Review Article

Contact lens assisted corneal cross linking in thin ectatic corneas – A review

Sanjana Srivatsa1, Soosan Jacob1,2, Amar Agarwal1

Contact lens‑assisted corneal cross‑linking (CACXL) was introduced by Jacob et al. in 2012 for treating thin Access this article online
keratoconic corneas using riboflavin soaked soft contact lens to artificially increase the functional corneal Website:
thickness. It is advantageous over other thin corneal cross‑linking techniques as it works independent of www.ijo.in
swelling properties of the cornea, is an epi‑off technique and does not require additional time, additional DOI:
expensive equipments or special solutions. The only additional requirement as compared to all other 10.4103/ijo.IJO_2138_20
techniques is a UV barrier‑free soft contact lens (SoflensTM, B&L) which is easily available and inexpensive. PMID:
*****
Advantages include simplicity, easy adaptability, early visual rehabilitation, good visual outcomes,
safety, and efficacy. Progression rates are acceptable and the need for re‑treatment has been low. CACXL Quick Response Code:
can help regularize corneal shape and may be used in isolation or synergistically with Intracorneal ring
segments (ICRS) or Corneal allogenic intrastromal ring segments (CAIRS). It gives about 70% stiffening
as compared to standard Dresden protocol CXL in less ideal porcine eye studies. Murine eye models that
closely mimic thin corneas and show greater cross‑linking effect as compared to porcine eyes may be a better
model for evaluation of CACXL, however further studies are needed. Care should be taken in selecting the
right kind of contact lens. Proper technique should be followed, especially by confirming thinnest functional
pachymetry to be above 400 microns intra‑operatively before application of UV‑A. The sub‑contact lens
riboflavin film should be avoided as also an excessively thick supra‑contact lens riboflavin film and too
many re‑applications.

Key words: Contact lens, contact lens assisted cross‑linking (CACXL), corneal allogenic intrastromal ring
segments (CAIRS), thin cornea

Keratoconus is a bilateral asymmetric condition which causes irradiation resulting in the formation of intrafibrillar and
progressive corneal thinning and protrusion leading to irregular interfibrillar covalent bonds in the anterior 250–300 µm of
astigmatism and visual deterioration.[1] It typically begins at puberty corneal stroma, thus increasing the overall biomechanical
and tends to progress until the 3–4th decade of life.[2] Progression of strength (usually upto 300%).[4,6‑8] Nevertheless, conventional
keratoconus is defined as increase in steepest keratometry (Kmax) CXL has the limitation that it can be safely performed only when
by >1 Diopter (D), increase in flattest Keratometry (Kmin) by >1D, the corneal thickness after de‑epithelialisation is >400 microns.[9]
increase in mean keratometry (Kmean) by >0.75D, increase in Wollensak et al. showed an irradiance of 0.37 mW/cm2 and above
manifest spherical equivalent >0.5D and decrease in central to be cytotoxic to the endothelial cell layer.[9] In a 400 microns
corneal thickness by >2%.[3] thick cornea saturated with riboflavin, the irradiance at the
endothelial level is 0.18 mW/cm2, which is 2‑fold lesser than the
Cross‑linking (CXL) was introduced by Wollensak et al.
damage threshold. Therefore 400 microns is considered as the
in 2003 to arrest the progression of keratoconus. [4] The
safe limit to protect the endothelium and intraocular structures
introduction of cross‑linking has significantly altered the
from the adverse effects of UV‑A irradiation. CXL in thinner
management of keratoconus, preventing irreversible corneal
corneas with the standard protocol is of concern considering the
damage and the need for keratoplasties.[5] The standard
possible complications such as permanent endothelial damage,
Dresden protocol (conventional CXL) involves removal of
stromal scarring, and the subsequent need for keratoplasty.[10,11]
central 8–10 mm of the epithelium, followed by application
of an iso‑osmolar riboflavin solution (riboflavin‑5‑phosphate In the past few years, various techniques have been
0.5% with dextran T500 20%) every 3 minutes for 30 minutes introduced for treating thinner corneas. These include
followed by UV‑A (370‑nm wavelength) exposure of irradiance use of a higher riboflavin concentration or an increase in
3 mW/cm2 for 30 minutes.[4] Riboflavin acts as a photosensitizer the thickness of the riboflavin film, decreasing surface
in the photo‑polymerization process when exposed to UV‑A irradiance, inducing stromal swelling by using hypo‑osmolar

1
Cornea and Refractive Servives, Dr. Agarwal’s Eye Hospital and This is an open access journal, and articles are distributed under the terms of
Research Centre, 2 Cornea, Refractive and Cataract Services, Dr. the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License,
which allows others to remix, tweak, and build upon the work non‑commercially,
Agarwal’s Refractive and Cornea Foundation, Chennai, Tamil Nadu,
as long as appropriate credit is given and the new creations are licensed under
India the identical terms.
Correspondence to: Dr. Soosan Jacob, Director and Chief at Dr.
Agarwal’s Refractive and Cornea Foundation, Dr.  Agarwal’s Eye For reprints contact: [email protected]
Hospital and Eye Research Centre, #222, TTK Road, Chennai ‑ 600 086,
Tamil Nadu, India. E‑mail: [email protected] Cite this article as: Srivatsa S, Jacob S, Agarwal A. Contact lens assisted
Received: 29-Jun-2020 Revision: 27-Aug-2020 corneal cross linking in thin ectatic corneas – A review. Indian J Ophthalmol
2020;68:2773-8.
Accepted: 16-Sep-2020 Published: 23-Nov-2020

© 2020 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

2774 Indian Journal of Ophthalmology Volume 68 Issue 12

solutions, localized and customized epithelial debridement, OCT (ASOCT), slit‑lamp examination, and dilated fundus
transepithelial cross‑linking and contact lens assisted evaluation are performed pre‑operatively. Pilocarpine 2%
cross‑linking (CACXL).[12,13] eye drops are applied pre‑operatively to constrict the pupil in
order to decrease the potential for any UV damage to deeper
Contact Lens‑Assisted CXL (CACXL) structures. Proparacaine 0.5% eye drops are also applied for
One of the authors (Jacob S) introduced the technique of the anesthetic effect as well as to aid in easier epithelial removal.
contact lens‑assisted corneal cross‑linking (CACXL) in 2012 for After the epithelium is removed, minimum corneal thickness
treating thinner corneas using a riboflavin‑soaked soft contact is measured using ASOCT pachymetry or ultrasound
lens to artificially increase the corneal thickness.[14] The contact pachymeter. For the sake of simplicity, it may also be calculated
lens provided the functional pachymetry necessary to overcome by deducting 50 microns from the pre‑operative epi‑on thinnest
the two major potential complications that are associated pachymetry. The decision on further management is then as
with cross‑linking thin corneas, namely ‑  ultraviolet‑related shown in the flowchart [Fig. 1].
endothelial cell damage and permanent stromal haze. This
The contact lens is soaked in 0.1% riboflavin for the same half
technique was initially employed for treating patients with
an hour that the de‑epithelialized cornea is soaked. Riboflavin
progressive keratoconus with the thinnest pachymetry ranging
is applied every 3 minutes for 30 minutes to maintain a uniform
from 350‑400 µm (after epithelial removal) but has subsequently
been used for even thinner corneas. film over the corneal surface and prevent corneal desiccation.
At the end of 30 minutes penetration of riboflavin through
Surgical technique corneal layers is confirmed by visualization of green flare in
Routine evaluation including visual acuity, rigid gas the anterior chamber. The functional pachymetry achieved
permeable (RGP) contact lens corrected visual acuity, may be measured after placing the contact lens over the cornea.
corneal topography, specular microscopy, anterior segment Alternatively, it may be calculated by measuring the thinnest

Figure 1: Flowchart on decision making for CACXL and accelerated CACXL

December 2020 Srivatsa, et al.: Contact lens assisted CXL (CACXL) 2775

a b

c d
Figure 3: Absorption of riboflavin into the soft contact lens
Figure 2: (a) Soft Contact lens soaked in riboflavin solution (b) Riboflavin
soaked contact lens placed over the cornea before UV application
(c) Infrequent application of a thin layer of riboflavin over the contact Which riboflavin may be used?
lens during UV exposure (d) Application of UV light (with contact lens Iso‑osmolar riboflavin 0.1% in 20% dextran T500 was used,
over the cornea) in view of easy availability. Dextran in iso‑osmolar riboflavin
is known to cause intra‑operative dehydration of the cornea
pachymetry and adding 100 microns that is provided by placing and therefore, riboflavin in HPMC 1.1% may be utilized to
the contact lens to the measured value. Once the functional avoid this disadvantage in already thin corneas. Malhotra
pachymetry at the thinnest zone is confirmed to be above 400 et al. reported that HPMC based riboflavin may be associated
microns, UV‑A application is done either following the classical with a deeper demarcation line than dextran based riboflavin.
Dresden protocol of 3 mW/cm2 for 30 min or accelerated CXL However, they also reported that both solutions were safe
protocol using an irradiance of 10 mW/cm2 for 9 minutes. At for the endothelium.[17] The deeper demarcation line with
the end of the treatment, the contact lens is removed, riboflavin HPMC based riboflavin could be explained by the difference
washed off and a fresh bandage contact lens is applied until in the properties of the two molecules. HPMC enhances the
complete epithelial healing [Fig. 2a‑d]. stromal penetration of riboflavin, whereas dextran, because
If the functional pachymetry achieved is less than 400 of its high viscosity, retards this diffusion. As mentioned
microns, a few drops of distilled water is applied over the earlier, riboflavin acts as a photosensitizer for the formation
cornea to achieve the small amount of swelling that may be of collagen covalent bonds by generation of reactive oxygen
required to take the functional pachymetry (with the soft species. Thus cross‑linking tends to occur more where there
contact lens on) to safe levels. In our experience, the number of is higher concentration of riboflavin explaining the deeper
cases where this is required is low and the increase in thickness demarcation line in HPMC group as against shallower
required is also lesser and easily and rapidly achieved. demarcation line in dextran group. As explained previously,
HPMC‑based riboflavin solutions (such as VibexRapid™,
Which contact lens may be used? Avedro) also reduces intra‑operative deturgescence and
A UV barrier‑free contact lens must be used for the treatment to prevents corneal thinning and ensures greater endothelial
be effective. UV transmittance of a contact lens may be checked safety.[17]
in the product literature or by checking the UV irradiance that
Safety profile Of CACXL
passes through the contact lens using a digital UV meter. The
contact lens used by the authors is the B&L Soflens™ Daily The rationale of applying the riboflavin‑soaked contact lens is
Disposable (made of Hilafilcon B) which has absent or negligible to increase the total functional corneal thickness to 400 microns
UV filter. A lens of negligible power is selected. The Soflens™ or more. In our study the contact lens contributed to an increase
has a thin lens design with a central thickness of 90 µm and a in functional corneal thickness by 107.9 ± 9.4 µm as measured
diameter of 14 mm. It follows the shape of the cornea and is by ASOCT. The pre‑contact lens riboflavin film along with the
hydrophilic in nature. Other contact lenses which have been contact lens contributes to UV‑A attenuation allowing about
studied for high UV‑A transmission include filcon IV, nelfilcon 60–70% UV transmittance. Thus, the irradiance at the level
A, enfilcon A, lotrafilcon A and lotrafilcon B and can be the of endothelium is below the endothelial toxic level which
treatment choice for CACXL technique in thin corneas though ensures adequate safety of the CACXL procedure. This was
their efficacy and safety profiles need to be studied in animal supported by the fact that there was no significant endothelial
and human models first.[15] Hydrophilicity and thickness of loss, pleomorphism, polymegathism or loss of corneal clarity
the contact lens are also important factors as discussed later.[16] post CACXL in any of the studies.[12,17‑19]

Our experiments showed absorption of riboflavin into the Efficacy of CACXL

substance of the soft lens as demonstrated by staining of the The demarcation line is considered as a measure of efficacy of
filter paper over which riboflavin filled soft contact lens is the cross‑linking procedure. It can be seen as early as 2 weeks
placed. [Fig. 3] Our experiments also showed that application of postoperatively and can be appreciated till 3‑6 months.
the riboflavin‑soaked contact lens gave an average of 107.9 ± 9.4 Kymionis et al. showed that the stromal demarcation line
microns of additional corneal thickness. An average of 100 represented the transition zone between anterior acellular
microns may be taken for quick calculation and to maintain treated zone with reduced number of keratocytes (due to
errors towards safety. cellular apoptosis) and posterior cellular untreated zone with
2776 Indian Journal of Ophthalmology Volume 68 Issue 12

unaffected keratocyte population, on examination by confocal The third lens studied was the Soflens® which has been used
microscopy after CXL.[20,21] in previous published studies on CACXL (hydration 59% and
thickness 90 microns).[12,17,18,24] Their experiments showed that
Seiler and Hafezi reported a demarcation line at 300 µm in
very highly hydrophilic contact lenses absorb more riboflavin
eyes with a minimum corneal thickness greater than 400 µm
and consequently also more UV‑A and thereby lead to less
and showed it to be an effective tool for assessment of extent
cross‑linking effect. When riboflavin soaked, the Air Optix
of CXL.[22] Doors et al. showed a mean central depth of the
Aqua®, SofLens® and Galifa® lens had a UV‑A absorption
stromal demarcation line of 313 µm ± 66 µm one month after
of 12%, 27% and 50% respectively showing the importance
corneal cross‑linking with a range of 225 to 448 µm in normal
of the choice of contact lens used. The subcontact lens film
thickness corneas after iso‑osmolar CXL.[23]
in the porcine eyes in their experiments was measured to
Our pilot study included 14 eyes of 12 patients with be between 80‑116 microns and the supra‑contact lens film
maximum and minimum keratometric values of 50.9 ± 3.1 D between 102‑124 microns unlike the measurement in human
and 45 ± 1.9 D. Preoperative corneal thickness after epithelial eyes in vivo which was between 10‑15 microns and 60–100
removal ranged from 350 to 398 µm. The mean postoperative microns, respectively. They omitted the supra‑contact lens
depth of stromal demarcation line in our study measured with film. Addition of a subcontact lens riboflavin film did not
ASOCT was observed at 252.9 ± 40.8 µm (range: 208 to260 µm). cause a significant biomechanical cross‑linking effect. This is
There was no progression of keratectasia seen in any patients. important while performing CACXL and riboflavin should
Regression was observed in 4 eyes. Corneas remained clear not be instilled under the contact lens. The supra contact
and there was no significant endothelial loss.[12] Since this pilot lens film should also not be replenished too often or made
study, our un‑published data of a much larger number of excessively thick. A lower viscosity riboflavin film with less
patients who underwent CACXL has been very encouraging thickness may be beneficial. Biomechanical measurements by
with good safety and efficacy results. These results have now Wollensak et al. in their experiments without both the sub‑and
been replicated from other centers worldwide. Malhotra et al. in pre‑contact lens riboflavin film showed Young’s modulus and
their study on CACXL showed a mean demarcation line depth stress at 8% strain in the Air Optix Aqua® group to reach
of 308.22 µm ± 84.19 in the HPMC group and 235.33 ± 64.87 in the 92.4% and 86.35% respectively of the standard CXL value
dextran group (P < 0.04).[17] In vivo confocal microscopy (IVCM) whereas it was lesser (67.04% and 65.28% in the SofLens®
performed on 10 eyes treated with CACXL by Mazzotta et al. group; 68.48% and 75.52% in the Galifa® group). Their
showed that cytotoxic effects of CACXL are similar to IVCM experiments clearly show the significance of selecting the right
changes seen in standard CXL and were concentrated in anterior type of contact lens, avoiding a thick riboflavin film and the
and mid stroma up to 300 ± 30 microns. Corneal endothelium importance of following the right technique intraoperatively.
did not show any morphological changes between pre‑and The Galifa® lens is thicker and more hydrophilic, thereby
post‑operative follow‑up. The importance of intraoperative absorbing more riboflavin and therefore causing a greater
pachymetry to ensure that functional pachymetry is above 400 shielding effect than what is required by virtue of both its
microns before starting UV light treatment was stressed on.[19] increased thickness and greater riboflavin content. The Air
Optix Aqua® is a thinner lens and also has lesser hydration
A recent study by Randleman et al. that compared the
than the contact lens (SofLens®) used by us and other authors,
biomechanical efficacy of CACXL and standard CXL in
therefore probably resulting in a greater biomechanical effect.
enucleated porcine eyes using brillouin microscopy and
This is obviously an advantage. Biomechanical effect needs
extensometry testing showed that CACXL achieved 70%
to be balanced by endothelial protective effect and further
stiffening effect of the standard CXL group. Both the groups
in vivo human eye studies are required to show endothelial
showed significant stiffening in the anterior and middle corneal
protection with the Air Optix Aqua®.[16] SofLens® has already
regions and no effect on the posterior corneal region. They also
proven endothelial protection and good biomechanical effect
noted that there was a significant difference in the stiffening
in in‑vivo studies.[12,17] The hydrothermal shrinkage pattern in
effect between the two groups only in the anterior one‑third
their study as shown by Wollensak et al. with the Galifa® lens
of the cornea, with CACXL achieving 71% effect of standard
would be expected to be less due to the thicker profile and
CXL. However, statistically significant difference was not noted
greater hydrophilicity and thereby greater UV‑A absorbing
in the other two regions between the groups. They concluded
effect of the Galifa® lens. Published in vivo human eye data
that the contact lens did not shift the CXL effect anteriorly but
from multiple centers as well as our un‑published data has
rather only blunted the effect of CXL in the anterior corneal
shown good endothelial protection as well as biomechanical
region. In thin corneas, as the primary concern is endothelial
efficacy with the SofLens®, however, the need for further
protection, even a blunted response may be sufficient.[24]
in vivo human eye studies with Air Optix Aqua® and other
In a study on post mortem porcine eyes, Wollensak et al. contact lenses to determine the best contact lens to be used
assessed the biomechanical efficacy of CACXL comparing it cannot be denied. It should be noted here that results of
with standard CXL and found it to be about one‑third less than porcine eye studies cannot be directly extrapolated as having
standard CXL.[16] They also tested CACXL with and without an equivalent results in thin cornea human eye cross‑linking
adherent precorneal riboflavin film of up to 100 µm thickness studies. This was shown by Hafezi et al. in their study that
and tested three different soft contact lenses (Air Optix Aqua®, showed that cross‑linking was more efficient in thin cornea
SofLens® and Galifa®) with different degrees of hydrophilic models like murine cornea than thick cornea models like
properties. Among the lenses studied, the Air Optix Aqua® porcine corneas.[25] In another study, Kling and Hafezi also
has less hydrophilicity and stained less (33% hydration, 80 similarly showed a linear decrease in the effect of standard
microns thickness) and the Galifa® lens had a considerably corneal collagen cross‑linking (CXL) treatment with increasing
higher thickness of about 160 microns and hydration of 72%.[16] corneal thickness in different species, with thinner corneas
December 2020 Srivatsa, et al.: Contact lens assisted CXL (CACXL) 2777

achieving more stiffening. [26] Thus the stiffening effect Corneal Allogenic Intrastromal Ring
obtained in human thin keratoconic corneas may possibly be
more than that reported in porcine experimental eye models,
Segments (CAIRS)
and further experiments are needed to know the exact effects. In severe keratoconus (with maximum K up to 80D) and where
there is enough thickness available for CACXL, a new technique
Oxygen availability was described by one of the authors (Jacob S) ‑ corneal allogenic
A study by Kling et al. compared different CXL treatment intrastromal ring segments (CAIRS), which can be inserted as
protocols for high corneal thickness (porcine eyes) representing a first step to flatten the cornea and also increase the corneal
standard corneas with a thickness >400 microns and low corneal thickness in the zone of implantation, following which CACXL
thickness (murine eyes) representing keratoconic corneas with can be safely performed to arrest the progression.[28] This can
a stroma less than 400 microns. This study showed that the avoid the need for DALK and its associated disadvantages in
efficacy of cross‑linking was different in thick (porcine) and many advanced cases of keratoconus.
thin (murine) corneas and that thin corneas cross‑link better
than thicker corneas. They postulated the different effect of Advantages of CACXL
CACXL in porcine (thick) and murine (thin) corneas to be due CACXL is advantageous over other thin corneal cross‑linking
to a higher oxygen availability in the murine cornea resulting techniques in that it works independent of the swelling
from faster oxygen diffusion and hence oxygen replenishment properties of the cornea, is an epi‑off technique and does not
during UV irradiation. Although it was found that cross‑linking require additional time, additional expensive equipments
was equally limited by oxygen in both thick and thin corneas, it or special solutions to perform the procedure. The SMILE
was more efficient in thinner corneas. It is probable that oxygen lenticule assisted CXL is another technique recently
availability and therefore the biomechanical stiffening effect proposed that employs the same principle as CACXL and
of CXL may be greater in thin corneas. They also found that uses a riboflavin soaked SMILE lenticule for artificially
the amount of absorbed UV light was much more important increasing functional corneal thickness.[29] Though similar in
in thick (porcine) than thin (murine) corneas. They reported principle, this technique has disadvantages of limited access
to donor SMILE lenticule; need for a lenticule of sufficient
a decrease in the long‑term modulus after CACXL by 15‑20%
thickness (generally 7‑8 Dioptres of refractive correction would
compared to standard CXL.[25]
be needed to get a lenticule of sufficient thickness to provide
The oxygen transmissibility (Dk) of the contact lens shielding effect for CXL); unpredictability and variability of
used may also play an important role in the effectiveness of donor tissue pachymetry depending on cylindrical correction
cross‑linking attained. The Dk of the SofLens™ is similar to performed in donor, days post‑harvest of lenticule and storage
the oxygen permeability of corneal stroma. The treatment medium used; erroneous shifts in pachymetry in case of edema
efficacy of CACXL may therefore be further improved by or dehydration of the lenticule; variable riboflavin absorption
using a contact lens with higher oxygen transmissibility or by based on hydration status of the donor lenticule; dependency
increasing the oxygen supply. on human donor tissue, need for serology of donor lenticule
and need for storage and eye banking facilities.
Accelerated CACXL
Since late 2013, we have been doing accelerated CACXL The additional requirement for CACXL as compared to
using UV power of 10 mW/cm2 for 9 minutes to give a total all other techniques is only a UV barrier‑free soft contact
energy level of 5.4 J/cm2. Advantages over Dresden protocol lens which is easily available and inexpensive. It is a simple
technique to perform and can be easily adapted to the surgical
include a decrease in the intraoperative dehydration which is
protocol. It provides early visual rehabilitation and in our
of significance in these already thin corneas. It also makes the
experience (unpublished data) and that of others, it can be
procedure shorter for patient and surgeon.[27]
safely performed in pediatric patients as well.[30] CACXL
Knyazer et al. performed accelerated CACXL on 24 eyes has been proven to be effective in regularising the corneal
with keratoconus. This study showed that accelerated CACXL shape and simultaneously preventing the progression of
halted keratoconus progression in 80%, led to flattening keratoconus in isolation and also with synergistic effect
in 45% and significantly improved uncorrected distance when combined with Intracorneal segments (INTACS) or
visual acuity (UDVA), maximum keratometry, anterior steep Corneal allogenic intrastromal ring segments (CAIRS).
keratometry, anterior astigmatism and posterior astigmatism CACXL has about 70% stiffening as compared to standard
without any evidence of damage to the corneal endothelium Dresden protocol CXL in the less ideal porcine eye studies.
or any permanent side effects. Five eyes (20.8%) showed Murine eye models that closely mimic thin corneas and show
progression which was defined as an increase of 1D or more in greater cross‑linking effect as compared to porcine eyes may
maximum keratometry or 1.5D or greater in mean keratometry. be a better model for evaluation of CACXL, however further
Four out of these five eyes with progression had stable or studies are needed.
improved uncorrected distance visual acuity and therefore did
not undergo additional treatment. The authors mention their
Conclusion
success rate of 80% in halting progression to the fact that they The safety and visual outcomes of CACXL have been comparable
included advanced cases of keratoconus and also that during to conventional CXL. Progression rates are acceptable and the
UV irradiation, instillation of the riboflavin solution was done need for re‑treatment has been low. Care should be taken
both above and below the contact lens. Success rate could have in selecting the right kind of contact lens in terms of oxygen
been better still if the sub‑contact lens riboflavin film had been transmissibility, material, thickness, hydrophilicity, and
omitted.[18] riboflavin absorption properties to increase effectiveness of
2778 Indian Journal of Ophthalmology Volume 68 Issue 12

cross‑linking and to decrease an excessive shielding response. 14. Cross-Linking Technique Uses Contact Lenses for Patients
Proper technique should be followed, especially by confirming with Thin Corneas. Ocular Surgery News Issue: Dec 10 2013;
that the thinnest functional pachymetry has gone above 400 Last accessed on 2020 Jun 06. Available from: https://www.
healio.com/news/ophthalmology/20131207/10_3928_1081_59
microns intra‑operatively before application of UV‑A. The
7x_20130101_01_1323906.
subcontact lens riboflavin film should be avoided as also an
excessively thick supra‑contact lens riboflavin film and too 15. Bilgihan K, Yuksel E, Deniz NG, Yuksel N. Can possible toxic
effect of ultraviolet-A after corneal cross-linking be prevented? In
many re‑applications. Further in vivo human eye studies are vitro transmittance study of contact lenses at 370 nm wavelength.
needed to assess the safety of omitting the riboflavin film Cutan Ocul Toxicol 2015;34:271-5.
altogether, changing the riboflavin concentration within the
16. Wollensak G, Spörl E, Herbst H. Biomechanical efficacy of
cornea, using different types of contact lenses, increasing oxygen contact lens-assisted collagen cross-linking in porcine eyes. Acta
availability by using lenses with better oxygen transmissibility, Ophthalmol 2019;97:e84-90.
increasing oxygen concentration in the atmosphere, etc. Future 17. Malhotra C, Jain AK, Gupta A, Ram J, Ramatchandirane B,
studies should aim at improving biomechanical efficacy further Dhingra D, et al. Demarcation line depth after contact lens‐assisted
while maintaining the proven safety of this technique. corneal crosslinking for progressive keratoconus: Comparison
of dextran‐based and hydroxypropyl methylcellulose‐based
Financial disclosure riboflavin solutions. J Cataract Refract Surg 2017;43:1263–70.
Soosan Jacob has a patent pending for special trephines, devices 18. Knyazer B, Kormas RM, Chorny A, Lifshitz T, Achiron A,
and processes used to create CAIRS segments as well as for Mimouni M. Corneal cross-linking in thin corneas: 1-year results of
various types of shaped corneal segments accelerated contact lens-assisted treatment of keratoconus. J Refract
Surg 2019;35:642-8.
Financial support and sponsorship
19. Mazzotta C, Jacob S, Agarwal A, Kumar DA. In vivo confocal
Nil. microscopy after contact lens-assisted corneal collagen cross-
linking for thin keratoconic corneas. J Refract Surg 2016;32:326-31.
Conflicts of interest
20. Kymionis GD, Grentzelos MA, Plaka AD, Tsoulnaras KI,
There are no conflicts of interest.
Diakonis VF, Liakopoulos DA, et al. Correlation of the corneal
collagen cross-linking demarcation line using confocal microscopy
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