameter>1/3PD, and≤1/2PD 
3□Hole diameter>1/2PD, and≤1PD 
4□Hole diameter>1PD 
Retinal detachment 
0□Nil 
1□Yes, Please describe: 
1□Within the arcade 
2□Beyond the arcade, and within the equator 
3□Beyond the equator 
Peripheral retinal split 
holes 
0□No 
1□Yes, Please describe: _________________________________ 
Posterior 
scleral 
staphyloma 
0□No 
1□Yes, Please describe: _________________________________ 
Other lesions 
0□No 
1□Yes, 
Please 
describe 
with 
words 
or 
pictures: 

 
Version number: Version 2     Version date: April 2, 2017 
_________________________________ 
 
Attachment 1  
Slit Lamp Examination Form (left eye)-I 
Whether to have slit lamp examination (left eye)?: 1□Yes→Please record as follows, 0□No 
Other lesions of 
eyelid 
0□No 
1□Yes, Please describe: _________________________________ 
1. Conjunctiva (right eye) 
Congestion 
0□Normal. It may appear white or reddish pink, without peripheral congestion. 
The conjunctival or bulbar conjunctival vessels are easily 
observed 
1□Slight redness, reddish color, mainly confined to the palpebral conjunctiva 
or bulbar conjunctiva 
2□Mild redness, reddish color, mainly confined to the conjunctiva or bulbar 
conjunctiva 
3□Moderate, palpebral conjunctiva or bulbar conjunctiva is bright red 
4□Severe, palpebral conjunctiva or bulbar conjunctiva is deep diffuse bright 
red 
Edema 
0□Normal, no swelling 
1□Slight, beyond normal and regional 
2□Mild, mild conjunctival swelling, beyond normal, regional 
3□Moderate, conjunctival swelling moderately 
4□Severe, large conjunctival swelling 
Subconjunctival 
hemorrhage 
0□Nil, no bleeding 
1□Slight, flat and less than 1 quadrant 
2□Mild, bulging, and 1 quadrant, or flat and more than 1 quadrants 
3□Moderate, bulging and >1 quadrant, but less than 2 quadrants 

 
Version number: Version 2     Version date: April 2, 2017 
4□Severe, bulging and more than 2 quadrants 
Other 
conjunctival 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
2. Cornea (left eye) 
Edema 
0□Nil, transparent and clear 
1□Slight, micro and local epithelial haze 
2□Mild, turbid vitreous appearance and may contain tiny droplets 
3□Moderate, turbid vitreous appearance with a large number of vacuoles 
4□Severe, bullous and / or stromal edema, localized or diffuse, with or without 
matrix streaks 
Other 
corneal 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
 
Slit Lamp Examination Form (left eye)-I 
3. Anterior chamber (left eye) 
Cell number 
0□Nil, no cells 
1□Slight, 1-5 cells  
2□Mild, 6-25 cells 
3□Moderate, 26-50 cells 
4□Severe, the number of cells is too large to count 
Anterior chamber flare 
0□Nil, no Tyndall effect 
1□Slight, almost cannot distinguish the Tyndall effect 
2□Mild, slight brightness 
3□Moderate, strong brightness 
4□Severe, very strong and aqueous humor is white or milky 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
4. Iris / pupil (left eye) 

 
Version number: Version 2     Version date: April 2, 2017 
Iris / pupil (right eye) 
Clinically significant abnormality: 0□No1□Yes, Please describe: 
_____________ 
5. Lens (left eye) 
Lens (right eye) 
1□Complete 
2□Artificial 
3□Nil 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Transparency 
Cortex  
0□Nil 
1□There are turbidity, but below standard pictures 
 
2□There are turbidity, and the severity of the standard picture is the 
same or more serious 
 
3□Not applicable 
Nucleus 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
Posterior capsule 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
 
Slit Lamp Examination Form (left eye)-I 

 
Version number: Version 2     Version date: April 2, 2017 
6. Vitreum (left eye) 
Anterior vitreous cell 
count 
0□Nil, no cells 
1□Slight, 1-10 cells  
2□Mild, 11-30 cells 
3□Moderate, 30-50 cells 
4□Severe, >50 cells 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Vitreous 
/ 
anterior 
retinal hemorrhage 
0□Nil 
1□Slight 
2□Mild 
3□Moderate 
4□Severe 
7. Macular and retina (left eye) 
Macular hole 
0□Nil 
1□Hole diameter≤1/3PD 
2□Hole diameter>1/3PD, and≤1/2PD 
3□Hole diameter>1/2PD, and≤1PD 
4□Hole diameter>1PD 
Retinal detachment 
0□Nil 
1□Yes, Please describe:  
1□Within the arcade 
2□Beyond the arcade, and within the equator 
3□Beyond the equator 
Peripheral retinal split 
holes 
0□No 
1□Yes, Please describe: _________________________________ 
Posterior 
scleral 
staphyloma 
0□No 
1□Yes, Please describe: _________________________________ 

 
Version number: Version 2     Version date: April 2, 2017 
Other lesions 
0□No 
1□Yes, 
Please 
describe 
with 
words 
or 
pictures: 
_________________________________ 
 
Attachment 2  
Slit Lamp Examination Form (study eye)-II 
Whether to have slit lamp examination (study eye)?: 1□Yes→Please record as follows, 0□No 
Other lesions of 
eyelid 
0□No 
1□Yes, Please describe: _________________________________ 
1. Conjunctiva (study eye) 
Congestion 
0□Normal. It may appear white or reddish pink, without peripheral congestion. 
The conjunctival or bulbar conjunctival vessels are easily 
observed 
1□Slight redness, reddish color, mainly confined to the palpebral conjunctiva 
or bulbar conjunctiva 
2□Mild redness, reddish color, mainly confined to the conjunctiva or bulbar 
conjunctiva 
3□Moderate, palpebral conjunctiva or bulbar conjunctiva is bright red 
4□Severe, palpebral conjunctiva or bulbar conjunctiva is deep diffuse bright 
red 
Edema 
0□Normal, no swelling 
1□Slight, beyond normal and regional 
2□Mild, mild conjunctival swelling, beyond normal, regional 
3□Moderate, conjunctival swelling moderately 
4□Severe, large conjunctival swelling 
Subconjunctival 
hemorrhage 
0□Nil, no bleeding 
1□Slight, flat and less than 1 quadrant 
2□Mild, bulging, and 1 quadrant, or flat and more than 1 quadrants 

 
Version number: Version 2     Version date: April 2, 2017 
3□Moderate, bulging and >1 quadrant, but less than 2 quadrants 
4□Severe, bulging and more than 2 quadrants 
Other 
conjunctival 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
2. Cornea (study eye) 
Edema 
0□Nil, transparent and clear 
1□Slight, micro and local epithelial haze 
2□Mild, turbid vitreous appearance and may contain tiny droplets 
3□Moderate, turbid vitreous appearance with a large number of vacuoles 
4□Severe, bullous and / or stromal edema, localized or diffuse, with or without 
matrix streaks 
Other 
corneal 
lesions 
0□No 
1□Yes, Please describe: _________________________________ 
 
Slit Lamp Examination Form (study eye)-II 
3. Anterior chamber (study eye) 
Cell number 
0□Nil, no cells 
1□Slight, 1-5 cells  
2□Mild, 6-25 cells 
3□Moderate, 26-50 cells 
4□Severe, the number of cells is too large to count 
Anterior chamber flare 
0□Nil, no Tyndall effect 
1□Slight, almost cannot distinguish the Tyndall effect 
2□Mild, slight brightness 
3□Moderate, strong brightness 
4□Severe, very strong and aqueous humor is white or milky 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 

 
Version number: Version 2     Version date: April 2, 2017 
4. Iris / pupil (study eye) 
Iris / pupil (study eye) 
Clinically significant abnormality: 0□No1□Yes, Please describe: 
_____________ 
5. Lens (studyeye) 
Lens (study eye) 
1□Complete 
2□Artificial 
3□Nil 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Transparency 
Cortex  
0□Nil 
1□There are turbidity, but below standard pictures 
 
2□There are turbidity, and the severity of the standard picture is the 
same or more serious 
 
3□Not applicable 
Nucleus 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
Posterior capsule 
0□Nil 
1□Turbid, but below standard pictures 
 
2□Turbid, the same or more serious than standard pictures 
 
3□Not applicable 
 
Slit Lamp Examination (study eye)-II 

 
Version number: Version 2     Version date: April 2, 2017 
6. Vitreum (study eye) 
Anterior vitreous cell 
count 
0□Nil, no cells 
1□Slight, 1-10 cells  
2□Mild, 11-30 cells 
3□Moderate, 30-50 cells 
4□Severe, >50 cells 
Other lesions 
0□No 
1□Yes, Please describe: _________________________________ 
Vitreous 
/ 
anterior 
retinal hemorrhage 
0□Nil 
1□Slight 
2□Mild 
3□Moderate 
4□Severe 
Air volume in vitreous 
cavity 
0□Nil 
1□≤30% 
2□>30%, and≤50% 
3□>50%, and≤70% 
4□>70% 
5□Not applicable 
Silicone oil volume in 
vitreous cavity 
0□Nil 
1□>50%, and≤70% 
2□>70%, and≤90% 
3□>90% 
4□Not applicable 
7. Macular and retina (research eye) 
Macular hole 
0□Nil 
1□Hole diameter≤1/3PD 
2□Hole diameter>1/3PD, and≤1/2PD 
3□Hole diameter>1/2PD, and≤1PD 

 
Version number: Version 2     Version date: April 2, 2017 
4□Hole diameter>1PD 
Retinal detachment 
0□Nil 
1□Yes, Please describe:  
1□Within the arcade 
2□beyond the arcade, and within the equator 
3□Beyond the equator 
Peripheral retinal split 
holes 
0□No 
1□Yes, Please describe: _________________________________ 
Posterior 
scleral 
staphyloma 
0□No 
1□Yes, Please describe: _________________________________ 
Other lesions 
0□No 
1□Yes, 
Please 
describe 
with 
words 
or 
pictures: 
_________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Version number: Version 2     Version date: April 2, 2017 
 
 
 
 
Attachment 3 
Low vision quality of life questionnaire 
5=Nil; 4-2=Moderate; 1=Severe; x=Unable to do. 
How well do you know about your current vision? 5=Much, 1=Little 
1. Because of your vision, in the following circumstances, do you feel difficult?. 
1. Feel tired (for example, only after a short time using eyes) 
□5 □4 □3 □2 □1□x □Others 
2. At home at night 
□5 □4 □3 □2 □1□x □Others 
3. Look at things in the right amount of light 
□5 □4 □3 □2 □1□x □Others 
4. Feel the light glare (such as car lamp or sun make you dazzle) 
□5 □4 □3 □2 □1□x □Others 
5. Look at road signs 
□5 □4 □3 □2 □1□x □Others 
6. Watch TV (or enjoy pictures) 
□5 □4 □3 □2 □1□x □Others 
7. Look at moving objects (such as cars on the road) 
□5 □4 □3 □2 □1□x □Others 
8. Determine the distance or depth of objects  
□5 □4 □3 □2 □1□x □Others 
9. See the stairs or railings 
□5 □4 □3 □2 □1□x □Others 
10. Walk outdoors (e.g., on an uneven sidewalk) 
□5 □4 □3 □2 □1□x □Others 
11. Cross the street when there is vehicles 
□5 □4 □3 □2 □1□x □Others 
12. Generally speaking 
□5 □4 □3 □2 □1□x □Others 
2. Because of your vision, so you 
1. Not satisfied with your current life 
□5 □4 □3 □2 □1□x □Others 
2. Be upset about not being able to do some work 
□5 □4 □3 □2 □1□x □Others 
3. Visiting relatives and friends is limited 
□5 □4 □3 □2 □1□x □Others 
4..How well do you know about your current vision 
□5 □4 □3 □2 □1□x □Others 
3. If you use visual aids or glasses, if there are difficulties when doing the following things 
1.Identify uppercase fonts  
□5 □4 □3 □2 □1□x □Others 
2. Read newspaper articles and books 
□5 □4 □3 □2 □1□x □Others 
3. Read labels (for example, on a bottle or kit) 
□5 □4 □3 □2 □1□x □Others 
4. Reading letters 
□5 □4 □3 □2 □1□x □Others 

 
Version number: Version 2     Version date: April 2, 2017 
5. Use some tools (such as sutures or scissors) 
□5 □4 □3 □2 □1□x □Others 
4. If you use visual aids or glasses, if there are difficulties when doing the following things 
1. Watch the clock to know the time 
□5 □4 □3 □2 □1□x □Others 
2. Sign or write cards 
□5 □4 □3 □2 □1□x □Others 
3. Identify your own handwriting 
□5 □4 □3 □2 □1□x □Others 
4. Do daily activities (such as housework) 
□5 □4 □3 □2 □1□x □Others 
 
 
 
 
 
 
Attachment 4 
Abbreviations 
Abbreviations and special terms 
Explanation 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BCVA 
Best corrected visual acuity 
CREA 
Serum creatinine 
Wide angle CP 
Wide angle fundus color photography 
GGT 
Glutamyl transferase 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
LDH 
Lactate dehydrogenase 
LogMAR visual acuity 
Standard logarithmic visual acuity 
MHRD 
Macular hole complicated with retinal detachment 
INR 
International normalized ratio 
IOP 
Intraocular pressure 
OCT 
Optical coherence tomography 

 
Version number: Version 2     Version date: April 2, 2017 
OD 
Right eye 
OS 
Left eye 
OU 
Both eyes 
PDR 
Proliferative diabetic retinopathy 
PVR 
Proliferative vitreoretinopathy 
TB 
Total bilirubin 
TPPA+RPR 
Treponema 
pallidum 
antibody 
gelatin 
particle 
agglutination test + syphilis serum test 
VA 
Vision acuity