The Impact of Physiologic Cataract Surgery on Patient Comfort and Medication Usage
Phase: NA
Conditions: Cataract and IOL Surgery, Cataract Surgery Anesthesia, Cataract Surgery Experience, Nuclear Cataract
Sponsor: Matthew Rauen

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Protocol: The Impact of Physiologic Cataract Surgery on Patient Comfort and Medication Usage 
IIT 98621123 - Matthew Rauen, MD 
DATE: 10-03-2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol: The Impact of Physiologic Cataract Surgery on Patient Comfort and Medication Usage 
IIT 98621123 - Matthew Rauen, MD 
 
 
 
NEED The advanced fluidics of Unity VCS/CS allow a more physiologic cataract surgery environment.  Limited research 
exists comparing the surgical experience for patients between Unity VCS/CS and Centurion with regards to patient comfort 
and pain. 
STUDY OBJECTIVE To investigate the impact of Unity VCS/CS with Intelligent Fluidics at a low IOP setting and Centurion 
with Active Sentry at a traditionally high IOP setting on the intraoperative experience for the patient and surgeon 
STUDY HYPOTHESIS Unity VCS/CS with Intelligent Fluidics during cataract surgery will result in significantly less 
discomfort/pain as assessed by the decreased need for rescue medication and lower VAS scores. 
SUPPORTS CLINICAL MESSAGE Unity VCS/CS allows for phacoemulsification at a more physiologic IOP with lower patient 
reported discomfort/pain and less pharmacologic use as compared to Centurion with Active Sentry at a traditionally higher 
intraoperative IOP 
STUDY DESIGN 
Cohort 
Bilateral 
visually 
significant 
cataract 
surgery 
 
Endpoints 
Primary endpoint: % of pts in each group requiring rescue medication 
for breakthrough discomfort/pain  
Secondary endpoints:  
• 
Discomfort/pain score at phaco, I/A, visco removal 
• 
Surgeon Experience: Assessment on cooperation & experience  
• 
Cost-analysis on intraoperative medications utilized in low and high 
IOP groups 
• 
Breakthrough pain and discomfort/pain score on subjects with axial 
length of >24.5mm 
• 
Post op day 1 patient survey on experience (Iowa Satisfaction with 
Anesthesia Scale (ISAS)  
• 
Post op day 1 survey on patient preference - What eye was more 
comfortable? (R/L) 
• 
What surgical experience did you enjoy more? (R/L) 
• 
x% of eyes would undergo the same procedure again  
• 
x% of eyes would recommend the procedure to family and friends 
• 
Time Interval between Surgery Completion and Discharge from 
Facility  
• 
Physiologic responses by masked anesthesiologist: BP, pulse rate 
Alcon Product 
Unity VCS/CS 
with 
Intelligent 
Fluidics 
 
Design 
Prospective, single-surgeon, eyes undergoing phacoemulsification will 
be randomized to low (IOP 25mmHg) or high (IOP 65mmHg) IOP, 
contralateral eye will receive other treatment 
 
Comparator 
Centurion 
with Active 
Sentry (AS) 
 
Time of 
follow-up 
POD1 
SAMPLE SIZE 
85 subjects (170 eyes) 
STUDY DURATION (Contract execution to CSR) 
13 Months 

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Introduction:   
The study will pertain to investigating the impact of high vs low IOP on the intraoperative experience 
and comfort for the patient and surgeon. Our hypothesis is that operating at a more physiological IOP 
using Unity VCS/CS and Centurion with Active Sentry at a higher, or more traditional IOP will result in 
significantly less discomfort/pain as assessed by the decreased need for rescue medication and lower 
VAS scores. 
 
Background:   
Although topical anesthesia provides for high patient comfort during cataract surgery, certain parts of 
the cataract procedure are associated with more patient discomfort.  To further increase patient 
comfort while undergoing cataract surgery under topical anesthesia, it was proposed to add 
intracameral lidocaine.1 Injection of intraocular lidocaine increases patient cooperation and decreases 
the degree to which patients are bothered by tissue manipulation, two outcomes that justify its use.2 
 
It is plausible that the use of intracameral lidocaine became ‘routine care’ in an era where surgeons 
strived for more efficient cataract surgery through altering fluidics by increasing vacuum level, flow rate, 
and infusion pressure.  The desire for increased efficiency also led to the addition of a variety of 
other pharmacological agents, such as sympathomimetic agents, other analgesics, NSAIDs, opioids, etc.3 
 
Despite technological and procedural advances in ophthalmic surgery, the prescription rate for opioids 
after ophthalmic procedures, including cataract surgery, has been paradoxically increasing4 
 
In Scarfone et al., the patient's subjective perception of pain was significantly lower for the low 
intraoperative pressure group (IOP 30 mmHg) as compared to high IOP group (80 mmHg) according to 
the Wong Baker faces scale5 
 
In Rauen et al., lower intraoperative pressures at the time of cataract surgery were associated with less 
pain by real-time VAS scoring and less medication usage.6 
 
The PI has completed thousands of cataract surgeries with physiologic (low) IOP (intraocular pressure) 
and standard (high) IOP (intraocular pressure). A previous study completed at our facility showed 
equivalent visual outcomes between the two conditions at day 1, 7, 30, and 90. Additionally, case time 
did not differ between the two conditions.  A preliminary study completed by the PI suggested 
physiologic (low) IOP surgery was more comfortable by Visual Analogue Scale (VAS).  Furthermore, in 
this same pilot study, physiologic (low) IOP surgery led to less narcotic and less anxiolytic medication 
use. While we recognize that high IOP surgery is standard of care, more physiologic (low) IOP surgery 
again has been proven safe and may be more comfortable.   
 
Objective/ Unmet Medical Need:  
To investigate the impact of Unity VCS/CS with Intelligent Fluidics at a low IOP setting and Centurion 
with Active Sentry at a traditionally high IOP setting on the intraoperative experience for the patient and 
surgeon. Limited research on phacoemulsification at near physiological IOP and its impact on patient 
discomfort/pain using the Unity VCS/CS system. 
 
 
 
 

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Design:  
Prospective, single-surgeon, eyes undergoing phacoemulsification will be randomized to high (IOP 
65mmHg) or low (IOP 25mmHg) IOP, contralateral eye will receive other treatment. 
Study treatment & Methods: 
 
Sequential cataract surgery with similar cataract grade 2-3+ based on LOCS III grading bilaterally; 
2nd eye to be completed within 2-3 weeks of first eye  
 
Randomize first eye to low vs high IOP, contralateral eye receives opposite IOP  
 
Patient education on VAS with standard script  
 
Standard pre-op drops: 2 drops of cyclopentolate 1%, tropicamide 1%, flurbiprofen sodium 
(Ocufen 0.03%), phenylephrine hydrochloride 2.5%, and 3 drops of marcaine 0.05%  
 
After draping, patients receive OcuCoat on cornea and 3 drops of lidocaine, 1mg of Versed 
(midazolam for anxiety with no analgesic effects)  
 
If patients experienced breakthrough pain during surgery, additional topical anesthetic, 
intracameral lidocaine, and/or opioid will be used per surgeon discretion and stage recorded  
 
Physiological responses recorded: Anesthesiologist will monitor patients per standard of care 
but will record additional BP/HR values at the start of the case (room entry), 4 minutes after 
versed is administered, during phacoemulsification, and during viscoelastic removal.    
 
Technique and Intraoperative recordings:  
o Single surgeon, uniform corneal incision construction (size, architecture) and use of 
Intrepid coaxial polymer I/A curved, Alcon OVD-Duovisc; Horizontal phaco-chop 
technique with preestablished, standardized, and optimized fluidic parameters   
o VAS score is asked at beginning of: phaco, cortex infusion /aspiration, viscoelastic 
removal  
o Surgeon assessment on patient cooperation and overall experience   
o Recording of intraoperative phacoemulsification metrics to ensure comparable 
parameters to eliminate variables other than IOP that may contribute to physiological 
changes  
o CDE, ASM activation, total aspiration time 
Key Assessments:  
Percent of patients in each group requiring treatment for breakthrough discomfort/pain 
Discomfort/pain score at phaco, I/A, visco removal (Real time VAS scoring) 
o VAS score : 0 – no pain, 10 – unbearable pain 
o VAS scored after each stage with false positive and false negative controls that are 
utilized to disqualify subjects out of study  
o False positive: visco injection/capsulorhexis - should not experience pain   
o False negative: drape removal – should experience pain/pressure (alert enough to 
participate)   
Physiologic Responses associated with pain/inflammation: Blood pressure, Pulse rate 
Surgeon Experience: Assessment on patient cooperation & surgeon intraoperative experience. Surgeon 
assessment on patient cooperation:  poor, good, excellent: 
o 1- Poor cooperation:  could not follow instructions, lid squeezing, patient had frequent 
eye & head movements 
o 2- Good cooperation: able to follow directions 50% of the time, some lid squeezing and 
patient movement 3- Excellent cooperation: able to follow directions >80% of the time 
with limited lid squeezing and patient movement 
Surgeon assessment on overall experience: poor, good, excellent 

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o 1- Poor: fluctuating chamber (reverse pupillary block or surge) and reduced 
efficiency (nucleus & cortex removal) 
o 2- Good: >75% chamber stability and adequate efficiency  
o 3- Excellent: Minimal to no fluctuating chamber and excellent efficiency  
Cost-analysis on intraoperative pharmacological agents utilized between high vs low IOP 
Sub-analysis on subjects with axial length >24.5mm 
Time Interval between Surgery Completion and Discharge from Facility to evaluate post-op efficiency 
and recovery time of patients 
 
Follow up- Patient Surveys: 
o Post op day 1 patient survey on experience (Iowa Satisfaction with Anesthesia Scale 
(ISAS) 
o Post op day 1 survey on patient preference - What eye was more comfortable? 
(R/L)What surgical experience did you enjoy more? (R/L) 
o x% of eyes would undergo the same procedure again  
o x% of eyes would recommend the procedure to family and friends 
 
Primary Endpoint: 
• 
Post op day 1 patient survey on experience (Iowa Satisfaction with Anesthesia Scale (ISAS)  
• 
Post op day 1 survey on patient preference - What eye was more comfortable? (R/L) 
• 
What surgical experience did you enjoy more? (R/L) 
• 
x% of eyes would undergo the same procedure again  
• 
x% of eyes would recommend the procedure to family and friends 
• 
Physiologic responses by masked anesthesiologist: BP, pulse rate 
• 
Time Interval between Surgery Completion and Discharge from Facility  
 
 
Study Procedures:  
Duration of study will be approximately 13 months. At the time of their initial evaluation, consent 
process will include regular discussion and informed consent for cataract surgery. Risks, benefits, and 
alternatives to cataract surgery will be discussed. Patients who meet inclusion criteria will be offered 
additional discussion regarding the study. This discussion will include the elective nature of the study 
and detailed discussion of the informed consent document provided by surgeon (with study 
coordinators readily available). In addition, a copy of the informed consent document will be provided 
to the patient for their review.  
 
Study Rationale: 
The study will involve MAC (Monitored Anesthesia Care) for all patients; this is used for all cataract 
surgeries in our center.  This style of anesthesia includes baseline topical anesthetic drops 
(Marcaine) placed in pre-op, anesthesiologist administering baseline anxiolytic medication (Midazolam) 
in the operating room, and just prior to initiating surgery surgeon administers lidocaine. With all cases in 
our facility, both the surgeon and anesthesiologist monitor for comfort, cooperation, and need for 
% of pts in each group requiring rescue medication for breakthrough discomfort/pain
 
Secondary endpoints:  
• 
Discomfort/pain score at phaco, I/A, visco removal 
• 
Surgeon Experience: Assessment on cooperation & experience  
• 
Cost-analysis on intraoperative medications utilized in high vs low IOP groups 
• 
Breakthrough pain and discomfort/pain score on subjects with axial length of >24.5mm 

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additional anxiolytic or analgesia. The goal of MAC anesthesia is to provide comfort. While we strive for 
a pleasant experience for our patients, this is not general anesthesia, and there is a desire for patients to 
have the ability to follow commands. While some patients have some element of amnesia with this form 
of anesthesia, not all do. Participation in the study will not prevent surgeon or anesthesia professionals 
from adding additional anesthesia throughout the case if required for comfort or cooperation.  
 
Subject Selection:  
Subjects who will require bilateral cataract surgery will be considered. Evaluations will occur in the clinic 
of the Principal Investigator (PI) Matthew Rauen, MD at the Wolfe Eye Clinic.  
Inclusion Criteria: 
 
Visually significant cataract 2-3+ undergoing uncomplicated cataract surgery with similar 
cataract grade in both eyes  
 
Unremarkable ocular health but inclusive of early AMD  
 
Exclusion Criteria:  
 
H/o ocular surgery including corneal refractive surgery  
 
Compromised zonular integrity or stability  
 
Uncontrolled diabetes and diabetic retinopathy   
 
Small pupils   
 
H/o systemic inflammatory disease/uveitis  
 
H/o chronic pain medications (including narcotics) and benzodiazepine usage  
 
Abnormal liver or renal function  
Study Cost/Reimbursement: 
 
Participation in this study will be of no additional cost to patients. Insurance will partake in the 
payment of study evaluation and standard cataract surgery. The additional data monitoring 
needed will be provided at no cost to patients and incurred by the Sponsor. 
 
At the completion of the study patients who have completed the study in its entirety will be 
mailed a check for $150.00.  
 
Planned Data Analysis:  
The following analysis will be performed using STATA software (v16.1, College Station, TX). All 
continuous variables will be summarized using mean, standard deviation and standard error. All binary 
measures will be summarized as proportions with standard deviation. The results of the test for 
normality on each continuous measure (the Shapiro-Wilk test) will determine whether the paired t-test 
or the Wilcoxan Sign Rank test will be used. McNemar’s test will be used to compare proportions in 
binary outcome data, and the chi-squared test will be used to analyze the categorical outcome. 
 The analysis will follow a hierarchical approach using the following order of testing, only proceeding to 
the next test if the prior test achieves statistical significance at a level of 0.05.  
 Primary endpoint: comparing low vs. high IOP groups 
1. Proportion of patients requiring rescue medication for breakthrough pain 
 Secondary Endpoints: comparing low vs. high IOP groups 
1. Discomfort/pain score (VAS) - CONTINUOUS 
a. Phacoemulsification 
b. I/A 
c. Visco removal 

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2. Surgeon Experience - CONTINUOUS 
a. Patient cooperation 
b. Surgeon experience  
3. Cost analysis of intraoperative medications used - CONTINUOUS 
4. Discomfort/pain score (VAS) on subjects with axial length of >24.5mm - CONTINUOUS 
a. Phacoemulsification 
b. I/A 
c. Visco removal 
5. Post op day 1 patient survey on experience (Iowa Satisfaction with Anesthesia Scale (ISAS) - 
CONTINUOUS 
6. Proportion of patients following each procedure who would undergo the same procedure again 
- BINARY 
7. Proportion of patients following each procedure who would recommend the procedure to 
family and friends - BINARY 
8. Time Interval between Surgery Completion and Discharge from Facility - CONTINUOUS 
9. Post op day 1 survey on patient preference - Which eye was more comfortable? (R/L/Neither) - 
CATEGORICAL  
10. Which surgical experience did you enjoy more? (R/L/Neither) – CATEGORICAL 
11. Proportion of patients who experience a significant (as defined by Crandall[1]) physiologic 
response by a masked anesthesiologist - BINARY 
a. Change in diastolic BP from baseline 
b. Change in systolic BP from baseline 
c. Change in pulse rate from baseline 
 
Sample Size Justification 
Assuming a power of 80%, a significance level of 0.05, and a two-tailed testing strategy, and assuming 
15% of patients in the high IOP group compared with 0% of patients in the low IOP group will require 
break-through medication (Rauen, prepublication), a sample size of 58 pairs and 116 eyes is needed to 
detect a difference. Accounting for 15% attrition, a sample size of 67 patients is recommended. If the 
site accounts for that correlation in the sample size calculation, the recommended sample size is 85 
patients, 170 eyes.   
 
Data Collection and Management:  
Study worksheets will be created before data collection. At the conclusion of each week, all completed 
patients will have data collected transferred to a password protected excel spreadsheet.  There will be 
no names placed into this document – only medical record numbers will be used for identification. To 
facilitate data entry, the worksheets coincide with excel. The design of the data entry screens will follow 
the same flow as the provided worksheets to ensure minimal issues during data entry. All worksheets 
collected for study (anesthesia and surgeon) will be placed into study binders. Study binders will be 
placed inside of locked cabinet.  
Any corrections to the worksheets will be made by drawing a single line through the incorrect entry, 
recording the correct information, and initialing and dating the change. The study worksheets and data 
entered in the Excel files will be audited by the study sponsor. 
Data is protected by preventing unauthorized users from accessing the system with the use of username 
and password combination. In addition, each individual user will be assigned a specific role in the 
Microsoft Excel which will grant that user the right to view, edit and/or delete the data. 

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All clinical data generated in the study will be submitted to the Sponsor or its designee for quality 
assurance review and statistical analysis. All worksheets and data entered in Excel files will be reviewed 
for completeness and evident recording errors will be rectified by contact with the appropriate clinical 
site.  
 
Study Administrations:  
Ethical and Regulatory Considerations- the study is conducted in accordance with the following: 
• Protocol and study-related plans and documents 
• Local regulations, as applicable 
• Good Clinical Practices, as outlined in the ICH Harmonized Tripartite Guideline for GCP (ICH E6(R2)) 
• The ethical principles established by the Declaration of Helsinki 
• Regional participant data protection laws and regulations 
 
Institutional Review Board (IRB): 
The study site must maintain an accurate and complete record of all reports, documents and other 
submissions made to the Institutional Review Board (IRB) concerning this protocol. 
The investigator must supply ongoing study progress reports to the IRB, per local requirements, such as 
updates on SAEs, protocol deviations and amendments, ICF revisions, relevant sponsor communication, 
enrollment updates, etc. In addition, the investigator must notify the IRB at the closure of the study. 
 
Informed Consent: 
It is the responsibility of the investigator or his/her designee to inform each subject of the purpose of 
this study, including possible risks and benefits and document the informed consent process in the 
subject’s chart. Prior to entry into the study or initiation of any study-related testing, the subject must 
read, sign and date the informed consent form. If the subject’s vision is impaired to the point where 
they cannot read the informed consent document, the document will be read to the subject. The person 
executing the consent must also sign and date the consent form. One original informed consent form is 
to be retained by the study site, and a copy is to be given to the subject. 
 
Protocol Amendments: 
This protocol must be followed as written. Any change or addition to this protocol that impacts subject 
safety, or the validity of the study requires a written protocol amendment that must be approved in 
writing by the IRB and any required regulatory authorities before implementation. 
 
Record Keeping and Retention: 
Data generated for the study should be stored in a limited-access file area and be accessible only to 
representatives of the study site. All reports and communications relating to study participants will 
identify participants only by subject identification number. Complete subject identification will be kept 
by the investigator. This information will be treated with strict adherence to professional standards of 
confidentiality. 
 
Documents Provided to Sponsor: A copy of the IRB approved informed consent form. 
 
Documents that study site will retain:  
o All original informed consent forms with required signatures. 
o All participant source documents, etc. 
o All IRB correspondence (i.e., informed consent [including any approved revisions], 
protocol, AE, advertisements, newsletters). 

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o  Copies of all pertinent correspondence pertaining to the study (except budget issues) 
between the Sponsor or its designee and the site 
Confidentiality: 
All clinical study findings and documents are regarded as confidential. Study documents (protocols and 
other material) must be stored appropriately to ensure their confidentiality. The investigator, site 
personnel, and members of the IRB must not disclose such information without prior written approval 
from the Sponsor. The anonymity of participants must be maintained per applicable local and national 
laws. Subjects are specified on all documents by subject number but not by name. Documents that 
identify the subject, e.g., the signed ICF, must be maintained in confidence by the investigator. Site 
personnel must obliterate participant names from study-required documents that identify the subject 
by name, e.g., hospital records, prior to transmitting these documents to Sponsor or its designee. 
 
Publication: 
Data and information generated in this study are the exclusive property of the Sponsor and are 
confidential. At the end of the study, a clinical study report will be written by the Sponsor or its 
designee. Written approval from the Sponsor is required before disclosing any information relative to 
this clinical study, and no publications initiated by investigators may be published until all protocol-
defined results are published in a manuscript. Publication of the results must be based on appropriate 
analyses and review of the complete data. Authorship may be determined based on enrollment of 
eligible subjects or contribution to the design, conduct, or interpretation of the study. Investigators 
agree to have their names listed as an investigator in any publication reporting the results from this 
study, whether they are an author on the publication. The preparation and submittal for publication of 
manuscripts and presentations containing the study results shall be in accordance with a process 
determined by mutual written agreement between the Sponsor and participating institutions. The 
publication or presentation of any study results shall comply with all applicable privacy laws. 
References: 
1.  Gills JP, Cherchio M, Raanan MG. Unpreserved lidocaine to control discomfort during cataract surgery 
using topical anesthesia. J Cataract Refract Surg. 1997 May;23(4):545-50.   
2. Crandall AS, Zabriskie NA, Patel BC, Burns TA, Mamalis N, Malmquist-Carter LA, Yee R. A comparison 
of patient comfort during cataract surgery with topical anesthesia versus topical anesthesia and 
intracameral lidocaine. Ophthalmology. 1999 Jan;106(1):60-6.   
3. Reddy AJ, Dang A, Dao AA, Arakji G, Cherian J, Brahmbhatt H. A Substantive Narrative Review on the 
Usage of Lidocaine in Cataract Surgery. Cureus. 2021 Oct 30  
4. Donnenfeld ED, Mychajlyszyn D, Mychajlyszyn A, Stein R. Pain control and reduction of opioid use 
associated with intracameral phenylephrine1.0%-ketorolac 0.3% administered during cataract surgery. J 
Cataract Refract Surg. 2022 Jul 1;48(7):759-764.  
5. Scarfone HA, Rodriquez EC. Evaluation of Early Changes of the Anterior Vitreous Interface after 
Cataract Surgery, using Low-Pressure Settings Determined by OCT. ASCRS 2023 May 6, San Diego 
Convention Center. https://ascrs.confex.com/ascrs/23am/meetingapp.cgi/Paper/88373  
6. Liu YC, Setiawan M, Ang M, Yam GHF, Mehta JS. Changes in aqueous oxidative stress, prostaglandins, 
and cytokines: Comparisons of low-energy femtosecond laser-assisted cataract surgery versus 
conventional phacoemulsification. J Cataract Refract Surg. 2019 Feb;45(2):196-203.  

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7. Rauen, MP, Joiner H, Kohler, RA, O’Connor, S.  Phacoemulsification using an Active Fluidics System at 
Physiologic versus High IOP: Impact on Anterior and Posterior Segment Physiology. JCRS (Journal of 
Cataract & Refractive Surgery 2024 Aug  50(8):p822-827  
8. Rauen, MP.  Cataract Surgery with Physiologic Intraocular Pressure:  Intraoperative Patient Experience 
and Patient Satisfaction.  ASCRS 2025 April 26.  Los Angeles Convention Center.