Version of Record: https://www.sciencedirect.

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Manuscript_02bb63585d965bd10c30c776aed744d1

SEQUENTIAL INTRACORNEAL RINGS SEGMENT IMPLANTATION FOLLOWED BY

TRANSEPITHELIAL THERAPEUTIC PHOTOABLATION

AND CORNEAL CROSS LINKING

Caroline DEBONO MD1, David SMADJA MD2, Valentine SAUNIER MD1,

David TOUBOUL MD, PhD1

(1) UNIVERSITY CENTER HOSPITAL OF BORDEAUX, KERATOCONUS

NATIONAL REFERENCE CENTER (CRNK), ANTERIOR SEGMENT UNIT,
BORDEAUX, FRANCE

(2) DEPARTMENT OF OPHTHALMOLOGY, REFRACTIVE SURGERY UNIT,

SHAARE ZEDEK MEDICAL CENTER, JERUSALEM, ISRAEL

© 2022 published by Elsevier. This manuscript is made available under the Elsevier user license
https://www.elsevier.com/open-access/userlicense/1.0/
EVALUATION RETROSPECTIVE DE LA PHOTOKERATECTOMIE

THERAPEUTIQUE

AU DECOURS DE LA MISE EN PLACE

D’ANNEAUX INTRA-CORNEENS

POUR LA PRISE EN CHARGE DU KERATOCONE

 Corresponding author:
Caroline Debono MD, 06 59 77 57 07, [email protected], Keratoconus

National Reference Center (CRNK), Bordeaux, France

Financial Disclosures:

Smadja MD (DS) is a paid consultant for Ziemer, Johnson & Johnson, iCan
Touboul MD, PhD (DT) is a paid consultant for Alcon, Allergan, Thea, Horus Pharma,
Santen, Shire, Johnson & Johnson

Running Title:
Sequential ICRS followed by PTK and corneal CXL for Keratoconus.
SEQUENTIAL INTRACORNEAL RING SEGMENT IMPLANTATION FOLLOWED BY

TRANSEPITHELIAL PHOTOTHERAPEUTIC KERATECTOMY

AND CORNEAL CROSS-LINKING

Evaluation rétrospective de la photokératectomie thérapeutique au

décours de la mise en place d’anneaux intra-cornéens pour la prise en

charge du kératocône

Running Title:
Sequential ICRS followed by PTK and corneal CXL for Keratoconus.

1
RESUME

But de l’étude : Evaluer la sécurité et les résultats visuels d’une implantation d’anneau intra-

cornéen suivie par une photokératectomie thérapeutique (te-PTK) et d’un cross-linking

cornéen (CXL) chez des patients présentant un kératocône de forme modérée.

Méthode : Les patients porteurs d’un kératocône modéré et intolérants aux lentilles de

contact qui ont bénéficié d’une implantation d’anneau intra-cornéen suivie d’une PTK et d’un

CXL entre Avril 2015 et Juillet 2018 ont été rétrospectivement inclus dans l’étude. Les

résultats visuels et réfractifs, un questionnaire de satisfaction et les complications ont été

reportés au dernier recueil (en moyenne 9.5 mois post opératoire).

Résultats : 20 yeux de 17 patients ont été inclus, dont 5 femmes et 15 hommes. Le délai

entre les 2 procédures était en moyenne de 16 mois. Des valeurs initiales à 9.5 mois,

l’acuité visuelle sans correction optique (AVSC) (0.80 +/- 0.35 logMAR vs 0.46 +/- 0.38

logMAR), la meilleure acuité visuelle corrigée (MAVAC) (0.38 +/- 0.23 logMAR vs 0.13 +/-

0.16 logMAR), la kératométrie maximale (56.11 +/- 4 dioptries [D] vs 50.6 +/- 3.56 D), la

kératromie moyenne (51.87 +/- 3.43 D vs 48.45 +/- 2.91 D), le Cylindre (7.99 +/- 3.94 D vs

4.23 +/- 3.49 D) et l’équivalent sphérique (-3.84+/- 3.36 D vs -0.99 +/- 2.15 D) (p <0.01) ont

été améliorés de manière significative. Au final, nous avons noté 5 (25%) taies cornéennes

superficielles (Haze), 75% des yeux ont gagné >= 1 ligne logMAR de MAVAC. 94.5 % des

patients ont reporté être satisfaits après la procédure.

Conclusion : La procédure associant la pose d’AIC suivie par une te-PTK et d’un CXL

cornéen semble être une approche sûre et efficace pour améliorer les résultats visuels et la

qualité de vie des patients atteints de Kératocône.

Mots Clefs : Kératocône, implantation d’anneau intra-cornéen, laser excimer, cross-linking

cornéen, photokératectomie thérapeutique, photoablation topoguidée.

2
ABSTRACT

Purpose: To evaluate the safety and visual outcomes of intrastromal corneal ring segment

(ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and

corneal cross-linking (CXL) in patients with mild keratoconus.

Methods: Patients with mild keratoconus and contact lens intolerance who underwent

sequential ICRS implantation followed by phototherapeutic keratectomy and corneal CXL

between April 2015 and July 2018 were retrospectively included in the study. Refractive and

visual outcomes, satisfaction questionnaire and complications were recorded at the last

follow-up (mean 9.5 months postoperatively).

Results: Twenty eyes of 17 patients were enrolled, including 5 women and 15 men. The

mean time between the two procedures was 16 months. Based on values before the first

procedure and 9.5 months after the second procedure, significant improvements were noted in

uncorrected distance visual acuity (UDVA) (0.80 +/- 0.35 logMAR vs 0.46 +/- 0.38

logMAR), corrected distance visual acuity (CDVA) (0.38 +/- 0.23 logMAR vs 0.13 +/- 0.16

logMAR), maximal K (56.11 +/- 4 diopters [D] vs 50.6 +/- 3.56 D), mean K (51.87 +/- 3.43 D

vs 48.45 +/- 2.91 D), cylinder (7.99 +/- 3.94 D vs 4.23 +/- 3.49 D), and spherical equivalent (-

3.84+/- 3.36 D vs -0.99 +/- 2.15 D) (p <0.01). Among the outcomes, we noted 5 (25%)

superficial corneal scarring (haze); 75% of eyes gained >= 1 logMAR line of CDVA. 94.5 %

of patients reported that they were satisfied with their outcomes.

Conclusion: Combining ICRS implantation followed by te-PTK and corneal CXL appears to

be a safe and effective approach for improving visual outcomes and quality of life in

keratoconus patients.

Keywords: Keratoconus, intrastromal corneal ring segment implantation, excimer laser,

phototherapeutic keratectomy, corneal cross-linking, topography-guided photoablation.

3
Introduction

1 2 3
Keratoconus (KC) is a bilateral, historically non-inflammatory , progressive corneal

disorder, mainly asymmetric, characterized by a progressive cone-shaped deformation and

corneal thinning inducing irregular astigmatism and visual impairment. Its patients can

exhibit central corneal scaring and Descemet’s membrane rupture at the ultimate stages. Its

prevalence varies from 0.5 % to 0.8 % around the world with an increasing trend in many
4
countries. Its etiopathogenicity remains partially unclear and is probably multifactorial,
5
involving different factors : genetic 6, inflammation 7 8
, environmental and behavioral

factors including excessive eye rubbing 9. The therapeutic approach is based on progression

inhibition and visual acuity rehabilitation. For more than a decade, corneal collagen cross-

linking (CXL) 10 was used to halt progression by a tissue photo reticulation based mechanism.
11
It has been shown that CXL can improve quality of vision and corneal regularity . In KC

with significant visual impairment and contact lens intolerance further surgical options can be
12 13
proposed and combined: intrastromal corneal ring segment (ICRS) implantation , laser
14 15
excimer photokeratectomy or the association of both , phakic intraocular lens

implantation. When those treatments are not sufficient or in case of central corneal scarring,

deep anterior lamellar keratoplasty (DALK) remains possible. Recently, a surge of interest

emerged about therapeutic trans epithelial photoablation (te-PTK) efficacy in treating highly

irregular corneas. This approach has been made possible by the recent advances in laser

ablation profile (topography guided [TG]) and OCT based epithelial mapping technologies

that contributed to a better understanding of the corneal photoablation strategy. While several
16 17 18
combined procedures have been tried (ICRS-CXL , PTK + ICRS , TG PTK + ICRS ),

there is still no consensus on which sequence and combination might be the most beneficial

for KC patients.

4
In this study, we wanted to investigate the safety and efficacy in a cohort of KC eyes that

underwent a sequential treatment by ICRS implantation in a first step followed by a te-PTK

and corneal CXL in a second step.

Material and Method

This retrospective case study involving consecutive patients with KC who underwent

sequentially ICRS implantation followed by te-PTK and corneal CXL at the National

Reference Center for Keratoconus (CRNK), Bordeaux Hospital and University (France) from

April 2015 until July 2018. The study adhered to the tenets of the Declaration of Helsinski.

Informed consent was obtained from all patients before being included in our analysis.

Patients were included when they met the following criterion: Mild to moderate KC according

to Krumeich classification19 with ICRS implanted because of contact lenses intolerance with

significant visual acuity impairment caused by corneal irregularity and reliable corneal

topography readings with at least 3 months follow-up after the rings procedure. Te-PTK was

performed only in case of unsatisfactory result after rings insertion and if laser safety criteria

were achievable (see below) associated systematically with an additional corneal CXL

procedure. Patients with central corneal scarring, central corneal pachymetry less than 400

micrometers (µm), pregnancy, lactation, severe dry-eye disease, severe amblyopia, systemic

autoimmune disease, history of herpetic corneal disease, were however excluded from the

study. All patients had preoperative baseline complete examination including uncorrected

distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal topography

with the TMS® Placido disk (Tomey, Japan) and a tomographic Scheimpflug analysis with

Galilei (Ziemer®) and Topolyzer (Alcon ® - linked to the Wavelight excimer laser platform).

Surgical procedures

All procedures were performed by the same experienced surgeon (DT). Femtosecond laser-

enabled (FS200, Wavelight-Alcon) creation of the intrastromal channel for ICRS implantation

5
was used in all eyes. One single ICRS design was implanted: including Ferrara rings (FR)

from Mediphacos®) or Keraring (KR) (Mediphacos®). ICRS channel parameters (depth,

outer and inner diameters) were determined according to the ICRS design (diameter of 5 mm

in all cases). One or two ICRS were implanted depending of the topographical pattern at 80%

of the corneal depth. The channel entry cuts were always positioned on the steepest meridian.

Fine-tuning of the final ICRS position was achieved by the surgeon according to the per

operative use of a keratoscope. Tobramycin-dexamethasone eye drops were administrated for

8 days post operatively.

Therapeutic photoablation was performed at least 3 months after ICRS implantation when the

CDVA was worse than 0.5 logMAR and patient was not satisfied. Anterior segment OCT

(CASIA 2 – TOMEY®) was systematically performed before photoablation. A minimum of

450 µm of central corneal thickness and at least 250 µm left above the ring were requested for

proceeding to laser ablation. A maximum of 50 µm of stromal photoablation was dedicated to

stromal photoablation in all cases. If the “topography-guided photoablation” link was not

achievable (TG-PTK) with Topolyzer, due to excessive surface irregularity or ICRS

reflexions, “plano-photoablation” was planned. Thus, two types of therapeutic photoablation

protocols were used as following: both started with a plano trans-epithelial PTK, with a 6.5

mm optical zone and 50 µm ablation. Then when possible, a TG-PRK was performed

targeting high order aberrations (HOA) more that refraction. In some cases, if this remaining

tissue was available, a certain amount of sphero-cylindrical photoablation was included.

Optical zone between 5.5 and 6.5 mm were used for treatment according to the specific

photoablation patterns. In the “plano-photoablation” group, a second photoablation was

performed after transepithelial PTK with a maximum of 50 µm depth. Epi-off accelerated

CXL procedure was performed directly after using the Avedro® crosslinker system, with

(0.1% in 20% dextran) isotonic riboflavin solution (VibeX Rapid; Avedro Inc., USA),

6
instilled during 8 min; followed by UVA irradiation (wavelength: 375 nm) for 3 min at a

power of 30 mW/cm2 (total dose: 5.4 J/cm2). Mitomycine-C (0.02 mg/ml) was applied in all

cases for 30 seconds after photoablation and abundantly rinsed with serum (BSS®). A

bandage contact lens was applied after flushing the corneal surface with tobramycin-

dexamethasone eyedrops. Postoperative medication included artificial tears during several

months and tobramycine-dexamethasone eyedrops 3 times daily for one month and a

progressive tapering over a three months period. Data were recorded preoperatively before

ICRS implantation, before and after photoablation. The patients were evaluated for UDVA,

CDVA, manifest refraction, topographical keratometry readings (diopters) corneal

topography. Complications and satisfaction rate through a questionnaire (Figure 1) were

filled up at the last follow up visit, and also analyzed.

Statistical analysis

All data were entered into a Microsoft Excel 2017 ® spreadsheet. The means, standards

deviation and minimal and maximal values were calculated and presented descriptively using

graphs and tables. All variables followed normal distribution and a paired T-test (Student test

p) were used to compare preoperative, postoperative values after ICRS and te-PTK and

corneal CXL. Differences were considered to be statistically significant when the p value was

less than 0.05.

Results

Our study comprised 20 eyes of 17 patients, including 5 women and 15 men. Mean patient

age was 25 years +/- 6.64 (16 to 44). The mean Follow-up after te-PTK was. 9.5 months. The

Table 1 summarizes the demographics and clinical baseline data. The Table 2 illustrates the

preoperative and postoperative visual and refractive outcomes after ICRS and te-PTK /

corneal CXL procedures.

7
Curvature changes (Keratometry outcomes)

Keratometry changes over procedures steps (before ICRS, between ICRS and te-PTK /

corneal CXL and after te-PTK/corneal CXL) are summarized in Table 2 and Figure 2a.

After ICRS implantation, there was a statistically significant decrease of maximal keratometry

(Kmax) (p<0.05) and cylinder (K cyl) (p<0.05). However, the addition of the te-PTK and

corneal CXL procedures, lead to an additional significant improvement in Kmax, Kcyl and

Kmean. The mean flattening of Kmax after ICRS and after te-PTK were 3.03 +/- 3.05 D (-

3.35 to 8.78) and 2.46 +/- 3.82 D (-5.15 to 9.86) respectively, for a total flattening of 5.5 +/-

4.53 D (-4.86 to 18.45). We observed a mean reduction in SimK cylinder of 3.07 +/- 3.55 D (-

6.32 to 9.21) after ICRS and 0.71 +/- 2.67 D (-2.26 to 8.18) after te-PTK and corneal CXL,

with an overall decrease achieved by the combined treatment of 3.79 +/- 2.22 D (0.55 to

9.01).

Visual and Refractive outcomes

An overall increase in UDVA and CDVA were observed at the last follow up visit by 3.5 +/-

4.2 (0.6 to 1.1) and 2.5+/- 2,7 (0.1 to 1.1) logMAR lines, respectively. Table 2 and Figures

2b/2c summarized the changes in refraction and visual outcomes. Figure 3 shows the

percentage distribution of patients with a gain or loss of their best-corrected vision after the

combined procedure. Nearly 95% of patients (n=19/20) experienced or no change or a gain in

their best-corrected visual acuity up to 5 lines, whereas about 5% had a loss of 1 or 2 lines of

their best-corrected visual acuity. The efficacity index (ratio between the final postoperative

UDVA/ baseline CDVA in logMAR) was 1.2. The safety index (ratio between the final

postoperative CDVA/ baseline CDVA in logMAR) was 0.34.

Complications

8
No intraoperative complication, KC progression occurred ICRS extrusion or removal were

observed at the last follow-up. Postoperative corneal haze was observed in 5 eyes (25 %) and

all resolved under an intensive topical steroid treatment. No patients were proposed to

underwent a deep anterior lamellar keratoplasty (DALK). No progression was noted finally.

Satisfaction questionnaire

Outcomes of the satisfaction questionnaire are summarized in Table 3. Overall, seventeen

patients (85 %) completed the questionnaire over the phone. Sixteen patients (94.5 %)

reported that they were satisfied with their vision, whereas one patient (5.5 %) reported that

he was still satisfied by ICRS but not after te-PTK and corneal CXL.

Discussion
In this retrospective study, we stressed to determine if ICRS implantation followed by te-PTK

and corneal CXL could lead to visual acuity improvement in patients with mild to moderate

KC when they were contact lenses intolerant with highly irregular cornea and poor visual

quality with spectacles.

ICRS implantation can significantly reshape the Keratoconic corneas. The first work
20
introducing ICRS in Keratoconus was published by Colin et al. in 2000. Later, a lot of

studies reported significant improvement in keratoconus after ICRS implantation alone or

combined with CXL. 9 21 22 In 1994, Mortensen et al. were the first to dare performing surface

excimer laser on KC corneas, aiming to treat refractive errors and reported relatively good
23
results, decreasing astigmatism and increasing visual acuity. Many studies were since

published, introducing asymmetrical photoablations with topoguided (TG) te-PTK, and all
12 24 14 25
exhibited significant topographical and visual acuity enhancements. The Athens’
26 13
protocol was proposed in 2014 by Kanellopoulos et al. and consist on a combined TG te-

PRK associated with “epithelium off” accelerated CXL demonstrating significant

9
improvement in refractive and keratometric outcomes. CXL was introduced previously by
27
Wollensak et al. to straighten the cornea and was associated with PTK to compensate

corneal weakening that PTK could induce. Accelerated protocols were developed to reduce

patient discomfort and demonstrated visual and keratometric outcomes comparable to the

conventional so called “Dresden protocol”. 28 29 30 31

32
Labiris et al. reported that CXL combined with TG te-PTK offered an improved self-

reported quality of life but lower than those of healthy controls. Combining te-PTK after

ICRS has been the subject of a few studies. The first study was published by Iovieno et al. in
33
2011 , initially reporting good and promising results. Studies reporting the safety and

efficacy of the combined treatment ICRS with an additional te-PTK were summarized in

Table 4. Only 3 studies involved more than 25 eyes, but less than 50 eyes, with at least 6 to

12 months of mean follow-up. 34 35 18

According to the literature36 16

, it has been reported an average of 2 to 3 D of corneal

flattening with a mean increase in CDVA of 1 to 3 logMAR lines after ICRS implantation.

Our study compares similarly with the literature with an average of 3.03 D of corneal

flattening and an average mean increase in CDVA of 1 logMAR line. A minimum of 3

months before considering any enhancement with a therapeutic photoablation has been

justified by many authors due to possible changes in several curvature related parameters up

to 3-6 months postoperatively.37 38

In our study, the efficiency / safety ratio of the additional te-PTK enhancement was favorable.

All parameters except the SimK cylinder and UDVA were improved significantly by the
37
additional te-PTK and corneal CXL procedures. Interestingly but similarly to Zeraid et al.

we didn’t find a significant increase in UDVA between the 2 procedures and improvement

rate induced by the photoablation appeared to be lower than after the initial ICRS

implantation.

10
Although the influence of an additional CXL procedure on the refractive and visual outcomes

of our studied cohort has not been analyzed it has been largely reported that CXL might lead

to a significant corneal flattening of 2-3 D on average. CXL associated with ICRS could act

synergistically to prevent further disease progression or ICRS effect regression. Combining

39 11
ICRS and CXL have shown additive effect in further studies , and even more, for some
40 41
authors, was better when performed simultaneously . Although previous studies have

shown that the simultaneous TG te-PTK with CXL leads to greater improvements in visual
38 42
function and keratometric measurements than PTK alone or in a sequential procedure ,a

recent literature review 43 showed contradictory results with these. In this meta-analysis, most

of the results (CDVA, ES, astigmatism) were better when CXL was followed by excimer

laser surface ablation than group without CXL or CXL with simultaneous excimer laser

surface ablation. We can note that CXL in previous studies was often performed at the same

time than PTK. 44 34 18 37 The combination of PTK, ICRS and CXL was also known to have an

additive effect on visual acuity and keratometry values .35 17 Nevertheless, we didn’t find any

study comparing PTK with and without CXL in non-progressive patients, after ICRS

implantation. The impact of CXL on visual outcomes and progression in patients with ICRS

enhanced by PTK should be studied in a prospective comparative study.

Similarly to our cohort, few complications following this combined treatment were reported
34
in literature, essentially corneal haze , nevertheless a majority of studies didn’t report any
37 45 17
complications. Interestingly, according to corneal topography, best results were

achieved when nipple or paracentral patterns were observed, whereas centered corneal

astigmatism patterns were associated with poorer outcomes. Probably, the answer to toric

photoabation was less predictable, axis misalignment and unpredictable biomechanical couple

effect issues could explain that observation. In case of significant but centered corneal

11
astigmatism, plano te-PTK pattern should be preferable to flatten and regularize the cornea,

playing with the beneficial epithelium compensation effect. Similarly to the high satisfaction

rate reported by the patients, with an overall 94.5% of patients satisfied, Al-Tuwairqi et al. 18

also reported a rate of 78% of satisfaction after the combined ICRS and te-PTK procedure.

The main drawbacks of our study reside in its retrospective design and therefore, the

limitations in preoperative data available such as biomechanical properties or ocular

wavefront data that would have been of interest in this study. Additionally, although the mean

last postoperative follow-up visit was nearly one year (9.5 months), 9 patients still had less

than 6 months follow-up, which might have influenced our results due to known continuous

change that can still occur beyond 6 months period43,34,46.

Conclusion

ICRS implantation followed by te-PTK and corneal CXL was safe and effective to decrease

refractive errors by corneal regularization in a minimally invasive strategy in patients with

mild to moderate KC. Visual acuity and topographical patterns can be significantly improved

with a low rate of complications. That combined procedure was associated with CXL to

prevent further progression without adverse outcomes. Studies with longer follow-up still

remain necessary to better evaluate this strategy and its predictive factors of success.

Financial Disclosures:

Smadja MD (DS) is a paid consultant for Ziemer, Johnson & Johnson, iCan
Touboul MD, PhD (DT) is a paid consultant for Alcon, Allergan, Thea, Horus Pharma,
Santen, Shire, Johnson & Johnson

12
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treatment of keratoconus: a meta-analysis. Acta Ophthalmol. (Copenh.) (2018).
doi:10.1111/aos.13814
30. Shajari, M. et al. Comparison of Corneal Collagen Cross-Linking Protocols Measured
With Scheimpflug Tomography. Cornea 37, 870–874 (2018).
31. Kato, N. et al. Corneal crosslinking for keratoconus in Japanese populations: one year
outcomes and a comparison between conventional and accelerated procedures. Jpn. J.
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32. Labiris, G. et al. Impact of keratoconus, cross-linking and cross-linking combined
with photorefractive keratectomy on self-reported quality of life. Cornea 31, 734–739 (2012).
33. Iovieno, A. et al. Intracorneal ring segments implantation followed by same-day
photorefractive keratectomy and corneal collagen cross-linking in keratoconus. J. Refract.
Surg. Thorofare NJ 1995 27, 915–918 (2011).
34. Kremer, I., Aizenman, I., Lichter, H., Shayer, S. & Levinger, S. Simultaneous
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1802–1807 (2012).
35. Elbaz, U. et al. Accelerated versus standard corneal collagen crosslinking combined
14
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and without C3-R on keratoconus. J. Cataract Refract. Surg. 33, 75–80 (2007).
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15
Table 1. Characteristics of eyes undergoing combined intracorneal ring segment implantation
followed by trans-epithelial photorefractive keratectomy and corneal CXL in patients with
keratoconus.

Characteristics (n=20)

Age (years old) 25 +/- 6.64 (16 to 44)

Sex (% women) 25
Refractive errors (D)
MRSE -3.84 +/- 3.36 (-12.5 to 1)
SimKcyl 7.99 +/- 3.94 (1.31 to 15.87)
Keratometric value
SimKmax 56.11 +/- 4 (46.31 to 65.5)
SimKmean 51.87 +/- 3.43 (44.56 to 61.85)
logMAR UDVA 0.80 +/- 0.35 (0.22 to 1.5)
logMAR CDVA 0.38 +/- 0.23 (0 to 1.1)
Ablation depth (µm) 59.79 +/- 28.86 (23 to 107)
CCT (µm) 473.25 +/- 24.63 (433 to 520)
Duration
Delay ICRS/PTK (month) 16.07 +/- 17.45 (2 à 65)
Last follow-up (month) 9.5 +/- 7.71 (0.5 à 29)
Planning treatment
TG-PTK 80%
Plano-PTK 20%

Results are expressed as means +/- standard deviation (range)

D diopters, µm micrometers, MRSE manifest refraction spherical equivalent, SimKmax simulated
maximal keratometry, SimKmean simulated mean keratometry, SimKcyl simulated cylinder, UDVA
uncorrected distance visual acuity, CDVA corrected distance visual acuity, CCT central corneal
thickness, ICRS intracorneal ring segment, te-PTK transepithelial phototherapeutic keratectomy

16
 Table 2. Preoperative and postoperative corneal indices, visual acuity and refractive

outcomes in eyes undergoing combined intracorneal ring segment implantation followed by

trans-epithelial photorefractive keratectomy and corneal CXL in patients with keratoconus.

Preoperative Post ICRS p1 Post te-PTK p2 p3

SimKmax (D) 56.11 +/- 4 53.1 +/- 4.17 < 0.05* 50.6 +/- 3.56 < 0.05 * < 0.00001*
SimKmean (D) 51.87 +/- 3.43 50.63 +/- 3.26 > 0.05 48.45 +/- 2.91 < 0.05 * < 0.01*
SimKcyl (D) 7.99 +/- 3.94 4.95 +/- 3.86 < 0.05* 4.23 +/- 3.49 > 0.05 < 0.01*
UDVA (logMAR) 0.80 +/- 0.35 0.60 +/- 0.35 > 0.05 0.46 +/- 0.38 > 0.05 < 0.01*
CDVA (logMAR) 0.38 +/- 0.23 0.30 +/- 0.27 > 0.05 0.13 +/- 0.16 < 0.05* < 0,001*
MRSE (D) -3.84 +/- 3.36 -2.83 +/- 2.15 > 0.05 -0.99 +/- 2.15 < 0.05* < 0.01*

Results are expressed as means +/- standard deviation

ICRS intracorneal ring segment, PTK phototherapeutic keratectomy, UDVA uncorrected distance
visual acuity, CDVA corrected distance visual acuity, MRSE manifest refraction spherical equivalent,
SimKmax simulated maximal keratometry, SimKmean simulated mean keratometry, SimKcyl
simulated cylinder, D diopters. p1 Comparison between preoperative and post ICRS values. p2
Comparison between post ICRS and post PTK /corneal CXL values. p3 Comparison between
preoperative and post te-PTK/corneal CXL values.
* Significative values.

17
 Table 3. Results of the subjective questionnaire

Satisfaction Visual acuity gain Advice Do it again Gain of autonomy More activities

YES 94.5% 88.2% 94.11% 94.11% 82.35% 76.47%

NO 0% 11.8% 0% 0% 17.65% 23.53%

Yes/No 5.5% 0% 5.88% 5.88% 0% 0%

YES/NO: patients satisfied by the first step (ICRS) but not the second (te-PTK and corneal CXL)

18
Table 4. Summary of study results about the two steps procedure for the treatment of keratoconus: ICRS implantation followed by PTK

Follow-up
Author Year Sample Size period Treatment Modality
Kymionis 2010 1 9 months ICRS followed by (12months after) PRK no TG+CXL same day
Lovieno 2011 5 6 months ICRS followed by (4 months after) PRK no TG+CXL same day
Kremer 2012 45 12 months ICRS followed by (6 months later) TG-PRK+CXL same day
Yeung 2013 16 6,9 months ICRS + PTK no TG + CXL standard same day
Coskunseven 2013 16 6 months ICRS followed by CXL followed by TG-PTK (6 months between each)
Al-tuwairqi 2013 13 6 months ICRS followed by (6 months later) TG-PTK + CXL same day
Zeraid 2014 21 3 months ICRS followed by (3 to 24 months after) TG-PTK +CXL standard same day
Dirani 2014 17 6 months ICRS followed by CXL followed by (6 months later) PTK no TG
Al-Tuwairqi 2015 41 12 months ICRS followed by (6 months) TG-PTK + CXL standard same day
Elbaz 2015 32 12 months ICRS +TG-PTK + CXL standard vs accelerated
Hun Lee 2017 23 6 monhts ICRS followed by (at least 1 month after) TG-PTK + CXL flash

19
Fig 1. Satisfaction questionnaire

Fig 2. Changes in CDVA, UDVA, MRSE, cylinder, mean and maximal keratometry in
patients with keratoconus who underwent combined intracorneal ring segment implantation
followed by te-PTK and corneal CXL.

ICRS: intracorneal ring segment, te-PTK: phototherapeutic keratectomy

Fig 3. Changes in logMAR lines of corrected distance visual acuity (CDVA) and uncorrected
distance visual acuity (UDVA) after the combined procedure.

20
Fig 1.

Are you satisfied by this procedure? YES/NO

Did you have an improvement in your quality of vision? YES/NO

Would you advise a close this procedure? YES/NO

Would you do it again now? YES/NO

Did you have a gain of autonomy than before procedure? YES/NO

Do you practice some activities which were previously impossible? YES/NO

What is your current visual equipment? Nothing, contact lenses, glasses…

 Fig 2.

2a
Changes in SimKmax / SimKmean
58
57
56
Diopters

55
54
53
52
51
50
49
48
47
46
Before ICRS After ICRS After PTK

SimKmax (D) SimKmoy (D)

2b
Changes in UDVA / CDVA
0.9

0.8

0.7

0.6

0.5
Diopters

0.4

0.3

0.2

0.1

0
Before ICRS After ICRS After PTK

logMAR CDVA logMAR UDVA

 2c
Changes in MRSE / Cylinder
12

10

8
Diopters

-2

-4

-6
Before ICRS After ICRS After PTK

MRSE (D) Cylinder (D)

Fig 3.

35.00%
33.00%

27.80%

25.00%

22.00%
20.00%

15.00%

11.00%

5.00% 5.50%
0.00% 0.00%

LOSS OF 2 OR LOSS OF 1 NO CHANGE GAIN OF 1 TO 2 GAIN 3 TO 4 GAIN 5 OR MORE

MORE

Line of logMAR CDVA Line of logMAR UDVA