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Poster 5297-B0250
Safety Evaluation of Cationic Emulsions Following Refractive Surgery Procedures
Quentric Y,1Daull P,2Gros E,1Antonelli S,1Mauro V,1Feraille L,1Garrigue JS2— 1Iris Pharma, La Gaude, France; 2Santen SAS, Novagali Innovation Center, Evry, France — jean-sebastien.garrigue@santen.fr
■Refractive surgery is a very common method for
correcting and improving vision. With the minimally
invasive LASIK and SMILE procedures compared to
photorefractive keratectomy (PRK), refractive surgery
is more and more popular among contact lenses and
glasses wearers; however, these surgery procedures
are often complicated by the development of a dry
eye condition. Cationic emulsions (CEs) are novel
eye drops designed for the management of signs
and symptoms of dry eye. Cationorm®clinical data
demonstrated that CEs are effective for the treatment
of patients with mild to moderate signs and symptoms
of dry eye,
1-3 and for the recovery of refractive surgery.4
Introduction
■This study demonstrated that the CEs
(Cationorm®and Cationorm Plus) are well
tolerated by the ocular surface that underwent
PRK-like or LASIK-like refractive surgery
procedures.
Conclusion
■The aim of the present study was to evaluate the
safety of local applications of CEs (Cationorm®and
Cationorm Plus) immediately after refractive surgery
procedures.
Purpose
■Re-epithelization of the cornea was almost complete
at the end of the treatment period; 87.2%±11.8%,
87.4%±14.8%, 94.8%±6.0% for Cationorm®, Cationorm
Plus, and saline, respectively. Cornea opacity scores
remained low for both CEs and were not different from
saline at Days 3, 7, and 10.
■SMA+ myofibroblast accumulation was higher following
PRK-like than LASIK-like. No difference was noted
between the 3 groups for both surgical procedures.
■In eyes subjected to PRK-like, IVCM pictures of the
anterior stroma at Days 7 and 10 confirmed the presence
of fibrosis that was identical in the 3 treatment groups.
Following LASIK-like, the eyes appeared normal
(epithelium, anterior and posterior stroma, endothelium)
in the 3 treatment groups at Days 3, 7, and 10.
■ZO-1 immunohistochemistry of the wounded area
did not reveal any increase in the percentage of
abnormal cell junctions for the 3 treatment groups
and 2 surgical procedures. Histopathology did not
reveal any complications related to the use of the
CEs immediately after the surgical procedures and
confirmed their good tolerance.
■PRK-like (manual superficial keratectomy, MSK) and
laser-assisted in situ keratomileusis (LASIK)-like were
performed in rabbits (n = 10 per surgical procedure
and treatment group). The instillations of the CEs
(Cationorm®and Cationorm Plus) or saline started
immediately (1 h) after the surgery and lasted for
10 days (QID). Corneal fluorescein staining (CFS),
cornea opacity scores (McDonald-Shadduck’s scale;
intensity 0–4, surface area 0–4), and in vivo confocal
microscopy (IVCM) evaluations were performed during
the course of the study. Corneal immunohistochemistry
(anti-SMA [smooth muscle actin] and anti-ZO-1
[zonula occludens-1]) and histopathology evaluations
were performed on Days 3 (n = 2), 7 (n = 2), and
10 (n = 6).
Methods
Results
Parameters Cationorm
® Cationorm Plus
Aspect White opaque to slightly translucent
pH 7.0 6.0
Osmolality (mOsmol/kg) 196 265
Mean droplet size (nm)a 168 (PDI 0.160) 155 (PDI 0.173)
Zeta potential (mV)b +26.4 +38.1
Sterility Sterile Sterile
Table 1. Summary of the Physico-Chemical
Parameters of the Cationic Emulsions.
aMean droplet size was determined by dynamic light scattering (HPPS, Malvern Instruments); bzeta potential by electrophoretic mobility measurement
(Zetasizer 2000, Malvern Instruments). PDI, polydispersity index.
Re-epithelization Following PRK-like
NaCI
% of Re-epithelization
** **
0
20
40
60
80
120
100
Day 3 Day 7 Day 10
Cationorm Plus
Cationorm®
Figure 1. Re-epithelization Over Time Following
PRK-like Surgical Procedure
Data are mean ±SD, statistical analysis vs. saline (Dunnett’s multiple comparisons test; **p<0.01). PRK, photorefractive keratectomy; NaCl, saline.
Figure 4. (A) IVCM Representative Pictures of the Ocular Surface Following PRK-like Surgical Procedure
at Days 3, 7, and 10, and (B) Representative Pictures at Day 3 Following LASIK-like Surgical Procedure
IVCM, In vivo confocal microscopy; PRK, photorefractive keratectomy; LASIK, laser-assisted in situ keratomileusis; NaCl, saline.
Day 3 Post PRK-like Day 7 Post PRK-like Day 10 Post PRK-like Day 3 Post LASIK-like
Presented at the 2017 Annual Meeting of the Association for Research in Vision and Ophthalmology; May 7–11, 2017; Baltimore, Maryland
References: 1. Robert PY. Efficacy and safety of a cationic emulsion in the treatment of moderate to severe dry eye disease: a randomized
controlled study. Eur J Ophthalmol. 2016;26:546-555; 2. Ousler G 3rd. An evaluation of Retaine™ophthalmic emulsion in the management of
tear film stability and ocular surface staining in patients diagnosed with dry eye. Clin Ophthalmol. 2015;9:235-243; 3. Daull P. Comparison of the
anti-inflammatory effects of artificial tears in a rat model of corneal scraping. J Ocul Pharmacol Ther. 2016;32:109-118; 4. Aragona P. Evaluation
of the efficacy and tolerability of Cationorm, a preservative free cationic emulsion, in the recovery after refractive surgery. ESCRS, Milan, Sept 2012.
Disclosures: Y. Quentric is employed by Iris Pharmaceuticals. P. Daull is employed by Santen SAS. E. Gross is employed by Iris Pharmaceuticals.
S. Antonelli is employed by Iris Pharmaceuticals. V. Mauro is employed by Iris Pharmaceuticals. L. Feraille is employed by Iris Pharmaceuticals.
J.S. Garrigue is employed by Santen SAS.
Cornea Opacity Score—PRK-like
Opacity Score
Day 3 Day 7 Day 10
ACornea Opacity Area Score—PRK-like
Opacity Area Score
Day 3 Day 7 Day 10
B
NaCI
Cationorm Plus
Cationorm®
NaCI
Cationorm Plus
Cationorm®
0
1
2
3
4
5
0
1
2
3
4
5
Figure 2. (A) Cornea Opacity Score (0–4), and
(B) Cornea Opacity Area Score (0–4) Following
PRK-like Surgical Procedure
Data are mean ±SD, statistical analysis vs. saline (Dunnett’s multiple comparisons test; p<0.05). PRK, photorefractive keratectomy; NaCl, saline.
SMA+ Volume—PRK-like
Volume (mm3)
0
0.1
0.2
0.3
0.4
0.5
Day 3 Day 7 Day 10
AZO-1+ Junction—PRK-like
% of Abnormal Junction
0
10
20
30
40
50
Day 3 Day 7 Day 10
B
*
NaCI
Cationorm Plus
Cationorm®
NaCI
Cationorm Plus
Cationorm®
Figure 3. (A) SMA+ Myofibroblast Accumulation,
and (B) Structural Evaluation Using ZO-1
Labelling (junction quality assessment) in
Subepithelial PRK-like Scared Region
Data are mean ±SD, statistical analysis vs. saline (Dunnett’s multiple comparisons test; *p<0.05). SMA, smooth muscle actin; ZO-1, zonula
occludens-1; PRK, photorefractive keratectomy; NaCl, saline.
Cornea Opacity Score—LASIK-like
Opacity Score
0
1
2
3
4
5
Day 3 Day 7 Day 10
ACornea Opacity Area Score—LASIK-like
Opacity Area Score
0
1
2
3
4
5
Day 3 Day 7 Day 10
B
NaCI
Cationorm Plus
Cationorm®
NaCI
Cationorm Plus
Cationorm®
Figure 5. (A) Cornea Opacity Score (0–4), and
(B) Cornea Opacity Area Score (0–4) Following
LASIK-like Surgical Procedure
Data are mean ±SD, statistical analysis vs. saline (Dunnett’s multiple comparisons test; p<0.05). LASIK, laser-assisted in situ keratomileusis; NaCl, saline.
SMA+ Volume—LASIK-like
Volume (mm3)
0
0.1
0.2
0.3
0.4
0.5
Day 3 Day 7 Day 10
AZO-1+ Junction—LASIK-like
% of Abnormal Junction
0
10
20
30
40
50
Day 3 Day 7 Day 10
B
*
NaCI
Cationorm Plus
Cationorm®
NaCI
Cationorm Plus
Cationorm®
Figure 6. (A) SMA+ Myofibroblast Accumulation,
and (B) structural evaluation using ZO-1
Labelling (junction quality assessment) in
Subepithelial LASIK-like Scared Region
Data are mean ±SD, statistical analysis vs. saline (Dunnett’s multiple comparisons test; *p<0.05). SMA, smooth muscle actin; ZO-1, zonula
occludens-1; LASIK, laser-assisted in situ keratomileusis; NaCl, saline.
NaCI
Posterior StromaAnterior StromaEpithelium Endothelium Posterior StromaAnterior StromaEpithelium Endothelium Posterior StromaAnterior StromaEpithelium Endothelium Posterior StromaAnterior StromaEpithelium Endothelium
Cationorm®
Cationorm Plus
A B
