Age-dependency of Cornea Biomechanics Measured by OCT Vibrography: A Pilot Study
Phase: NA
Conditions: Cornea
Sponsor: Massachusetts General Hospital

 
 
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Identifiers: NCT03230981   Unique Protocol ID: 2017P000867 
Brief Title: Age-dependency of Cornea Biomechanics Using OCT 
Vibrography 
 
I. BACKGROUND AND SIGNIFICANCE 
A) Background 
The cornea, the clear front window of the eye, consists of finely intertwined collagen fibers, which 
give the cornea a microstructure that provides mechanical integrity necessary to maintain its 
typical dome-shape against the intraocular pressure (IOP). Changes in the biomechanical 
properties can lead to an abnormal corneal shape and refractive errors. As a result, light is not 
perfectly focused onto the retina and the vision is affected. A typical example of alterations in the 
cornea’s biomechanical properties is found in patients with an eye disorder called Keratoconus, 
which leads to progressive thinning of the cornea. Keratoconus explants have shown disrupted 
collagen orientation [1] and decreased mechanical modulus [2]. Similar findings have been 
observed in corneas that developed ectasia after refractive surgery like LASIK (laser-assisted in 
situ keratomileusis, the most widely performed type of refractive surgery), where a laser is used to 
reshape the cornea [3]. With LASIK surgery becoming increasingly popular (more than 28 million 
LASIK procedures have been performed worldwide), the incidence of post-LASIK ectasia has 
increased continuously.  
Numerous studies have shown that promising interventions like collagen crosslinking (CXL) can 
slow down an arrest progression of ectatic eye diseases [4]. Keratoconus, as a typical example, 
although it cannot be cured, could be at least halted by CXL. Therefore, early diagnosis of ectasia 
is crucial for the patient. Current diagnostic methods of ectasia are based on morphological rather 
than biomechanical analysis. The irregular patterns of the cornea can be detected by pachymetry 
and topography before clinical signs occur, but these tests cannot reliably differentiate truly weak 
or keratoconic corneas from atypical normal ones [5, 6].  
Additionally, the screening protocols for LASIK surgery that rely on indirect morphological risk 
factors have had limited success in the clinic. About 15% of patients seeking laser vision correction 
are considered at-risk and are thus denied treatment. On the other hand, patients with normal 
appearing pachymetry and topography and no other risk factors have gone on to develop post-
LASIK ectasia [7-9]. 
These are compelling needs for improved diagnostic methods. More recently, and triggered by 
those unmet needs, an interest in the mechanical properties of the cornea has emerged. Typical 
examples of mechanical properties are elastic modulus and corneal stiffness. The corneal stiffness 
is known to increase with age with the behavior closely fitting an exponential power function 
typical of collagenous tissue [10]. Further research suggests that corneal stiffness increases by as 
much as a factor of approx. 2 between the ages of 20 and 100 years [11]. 

 
 
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The connection of the mechanical properties to the pathophysiology of the condition of the cornea 
makes them highly suited for early identification of patients at risk to develop ectasia [9, 12]. 
Consequently, there have been considerable efforts to develop noninvasive, sensitive methods to 
characterize corneal biomechanics in vivo. The most widely used approach employs air-puffs to 
induce a burst of pressure on the cornea and analyzes corneal deformation and recovery. The 
Ocular Response Analyser, for example, is an instrument based on this principle and has been 
approved for in vivo measurement of properties, so-called corneal hysteresis, which is associated 
with viscous damping of tissue deformation [13]. Corneal hysteresis has shown to be reduced in 
ectatic disease, but its sensitivity and specificity have been insufficient to differentiate normal eyes 
from low-grade keratoconus [14]. Air-puff can be combined with Scheimpflug camera [15] or 
optical coherence tomography (OCT) [16] for image-based analysis and estimates of corneal 
viscoelastic parameters [17]. Other emerging techniques for measuring elastic modulus with 
spatial resolution include supersonic shear imaging [18], optical coherence elastography [19-24], 
and Brillouin microscopy [25]. 
In this pilot study we propose to investigate the ability of OCT Vibrography to determine cornea 
material parameters. More precisely, we want to study the oscillation response in human corneas 
in vivo using sound excitation (110-110dB) together with phase-sensitive OCT to measure the 
frequency response function of the human cornea in vivo and to analyze the dependency of the 
frequency response function on age. Additionally we will use Brillouin Microscopy data for 
computer simulations to validate OCT Vibrography results. 
The level of light exposure to the retina, cornea, and skin are within the safety standards as 
described by the ANSI Z136.1-2014 safety standard. A detailed laser safety calculation is added 
in Section XII.  
B) Swept-Source Optical Coherence Tomography (OCT)  
Over the past two decades, OCT has undergone a rapid development from its technological 
inception to adoption as standard-of-care in ophthalmology. Swept-Source OCT (or, Optical 
Frequency Domain Imaging, OFDI), is a relatively new method for OCT that employs a 
wavelength-swept light source to probe the amplitude and phase of back scattering light from 
tissue [26-28]. This frequency-domain method has enabled significant improvements in imaging 
speed, sensitivity, and ranging depth over conventional time-domain OCT systems, and has been 
demonstrated for imaging anterior eye segments [28-35]. Compared to Spectral domain OCT, 
swept source OCT offers several advantages such as immunity to motion-induced signal fading 
[36], simple polarization-sensitive or diversity scheme [29], and long ranging depth [28]. Swept 
source OCT has been successfully used to image the human eye in vivo [37]. 
C) OCT Vibrography 

 
 
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Our group has recently developed a new technique capable of visualizing acoustic vibrations. This 
technique, named OCT Vibrography, is based on the synchronized acquisition of phase 
information that is directly related to the vibration of the 
sample. It was shown that, after post processing of the data, 
3-D snapshots of an object vibrating at acoustic frequencies 
in response to applied stimuli could be obtained [38]. As a 
proof-of-concept experiment, OCT Vibrography was 
successfully applied to the visualization of the acoustic 
resonance modes of a miniature drum driven acoustically 
at several kHz. Figure 1 (taken from [38]) shows (a) the schematic setup with a latex drum, (b) 
vibrography snapshot images of a vibrating miniature drum at a frequency of 800 Hz, and (c) a 
cutaway image showing the motion in a cross-section of the membrane.  
D) OCT Vibrography imaging to estimate corneal biomechanics 
We have recently demonstrated the ability of OCT Vibrography to observe sound-induced 
resonance modes of the cornea, and, therewith, to determine corneal biomechanical properties. 
Experiments were conducted on ex vivo bovine [39, 40] and porcine globes [40], and modal 
analysis was performed in a finite-element model to study oscillation response and to analyze the 
dependency of the frequency response function on biomechanical properties and corneal 
topography, among others. 
The experimental set up consisted of a home-built 
phase-sensitive OCT system (an updated version 
of before mentioned device from Chang et al. 
[38]) which employed a polygon scanner swept 
laser in the spectral range from 1.23 to 1.34 µm 
with a typical sweep rate of 45 kHz and an optical 
power of 15 mW on the sample. The sound source 
was a high-fidelity loudspeaker, which was 
controlled by an arbitrary waveform function 
generator.  Figure 2 (taken from [39]) shows the 
schematic of the set up: The sound wave emitted from the loudspeaker is directed toward the 
eyeball, and the motion of the cornea is captured and recorded by the OCT system. Figure 2 b) and 
2 c) describe the signal processing sequence for the measurement of vibration spectrum at a fixed 
spatial location in the cornea (b) and to generate vibrography images at a specific sound frequency 
(c). Figure 3 shows the frequency response curve of a sample measured at the center of the cornea. 
These results indicated three distinctive peaks at 86 Hz, 200 Hz, and 310 Hz (Figure 3 a). The 
amplitude of the first peak was around 8µm at 100 dB SPL (2 Pa). The vibration amplitude was 
proportional to the sound pressure over a range of 80 to 120 dB SPL. The variation in repeated 
frequency sweeps was less than +/-2%.  

 
 
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Amplitude and frequencies of the modes and their specific spatial distributions in the cornea are 
thought to provide rich information about 
the 
corneas’ 
biomechanics. 
Further 
research, especially in vivo, is necessary 
to understand how different corneal 
parameters 
manifest 
themselves 
in 
vibrational resonance, and how these 
resonances are dependent on age.  
Another relevant biomechanical marker is the velocity of shear acoustic waves in the corneal 
tissue. There is a direct mathematical relationship between the shear wave velocity and the 
elastic moduli of the cornea:  
𝜇= 𝜌𝑐𝑠
2 ≈𝐸
3 
where μ is the shear modulus, E is Young’s modulus, ρ is the density and 𝑐𝑠 is the shear wave 
velocity. This approach is therefore promising to obtain local and quantitative measurements of 
corneal biomechanical properties. Figure 4 below shows a typical experiment conducted on ex 
vivo porcine corneas.  
 
Figure 4. a) Schematic of shear wave generation in the cornea used in previous ex vivo studies. b) Shear wave propagation in the 
cornea measured by OCT vibrography.  
  
E) Additional Technologies used for Imaging 
Brillouin microscopy measurements are planned to support and complement OCT Vibrography 
data, more specifically, to obtain data of the Brillouin modulus/stiffness.  Brillouin Microscopy 
has recently been developed in our group and has been used in vivo in previously approved 
Partners IRB protocols: 2015P002404, 2012P002178, 2008P002176. The technique is based on 
light scattering: When laser light is illuminated to a sample (e.g. the cornea), a portion of the light 
is reflected due to the acoustic waves that are weak but naturally present in the material by thermal 
fluctuations [41]. The acoustic waves propagate with a speed that is directly related to the sample’s 
elastic modulus. The acoustic speed (therefore the elastic modulus) is obtained by measuring the 
frequency shift of the reflected light using a specially designed spectrometer. Combining the 
spectrometer with a confocal microscope, 3D elasticity imaging can be performed.  

 
 
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The Brillouin data will serve as input data for computer simulations on the cornea’s modulus 
value. Simulations are thought to complement experimental data.  
II. SPECIFIC AIMS 
In this study we aim to: 
• Assess measurement repeatability and overall sensitivity of OCT Vibrography for 
measurements in vivo 
• Use OCT Vibrography to measure the mechanical resonance modes of the cornea and 
their according vibration amplitude in healthy individuals of different ages to investigate 
age-related changes.  
• Use OCT Vibrography to measure the shear wave velocity of the cornea in healthy 
individuals of different age.  
• Use Brillouin Microscopy data for computer simulations to validate OCT Vibrography 
results 
 
 
III. SCHEMATIC OF DEVICE 
 

 
 
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IV. SUBJECT SELECTION 
Source of subjects and recruitment methods 
Subjects will be recruited as described in the following: 
Subject recruitment among MEEI patients  
Normal and healthy volunteers (Group 1) and keratoconus patients (Group 2) will be recruited 
from patients of the contact lens service center at MEEI. The treating ophthalmologist at MEEI 
will initially introduce the study to the patient, and obtain a patient’s permission to be contacted 
by study staff either (1) verbally during the course of providing medical care or (2) through the 
use of a recruitment letter.  
If the patient agrees, the treating ophthalmologist at MEEI gives approval for their patient to be 
contacted for research purpose and obtains the patient’s permission to be contacted by study staff. 
In case a recruitment letter is used for initial contact of the patient, it will be mailed to the potential 
subjects at least a week prior to the potential subject’s eye exam appointment. The subject will be 
encouraged to contact the research staff or their treating ophthalmologist by phone or email if they 
have any questions. If the treating ophthalmologist does not hear from the potential subject, they 
may follow up by phone. 
Subject recruitment via email announcements or ad at PHC and MEEI 
Normal and healthy volunteers can be recruited by PHC email announcement, the PHC Research 
website, the MEEI website, or through paper advertisements. Requirement for participation is 
either (a) having undergone a routine eye exam at MEEI within the last 12 months or (b) having a 
routine eye exam scheduled and completed at MEEI prior to study enrollment. Potential subjects 
who are interested in the study will contact the study staff.  Eligibility will be determined and a 
study visit will be scheduled The subject may be contacted by regular mail, electronic mail, or 
phone call to confirm date and time of scheduled study procedure as well as additional logistical 
information.   
 
INCLUSION/EXCLUSION CRITERIA 
Inclusion criteria 
• 
Male or female subjects between the ages of 18 to 79 years 
• 
Group 1 (N = 80): Healthy normal subjects with no significant eye disease and no 
significant refractive errors  
• 
Group 2 (N = 10): Patients diagnosed with keratoconus 
 
 

 
 
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Exclusion criteria 
• 
Volunteers with implanted intraocular lenses 
• 
Volunteers with LASIK or any other eye surgery, and monocular volunteers 
• 
Volunteers with restricted mobility, who cannot stand up, walk or sit still on a chair 
without a back  
• 
Subjects who do not or cannot understand the instructions for imaging 
• 
Subjects with diabetes, glaucoma family history 
• 
Subjects who are pregnant and/or breastfeeding.  
 
V. EQUITABLE SELECTION OF SUBJECTS 
    Subjects will be recruited from the Massachusetts Eye and Ear Infirmary (MEEI) and PHC. 
Eligibility will be determined by the inclusion/exclusion criteria.  There will be no exclusion based 
on gender or ethnicity.  
    Because there is no direct benefit to the study, the study only involves the use of a non-marketed 
device, and we will image healthy subjects, we will not enroll non-English speaking subjects. 
 
VI. SUBJECT ENROLLMENT 
Study staff will confirm with potential subjects that they are interested in participating in the 
research study prior to enrollment in the study.  The potential subject will be informed that 
participation is entirely voluntary and that his/her participation will not affect his/her healthcare 
now or in the future. If the potential subject is willing to participate in the research study, consent 
will be obtained by trained study staff. During the visit, the study procedures will be explained and 
any questions will be answered. Because all imaging devices used in this study are non-significant 
risk devices, and the study procedures will not interfere in any way with the standard of care 
procedures or medical care that the subjects would otherwise receive, approved study staff 
members can obtain the signed informed consent from the subject. Obtaining informed consent 
does not need to be limited to licensed physicians in this study. The subject will sign the written 
consent form prior to any scheduled standard of care eye and pupil dilation to avoid difficulties in 
reading and writing. The time of consent will be added to the signature, together with the date, to 
document that the informed consent was obtained prior to the imaging session at the Wellman 
Center. The estimated time for the review and the explanation of the consent form is up to 30 
minutes.  
Two copies of the signed and dated written consent form will be obtained. The original form will 
be retained in the research records and securely stored in a locked cabinet. A copy of the signed 
consent form will be given to the subject. 

 
 
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If a clinical eye exam is performed immediately preceding the study procedures, and in the unlikely 
scenario that the eye examination reveals a condition that changes the eligibility of the subject, the 
study staff will inform the subject of this change and further imaging at the Wellman Center will 
not be performed.  
 
VII. STUDY PROCEDURE  
A single visit at the Wellman Center will be scheduled for immediately after the subject’s 
scheduled eye exam. Prior to all imaging sessions, the subject will be given time to ask questions 
regarding the study. The subject may change his/her mind regarding study participation at any 
time. The complete session is planned as follows: 
-Informed Consent Process: ~30 min  
-OCT Vibrography with Brillouin Microscopy Imaging: ~60 min 
If eye exam at MEEI immediately precedes study procedures: 
-Walk from MEEI to the Wellman Center, MGH: ~ 10-15 min 
During the ophthalmology exam, the study doctor may do corneal topography with Pentacam (to 
map the curvature and thickness of the cornea). 
Subjects in Group 1 will be asked if interested in a follow-up visit in future by contacting by phone 
or email. 
 
Imaging Sessions 
The entire session includes OCT Vibrography measurements and Brillouin microscopy 
measurements. The complete session may take up to 60 minutes. OCT Vibrography and Brillouin 
imaging may be performed on one or two eyes in a subject depending on eligibility. 
Imaging Session 1: OCT Vibrography 
Prior to OCT Vibrography measurements, the subject will be administered anesthetic drops 
(Proparacaine Ophthalmic 0.5%, one drop) by a trained technician. During the imaging session of 
the cornea, the subject will be seated in a chair with his/her chin and forehead on a chin and 
forehead rest, respectively. The contact areas will be disinfected with alcohol wipes between 
volunteers. Both eyes may be sequentially imaged. During scanning, the non-imaged eye will be 
covered using an eye patch. At operator’s instructions, the subject will fix his/her eye on a fixation 
target. No mechanical devices for immobilizing the eye will be used. The operator will adjust the 
chin rest and the head position in order to create the best accessible angle to start imaging of the 
cornea. The operator adjusts the position of the vibrating probe tip until it touches patient’s cornea. 
At this point, the subject sits still for up to 5 seconds while the instrument gathers data. The subject 
will be asked to comply with the procedure up to 20 times per eye. This repetition of measurement 
may be necessary since the instrument is highly motion sensitive. If data acquisition after 20 

 
 
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repetitions is not successful, it is probably due to high movement of the subject. In this case, the 
subject should be dropped from the study. 
Each scan may take no longer than 20 seconds, and will be followed by short break. The subject 
may ask for breaks or stopping the imaging at any point. 
Imaging session may be taken on the skin of the healthy subjects as a comparison. Each scan may 
take no longer than 10 seconds, and no more than 20 scans will be taken.  
Imaging Session 2: Brillouin Microscopy 
During the imaging session of the cornea the subject will seated in a chair with his/her chin and 
forehead on a chin and forehead rest, respectively. The contact areas will be disinfected with 
alcohol wipes between volunteers. During scanning, the non-imaged eye will be covered using an 
eye patch. At operator’s instructions, the subject will fix his/her eye on a fixation target. No 
mechanical devices for direct immobilization of the eye will be used. The operator will adjust the 
chin rest, the head position, and the orientation of the Brillouin instrument in order to create the 
best accessible angle to start imaging of the cornea. The localization of the near infrared light in 
the eye, and the eye gaze angle will be recorded with a near infrared bright field microscopy. Then, 
the subject will be asked to hold still while fixing the study eye on the target light or projected 
object for up to 10s for each data point during which the instrument gathers the Brillouin spectrum. 
The subject will be asked to comply with this procedure at least six times and up to 30 times per 
session (depending on subject commitment and time). A break between the imaging scans will be 
provided to rest and to blink the eye. The subject may ask for breaks or stopping the imaging 
session at any point. During the pause between imaging sessions, the subject will be asked whether 
they have felt any discomfort related to their positioning, with the imaging near infrared light 
(=780nm), or with the imaging procedure.  
Renumeration 
A remuneration of $50 will be offered for the completion of each imaging session. The 
volunteers will not be charged for the imaging session at the Wellman Center. There will be no 
compensation if the subjects are measured on the skin only.  
A study subject may contact study PIs for any concerns or questions he/she may have after the 
study procedures are completed. The contact person at the Wellman Center (MGH) is Andy (SH) 
Yun, PhD, Phone # 617-768-8698, and the contact person at the MEEI is Amy Watts, MD, 
Phone # 617-573-3185. There is no extra cost associated with the research study 
 
VIII. STATISTICAL METHODS AND POWER ANALYSIS 
Hypothesis: OCT Vibrography is able to detect sound induced resonance modes in the cornea 
and mode changes with age. 

 
 
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Analysis Plan: The relationship between the age of the subject (continuous explanatory variable) 
and the change in resonance mode (continuous outcome variable) will be investigated with linear 
regression. 
Sample Size and Power for Group 1: Age-variation in sound induced resonance modes of the 
cornea has not been previously measured in vivo. As an approximation we considered the cornea 
to be a plate with a Young’s Modulus of previously published data of corneas of human corneas 
with different ages [43]. Furthermore, we used previously published literature which deal with 
vibrations of circular plates in air [44] and water [45] to calculate resonance modes using above 
mentioned Youngs Modulus. We estimated the slope of variation in the cornea’s (first) resonance 
mode with age to 5.6 Hz/year. If we measure an expected Gaussian distributed sample of healthy 
volunteers, we will need to measure 42 subjects to be able to reject the null hypothesis that this 
slope equals zero with probability (power) 0.9. The Type I error probability associated with this 
test of this null hypothesis is 0.05.  
To account for any potential subjects lost in the study, we will have a total target enrollment of 
up to 80 subjects.  
Sample Size and Power for Group 2: Currently, we do not know the effect size (difference in 
elastic modulus) required for power calculation. We are interested to test the performance of our 
device in detecting keratoconus over a small group of patients (N = 10).  
 
IX. RISKS AND DISCOMFORTS 
Risks and discomforts: OCT Vibrography 
OCT is currently the standard-of-care for ophthalmology procedures and the device used for OCT 
Vibrography does not change the safety-related optical parameters relative to clinically deployed 
OCT imaging instruments. The OCT in use is a home built phase-sensitive OCT system which 
employs a polygon scanner swept laser in the spectral range from 1.23 to 1.34 um with a typical 
sweep rate of 45 kHz and an optical power of 15 mW on the sample.  
Direct contact with the cornea is routinely performed for intraocular pressure screening 
measurements by clinically-approved devices, including the Goldmann tonometer, TonoPen and 
iCare. It is a safe and well tolerated procedure provided the following criteria are met:  
• Anesthetic drops are used to numb the cornea (eliminates pain and avoids the corneal 
blinking reflex). The drops will be applied by a trained ophthalmology technician at the 
beginning of the OCT Vibrography session.  
• The contacting surface is smooth and has no sharp edges.  
• The applied force is low 
To the best of our knowledge, there are no official safety limitations describing the minimum 
radius of curvature to contact the cornea. Therefore, we use the parameters of an existing clinical 
instrument (TonoPen XL (Reichert Technologies), which has a diameter of 1mm as the lower 
bound for our tip radius of curvature.  

 
 
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The force applied by our instrument has 2 components: a steady-state force to ensure contact with 
the cornea, and an oscillation to generate shear waves in the cornea. The steady-state force is 
controlled by a spring with a low stiffness constant (a design similar to the Goldmann applanation 
tonometer). The spring is adjusted to produce a maximum force of 50mN (5g), measured by a 
calibrated dynamometer. This force level is very low and can barely be felt. The oscillating force 
generates vibrations in the cornea with an amplitude on the order of 1μm. This vibration level is 
significantly lower than that produced by approved clinical instruments (air-puff tonometers), 
which produce vibrations on the order of 1mm, and is therefore considered largely safe.  The 
actuation force for the vibration is provided by a pair of electrodynamic actuators which operate 
at low voltage (less than 5V).  
Risk of infection from the probe tip, chin and headrest (modified rest from a commercial slitlamp) 
will be minimized by disinfecting the probe, chin rest and forehead rest with alcohol in between 
subjects. To ensure compliance with the ANSI standards, the light source power used in the OCT 
imaging is measured before each imaging session. The values are logged into the experiment book 
for each imaging session and kept on record. If any adjustments are made to the system during a 
session, the power will be measured and recorded again before continuing the imaging session. 
Risks and discomforts: Brillouin Microscopy 
Risks are minimal as the Brillouin Ocular Scanner light source power is within ANSI and ISO 
standards, and it is also less than that of the current commercially available systems that use similar 
light sources. The Brillouin Ocular Scanner has been approved by the radiation safety office and 
biomedical engineering office at Massachusetts General Hospital in previously approved IRB 
protocols. In case of any emergency, a mechanical shutter will block the near infrared laser beam 
by the push of an emergency button. Subjects will be constantly monitored and asked about their 
well-being. Risks of infection are minimal as the BOS obtains images without direct contact to the 
eye itself.  Disinfecting the chin and forehead rests with alcohol wipes in between patients 
minimizes the risk of infection from subject to subject. Discomfort may occur from eye straining 
due to the subject restraining the blinking reflex during scanning. 
We are not aware of any uncommon risks. To ensure compliance with the ANSI 2007 standards, 
the light source power used in the Brillouin imaging is measured before each imaging session. The 
values are logged into the experiment book for each imaging session and kept on record. If any 
adjustments are made to the system during a session, the power will be measured and recorded 
again before continuing the imaging session. 
There may be risks that unknown at this time. 
 
X. POTENTIAL BENEFITS 
There are no direct benefits to the study participants. This study may demonstrate the feasibility 
of using OCT vibrography technology in ophthalmology, which could potentially benefit patients 
with keratoconus and other eye diseases in the future. 

 
 
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XI. MONITORING AND QUALITY ASSURANCE 
The Principal Investigator will be responsible for overseeing all aspects of the study including: 
ensuring that the study is conducted according to the IRB-approved protocol, performing 
monitoring of data and confirming compliance of the study, and protecting the rights, safety, and 
welfare of the subjects. Should the Principal Investigator at any point feel that the health and 
well-being of the subject is compromised, the study procedures will be immediately suspended.  
Therefore, the Principal Investigator will be responsible for determining whether the research 
should be altered or stopped. 
Monitoring of the study data will be made to ensure that all aspects of the current, approved 
protocol/amendment(s) are followed. A monitoring log will be completed for proper 
documentation. 
Subject data will be collected via case report forms. An enrollment log will be maintained and 
will contain the subject’s personal information and hospital record number. It will be only 
available to the approved study staff members and will be stored in a secure location. Subjects 
will be assigned a unique number generated when they enroll in the study. This identification 
number will be the link to the enrollment log.  
The Principal Investigator will ensure the accuracy and completeness of the recorded data. The 
data will be reviewed regularly by the designated study staff and the Principal Investigator. 
Adverse events will be reviewed by the Principal Investigator and will be reported to the Human 
Research Committee within the required time frame and to all participating investigators 
according to the Partners Human Research Committee guidelines.   
Access to study data will be restricted to the study staff listed on the current and approved 
protocol/amendments(s). Data will be recorded, generated, and stored electronically on a secure, 
password-protected server at the Wellman Center, MGH. 
 
XII. LASER EXPOSURE SAFETY CALCULATION 
A. Description:  
A laser exposure safety calculation is added in this section for the OCT Vibrography. The 
rationale is to make sure the laser power is below the maximum permissible exposure (MPE) of 
retina, cornea, and skin.  
From the calculation, the effective output of the laser power used in this study (≤ 15 mW) 
complies with the ANSI Z136.1-2014 safety standard.  
B. Assumptions: 

 
 
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• We use a swept-source laser with wavelength range of 1200-1400nm. MPE for individual 
wavelengths is calculated in section F below. Because the laser source has a broad 
spectrum, the average MPE weighted by the spectrum source is calculated in Section G 
below. 
• Exposure time: >10s (safest case) 
• Source type: point source (safest case) 
C. MPE for ocular exposure (Table 5c) and skin exposure (Table 7b):  
Retina (Table 5c):  5.0 𝐶𝐶× 10−3 [W/cm2] 
Cornea (Table 5c): 0.03 𝐾𝜆+ 0.07 [W/cm2]  
Skin (Table 7b): 0.2 𝐶𝐴 
With (from Table 6a): 
𝐶𝐴=  5.0  
𝐶𝐶= 8 + 100.04(𝜆−1250)  
𝐾𝜆= 100.01 (1400−𝜆)  
D. Limiting apertures (Table 8a and 8b) 
Skin: 3.5 [mm] diameter;  9.62e-2 [cm2] area  
Retina: 7.0 [mm] diameter; 0.385 [cm2] area 
Cornea: 3.5 [mm] diameter; 9.62e-2 [cm2] area 
F. Maximum power  
At 1280 nm (previously used in calculations) 
• Retina: 45.9 mW 
• Cornea: 52.5 mW 
• Skin: 96.2 mW 
At 1300 nm:  
• Retina: 207.9 mW 
• Cornea: 35.6 mW 
• Skin: 96.2 mW 
As a function of wavelength:  

 
 
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G. Average MPE weighted by the source spectrum:  
 
• Retina: 68.6 mW 
• Cornea: 30.0 mW 
• Skin: 96.2 mW 
H. References for broadband calculation: 
F. C. Delori, R. H. Webb, and D. H. Sliney, "Maximum permissible exposures for ocular safety 
(ANSI 2000), with emphasis on ophthalmic devices," J. Opt. Soc. Am. A 24, 1250 (2007). 
[section 8] 
I. Detailed derivation of broadband calculation:  
Starting from Eq.24 in Delori et al (2000), in continuous form:  

 
 
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∫
𝜙(𝜆)
𝑀𝑃Φ(𝜆) 𝑑𝜆< 1 
Where 𝜙(𝜆) is the source power spectral density [mW/nm], and 𝑀𝑃Φ(𝜆) is the maximum 
permissible radiant power [mW].  
Define Φ𝑡𝑜𝑡 the total power of the laser (measured with a power meter):  
Φ𝑡𝑜𝑡= ∫𝜙(𝜆) 𝑑𝜆 
This equation implies:  
𝜙( 𝜆) = Φ𝑡𝑜𝑡[
𝜙(𝜆)
∫𝜙(𝜆)𝑑𝜆] = Φ𝑡𝑜𝑡𝜙̃(𝜆) 
The term between square brackets, noted 𝜙̃(𝜆), represents a normalized power spectrum, which 
can be calculated regardless of the units and at any point in the system (such as measured with an 
OSA). Substituting in the MPE equation:  
∫
𝜙(𝜆)
𝑀𝑃Φ(𝜆) 𝑑𝜆= Φ𝑡𝑜𝑡∫
𝜙̃(𝜆)
𝑀𝑃Φ(𝜆) 𝑑𝜆< 1 
If we rearrange the terms, we can express in the form of a maximal total power Φmax:  
Φ𝑡𝑜𝑡< (∫𝜙(𝜆) (𝑀𝑃Φ(𝜆))
−1𝑑𝜆
∫𝜙(𝜆) 𝑑𝜆
)
−1
= Φmax 
Which is the equation implemented in the Matlab code.  
NOTE: this equation implies that the response of the photodetector used to measure the total 
power is relatively flat around the center wavelength.  
 
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