Clinical trial NCT02909140
Conditions: Cataract
Sponsor: Johns Hopkins University
Start date: 2016-09-01; Completion date: 2018-08-15
Enrollment: 3 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Obtaining appropriate mydriasis prior to cataract surgery is an important variable in successful surgery. The current practice includes using topical anticholinergic and sympathomimetic agents in the preoperative area prior to cataract surgery, but the pupils are sometimes insufficiently dilated and can often need additional mydriasis with intracameral agents during cataract surgery. Pre-operative topical mydriatic drops take time to take effect, are mildly uncomfortable for the patient, and have a cost to the healthcare system. If intracameral mydriasis alone can achieve adequate pupil dilation, perhaps topical mydriatics would not be needed. The purpose of this study is to evaluate whether topical versus intracameral versus topical + intracameral mydriasis is the optimal way to dilate pupils during routine cataract surgery. The results of this study have implications for improving the efficiency and reducing time prior to cataract surgery. In addition, it has significant potential to reduce the cost associated with cataract surgery if preoperative drops can be eliminated.

Detailed description:
Recent research has compared the use of intracameral and topical agents with the preoperative pupil size and cataract surgery success. Studies have compared topical mydriatics with intracameral lidocaine and found no significant difference in dilation. , Other studies have compared topical mydriatics with intracameral dilation that includes solutions with and without epinephrine in the irrigating solution and concluded that irrigating solutions without epinephrine can safely be used with intracameral mydriatics but epinephrine is useful when using topical mydriatics. There have also been studies comparing the success of longer acting drug inserts of mydriatic agents with the use of intracameral agents. In addition to these standard agents, different surgeons have used various formulations of topical and intracameral agents to perform mydriasis. As of yet, there is no formal, standardized method for mydriasis and no large prospective study comparing the outcomes of the various methods. Considerations such as cost and time spent on preoperative mydriatic agents in light of the amount of success seen with these agents calls into question the need for such agents. The investigators would like to study the amount of pupillary dilation seen with topical preoperative mydriatic agents compared to intracameral agents compared to the use of them both together.

This will be a prospective randomized controlled trial. Patients will be consented and enrolled at their pre-op visit. They will be randomized to topical drops alone, intracameral injection alone, or topical plus intracameral mydriasis. All patients will receive intracameral lidocaine, as this is used for its anesthetic effect but also has some mydriatic effect. The intervention will take place on the day of the operation. Patients will be followed until post-operative month #1.

Data will be gathered on 4 visits: pre-op clinic visit, day of operation, and post-operative day #1 and post-operative month #1. These are all standard visits for routine cataract surgery, and this study will not require the patient to make any extra visits. Enrollment will continue until the sample size is met.

Patients cannot be blinded to whether or not they receive topical mydriasis eyedrops, and no placebo drops are necessary because patients cannot voluntarily control their pupillary constriction, so no placebo effect would be expected. The surgeon cannot be blinded to whether or not the patient has received topical mydriasis eyedrops in the pre-op area because it will be evident based upon whether or not the patient's eye is dilated. Another researcher who was not present in the operating room will grade the photographs and measure the pupil size, and this researcher will be blinded to which intervention the patient received.

Currently, some surgeons use topical plus intracameral mydriasis for mydriasis during cataract surgery. It is hypothesized that intracameral mydriasis alone may be sufficient to adequately dilate the pupil for cataract surgery. Patients who are not adequately dilated at the time of pupil size measurement immediately before the capsulorrhexis step will subsequently receive additional pharmacologic mydriasis, visco-dilation, or iris expansion devices to dilate their pupil to a size that is adequate for their surgery. Therefore, no matter which group the patient is in, their pupil will be eventually dilated to a size that is adequate to proceed with surgery.

There is no placebo or non-treatment group, since all patients must be somehow dilated in order to undergo cataract surgery. The purpose of this study is to compare 3 methods of dilation.

The pupil size will be measured after the viscoelastic is injected and before the capsulorrhexis is performed. Treatment failure is defined as a pupil size that is clinically deemed too small to safely proceed with surgery (approximately less than 5 mm). At this point, a rescue intervention will be implemented with additional pharmacologic mydriasis, visco-dilation, or iris expansion devices, until the pupil is adequately dilated to proceed with surgery. These patients will still be included in the study, and their pupil size prior to the rescue intervention is still the primary outcome.

Participants can choose to stop participating in the study prior to receiving any of the mydriasis agents. Should they choose to withdraw from the study, they would end up receiving routine mydriasis with topical plus intracameral agents. The study ends on post-op month #1 for all individual patients. The study enrollment period will end when the sample size is met.

Arms: arm 1: Topical mydriasis will be with 1 drop of phenylephrine 2.5% and 1 drop of cyclopentolate 1% x 4 doses each, with each drop spaced 5 minutes apart given in the pre-op area. These are the standard dilating drops used for cataract surgery. These patients will also receive intracameral lidocaine 1% for anesthesia. arm 2: Intracameral mydriasis will be with 0.2ml to 0.3ml of epinephrine 1:10,000 injected into the anterior chamber at the beginning of the cataract surgery procedure. This is the standard concentration use for intracameral mydriasis in cataract surgery. These patients will also receive intracameral lidocaine 1% for anesthesia. arm 3: Topical mydriasis will be with 1 drop of phenylephrine 2.5% and 1 drop of cyclopentolate 1% x 4 doses each, with each drop spaced 5 minutes apart given in the pre-op area. These are the standard dilating drops used for cataract surgery. These patients will also receive intracameral lidocaine 1% for anesthesia. Intracameral mydriasis will be with 0.2ml to 0.3ml of epinephrine 1:10,000 injected into the anterior chamber at the beginning of the cataract surgery procedure. This is the standard concentration use for intracameral mydriasis in cataract surgery. These patients will also receive intracameral lidocaine 1% for anesthesia.
Interventions: intervention 1: Topical phenylephrine 2.5% intervention 2: Topical cyclopentolate 1% intervention 3: Intracameral Lidocaine 1% intervention 4: Intracameral 0.2- 0.3ml of epinephrine 1:10,000
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
NCT: 02909140 
PI: Fasika Woreta 
DATE: 04/12/17 
TITLE:  Optimal Method for Mydriasis in Cataract Surgery 


 
 
JHMIRB eFormA  01Version 3 Dated:   06/2007 
 
Page 1 of 6 
 
Date: ____04/12/2017________________    
Principal Investigator: _____F.Woreta__________ 
Application Number: __ IRB00091874_________ 
 
JHM IRB - eForm A – Protocol 
 
1. 
Abstract 
a. Provide no more than a one page research abstract briefly stating the problem, the research 
hypothesis, and the importance of the research. 
 
Obtaining appropriate mydriasis prior to cataract surgery is an important variable in successful 
surgery. The current practice includes using topical anticholinergic and sympathomimetic agents 
in the preoperative area prior to cataract surgery, but the pupils are sometimes insufficiently 
dilated and can often need additional mydriasis with intracameral agents during cataract surgery. 
Pre-operative topical mydriatic drops take time to take effect, are mildly uncomfortable for the 
patient, and have a cost to the healthcare system. If intracameral mydriasis alone can achieve 
adequate pupil dilation, perhaps topical mydriatics would not be needed. The purpose of this 
study is to evaluate whether topical versus intracameral versus topical + intracameral mydriasis  
is the optimal way to dilate pupils during routine cataract surgery. The results of this study have 
implications for improving the efficiency and reducing time prior to cataract surgery. In 
addition, it has significant potential to reduce the cost associated with cataract surgery if 
preoperative drops can be eliminated.   
 
2. 
Objectives  
 
To determine the optimal method of mydriasis for routine cataract surgery, comparing 
preoperative topical versus intracameral versus both, measured by pupil size just prior to 
capsulorrhexis.  
 
3. 
Background 
 
Recent research has compared the use of intracameral and topical agents with the preoperative 
pupil size and cataract surgery success. Studies have compared topical mydriatics with 
intracameral lidocaine and found no significant difference in dilation.1,2 Other studies have 
compared topical mydriatics with intracameral dilation that includes solutions with and without 
epinephrine in the irrigating solution and concluded that irrigating solutions without 
epinephrine can safely be used with intracameral mydriatics but epinephrine is useful when 
using topical mydriatics.3 There have also been studies comparing the success of longer acting 
drug inserts of mydriatic agents with the use of intracameral agents.4  In addition to these 
standard agents, different surgeons have used various formulations of topical and intracameral 
agents to perform mydriasis. 5 As of yet, there is no formal, standardized method for mydriasis 
and no large prospective study comparing the outcomes of the various methods. Considerations 
                                                          
1 Samarai V, HaghighiN, Sharifi N. Pupil dilation with intra-cameral lidocaine versus topical midriatics during 
phacoemulsification. Global Journal of Health Science  2014;6:8-12 
2 Lundberg B, Behndig A.  Intracameral mydriatics in phacoemulsification cataract surgery. JCRS 2003;29:2366-71   
3 Lundberg B, Behndig A.  Intracameral mydriatics in phacoemulsification surgery obviate the need for epinephrine 
irrigation. Acta Ophthalmol Scan 2007 Aug;85(5):546-50 
4 Morgado et al Comparative study of mydriasis in cataract surgery: topical versus Mydriasert versus intracameral 
mydriasis in cataract surgery. Eu J Ophthalmol 2010; 20 (6): 989-993 
5 MyersWG and Shugar JK.  Optimizing the intracameral dilation regimen for cataract surgery: prospective 
randomized comparison of 2 solutions. JCRS 2009;35:273-76 


 
 
JHMIRB eFormA  01Version 3 Dated:   06/2007 
 
Page 2 of 6 
 
such as cost and time spent on preoperative mydriatic agents in light of the amount of success 
seen with these agents calls into question the need for such agents. We would like to study the 
amount of pupillary dilation seen with topical preoperative mydriatic agents compared to 
intracameral agents compared to the use of them both together.  
 
 
4. 
Study Procedures 
a. Study design, including the sequence and timing of study procedures  
 
This will be a prospective randomized controlled trial. Patients will be consented and enrolled at 
their pre-op visit. They will be randomized to topical drops alone, intracameral injection alone, 
or topical plus intracameral mydriasis. All patients will receive intracameral lidocaine, as this is 
used for its anesthetic effect but also has some mydriatic effect. The intervention will take place 
on the day of the operation. Patients will be followed until post-operative month #1. This is 
timeline is identical to the routine standard of care for cataract surgery at the Wilmer Eye 
Institute.  
  
b. Study duration and number of study visits required of research participants. 
 
Data will be gathered on 4 visits: pre-op clinic visit, day of operation, and post-operative day #1 
and post-operative month #1. These are all standard visits for routine cataract surgery, and this 
study will not require the patient to make any extra visits. Enrollment will continue until the 
sample size is met.  
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. 
 
Patients cannot be blinded to whether or not they receive topical mydriasis eye drops, and no 
placebo drops are necessary because patients cannot voluntarily control their pupillary 
constriction, so no placebo effect would be expected. The surgeon cannot be blinded to whether 
or not the patient has received topical mydriasis eyedrops in the pre-op area because it will be 
evident based upon whether or not the patient’s eye is dilated. Another researcher who was not 
present in the operating room will grade the photographs and measure the pupil size, and this 
researcher will be blinded to which intervention the patient received.  
 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped. 
 
Currently, routine care for cataract surgeries includes topical plus intracameral mydriasis. It is 
hypothesized that intracameral mydriasis alone may be sufficient to adequately dilate the pupil 
for cataract surgery. Patients who are not adequately dilated at the time of pupil size 
measurement immediately before the capsulorrhexis step will subsequently receive additional 
pharmacologic mydriasis, visco-dilation, or iris expansion devices to dilate their pupil to a size 
that is adequate for their surgery. Therefore, no matter which group the patient is in, their pupil 
will be eventually dilated to a size that is adequate to proceed with surgery.  
 
e. Justification for inclusion of a placebo or non-treatment group. 
 
There is no placebo or non-treatment group, since all patients must be somehow dilated in order 
to undergo cataract surgery. The purpose of this study is to compare 3 methods of dilation.  
 
f. Definition of treatment failure or participant removal criteria. 


 
 
JHMIRB eFormA  01Version 3 Dated:   06/2007 
 
Page 3 of 6 
 
 
The pupil size will be measured after the viscoelastic is injected and before the capsulorrhexis is 
performed. Treatment failure is defined as a pupil size that is clinically deemed too small to 
safely proceed with surgery (approximately less than 5 mm). At this point, a rescue intervention 
will be implemented with additional pharmacologic mydriasis, visco-dilation, or iris expansion 
devices, until the pupil is adequately dilated to proceed with surgery. These patients will still be 
included in the study, and their pupil size prior to the rescue intervention is still the primary 
outcome.  
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely  
 
Participants can choose to stop participating in the study prior to receiving any of the mydriasis 
agents. Should they choose to withdraw from the study, they would end up receiving routine 
mydriasis with topical plus intracameral agents. The study ends on post-op month #1 for all 
individual patients. The study enrollment period will end when the sample size is met.  
 
5. 
Inclusion/Exclusion Criteria 
 
Inclusion criteria:  
Patients aged 40 or older who are undergoing routine cataract surgery under topical anesthesia 
with monitored anesthesia care at the Wilmer Eye Institute. 
 
Exclusion criteria:  
• Need for general anesthesia  
• Maximum pupillary dilation <6.0mm at the pre-op clinic visit.  
• Prior intra-ocular surgery   
• Prior trauma  
• Any pre-existing iris abnormalities including pupillary deformity, posterior synechiae, 
peripheral anterior synechiae, zonular dehiscence 
• Pseudoexfoliation  
• Allergy to any of the mydriasis agents 
• Pregnancy or breastfeeding  
 
6. 
Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used. 
 
Topical mydriasis will be with 1 drop of phenylephrine 2.5% and 1 drop of cyclopentolate 1% x 
4 doses each, with each drop spaced 5 minutes apart given in the pre-op area. These are the 
standard dilating drops used for cataract surgery. These patients will also receive intracameral 
lidocaine 1% for anesthesia.  
 
Intracameral mydriasis will be with 0.2ml to 0.3ml of epinephrine 1:10,000 injected into the 
anterior chamber at the beginning of the cataract surgery procedure. This is the standard 
concentration use for intracameral mydriasis in cataract surgery. These patients will also receive 
intracameral lidocaine 1% for anesthesia.  
 
b. Justification and safety information if FDA approved drugs will be administered for non-FDA 
approved indications or if doses or routes of administration or participant populations are 
changed. 
 


 
 
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Not applicable. The interventions are all standard FDA approved drugs used for cataract 
surgery.  
 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.  
 
Not applicable. The interventions are all standard FDA approved drugs used for cataract 
surgery.  
 
7. 
Study Statistics 
a. Primary outcome variable. 
 
Pupil size immediately prior to the capsulorrhexis step of cataract surgery. This will be recorded 
by digital photography and measured by a researcher who is masked to the intervention. 
 
b. Secondary outcome variables. 
Pupil size immediately after nuclear disassembly, immediately prior to IOL insertion, upon 
completion of case, and on post-operative day #1. 
Need for another mydriatic agent or iris expansion devices during the procedure.  
Phaco time and cumulative dispersed energy 
Total surgery time 
Blood pressure and heart rate in pre-operative area, upon entry into the room, and at the end of 
the operation. 
 
Other data which will be collected:  
DOB  
Gender 
Race 
Iris color 
Use of alpha blocker medication 
Type and severity of cataract  
Complications 
• Anterior capsule radialization  
• Posterior capsular tear  
• Dropped nucleus  
• Zonular weakness  
• Descemet’s tear  
• Iris prolapse  
 
      Patient Satisfaction Score from 1-10 
 
 
c. Statistical plan including sample size justification and interim data analysis. 
 
Based on select prior studies on topical versus intracameral mydriasis, the approximate amount 
of dilation and approximate size of the dilated pupil can be extrapolated to our study population.  
Lundqvist et al in 2014 reported that “the pupils dilated with topical mydriatics were 7.45 +/-
1.08 mm at the initiation of the procedure, compared with 7.16 +/- 0.85 mm for the intracameral 
mydriatics eyes 60 seconds after intracameral mydriatics injection (p = 0.056). We would expect 
the pupil size for pupils dilated with both topic and intracameral mydriatics to be approximately 
7.50mm +/- 1.00 mm. The effect size that we are aiming to detect in the size of the dilated pupil 
is 0.5mm. The alpha is 0.05 and the beta is 0.80.  
 


 
 
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In a one-way ANOVA study, sample sizes of 70, 70, and 70 are obtained from the 3 groups 
whose means are to be compared. The total sample of 210 subjects achieves 80% power to 
detect differences among the means versus the alternative of equal means using an F test with a 
0.05 significance level. The size of the variation in the means is represented by their standard 
deviation which is 0.22. The common standard deviation within a group is assumed to be 1.00. 
 
d. Early stopping rules. 
 
The patient will be removed from the study if they cannot undergo capsulorrhexis and proceed 
with cataract surgery. Patients with any complications during the surgery will still remain in the 
study.  
 
8. 
Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency. 
 
Risks of topical mydriasis include: hypertension, tachycardia, ocular discomfort  
 
Risks of intracameral mydriasis include: hypertension, tachycardia, ocular discomfort  
 
Since the current routine protocol for cataract surgery mydraisis involves both topical and 
intracameral mydriasis, patients participating in this study will not be subject to any increased 
risk.  
 
b. Steps taken to minimize the risks. 
 
Patients cardiovascular status will be monitored by anesthesia, and anti-hypertensives are given 
intraoperatively if needed.  
 
c. Plan for reporting unanticipated problems or study deviations. 
 
Unanticipated problems will be reported to Dr Woreta who will report immediately to the IRB.  
 
d. Legal risks such as the risks that would be associated with breach of confidentiality. 
 
There are no legal risks in this study. The data will be de-identified at the time of data entry and 
subjects will be assigned a subject ID number. The log of subject name to ID number will be 
stored on a password protected computer.   
 
e. Financial risks to the participants. 
 
There are no financial risks to the participants.  
 
9. 
Benefits 
a. 
Description of the probable benefits for the participant and for society. 
 
The patients in the intracameral alone group may be more comfortable because they will not 
require any eye drops in the pre-operative area. Due to the fact they are not receiving topical 
mydriatics, they may have less hypertension and tachycardia as intracameral administration of 
antibiotics is associated with less systemic absorption.  
 


 
 
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Current standard of practice is to bring the patients to the preoperative area 90-120 minutes 
before surgery so they have time to administer topical drops and achieve sufficient dilation.  
Thus for society, the results of this study have implications for improving the efficiency and  
reducing time prior to cataract surgery. In addition, it has significant potential to reduce the cost 
associated with cataract surgery if preoperative drops are eliminated.   
 
10. 
Payment and Remuneration 
a. 
Detail compensation for participants including possible total compensation, proposed bonus, 
and any proposed reductions or penalties for not completing the protocol. 
 
There will be no compensation for participants.  
 
11. 
Costs 
a. 
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them. 
 
There will be no additional costs beyond the usual standard of care.