Femtosecond Laser Assisted Keratotomies for the Management of Corneal Astigmatism
Phase: NA
Conditions: Astigmatism, Cataract
Sponsor: Milton S. Hershey Medical Center

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HRP-591 - Protocol for  
Human Subject Research 
 
Protocol Title: 
Femtosecond Laser Assisted Keratotomies for the Management of Corneal Astigmatism  
 
Principal Investigator: 
Name: Seth Pantanelli  
Department: Ophthalmology 
Telephone: 289897 
E-mail Address: spantanelli@pennstatehealth.psu.edu 
 
Version Date: 
 1/05/2021 
Clinicaltrials.gov Registration #: 
Not applicable 
 
Important Instructions for Using This Protocol Template: 
1. 
Add this completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic Information” 
page, item 7.  
2. 
This template is provided to help investigators prepare a protocol that includes the necessary information needed 
by the IRB to determine whether a study meets all applicable criteria for approval.  
3. 
Type your protocol responses below the gray instructional boxes of guidance language.  If the section or item is 
not applicable, indicate not applicable. 
4. 
For research being conducted at Penn State Hershey or by Penn State Hershey researchers only, delete the 
instructional boxes from the final version of the protocol prior to upload to CATS IRB (http://irb.psu.edu).  For all 
other research, do not delete the instructional boxes from the final version of the protocol. 
5. 
When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in the Study 
Submission Guide available in the Help Center in CATS IRB (http://irb.psu.edu) for using track changes.  
 
If you need help… 
University Park and other campuses: 
Office for Research Protections Human Research Protection Program 
The 330 Building, Suite 205 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
College of Medicine and Hershey Medical Center: 
Human Subjects Protection Office 
90 Hope Drive, Mail Code A115, P.O. Box 855 
Hershey, PA 17033 
(Physical Office Location: Academic Support Building Room 1140) 
Phone: 717-531-5687 
Fax number: 717-531-3937 
Email: irb-hspo@psu.edu 
 
Table of Contents 
1.0 
Objectives 
2.0 
Background 

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3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7.0 
Study Design and Procedures 
8.0 
Subject Numbers and Statistical Plan 
9.0 
Confidentiality, Privacy and Data Management 
10.0 
Data and Safety Monitoring Plan 
11.0 
Risks 
12.0 
Potential Benefits to Subjects and Others 
13.0 
Sharing Results with Subjects 
14.0 
Subject Stipend (Compensation) and/or Travel Reimbursements 
15.0 
Economic Burden to Subjects 
16.0 
Resources Available 
17.0 
Other Approvals 
18.0 
Multi-Site Research 
19.0 
Adverse Event Reporting 
20.0 
Study Monitoring, Auditing and Inspecting 
21.0 
Future Undetermined Research: Data and Specimen Banking 
22.0 
References 
 
 

Page 3 of 13 (V.04/27/2017)  
1.0 
Objectives 
 
1.1 
Study Objectives 
 
1. To determine the degree of surgically induced astigmatism of femtosecond laser clear corneal 
incisions 
2. To determine the post-operative mean reduction in keratometric astigmatism and uncorrected 
distance visual acuities in patients undergoing  femtosecond laser-assisted cataract surgery with 
astigmatic keratotomy (AK) 
3. To determine the role of corneal biomechanics (hysteresis) on AK calculations. 
4. To develop a nomogram that may be utilized in determining location and arc length of AKs for 
femtosecond laser-assisted cataract surgery with astigmatic keratotomy  
 
1.2 
Primary Study Endpoints 
 
The primary outcome measures are as follows (collected at post-operative month one): 
• 
Uncorrected visual acuity 
• 
Post-operative corneal curvature measurements and astigmatism as assessed using optical 
biometer 
• 
Post-operative auto-refraction 
 
1.3 
Secondary Study Endpoints 
 
The secondary outcome measures are as follows (collected at post-operative month one): 
• 
Mean change in astigmatism in eyes with ‘with the rule’ (WTR) astigmatism 
• 
Mean change in astigmatism in eyes with ‘against the rule’ (ATR) astigmatism 
• 
Complications related to placement of femtosecond laser AKs 
 
2.0 
Background  
 
2.1 
Scientific Background and Gaps 
 
1.1. 
Nearly 20% of people undergoing cataract surgery have significant corneal astigmatism (1.5 D or 
greater). Patients increasingly expect spectacle independence after cataract surgery, which requires 
correction of this astigmatism. Femtosecond laser astigmatic keratotomies (AKs) can be used to treat 
corneal astigmatism, but there are no nomograms developed to guide surgeons on the parameters (i.e. 
depth and arc length) to use to correct specific amounts of astigmatism. Instead, surgeons must rely on 
old nomograms that were developed for manual incisions and adapt them for use with the laser. 
 
A well-validated nomogram exists for determining location and arc length of limbal relaxing incisions 
(LRI), another type of refractive procedure used to treat astigmatism.1 This calculator specifically states 
that it is “intended to support the use of LRIs only, it is not intended for the calculation of femtosecond 
laser incisions.1” 
 
If we could accurately determine the effect femtosecond laser performed AKs have on corneal 
astigmatism at the time of cataract surgery, a nomogram to be used specifically with the laser could be 
reverse engineered. 
 
2.2 
Previous Data 
 

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One previous prospective study has been published evaluating the effectiveness of femtosecond laser 
corneal relaxing incisions in reducing corneal astigmatism during cataract surgery.2 This study also 
proposed a preliminary nomogram based on the 51 eyes that were included in the study.2 While this 
study is a landmark paper in proposing a nomogram for AKs, the authors conclude that further study is 
required to refine and validate the nomogram. In addition, the role of corneal biomechanics, such as 
corneal hysteresis is not factored into their nomogram. Another study demonstrated that corneal 
biomechanical parameters are independent predictors of the efficacy of femtosecond laser AKs.3 
 
2.3 
Study Rationale 
 
The purpose of this study is to build upon the existing literature to create a nomogram based on a large 
number of eyes that may be utilized to accurately predict location and arc length of AKs to minimize 
post-operative astigmatism. This nomogram will incorporate corneal biomechanics, including corneal 
hysteresis.  
 
3.0 
Inclusion and Exclusion Criteria 
 
3.1 
Inclusion Criteria 
 
 Age: ≥18 years of age 
 Sex: male or female 
 Patients who are planned to undergo femtosecond laser-assisted cataract surgery with astigmatic 
keratotomy at the Schein Ernst Mishra Eye clinic within the next 60 days of their cataract 
consultation visit.  Subjects with planned single or bilateral cataract eye surgeries are eligible.  
Planned opposite eye surgery must be within 2-4 weeks of first cataract surgery. 
 Fluent in written and spoken English 
 
3.2 
Exclusion Criteria 
 
 Patients with corneal dystrophies, including anterior basement membrane dystrophy, keratoconus, 
and Fuch’s endothelial corneal dystrophy. 
 Age < 18 years 
 Pregnant women 
• 
Cognitive impairment 
 Prisoners 
 
3.3 
Early Withdrawal of Subjects 
 
3.3.1 Criteria for removal from study 
 
Subjects may withdrawal from the study if they no longer wish to participate in the study.  
 
Subjects may withdrawal from the study if they no longer plan to undergo femtosecond laser-
assisted cataract surgery with astigmatic keratotomy. There are no anticipated safety reasons 
for which a subject would need to withdrawal from the study. There is no disease progression 
that would require a subject to withdrawal from the study. 
 
3.3.2 
Follow-up for withdrawn subjects 
 

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Subjects may withdrawal from the study at any point up to their post-operative one-month 
exam. Data will be collected for the number and the reason for withdrawal of subjects (eg. 
withdrawal of consent). A patient disposition flow diagram will be constructed. Subjects that 
withdrawal from investigational treatment will be treated as any other patient who is 
undergoing cataract surgery outside of the study. 
 
4.0 
Recruitment Methods 
 
4.1 
Identification of subjects 
 
Participants will be identified by Dr. Brett Ernst during a scheduled patient clinic visit to review the 
medically planned femtosecond laser-assisted cataract surgery with astigmatic keratotomy standard of 
care cataract surgery consent. 
 
4.2 
Recruitment process 
 
All eligible patients will be offered the opportunity to participate in the research study.  The Dr. Ernst 
will explain the research study to potential subjects at their pre-surgery clinic visit. 
 
4.3 
Recruitment materials 
 
None 
 
4.4 
Eligibility/screening of subjects 
 
Not applicable 
 
5.0 
Consent Process and Documentation  
 
5.1 
Consent Process  
  
5.1.1 Obtaining Informed Consent 
 
5.1.1.1 Timing and Location of Consent 
 
Informed consent is a process.  Consent will take place in the ophthalmology 
clinic when a patient would be regularly consented to undergo cataract surgery 
(within 60 days of surgery date). As the patient presents for surgery, the 
consent will be reviewed once again and any additional questions will be 
addressed to confirm they still want to participate in the study. 
 
5.1.1.2 Coercion or Undue Influence during Consent 
 
Subjects will be informed that participation is voluntary and that their decision 
will not affect their care.  Physician investigators will discuss the study with the 
patients and answer all questions. 
 
5.1.2 Waiver or alteration of the informed consent requirement 
 

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A waiver of consent is requested to review medical record information to determine preliminary 
eligibility to participate in the research. 
 
5.2 
Consent Documentation 
 
5.2.1 
Written Documentation of Consent 
 
The consent process will be documented in writing with the long form of consent documentation: 
• 
The current IRB approved consent form will be obtained. 
• 
We will verify that we are using the most current IRB-approved version of the study specific 
consent form and that the consent form is in language understandable to the subject. 
• 
A copy of the consent form will be provided to the subject. Whenever possible the consent 
form will be provided to the subject in advance of the consent discussion. 
 
5.2.2 
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.) 
 
Not applicable 
 
5.3 
Consent – Other Considerations  
 
5.3.1 
Non-English Speaking Subjects 
 
Not applicable 
 
5.3.2 
Cognitively Impaired Adults 
 
5.3.2.1 Capability of Providing Consent 
 
Not applicable 
 
5.3.2.2 Adults Unable To Consent 
 
Not applicable 
 
5.3.2.3 Assent of Adults Unable to Consent 
 
Not applicable 
 
5.3.3 
Subjects who are not yet adults (infants, children, teenagers)  
 
5.3.3.1 Parental Permission 
 
Not applicable 
 
5.3.3.2 Assent of subjects who are not yet adults 
 
Not applicable 
 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
 

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6.1 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
  
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable] 
 
 
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
 
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
 
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3] 
 
 
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3] 
 
6.2 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1 
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
 
6.2.1.1 Plan to protect PHI from improper use or disclosure 
 
Information is included in the “Confidentiality, Privacy and Data Management” 
section of this protocol. 
 
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers  
 
Study information will be destroyed after the research has ended and all 
institutional/regulatory requirements for data retention have been met.  
 
6.2.2 
Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
 
Information must be obtained from the subject’s electronic medical record during recruitment 
to determine eligibility and, in some cases, to confirm information discussed with the subject in 
regards to their medical history. 
 
6.2.3 
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
 
The waiver is requested only for recruitment to determine subject eligibility to ensure that no 
medical conditions that fall into the exclusion criteria are present and would thus preclude 
enrollment.  This waiver will minimize the enrollment of subjects’ who may ultimately fail to 
meet the study inclusion/exclusion criteria. 
 
6.3 
Waiver or alteration of authorization statements of agreement 
 

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Protected health information obtained as part of this research will not be reused or disclosed to any 
other person or entity, except as required by law, for authorized oversight of the research study, or for 
other permitted uses and disclosures according to federal regulations.  
 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) 
per federal regulations.  
 
Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented. 
 
7.0 
Study Design and Procedures 
 
7.1 
Study Design 
 
This is a prospective cohort study of patients who are undergoing femtosecond laser-assisted cataract 
surgery with astigmatic keratotomy. Patients will be selected to participate in the study based on 
inclusion/exclusion criteria.  
 
It should be noted that this is an observational, not interventional study. The parameters to be chosen 
for the femtosecond AKs will be determined using best practices (surgeon’s choice using algorithms 
created for manual LRIs but adapted for use with the laser). Whether a patient is enrolled in the study or 
not will not influence the architecture or plan for the femtosecond AKs. The purpose of the study is to 
carefully examine the effects of these femto AK on corneal astigmatism in a retrospective fashion (after 
the 1 month post-operative visit) so that a nomogram can be developed using regression analysis. As 
such, the only ‘intervention’ patients enrolled in the study will receive that un-enrolled patients will not 
is measurement of corneal hysteresis and corneal biometry at their 1 month post-operative visit. 
 
7.2 
Study Procedures 
 
7.2.1 
Visit 1 or Day 1 or Pre-test, etc. (format accordingly) 
 
Pre-operative visit: Inclusion/exclusion criteria will be assessed. Consent will be obtained from 
eligible subjects who wish to participate in the study. Demographic and baseline characteristics 
will be recorded. Pre-operative biometry, refraction, and corneal hysteresis data will be 
collected. 
 
7.2.2 
Visit 2 
 
Day of surgery: Data from the femtosecond laser will be collected, including the various laser 
parameters that are used to make the astigmatic keratotomies and clear corneal incisions. 
 
7.2.3 
Visit 3 
 
Day of surgery for contralateral eye: Data from the femtosecond laser will be collected, 
including the various laser parameters that are used to make the astigmatic keratotomies and 
clear corneal incisions. 
 
7.2.4 
Visit 4 or post-operative month #1 visit (1 month after 2nd operative procedure) 
 

Page 9 of 13 (V.04/27/2017)  
Post-operative month 1 visit: One-month post-operative IOL master, autorefraction, manifest 
refraction, and uncorrected visual acuity will be collected.  
 
7.3 
Duration of Participation 
 
The individual subject will participate in the study from the time consent is obtained at their pre-
operative visit, through their femtosecond laser-assisted cataract surgery with astigmatic keratotomy on 
both eyes, and until their one-month post-operative visit.  
8.0 
Subject Numbers and Statistical Plan 
 
8.1 
Number of Subjects 
 
300 
 
8.2 
Sample size determination 
 
Eyes may have with-the-rule, against-the-rule, and oblique astigmatism. Corneas with varying forms of 
astigmatism will respond differently to the AKs; thus it is necessary to have a sufficient number of eyes 
to produce results for all forms of astigmatism. Approximately 50% of eyes have against-the-rule 
astigmatism, 30% with-the-rule, and 20% oblique. 20% of 300 eyes = 60, which was  felt to be the 
minimum number to produce meaningful results for this group. 
 
8.3 
Statistical methods 
 
Eyes that do not obtain a final best-corrected visual acuity of 20/40 or better will be excluded from the 
final data analysis. Mean change in keratometric astigmatism will be determined by subtracting 
preoperative astigmatism  from postoperative mean astigmatism. Vector analysis and double-angle plot 
will be used to analyze aggregate astigmatism. We will require assistance from a statistician.  
 
A sub-group analysis will likely include patients that had prior refractive surgery (i.e. LASIK). 
 
9.0 
Confidentiality, Privacy and Data Management  
 
See the Research Data Plan Review Form 
 
10.0 Data and Safety Monitoring Plan 
 
 Not applicable 
 
11.0 Risks 
 
Risk of loss of confidentiality 
 
12.0 Potential Benefits to Subjects and Others 
 

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12.1 
Potential Benefits to Subjects 
 
None 
 
12.2 
Potential Benefits to Others 
 
Accurate correction of astigmatism in patients undergoing femtosecond laser-assisted cataract surgery 
with astigmatic keratotomy is vital for patients to achieve spectacle independence. While there is a 
universal LRI calculator readily available to the refractive cataract surgeon, a similar calculator does not 
exist for AKs. A validated calculator to determine AK parameters would potentially allow for more 
patients undergoing femtosecond laser-assisted cataract surgery with astigmatic keratotomy to achieve 
spectacle independence. 
13.0 Sharing Results with Subjects 
 
Not applicable 
 
14.0 Subject Stipend (Compensation) and/or Travel Reimbursements 
 
Subjects will receive a thirty dollar gift card for participating in the study.  
 
15.0 Economic Burden to Subjects 
 
15.1 
Costs  
 
The subjects will not be responsible for any research-related costs (data collection from standard of care 
procedures and the one month follow-up research visit) for participating in the research.  
 
15.2 
Compensation for research-related injury 
 
Not Applicable:  no greater than minimal risk (loss of confidentiality) research. 
 
16.0 Resources Available 
 
16.1 
Facilities and locations 
 
Patients will be recruited from Schein Ernst Mishra Eye (10 Capital Drive Harrisburg PA 17110 or 717 
Market St., Ste. 112 Lemoyne, PA 17043). All cataract surgeries for the study will be performed at 
Capital Surgery and Laser Center (10 Capital Drive, Suite 200 Harrisburg, PA, 17110).  
 
16.2 
Feasibility of recruiting the required number of subjects 
 
The study team has access to approximately 10-20 potential subjects per week. At a minimum, 25% of 
subjects (4-5 per week) would need to be recruited in a one year period to reach the required number of 
participants for the desired study power. 
 

Page 11 of 13 (V.04/27/2017)  
16.3 
PI Time devoted to conducting the research 
 
The PI has 20% academic time and will be contributing half of this to research activities, for a total 
percentage effort of 10%. 
 
16.4 
Availability of medical or psychological resources 
 
Not applicable 
 
16.5 
Process for informing Study Team 
 
Team members will meet with the PI periodically during the course of the study to ensure proper 
training on study protocol and duties. 
17.0 Other Approvals 
17.1 
Other Approvals from External Entities 
 
Not applicable 
 
17.2 
Internal PSU Committee Approvals 
 
Check all that apply: 
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library.   
 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
 
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA 
or gene therapy). 
 
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body 
fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that 
had been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of 
HRP-901 - Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. 
This form is available in the CATS IRB Library.  
 
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of 
CRC services in any way. 
 
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload a 
copy of HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This 
form is available in the CATS IRB Library. 
 

Page 12 of 13 (V.04/27/2017)  
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE. 
 
  Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The 
scientific review requirement may be fulfilled by one of the following: (1) external peer-review 
process; (2) department/institute scientific review committee; or (3) scientific review by the Clinical 
Research Center Advisory committee.  NOTE: Review by the Penn State Hershey Cancer Institute 
Scientific Review Committee is required if the study involves cancer prevention studies or cancer 
patients, records and/or tissues. For more information about this requirement see the IRB website 
at: http://www.pennstatehershey.org/web/irb/home/resources/investigator  
 
18.0 Multi-Site Research 
 
Not applicable 
19.0 Adverse Event Reporting 
 
19.1 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
20.0 Study Monitoring, Auditing and Inspecting 
 
20.1 
Auditing and Inspecting 
 
The investigator will permit study-related monitoring, audits, and inspections by the Penn State quality 
assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities 
(e.g., pharmacy, diagnostic laboratory, etc.). 
 
21.0 Future Undetermined Research: Data and Specimen Banking 
 
Not applicable 
 
22.0 References 
 
1LRIcalculator.com. Abbott Laboratories Inc. Abbott Park, Illinois, USA. Accessed from 
http://www.lricalculator.com. Accessed August 13, 2017. 
 

Page 13 of 13 (V.04/27/2017)  
2Wang L, Zhang S, Zhang Z, Koch DD, Jia Y, et al. Femtosecond laser penetrating corneal relaxing incisions 
combined with cataract surgery. J Cataract Refract Surg. 2016;42:995-1002. 
 
3Day AC, Stevens JD. Predictors of femtosecond laser intrastromal astigmatic keratotomy efficacy for 
astigmatism management in cataract surgery. J Cataract Refract Surg. 2016;42:251-7. 
 
Yang J, Wang X, Zhang H, Pang Y, Wei R. Clinical evaluation of surgery-induced astigmatism in cataract surgery 
using 2.2 mm of 1.8 mm clear corneal micro-incisions. Int J Ophthalmol. 2017;10(1):68-71. 
 
Chan TCY, Cheng GPM, Wang Z, Tham CCY, Woo VCP, Jhanji V. Vector analysis of corneal astigmatism after 
combined femtosecond-assisted phacoemulsification and arcuate keratotomy. Am J Ophthalmol. 
2015;160(2):250-255.