CORNEAL COLLAGEN CROSS-LINKING WITH RIBOFLAVIN
TREATMENT GUIDELINES - STANDARD
LIGHTLINK-CXL™ CORNEAL CROSS-LINKING SYSTEM
The following information have been based on the results of various clinical studies and are provided with the intention of
serving as general guidance only. Corneal Collagen Cross‐Linking with Riboflavin is considered as an revolutionary and still
emerging technique under clinical investigation, it is the ophthalmologist’s responsibility to familiarize themselves with the
latest recommended treatment techniques. This document should be used in conjunction with the LIGHTLink CXL™ Cross‐
linking system Operators’ Manual.
Theory of Operation
Corneal collagen cross‐linking is being in‐
creasingly renowned as the most innova‐
tive and revolutionary para‐surgical proce‐
dure designated for treatment of progres‐
sive keratoconus of many other corneal
disorders.
Evidence from numerous research institu‐
tions worldwide, demonstrates that Cor‐
neal Collagen cross‐linking is the first real
possibility of successful clinical treatment
of keratoconus and corneal disorders fast
evolving into a “Standard of Care” proce‐
dure.
Based on the current clinically approved
protocols, the corneal cross‐linking proce‐
dure takes approximately 1 hour (30 mi‐
nute corneal soaking plus 30 minute UV‐A
irradiance).
Corneal collagen cross‐linking utilizes Ri‐
boflavin (vitamin B²) such as LightLink
CXL™ as a photosensitizing agent applied
onto the eye, and an ultraviolet light (UV‐A
365±5nm) as activation source from de‐
vice such as the LightLink CXL™.
It is an enzymatic process that adds bonds
between the corneal molecules and elastic
(collagen) fibers. As result, he treatment
increases the corneal resistance which
leads to a complete arrest of thinning of
the cornea and further progression of
keratoconus.
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Mechanism of Action
The combination of Riboflavin and ultravi‐
olet radiation induces a photopolymeriza‐
tion process that increases the corneal
biomechanical resistance through for‐
mation of new inter‐fibrillar covalent
bonds of the corneal collagen.
The UV‐A activated riboflavin stimulates
production of singlet oxygen O² assisting
in a physical formation of new cross‐linked
bonds, across adjacent collagen strands in
the stroma.
The irradiation of the riboflavin molecules
by UV‐A then causes them to lose their
internal chemical balance producing oxy‐
gen free radicals, at which point, the ribo‐
flavin molecule is unstable, and only be‐
comes stable when it is linked to two colla‐
gen fibrils.
It creates a crossed bridge between the
collagen fibrils (thus the term cross‐
linking), producing a general strengthen‐
ing of the cornea. Ongoing clinical re‐
search has demonstrated successful me‐
chanical strength recovery of the cornea,
leading to a complete arrest of Kerato‐
conus progression and increasing corneal
rigidity up to 329%.
Continued
Pg 1 of 4
LIGHTLink CXL™PRODUCT HIGHLITES:
 CUSTOMISABLE TREATMENT OPTIONS:
CAPABLE OF PERFORMING TRADITIONAL AND
RAPED CROSS LINKING TREATMENT IN AS LITTLE AS 3
MINUTES.
OPTIMUM TREATMENT EFFICACY ASSURED BY BUILT IN
PROTOCOLS THAT MAINTAIN THE TOTAL ENERGY AT
INDUSTRY STANDARDS OF 5.4 J/CM².
 Standard: 30 mins protocol
 Intermediate: 10 mins protocol
 Accelerated: 5 mins protocol
 Rapid: 3 mins protocol
 Custom: fully adjustable power and time
settings.
 UNMATCHED CHARACTERISTICS:
 INTELLIGENT OPTI‐ELECTRONICS
 MOST POWERFUL 0‐30 MW UV‐A UNIT
 PANTOGRAPHIC ARM GRIP HANDLES
 INCOMPARABLE SYSTEM INTERFACE
 TREATMENT INSTRUMENT TRAY
 HEIGHT ADJUSTABLE
 INTEGRATED STAND
 BATTERY BACKUP UNIT
 VIDEO & PHOTO FUNCTION:
LIGHTLINK‐CXLTM FEATURES THE ALL‐NEW ELECTRON‐
ICS AND SOFTWARE ALGORITHMS PERMIT TO TAKE
PICTURES AND RECORD THE TREATMENT VIDEOS,
ALLOWING THE PHYSICIANS TO CONVENIENTLY REC‐
ORD THE TREATMENT SESSION, PREFERENTIAL FOR
RESEARCH AND INVESTIGATIONAL USE.
 PERFECT OPTICAL WORKING DISTANCE:
THE OPTICAL HEAD PERMITS A 10.5 CM WORKING
DISTANCE (FROM THE OPTICAL HEAD OBJECTIVE
LENS TO THE PATIENTS EYE).
IT ENHANCES THE OVERALL TREATMENT CONNIV‐
ANCE AS IT ALLOWS THE PHYSICIAN MORE SPACE
TO APPLY RIBOFLAVIN DURING THE PROCEDURE,
AND OFFERS THE PATIENT MORE OPEN SPACE.
Copyright ‐ LightMed

LIGHTLink CXL™PRODUCT HIGH-
LITES: (CONTINUTED)
 PULSED CROSS LINKING FUNCTION:
PULSED CROSS‐LINKING IS BEING INCREASING‐
LY DISCUSSED ABOUT BY PRACTITIONERS AND
INSTITUTIONS, AS THE POTENTIAL PREFERRED
METHOD FOR ACCELERATED CROSS LINKING IN
TREATMENT OF KERATOCUNUS AND PREVEN‐
TION OF POSL LASIK ECTASIA. THE CONCEPT IS
BORNE BY THE FACT THAT UV IRRADIATION
CUTS OFF THE OXYGEN SUPPLY TO THE CORNEA
(AS THE AMBIENT AIR IS THE ONLY WAY OF
OXYGENATING THE CORNEA) IT IS BENEFICIAL
TO ASSURE OXYGENATION PROCESS OF THE
CORNEAL SURFACE DURING THE PROCEDURE.
ALTHOUGH IN EARLY CLINICAL PHASE, THIS
ADJUSTABLE PULSED CROSS LINKING FEATURE
WILL ALLOW OUR CUSTOMERS TO CONDUCT
FURTHER RESEARCH AND INVESTIGATIONS
WITH CONVENIENCE AND SAFETY.
 BUILT IN PATIENTS DATABASE:
THE LIGHTLINK CXLTM FEATURES A BUILD IN
PATIENT DATABASE, WHERE THE PHYSICIAN IS
ABLE TO ENTER THE PATIENTS DETAILS INTO
THE SYSTEM AND RETRIEVE THEIR PERSONAL
DETAILS, INCLUDING PAST TREATMENT SET‐
TINGS. THIS FUNCTION WILL BE FURTHER DE‐
VELOPED IN DUE COURSE, ALLOWING THE
SYSTEM TO GENERATE A TREATMENT REPORT
OR INTEGRATE WITH HOSPITAL EMR DATABASE
MANAGEMENT STEMS.
 SAFETY, PRECISION AND CONVENIENCE:
DESIGNED BY THE OPHTHALMIC LASER EX‐
PERTS, THE LIGHTLINK‐CXLTM OFFERS HIGHLY
SOPHISTICATED TECHNOLOGY AND LASER‐LIKE
FUNCTIONALITY FOR HIGHEST STANDARDS OF
SAFETY AND CLINICAL EFFECTIVENESS, COMPLE‐
MENTED BY CONVENIENT FEATURES.
 BUILT IN POWER METER ASSURES
TREATMENT PRECISION AND SAFETY
 CLOSED LOOP POWER FEEDBACK
SYSTEM ELIMINATES THE NEED FOR
CALIBRATION
 PATIENT FIXATION
 KEY ACTIVATED SYSTEM
 SAFETY INTERLOCK
 ULTRA EFFICIENT QUAD LED CLUSTER
SYSTEM
 TWIN HOMOGENIZER OPTICS FOR
SUPERBLY PROFILED TREATMENT
BEAM.
CORNEAL COLLAGEN CROSS - LINKING WITH RIBOFLAVIN
TREATMENT GUIDELINES - STANDARD
LIGHTLINK-CXL™ CORNEAL CROSS-LINKING SYSTEM
Crosslinks change several physio‐chemical
properties of collagen which is an indirect
evidence for cross‐linking. The following
diagram illustrates the physio‐chemical
properties of collagen induced by Cross‐ Pre-Treatment
linking. Pre operative requirements require prepa‐
ration of the following equipment and sur‐
Eligibility and Exclusion Criteria gical tools:
Ongoing clinical studies and publications 
demonstrate the Corneal collagen cross‐ 
linking with Riboflavin as safe and effective 
treatment indicated for Grades I and II Kera‐

toconus and Iatrogenic Ectasia. Corneal Col‐
lagen Cross‐Linking has also demonstrated 
to be highly effective in conditions such as: 
 Post‐Lasik Ectasia 
 Keratoconus grades I and II 

 Iatrogenic Keratectasia

 Corneal Melting

 (ICR, CK, Ortho K) 
 (Central island prevention) 
 Extended PRK/EPI/LASEK
Preoperative patient assessment is still nec‐
essary to determine whether a patient with
keratoconus or other corneal disorder is an
appropriate candidate for Corneal collagen
cross‐linking procedure. The primary contra‐
diction for the corneal collagen cross‐linking
procedure would be for patients with:
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 Patients with corneal thickness be‐
low 350μm (after removal of epitheli‐
um) in order to prevent the retinal ex‐
posure to the UV light.
 Patients with severe corneal tissue
scarring as uneven cornea (scarred cor‐
neal tissue) may result in hot spots or
penetration of the UV light to the reti‐
na.
 Patients with Keratometry measure‐
ment greater than 58 Diopters as the
cornea may not flatten enough to make
the procedure worthwhile.
 Patients with history of severe cor‐
neal herpes simplex virus, as the expo‐
sure to the UV‐A light may reactivate
the virus.
 Patients with pre‐existing severe dry
eye disease requires preoperative treat‐
ment, because the condition may delay
epithelial healing after corneal collagen
cross linking.
LIGHTLink‐CXL™ System
Collagex™ Isotonic Solution
Collagex™ Hypotonic Solution
Pachymeter
Surgical Microscope
Topical anesthesia drops
Lid speculum
Corneal marker (large edge)
Alcohol 20%
Eye sponges
Eye pad
Antibiotic eye drops
Bandage contact lens
Copyright ‐ LightMed
CORNEAL COLLAGEN CROSS - LINKING WITH RIBOFLAVIN
TREATMENT GUIDELINES - STANDARD
LIGHTLINK-CXL™ CORNEAL CROSS-LINKING SYSTEM

Standard Treatment Procedure (about 10 mins) till you are sure that the cornea swelled > 400
microns by re‐measuring the corneal thickness.
Step A:
3. Check the riboflavin diffusion in the anterior chamber at the
Prepare the patient bed with the LIGHTLink‐
slit lamp if you can.
CXLTM System well‐adjusted before laying
down the patient, and make sure that the Step D: UV Application
pachymeter work correctly. 1. Adjust the LIGHTLink‐CXLTM System and let the pa‐
Step B: Corneal Abrasion tient looks steady inside at the fixation target, me‐
1. Place the patient comfortably in a clean dium aperture (must avoid the limbus).
well conditioned room (will remain 2. Select the desired treatment spot size.
more than 1 hour).
a. The size of the treatment beam should be the
2. Put on drop topical anesthesia. largest possible but smaller than the limbus diam‐
3. Check the corneal thickness by the eter to avoid destruction of corneal stem cells.
pachymeter at the thinnest location 3. Start irradiation by delivering 3 mw/ cm2 for 30
which is slightly de‐centered inferiorly mins (very easily set with the Cross‐Linking con‐
in keratoconus patients. Usually is >400 sole).
micron, if lower then expect a thin cor‐
4. Continue riboflavin drops every 4‐5 mins till the end
nea after removing the epithelium.
of the procedure (reminder sound timer 0‐8
4. Place the speculum. minutes can be very easily set on the Cross‐Linking
5. While looking through the microscope, system).
place firmly the corneal marker on the 5. Make sure all these 30 mins that the UV light is well
cornea well centered and put in it few cantered and in focus.
drops of alcohol 20% for 30 seconds
6. The LIGHTLink CXLTM system will turn off automati‐
then soak the alcohol with the eye
cally at the end of the procedure.
sponge.
6. With a new corneal sponge remove
Step E: Finishing the Procedure
easily the fragile epithelium (Usually 1. Put one drop antibiotic eye drops.
epithelium thickness is about 50 mi‐ 2. Put a bandage contact lens.
crons).
3. Remove the eye speculum.
a. Epithelium abrasion usually 8‐9mm
Step F: Post Treatment
7. Check again the corneal thickness:
 Start both the antibiotic eye and topical steroids 4
a. If>400 microns, then proceed with
times for 4 days.
only riboflavin with dextran,
 Apply Analgesics as needed.
b. If below< 400 microns, then pre‐
pare also riboflavin without dex‐  May use artificial eye drops.
tran.  Follow up daily, remove the lens on Day 4.
Step C: Corneal Soaking with Riboflavin
1. Proceed by installing one drop of ribo‐
flavin with Dextran 3 mins for 30 mins
(Cross‐Link timer reminder can be set,
however if the buzzing sound is found
to be distracting simply of follow the
timing of the watch).
2. At the end of the 30 mins, recheck the
corneal thickness by the pachymeter
again, if < 400 microns then start using
the riboflavin without dextran 2‐3 mins

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CORNEAL COLLAGEN CROSS - LINKING WITH RIBOFLAVIN
TREATMENT GUIDELINES - STANDARD
LIGHTLINK-CXL™ CORNEAL CROSS-LINKING SYSTEM

CollagexTM ISOTONIC & HYPOTONIC Solution Method and duration of use:

1. The application of the drip operation begins 30 minutes be‐
fore the light therapy.
2. Depending on individual circumstances and as per the doc‐
tor's advice, 1 drop each will be instilled onto the cornea
every 3 minutes throughout the treatment period.
3. The duration of usage is determined by the doctor.

Side effect:
Hypersensitivity reactions (burning) may occur temporarily.
collagex – ISOTONIC (0.1%) with 20% Dextran T500 Ultra Hi‐ These symptoms usually begin in discontinuation.
Quality riboflavin solution for Normal Corneas of 350μm and
above. In 1ml glass syringe. ‐ In 3ml glass syringe applicator. ‐ Contraindications: The medical device may not be used in
Individually Packed in Sterile pouches. 1. Pregnancy
2. Simultaneously with the eye to be administered drugs
collagex – HYPOTONIC (0.1%) Riboflavin Ultra Hi‐Quality ribofla‐ 3. Hypersensitivity against any of the components exists
vin solution for treatment of thin corneas of below 400μm In
1ml glass syringe. ‐In 1ml glass syringe applicator. ‐Individually Precaution:
Packed in Sterile pouches. 1. The product is sterile, do not use if package is damage.
2. Storage keeps in dark.
Composition of Collagex™ ISOTONIC & HYPOTONIC 3. For single use only, do not re‐sterilize.
Solution 4. Discard after open 12 hours. Dextran in solution is a good
Name ISOTONIC HYPOTONIC culture medium for any kind of germs.
Volume/does 3ml 1.5ml
PH Shelf life: 2 Years
6~7.6 6~7.6
Formula Riboflavin > 0.1% Riboflavin > 0.1%
Dextran 500 20% Na2HPO4
Na2HPO4 NaH2PO4
NaH2PO4 Water for injec‐
Water for injec‐ tion
tion

Instructions for use CollagexTM Solution

Intend for use:
CollagexTM Solution is intended to provide the barrier against
For more information visit or contact us at:
UVA penetration the corneal stroma, and thus protect the
delicate internal structures of the eye (corneal endothelium, LightMed USA
lens and retina) from damage. 1130 Calle Cordillera,
San Clemente, CA 92673
Note to the patient: USA
The application is temporarily reduced visual acuity. Don’t T: + 1‐949‐218‐9555
drive, operate machinery, and write until the normal visual F: + 1‐949‐218‐9556
acuity has come back. E‐mail: sales@lightmed.com
Web: www.lightmed.com
Properties:
1. The water‐soluble riboflavin is the cause of yellowing of the LightMed Corporation
eye drops. No.1‐1, ln.1 Pao‐An St. sec.3
2. CollagexTM Solution was applied when the patient receive Shulin Dist, New Taipei City 23861
the corneal collagen cross‐linking treatment with UVA colla‐ Taiwan
gen cross‐linking instrument.
T: + 886‐2688‐1726
3. Corneal collagen cross‐linking treatment is indicated for
F: + 886‐2676‐4920
Progressive keratectasia of any form, Iatrogenic keratecta‐
E‐mail: sales@lightmed.com
sia after LASIK, Pellucid marginal degeneration, and Corneal
melting.
Web: www.lightmed.com

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