CRYSTALSIGHT: Clinical Evaluation of OCCUTRACK's CRYSTALSIGHT Device Through Remote Monitoring for Disease Recurrence of Wet Aged-Related Macular Degeneration Using Eye Gaze Tracking (Cohort 2.0).
Phase: NA
Conditions: Maculopathy
Sponsor: Tan Tock Seng Hospital

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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CRYSTALSIGHT: Clinical Evaluation of 
OCCUTRACK’s CRYSTALSIGHT Device through 
Remote Monitoring for Disease Recurrence of Wet 
AMD (Cohort 2.0) 
 
Main Study Site: Tan Tock Seng Hospital, Singapore 
Principal Investigator: 
Dr Augustinus Laude 
Senior Consultant 
NHG Eye Institute, 
Tan Tock Seng Hospital 
National Healthcare Group, Singapore 
 
Co-Investigator(s): 
Dr Elizabeth May Chin Tan 
Senior Resident 
NHG Eye Institute, 
Tan Tock Seng Hospital 
National Healthcare Group, Singapore 
 
Collaborators: 
Mr Soh Zheng Kuang Noel 
 
Mr Mark Wong 
Clinical Research Coordinator 
 
Chief Executive Officer 
NHG Eye Institute,  
 
 
OCCUTRACK Medical Solutions Pte Ltd 
Tan Tock Seng Hospital 
National Healthcare Group, Singapore 
 
 
Study Summary 
 
Age-Related Macular Degeneration (AMD) and Diabetic macular Edema (DME) is one 
of the main causes of central vision loss. Most patients require pharmacologic 
treatment with anti-vascular endothelial growth factor (VEGF) agents with multiple 
follow-up visits that include optical coherence tomography (OCT), visual acuity testing 
and multiple injections.  
 
The high frequency of visits puts pressure on eye clinics and can be extremely 
stressful for both patients and their caregivers. Therefore, portable and rapidly 
deployable self-administered home-based examination devices are key to making 
telemedicine a reality.  
 
OCCUTRACK Medical Solutions has developed a portable, self-administered device 
designed for gaze-tracking and monitoring of patients with retinal diseases such as 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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AMD and DME, and choroidal neovascularization (CNV) that require multiple anti-
VEGF injections.  
 
The team have confirmed the performance of the CRYSTALSIGHT device and 
validated the retinal thickness measurements obtained with this device by comparing 
it to in-hospital Optical Coherence Tomography (OCT) (Heidelberg Spectralis). In this 
study, the team will conduct a randomized clinical trial RCT to compare the efficacy 
and cost-effectiveness of a Pro Re Nana (PRN) management regimen enhanced with 
the CRYSTALSIGHT home monitoring device for the detection of central 
metamorphopsia with existing PRN standard of care for patients with AMD or DME 
exiting the anti-VEGF injection regimen.  
 
Study Objectives 
Primary Objective: 
To demonstrate that the home monitoring of a PRN regimen with the CRYSTALSIGHT 
telemonitoring system is non-inferior to the Amsler grid1 in detecting recurrence of wet 
AMD based on central retinal thickness (CRT) increase of at least 50 microns or a loss 
of best-corrected visual acuity (BCVA) of 5 letters or more. 
Detection of using visual field test gaze tracking results in earlier detection of 
AMD/DME associated with (CNV), as reflected by better visual acuity compared with 
standard care. Outcome of this trial is to determine the sensitivity and specificity of 
CRYSTALSIGHT with reactivation subtle neovascular age-related macular 
degeneration that was detected by the regular use of a home monitoring device based 
on gaze-based preferential hyperacuity visual field testing.  
An important predictor of the benefit of treatment with anti-vascular endothelial growth 
factor (VEGF) agents is visual acuity at the time of CNV treatment. 
Secondary Objectives 
1. Correlate CRYSTALSIGHT scores with BCVA and OCT findings. 
2. Identify diagnostic performance of CRYSTALSIGHT (ROC, AUC). 
3. Develop risk scoring algorithms for wet AMD recurrence. 
Background work 
 
For patients who have lost vision in one eye due to wet age-related macular 
degeneration (wAMD), preservation of functional visual acuity in the other eye is of 
paramount importance. However, clinical experience and research have shown that 
these and other high-risk patients often fail to use the Amsler grid between clinic visits 
to detect the earliest signs of neovascularization in their good eye.  
 
Normal human vision consists of a series of rapid eye movements called saccades 
that abruptly change the fixation point depending on the area of the person's eye. 
OCCUTRACK’s CRYSTALSIGHT device tracks these eye movements with generated 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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patterns on the screen, a visual assessment of affected and unaffected eyes is 
achieved without expensive optics and at home on any tablet or laptop computer. 
 
CRYSTALSIGHT is a home-based gaze-tracking readily available for home 
hyperacuity monitoring for these and other high-risk eyes with diagnosed wet-AMD.  
 
The Device 
 
  
Figure 1 CRYSTALSIGHT device being used in a home-based setting.  
The system consists of a gaze-based hyperacuity perimetry device that requires no physical 
interaction, the software generates proprietary metamorphopsia detection algorithms, and the 
specific telemonitoring protocols that are followed at a prescribing trial centre. Occutrack 
supplies the devices to patients who have received a prescription from an ophthalmologist. 
 
 
 
A 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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Figure 2 A: The device comprises of a proprietary camera that tracks the user’s gaze point. B: Perspective of the 
camera 
with 
machine 
vision 
augmentation.
 
Figure 3 Participants in the study will be provided with a monocular occluder that is attached to A: corrective 
prescription frames (a) or a B: lensless frame, gaze-tracking accuracy is unaffected by lenses. 
When an wAMD patient takes a test done twice weekly — the results are transmitted 
electronically to the clinical trial site. If the algorithm detects suspicious results, a digital 
flag is raised and a manual comparison to the patient’s baseline is reviewed by the 
principal investigator (PI).  
 
As for test results, the location and size of metamorphopsias and scotomas are 
inferred from the patient’s reaction patterns to a series of generated dot patterns that 
the CRYSTALSIGHT device flashes at various points in the visual field. Some dots 
appear, move and disappear pseudo-randomly on the screen, the patient simply 
needs to look at the screen.  
 
The purpose of this clinical validation study is to demonstrate that the 
CRYSTALSIGHT automated vision screening device is suitable for use at home twice 
a week to detect the recurrence of wet AMD in all ethnic groups. 
 
Compared with the patient’s baseline tests, erroneous or absent clicks indicate 
metamorphopsia, which could be due to early choroidal neovascularization (CNV). 
The threshold for a positive test for each parameter before this study start is 
determined by the on-going cohort-1 clinical study in progress. 
 
Patients are automatically reminded if they fail to test themselves regularly. The 
treating ophthalmologist receives monthly longitudinal reports and immediate 
A 
B 
A 
B 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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notification of abnormal readings so that an examination can be scheduled 
immediately. 
 
The patterns of the dots are described as follows:  
 
Static Fixation 
Evaluation (SFE) 
Static Perimetry 
Assessment (SPA) 
Static Perimetry 
Sensitivity 
Assessment (SPSA) 
Pursuit 
Visual Field 
fixation 
Saccadic visual 
field 
Saccadic Visual Field 
Sensitivity 
Ocular motility 
A single large 
discrete target is 
displayed filling 
the entirety of the 
screen and shrinks 
to 10pixels for 5 
seconds. The 
target is presented 
twice.  
The user under 
test’s fixation 
radius is scored as 
a Circular-Error 
Probable (CEP) 
size. The smaller 
the CEP radius, 
the better the test 
result. 
A set of 13 discrete 
targets are 
displayed randomly 
and twice 
repeatedly on fixed 
coordinates for a 
preset duration of 1 
second (adjustable) 
on the screen for 
the user under test.  
Targets are 
presented in a 
pseudo-randomly to 
avoid bias in gaze 
point detection. An 
area-of-effect 
radius is scored if 
the user’s gaze 
intersects with the 
presented target.  
A set of 13 discrete 
targets that increases 
in radius at 10 
pixels/second are 
displayed randomly 
on fixed coordinates 
on the screen for the 
user under test.  
Targets are presented 
in a pseudo-randomly 
to avoid bias in gaze 
point detection.  
The target radius is 
scored if the user’s 
gaze intersects with 
the presented target 
at the presented 
radius size. The 
smaller the radius, the 
better the test result. 
Subject under 
test to pursue a 
generated target 
moving in a 
sinusoidal 
pattern at a 
speed of 5cm/s. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Methodology 
 
This study aims to determine whether home-based monitoring using the CRYSTALSIGHT 
gaze-based Hyperacuity Perimetry system, when added to a PRN treatment regimen, is non-
inferior to standard care using the Amsler Grid in detecting recurrence of choroidal 
neovascularisation (CNV) associated with wet age-related macular degeneration (AMD). 
 
Recurrence is defined by a central retinal thickness (CRT) increase of ≥50 microns or a loss 
of best-corrected visual acuity (BCVA) of ≥5 letters. 
 
The study also aims to evaluate whether CRYSTALSIGHT enables earlier detection of CNV 
progression, as reflected by better VA and CRT values at the time of detection, through 
biweekly self-tests conducted in an unsupervised home setting. 
Study Design 
 
This is a randomised, open-label, non-inferiority clinical trial comparing two parallel arms: a 
standard care arm using Amsler Grid home monitoring (PRN), and an intervention arm using 
the CRYSTALSIGHT gaze-tracking system (PRN+). A total of 220 (Singapore – 60, United 
Kingdom – 80, United States – 80) participants will be randomised in a 1:1 ratio. Participants 
in the intervention arm will self-administer biweekly CRYSTALSIGHT tests at home, while 
those in the control arm will use the Amsler Grid. Both arms will attend monthly clinic visits for 
standard evaluations, including VA, BCVA, and OCT. Alerts generated by the 
CRYSTALSIGHT system based on deviation thresholds will trigger early clinic recall for 
confirmatory imaging and potential re-treatment. 
 
 
Figure 4 Details of the home-use clinical trial study design. The trial objective: show that PRN+ is non-inferior to 
standard of care PRN with better VA/VF outcomes 
Development of CRYSTALSIGHT cutoff scores should have been conducted in the cohort-1 
1 study [NCT: NCT06518512] (Analysis).  This Phase 2 should be the application of validated 
cut-off scores. The second aim will be to compare the accuracy of CRYSTALSIGHT and 
Amsler, and sensitivity and specificity check. 
 
In addition to identifying CRYSTALSIGHT visual risk prediction cut-off scores, detection yields, 
and diagnostic Performance indicators will also be evaluated. Progression to CNV was 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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determined by the investigator, based on standardised OCT confirmation. At the clinical trial 
site, these events were confirmed by gradings conducted by masked, certified independent 
personnel who did not know the treatment assignment. Events from both arms are graded 
using a standardised protocol. 
 
 
Figure 5 In Cohort 2, home-based score deviation detected, study coordinator will schedule hospital checkup 
immediately. If CRYSTALSIGHT correctly detects wet AMD recurrence confirmed by OCT, subject exits the study. 
 
This study will use the CRYSTALSIGHT system in an unsupervised home setting. 
Participants will perform biweekly self-monitoring with the CRYSTALSIGHT device. 
The threshold algorithm will be implemented and validated with subjects. Threshold 
information from Cohort 1 will thus be incorporated into the Cohort 2 intervention 
measures. Figure 5 illustrates the function of the CRYSTALSIGHT score as the basis 
for an intervention measure: an earlier-than-expected clinic visit should be scheduled 
immediately for clinic vision testing and urgent anti-VEGF administration. 
 
Pro Re Nata (PRN): Standard treatment (control arm) 
 
Participants randomized to the standard treatment arm received specific instructions 
from investigators for self-monitoring of vision at home to detect progression of AMD. 
Aids such as the Amsler grid. This group is referred to below as the standard treatment 
group. If participants experienced symptoms, they were instructed to call their clinical 
centre immediately and schedule an appointment within 72 hours. 
 
 
PRN+: Home monitoring device (device arm) 
 
In addition to the same standard of care instructions, participants will receive a 
CRYSTALSIGHT home monitoring device with instructions for installation and use. 
This arm is referred to below as the device arm. In cases where baseline 
measurements could not be obtained due to a pre-existing visual field defect in at least 
one study eye, participants returned the device and continued monitoring with 
standard treatment only but were still included in the final analyzes in the intent-to-
treat (ITT) cohort as part of the device arm. 
 
Participants were encouraged to use the device twice a week, and results were 
automatically transmitted via internet cloud to a Occutrack’s data monitoring center. If 
testing of the device indicated a change from baseline measurements, an alert was 
sent from the monitoring center to the participant’s clinical center, prompting staff to 
schedule an appointment with the study ophthalmologist within 72 hours. 
 
This study is an open-label, randomized study designed to evaluate the safety and efficacy 
of the CRYSTALSIGHT device when used by patients in their own homes. The study will 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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recruit a group of patients who meet certain eligibility criteria and provide them with the 
CRYSTALSIGHT device for use at home.  
 
The Cohort 2 study typically several phases, including a screening phase to identify eligible 
patients who could be recruited patients exiting the anti-VEGF injection clinic. The phases 
are:  
 
• 
Training: a training phase for the device to ensure that patients know how to use the 
device properly, a testing phase in which patients use the device to monitor their vision 
condition using the CRYSTALSIGHT device over a period of time until the device 
detects deterioration in vision and meets the criteria for deterioration established by 
the Cohort 1 results, and a follow-up phase to assess results and obtain feedback from 
patients. 
• 
Monitoring: During the study, patients will be asked to follow the specific protocols 
and guidelines for use of the CRYSTALSIGHT device, such as completing the bi-
weekly regular testing. Patients will also be asked to report or provide feedback on any 
adverse events or problems encountered while using the device. 
• 
Intervention: Should the CRYSTALSIGHT device determine that a threshold for vision 
deterioration has been reached (delta deviation of 10 points from the nominal 
baseline), the patient/participant will receive a notification from the prescribing 
physician and the electronic alert system via email to the subject's personal mobile 
device instructing them to schedule an appointment for confirmation OCT -A that the 
subject's wet AMD has recurred, see Figure 6 below. 
 
 
Figure 6 True-False confusion matrix of cohort-2 will require OCT confirmation of wet AMD disease recurrence that 
was detected by CRYSTALSIGHT.  
 
This cohort 2 intervention study is designed to collect data on the safety and efficacy 
of the device, including information on the accuracy, reliability, and ease of use of the 
device. The study may also examine the impact of the device on patient outcomes, 
such as changes in visual status or quality of life. 
 
Once the study is complete, the data will be analyzed to determine if the device is safe 
and effective for home use. If the results are positive, the device can be submitted to 
the FDA for approval and made available to patients who need it. 
 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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Cohort-2 study relationship to the cohort-1 
 
The CRYSTALSIGHT eye tracking system is a medical monitoring system used to 
treat age-related macular degeneration (AMD). AMD is a disease that affects the 
macula, the part of the eye responsible for central vision. CRYSTALSIGHT helps 
people with AMD maintain their quality of life by improving their ability to perform 
everyday activities. 
 
 
Figure 7 Cohort 1 results of a single test subject showing the correlation of OCT scores to CRYSTALSIGHT at two 
clinic visits. 
 
 
Figure 8 Population of cohort-1 study, each box represents a tested eye (total 36 eyes in this plot), each dot 
represents a single clinic visit, green =CRYSTALSIGHT, blue = OCT.  
 
 
 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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Cohort 1 
Cohort 2 
Trial 
objectives 
Verify OCT versus 
CRYSTALSIGHT correlation 
(threshold score) 
wAMD/DME recurrence detection - 
(intervention alerts) 
Device 
CRYSTALSIGHT camera with 
Tobii ET5L 
CRYSTALSIGHT camera only 
 
OR 
 
Digitized amsler Grid 
Physician 
interaction 
Four times:  
1. Registration 
2. First follow up  
3. 2nd follow up  
4. Exit 
 
 
 
PRN* regimen: 
1. Registration 
2. Monthly clinic visits 
3. Intervention 
4. Exit 
 
*(PRN scheduled clinic visits will 
proceed normally) 
Size 
100 
220 
Intended 
use 
Clinic based 
Home-based 
 
In Cohort-1, the CRYSTALSIGHT system will be used in a clinical setting under the 
guidance of a trained healthcare professional to confirm the correlation between 
CRYSTALSIGHT and OCT in the same study participant longitudinally and establish 
a threshold for "deterioration." 
 
Recruitment 
1. Eligibility Diagnosis: The PI determine eligibility and will inform a potential 
participant (diagnosed with wAMD who is on a treatment regimen) to 
determine if CRYSTALSIGHT is an appropriate monitoring option. 
2. Enrolment: If CRYSTALSIGHT is deemed appropriate for the patient, the PI 
or study coordinator will enroll the patient in the trial for the device and provide 
the patient with instructions for using the device. 
3. Training: the study coordinator trains the participant on a CRYSTALSIGHT 
device to familiarise the patient with the device and ensures that the patient 
understands and follows the rules for home use.  
4. Initial monitoring: The PI will start the participant on self-monitoring with 
CRYSTALSIGHT twice a week and monitor the participant's baseline gaze 
performance via the CRYSTALSIGHT electronic database. 
5. Maintenance Monitoring: Once the participant has achieved a nominal 
baseline level of visual performance, the system will remind the participant to 
regularly monitor their visual performance with the CRYSTALSIGHT device at 
the scheduled frequency. 

 
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6. Follow-up: The PI will schedule regular follow-up appointments to monitor the 
participant's progress and adjust monitoring frequency as needed. 
It is important to note that CRYSTALSIGHT does not work for all participants 
and it may take several months to detect disease relapse. 
Study Schedule Table 
Baseline 
Visit #1 
Month 1 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) 
 
Research Procedure 
• CRYSTALSIGHT Eye Gaze Tracking for investigative arm and 
insurance of CRYSTALSIGHT device for home monitoring. 
 
OR 
 
• Amsler Grid for Amsler Grid arm 
 
Follow Up 
Visit #2 
Month 2 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
 
Follow Up 
Visit #3 
Month 3 
(+/- 
Four weeks) 
 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #4 
Month 4 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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Follow Up 
Visit #5 
Month 5 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #6 
Month 6 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #7 
Month 7 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #8 
Month 8 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #9 
Month 9 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Follow Up 
Visit #10 
Month 10 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
 

 
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Follow Up 
Visit #11 
Month 11 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• 
Colour Fundus Photography 
• Clinical Consultant Review 
 
Study Exit 
Visit #12 
Month 12 
(+/- 
Four weeks) 
Standard Routine Care 
• Visual Acuity (VA) 
• BCVA (Optional) 
• Optical Coherence Tomography (OCT) 
• Colour Fundus Photography 
• Clinical Consultant Review 
• Intravitreal Injections (IVT) (Optional) 
 
Locations 
Three study sites are proposed:  
 
1. Dr. Dorothy L. Hitchmoth, PLLC, New London, United States 
2. The Princess Alexandra Eye Pavilion in Edinburgh, Scotland, United Kingdom 
3. Tan Tock Seng Hospital, Singapore 
Timeframe 
 
Estimated Start Date: June, 2025 
Estimated Completion Date: August, 2026 
Eligibility  
 
Inclusion / exclusion criteria of this study are as follows.  
 
Participation Requirements: 
Genders: Both 
Minimum Age: 55 
Healthy Volunteers: No 
 
 
Inclusion criteria 
1. Subjects in the age group ≥ 55 to 99 years old. 
2. Both genders 
3. Able to understand verbal spoken instructions in British/American English, 
Chinese or Bahasa Melayu and demonstrate device functionality and 
implementation.  
4. Able to turn on and connect the CRYSTALSIGHT device to a computer 
independently or with the help of family. 
5. Subjects undergoing treatment for Wet-AMD without any signs and symptoms 
of recurrence of active AMD (AMD recurrence: choroidal neovascularisation, 

 
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intraretinal or subretinal fluid is present) with OCT lesion fluid volume more than 
2 mm2 or ILM height more than 300µm.  
6. Ability to comply with the study protocol, in the investigator's judgment. 
7. Subjects must be able to understand and provide informed consent. A signed 
informed consent form must be provided before any study assessments. 
 
Exclusion criteria 
1. Unable to understand verbal spoken instructions and demonstrate device 
functionality and implementation.  
2. Unable to turn on and connect the CRYSTALSIGHT device to a computer 
independently. 
3. Any ocular surgery in the previous 3 months, or vitrectomy in the previous 12 
months 
4. Any history of macular pathology unrelated to AMD affecting vision or 
contributing to the presence of intraretinal or subretinal fluid in the study eye 
5. Any concurrent intraocular condition in the study eye that, in the opinion of the 
investigator, could either reduce the potential for visual improvement or require 
medical or surgical intervention during the study 
6. Any prior or concomitant treatment for CNV or vitreomacular-interface 
abnormalities in the study eye.   
7. History of idiopathic or autoimmune-associated uveitis in either eye 
8. Active ocular inflammation or suspected or active ocular or periocular infection 
in either eye. 
 
Study population: patients with recurrent vision problems diagnosed with active Wet-AMD 
at TTSH eye clinics.  
 
Pre-specified clinical outcome: The prespecified adverse clinical outcome used in this 
study will be the recurrence of Active Wet AMD, which will be identified by an increase in 
central retinal thickness (CRT) of at least 50 microns or a loss of best-corrected VA of 5 
letters or more.  
 
Training 
To prepare for home use of the CRYSTALSIGHT device, the following processes are 
performed in the clinic: 
• The examining physician or study coordinator will unpack a CRYSTALSIGHT 
training unit for the patient to help the patient understand the device and ensure 
that the home user understands the device, its purpose, and how it works. 
Instructions on how to set it up at home include connecting the device to a 
laptop with an Internet connection. 
• The study coordinator will explain the testing procedure in the language the 
patient knows (English, Chinese, Malay, and Tamil). The study representative 
from the clinical trial site hospital will train the subject on using the device. This 
involves demonstrating how to take the test and interpret the results. The user 
should learn the test procedure, including how to prepare for the test, perform 
the test, and interpret the results. 

 
CRYSTALSIGHT Cohort 2.0, Version 1.0, Dated 5 June 2025 
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• A training video is then played to illustrate how the device works. The study 
participant must watch the 5-minute video. 
• After watching the video, the user should be familiar with the device's various 
parts, such as how to position the device on a computer best and how to launch 
the test program in the computer's browser. 
• Practice with the device: then the user practices using it on himself/herself to 
get a feel for how it works. This will help him/her become more confident and 
familiar with the CRYSTALSIGHT device. 
• Weekly Use: The subject will be instructed to use the CRYSTALSIGHT device 
twice a week, usually in the evening or when they are most likely to be relaxed 
and focused. 
• All records are sent electronically to Occutrack's cloud server. The records 
include each user's unique identification number (UUID), vision test results, and 
the date, time, and results of each test. This helps them track their progress 
and identify trends or patterns in their wet AMD disease. 
Troubleshooting 
If a participant experiences technical difficulties, the study coordinator is available for 
teleconsultation on weekdays from 9 am to 5 pm during office hours. For the Cohort 
2 study, there are several options for remediation. 
1. 
Participants may contact their physician, the study coordinator PI, or a 
trained health care professional if they have questions or concerns about 
using the device or interpreting the results. 
2. 
Read the manual: The participant can carefully read the manual included 
with the device. The manual provides instructions on how to properly use 
the device, interpret results, and troubleshoot common problems. 
3. 
Troubleshooting: The subject should be familiar with common problems 
that may occur when using the CRYSTALSIGHT device and how to 
correct them. These may be problems with the camera, mounting position, 
or software interface. 
4. 
Follow best practices: The participant should follow best practices when 
using the device, including placement, head position, and attention to 
stimulation targets on the screen. 
By following these steps, a new user can master the CRYSTALSIGHT health 
monitoring device and effectively manage their AMD condition. 
How are they going to get the device 
One CRYSTALSIGHT boxed unit will be signed over to the study participant to bring 
home after the recruitment administration is done during the regular clinic check-up 
and when the participant has agreed and signed the Informed Consent Form (ICF) to 
be included in the study.  
System reminders 
A study coordinator will monitor the electronic records system and will call the 
participant to conduct a self-test at home if they miss the test by 1 day. A system 

 
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reminder will automatically send a message and email to remind the user to take the 
test if a scheduled self-test is missed by a day.  
Results and reporting: The results of the tests will be transmitted to a secure 
server where they will be analyzed by the principal investigator and study 
coordinator. If any changes in vision are detected, the subject will be contacted by 
the study coordinator and a follow-up appointment will be scheduled.  
 
Sample size calculation:  
According to the workflow, all participants will have routine visits to clinic with OCT 
scans performed once every 4 weeks. Participants randomised into the 
CRYSTALSIGHT group will have measurements taken twice a week if the testing 
results are all negative. In case of a positive result with CRYSTALSIGHT, another 
test will be done on the next day. Participants will be recalled for review after two 
consecutive positive results are presented. Depending on the pathology presented 
on the OCT scan, IVT may be given for disease management. On the other hand, 
participants randomised into the Amsler Grid group will be evaluated by Amsler Grid 
and by OCT. 
 
For participants in the CRYSTALSIGHT group, each participant will have a testing 
result by CRYSTALSIGNT and by OCT every 4 weeks or less if the positive result 
triggers a clinical visit. The result is considered correct if it is consistent with the 
findings of the OCT scan. During the one-year study period, the total number of 
correct results generated by CRYSTALSIGHT will be counted and the accuracy for 
these participants will be calculated as number of correct results divided by the total 
number of clinical visit. For participants in the Amsler Grid group, the accuracy for 
each participant will also be calculated. 
 
According to literature, the accuracy of Amsler Grid in detecting disease activity was 
about 80%, we will assume that CRYSTALSIGHT has the same accuracy. For the 
Singapore population, we will also assume that standard deviation of the accuracy to 
be 0.12 and setting the maximum allowable difference in accuracy (non-inferiority 
margin) between the two groups to be 0.09, with one-sided type 1 error of 0.025 and 
a power of 0.8, a total of 52 participants will be required (26 per group). Considering 
of 15% attrition rate, a total of 60 participants will be required. 
 
For global study, we assume a higher standard deviation of the accuracy to be 0.21 
and a dropout rate of 21%, a total of 220 participants will be required (110 per 
group).