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Keratoconus treatment. The treatment carried out up until now
for this pathology was as follows: At the initial state, grade 1,
correction with glasses. At the moderate stage, grades 2 and 3,
correction with rigid gas permeable contact lenses. At an
advanced state or grade 4, corneal transplant.
Today, keratoconus is treated as follows:
At the initial state, grade 1, correction with glasses, soft or rigid
gas permeable contact lenses and crosslinking. At the
moderate state, grade 2 y 3, correction with rigid gas
permeable contact lenses, intrastromal rings, crosslinking or combinations.
At the advanced state or grade 4, intrastromal
rings, not in all cases, and corneal transplant.
Keratoconus treatment - corneal crosslinking
Collagen is a polymer consisting of proteins and
it forms part of the inner frame of the cornea,affording
it flexibility and elasticity. Any ruptures of this linking give rise
to ectasias. In keratoconus sufferers resistance to corneal deformation falls
50% more than compared with a
healthy patient. With regards to
the history of crosslinking, this technique has been used in medicine for more than 30
years. In odontology, for curing compound with
ultraviolet light (fotopolimerization), in cardiology
crosslinking and glutaraldehyde reduce early calcification and
damaged heart valve tissue. In the 1990’s
photo-oxidative crosslinking started to be used.
This produces activation of the molecular bonds between collagen fibres
by means of ultraviolet light and a photoactivator increases the
corneal biomechanical resistance. A group of researchers
from the University of Dresden, Germany, realised that young
diabetic patients did not develop keratoconus. The glucose caused
a natural crosslinking effect.
The riboflavin at a concentration of 0.1 %
optimises its absorption coefficient and the maximum absorption peak
is at 370 nanometres. Riboflavin
activates with ultraviolet light, releasing free radicals which
form unions between the collagen fibres and acts like an
ultraviolet radiation filter. Only 5% of the energy
applied passes to the intraocular structures.
There are different types of riboflavin. The original
riboflavin requires deepethelisation and instillation
for 20 minutes. Rapid-spreading riboflavin
requires deepethelisation and instillation
for 10 minutes. And transephitelial riboflavin
does not require deepethelisation and instillation for
20 minutes. The following scientific study published in
the Journal of Cataract and Refractive Surgery evaluates the
toxicity threshold after the surface irradiated power with
ultraviolet light. It concludes that there is endothelial cytotoxicity
from 0,36 mW/cm2
in corneas with a thickness under 400 microns.
Another study published in the Corneal Magazine
also evaluates the endothelial toxicity threshold. It concludes that
over 3mW/cm2 during 30
minutes (which is a total exposure of 5,4 J/cm2)
there could be endothelial damage in
corneas with a thickness under 400 microns. The main
indications of crosslinking would be: keratoconus,
pellucid marginal degeneration, Postlasik iatrogenic ectasia,
bullosa cheropathy, corneal melting, infectious
keratitis or associated with other corneal molding techniques such as
intrastromal ring implants, corneal molding
by microwaves and orthokeratology. The
contraindications for this technique would be: pachymetry of less than
400 µ, pregnancy or breastfeeding, important corneal opacities,
autoimmune diseases, patients with a propensity
to keloids, endothelial damage, severe ocular dryness,
corneal infections and a history of herpetic keratitis.
The procedure for traditional crosslinking would consist of:
instillation of topical anaesthetic 5 minutes before,
removal of the epithelium at a diameter of 8.5 to 9 mm.
Administrate riboflavin, a drop every 3 minutes
for 15 to 30 minutes. Check the riboflavin saturation
in the cornea. Once saturation has been tested,
apply ultraviolet light at a power of 3 mW/cm2
for 30 minutes and during
irradiation instil one drop of riboflavin every 5 minutes.
After irradiation, a few antibiotic drops are applied and a
therapeutic contact lens is placed.
A study by the American Journal of Ophthalmology evaluates
the results in the wake of 4 years of monitoring after traditional crosslinking.
There were no major changes in the pachymetry
nor in the density of endothelial cells, in the intraocular pressure
nor in the spherical aberration. A
reduction was observed in the K´s of around 2 diopters,
a reduction in the astigmatism of around 0.55 diopters,
an improvement in uncorrected visual acuity of around 2.85
Snellen E lines and an improvement
in corrected visual acuity of around 2 Snellen E lines.
The coma aberration was also reduced and the keratoconus
did not progress in 92% of cases.
Another multicentric study of the Journal of Cataract and Refractive Surgery
evaluates traditional crosslinking after a year of follow-up.
There were no mayor changes found of endothelial density
nor in the corneal biomechanics. A reduction was observed
in the K´s of around 2 diopters in a 21,3%
of cases. The corrected visual acuity was
stable in a 47,6% of cases, and gained
one line in 40% of cases, and lost one line in 8% of cases.
There was no progression of keratoconus in 68.8%
of cases. Complications
after traditional crosslinking according to this study happen
in a 2,9% of cases due to corneal edema, haze,
bacterial keratitis or herpetic keratitis. The higher
number of complications occurs when the K´s are higher than
58 diopters or patient is over 35 years of age
or the visual acuity is higher than 0,8. If we don´t
exceed these parameters complications can be reduced by 1%.
A common conclusion to both studies is
that the crosslinking results coincide with a reduction in
the K´s of approximately 2,26 diopters, the visual acuity
improves in two lines in a high percentage, the coma aberration
is reduced and the topographic stability is maintained in more than 80%
of cases. Another possibility of carrying out
this technique is by using Avedro´s System for Accelerated Cross-linking.
It uses one of the treatments depending on the total energy
received. The procedure consists of
rapid-spreading riboflavin instillation during
10 minutes and exposure to uniform ultraviolet light
30 mW/cm2 during 3 minutes.
The procedure lasts 13 minutes in total.
Avedro achieves equivalent treatments
in less time, the most traditional one is 3mW/cm2
during 30 minutes with a total exposure to energy
of 5,4 J/cm2.
And with Avedro 30 mW/cm2
during 3 minutes receiving the same total exposure to energy
of 5,4 J/cm2.
¿What are the advantages of this technique?
Greater efficiency and reliability, easy to focus during the procedure,
better endothelial cell count, uniform light beam throughout
the cornea, and prevents the bleaching effect of riboflavin decomposition
due to a reduction of ultraviolet light exposure to 3 or
5 minutes. During transepithelial crosslinking
we instil one or two drops of riboflavin every 2
minutes approximately during the 30 minutes prior to the start
of the radiation. During the ultraviolet light treatment
at 3mW/cm2, 1 or 2 drops
are instilled every 2 - 3 minutes during the total time of exposure
(30 minutes in total).
The following case study published in the Journal of Cataract and Refractive Surgery
transepithelial crosslinking results are compared to traditional crosslinking results
finding similar results but with a lower
penetration. This technique would be a very good options for patients that do not
cooperate and have epithelisation problems, pediatric patients or
with pachymetries equal or higher than 380 microns.
Ocular Ionophoresis induces ion mobility
through a low electric field with low voltage to achieve
an increased penetration speed and a greater local concentration of the drug.
This system could improve transepithelial riboflavin
penetrability. But for now, more studies are needed.
To conclude, traditional crosslinking is a safe and effective
treatment to stabilize keratoconus progression.
And transepithelial and accelerated crosslinking with Avedro can provide
an improvement in the number of complications and can reduce the
duration of the treatment but for now, more studies are needed.