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Original Paper

Ophthalmic Res Received: October 11, 2017


Accepted after revision: February 25, 2018
DOI: 10.1159/000487951 Published online: June 8, 2018

Plasma Rich in Growth Factors for the


Treatment of Dry Eye after LASIK Surgery
Ronald Mauricio Sanchez-Avila a Jesus Merayo-Lloves a Maria Laura Fernandez a
     

Luis Alberto Rodriguez-Gutierrez a Nancy Jurado a Francisco Muruzabal b, c


     

Gorka Orive b–e Eduardo Anitua b, c


   

a Fundación de Investigación Oftalmológica, Instituto Universitario Fernández-Vega, Oviedo, Spain;


b University
Institute for Regenerative Medicine and Oral Implantology – UIRMI (UPV/EHU-Fundación Eduardo
Anitua), Vitoria, Spain; c Biotechnology Institute (BTI), Vitoria, Spain; d Laboratory of Pharmacy and Pharmaceutical
   

Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria, Spain; e Networking Biomedical  

Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, SLFPB-EHU, Vitoria, Spain

Keywords tically significant improvement in the Ocular Surface Dis-


Dry eye · Cornea · Refractive surgery · Ocular surface · ease Index (38.12%), visual analogue scale scores for fre-
Growth factors quency (41.89%) and severity (42.47%), and the Schirmer
test scores (88.98%) after PRGF treatment (p < 0.05). No ad-
verse events were reported after PRGF treatment. Conclu-
Abstract sions: These results suggest that PRGF eye drops are effec-
Purpose: The aim of this study was to evaluate the use of tive for the improvement of dry eye symptoms in patients
plasma rich in growth factors (PRGF) eye drops in patients who underwent LASIK surgery in comparison to the conven-
with dry eye disease after laser-assisted in situ keratomileu- tional therapy. The treatment with PRGF is an alternative for
sis (LASIK) surgery. Material and Methods: This is a longitu- patients who suffer from postoperative dry eye.
dinal, retrospective, comparative, and descriptive study of © 2018 S. Karger AG, Basel
77 eyes of 42 patients with dry eye disease following LASIK
surgery. This study was designed to evaluate the efficacy of
PRGF treatment compared to conventional therapy (control Introduction
group). Outcome measures including signs and symptoms
of dry eye disease were evaluated before and after treat- Laser-assisted in situ keratomileusis (LASIK) is an
ment. The percentage of change before and after treatment ophthalmological procedure used to correct refractive er-
for each clinical variable measured was compared between rors; in the United States, approximately 650,000 LASIK
both groups. Results: There were 1–4 treatment cycles with surgeries are performed each year [1]. It involves the cre-
PRGF eye drops (1 cycle = 6 weeks). Results showed a statis- ation of a thin superficial corneal flap by a microkeratome
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Kaohsiung Medical University Library

© 2018 S. Karger AG, Basel Ronald M. Sanchez-Avila


Fundación de Investigación Oftalmológica
Instituto Universitario Fernández-Vega
E-Mail karger@karger.com
Av. Doctores Fernández-Vega, 34, ES–33012 Oviedo (Spain)
www.karger.com/ore
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E-Mail ronald.sanchezavila @ gmail.com


followed by corneal tissue ablation with an excimer laser patient’s peripheral blood; the leukocytes are discarded;
and, finally, the repositioning of the flap [1]. Dry eye therefore, they are not present in the PRGF formulations.
symptoms are a remarkably frequent consequence in a In addition, the PRGF eye drops are not diluted, as usu-
wide range of patients after LASIK surgery, and they are ally happens with AS [18]. The efficacy of PRGF eye drops
a primary reason for patient dissatisfaction [2]. The main has been evaluated for the treatment of several ocular sur-
proposed cause of dry eye after LASIK surgery is iatro- face disorders, such as evaporative dry eye, persistent epi-
genic corneal nerve damage. During the procedure of the thelial defects, or refractory ocular surface disorders [19–
anterior stromal flap and excimer laser ablation of the 22].
cornea, both the dense sub-basal nerve plexus and stro- This study evaluated the efficacy of PRGF (Endoret)
mal corneal nerves are disrupted [3]. Immediately after eye drops for the corneal wound healing process and pa-
the procedure, patients present symptoms of dry eye syn- tient satisfaction after LASIK surgery. The use of blood
drome, including dryness, burning sensation, stinging, derivatives represents an alternative therapeutic ap-
photophobia, ocular discomfort, and even reduction of proach that has gained interest in regenerative medicine
postoperative visual acuity [4]. due to its potential to stimulate and accelerate tissue heal-
The condition usually peaks in the first few months ing. This study aimed to evaluate a new clinical use of this
after surgery, and then symptoms start to improve in the new generation of blood-derived therapies.
vast majority of patients until nearly complete resolution
at 6–12 months after surgery [5]. Conventional treatment
Materials and Methods
includes the use of artificial tears as the initial therapy try-
ing to lubricate the ocular surface, but, unfortunately, ar- A longitudinal, observational, retrospective, comparative, and
tificial tears do not always provide enough relief [6]. descriptive study was performed including 77 eyes of 42 patients
Punctal plugs and corticosteroids can also be used for the with dry eye disease after LASIK surgery between January 2012
and June 2015 at a single private center (Ocular Surface Unit of the
management of post-LASIK dry eye. However, the latter Fernandez-Vega University Institute, Oviedo, Spain). Informed
is not a good long-term treatment owing to potential side consent was obtained from all patients included in this study for
effects of increased intraocular pressure (IOP) and cata- the use of autologous PRGF in dry eye. Institutional review board
ract formation [7]. Several studies have demonstrated approval was obtained for this study. The research adhered to the
that a reduction in corneal sensitivity leads directly or in- tenets of the Declaration of Helsinki.
This study was designed to evaluate the efficacy of PRGF treat-
directly to the development of corneal epitheliopathy [8, ment compared to conventional therapy (control group) in pa-
9]. Hence, a rapid recovery of corneal innervation is es- tients with dry eye disease following LASIK surgery. Patients were
sential for restoring the corneal homeostasis. Numerous divided into 2 groups: those who received a standard treatment for
studies suggest the used of proteins and growth factors, dry eye (artificial tears, corticosteroids, AS, cyclosporine, etc.) for
such as nerve growth factor (NGF), substance P-derived at least 3 months, without achieving improvement in their dry eye
symptoms (n = 39), and those who received a PRGF eye drops
peptide, or insulin-like growth factor-1, to accelerate the regimen (n = 38). Data were obtained retrospectively from the pa-
recovery of corneal sensitivity after LASIK surgery [10– tients’ medical records. Previous surgical treatments were per-
12]. However, in spite of their encouraging results in clin- formed using the same excimer laser (STAR S4 IR® Excimer Laser,
ical trials, their use is limited as recombinant growth fac- Abbott Laboratories Inc., IL, USA) by corneal surgeons. LASIK
tors are still not cost-efficient. procedures were performed using an IntraLase 60-kHz femtosec-
ond laser to create a flap thickness of 100 μm. All femtosecond flaps
Autologous serum (AS) has also been used previously were created with the hinge positioned superiorly. After LASIK,
to treat dry eye syndrome after LASIK [13]. The satisfac- patients were prescribed moxifloxacin and dexamethasone 0.1%,
tory results obtained after AS treatment are suggested to each 4 times per day for 1 week, and were instructed to use an ar-
be due to the high number of growth factors related to tificial tear solution 4 times per day for 1 month, and a bandage
ocular surface tissue regeneration, which are mainly pro- contact lens was inserted for 1 week. Patients received a postop-
erative follow-up of at least 3 months and a preoperative and post-
vided by blood platelet content [14, 15]. However, the operative consultation.
content of proinflammatory cytokines involved in the in- Inclusion criteria included patients >18 years of age with a his-
flammatory process of some ocular diseases, such as IL-6, tory of LASIK surgery between January 2012 and June 2015, with
IL-1β, and TNF-α, is increased during the AS preparation dry eye disease lasting >6 months after LASIK surgery, and treated
procedure due to the presence of leucocytes [16, 17]. Plas- with standard (control group) or PRGF eye drops therapy. Patients
had to meet symptoms of dry eye disease defined as Schirmer test
ma rich in growth factors (PRGF) is an autologous 100% <10 mm, tear breakup time (TBUT) <10 s, and severity of subjec-
platelet-rich plasma which is mainly characterized by a tive symptoms on the level of moderately to severely dry eye (as
2-fold increased platelet concentration compared to the defined by the EDE Workshop Committee in 2007).
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2 Ophthalmic Res Sanchez-Avila et al.


DOI: 10.1159/000487951
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For the preparation of PRGF eye drops, blood was collected Table 1. Preoperative and postoperative data and statistical values
into 9-mL tubes. Samples were centrifuged at 580 g for 8 min at of outcome variables analyzed in the control group
room temperature in an Endoret System centrifuge (BTI Biotech-
nology Institute, S.L., Miñano, Álava, Spain). The whole column Baseline Final Wilcoxon
of PRGF was collected after centrifugation using Endoret ophthal- evaluation evaluation test
mology kit (BTI Biotechnology Institute) and avoiding the buffy p value
coat that contains the leukocytes. PRGF eye drops were incubated
at 37 ° C for 1 h. The obtained supernatant was then heat treated at
    
OSDI 20.33±12.17 17.51±10.68 0.115
56 ° C for 60 min in order to reduce the immunologic components
    
BCVA 0.096±0.198 0.111±0.207 0.327
(immunosafe PRGF). Finally, plasma supernatants were filtered, VAS frequency 35.38±25.09 32.05±23.75 0.336
aliquoted, and stored at –20 ° C until use. All procedures were per-
    
VAS severity 34.10±25.39 30.00±20.65 0.237
formed under highly sterile conditions, operating inside a laminar Schirmer test 7.78±2.08 8.11±2.50 0.194
flow hood. Before initiating the treatment, patients were instructed TBUT 7.00±2.13 7.55±2.39 0.002*
to keep the PRGF eye drop dispensers at –20 ° C for a maximum of
     IOP 12.05±2.34 11.72±2.16 0.491
3 months; and each dispenser was used for 3 consecutive days. The Sphere –0.30±0.74 –0.32±1.27 0.448
PRGF Endoret eye drops were applied topically 4 times daily for 6 Cylinder –0.21±0.67 –0.17±0.78 0.569
weeks in the affected eye (1 cycle = 6 weeks). In case of poor re- Axis 35.77±58.74 34.44±58.53 0.887
sponse, an additional cycle of 6 weeks with PRGF was added, up to
4 cycles. PRGF treatment did not exclude the use of other con- Values are means ± standard deviations. OSDI, Ocular Surface
comitant treatments (antibiotic agents, anti-inflammatory agents, Disease Index; BCVA, best-corrected visual acuity; VAS, visual
artificial tears, etc.) when considered necessary. analogue scale; TBUT, tear breakup time; IOP, intraocular pres-
Both demographic (gender, age) and clinical variables of pa- sure. * Statistically significant difference (p < 0.05) before versus
tients were collected from clinical records. The following variables after treatment with standard therapy (control group).
were analyzed before starting treatment (PRGF or control) and
after 1 week, 1 month, and on subsequent visits (patients were fol-
lowed for nearly 1 year): visual analog scale (VAS) (frequency and
severity of symptoms), dry eye psychometric survey (Ocular Sur-
face Disease Index [OSDI]), best-corrected visual acuity (BCVA) tients, and they were distributed as follows: 17 females
(LogMAR), TBUT, Schirmer test, and IOP (in mm Hg). Manifest and 4 males in the control group (treated with conven-
refraction values, including sphere, cylinder, and axis, were also tional therapy) and 15 females and 6 males in the PRGF
evaluated at each follow-up. group.
Data were analyzed using Statistical Package for the Social Sci- Patients were treated with 1–4 cycles of PRGF eye
ences (SPSS) version 15.0 for Windows (SPSS Inc., Chicago, IL,
USA). Descriptive statistics were performed using absolute and drops (1 cycle = 6 weeks of treatment). Fifteen of 21 pa-
relative frequency distributions for qualitative variables and mean tients received 1 cycle of PRGF (71.4%), 3 patients re-
values and standard deviations for quantitative variables. Different ceived 2 cycles (14.3%), while 2 cases received 3 cycles
normality tests (Kolmogorov-Smirnov and Shapiro-Wilk) were (9.5%) and only 1 case received 4 cycles (4.8%) of PRGF
performed on each variable sample. Potential differences between eye drops.
baseline (before) and after treatment (PRGF or control group)
were analyzed using the nonparametric Wilcoxon statistical test The results of different outcome variables measured
for each evaluated clinical variable. In addition, we evaluated the in patients of the control group before and after follow-
mean differences between PRGF and control treatment after up are summarized in Table 1. After the follow-up pe-
LASIK surgery for each variable using the nonparametric Mann- riod, the control group showed a significant change (p <
Whitney U test. Statistical significance was set at p < 0.05. 0.05) between before and after treatment only in the
TBUT outcome variable. However, the other clinical ob-
jective symptoms (BCVA, Schirmer test, and IOP)
Results showed no significant changes before and after treat-
ment with conventional therapy. Moreover, no signifi-
Forty-two patients (77 eyes) who underwent bilateral cant changes (p > 0.05) were found in the eye discomfort
LASIK between January 2012 and June 2015 were includ- variable measured by the OSDI scale or in subjective oc-
ed in the study. The overall mean age was 51.1 years (SD ular symptoms (discomfort, dryness, burning/stinging,
14.1, range 28–81). In the PRGF group (38 cases), the photophobia, foreign body sensation, blurred vision,
mean age was 53.5 years (SD 14.7, range 28–73), and in itching, and pain) measured by the VAS score (frequen-
the control group (39 cases), the mean age was 48.8 years cy and severity). Likewise, the control group patients
(SD 13.2, range 31–81). No statistically significant differ- also did not experience a significant change in refractive
ence was found for age in the 2 treatment groups (p = variables (sphere, cylinder, and axis) over the follow-up
0.192). There were 32 female patients and 10 male pa- period.
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PRGF in LASIK Surgery Ophthalmic Res 3


DOI: 10.1159/000487951
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Table 2. Preoperative and postoperative data and statistical values baseline value of 52.97 (SD 21.66) to a final post-treat-
of outcome variables analyzed in the PRGF group ment value of 31.13 (SD 11.92). The latter represents a
Baseline Final Wilcoxon
total reduction of 38.13%, which was statistically signifi-
evaluation evaluation test cant (p < 0.05). The BCVA showed a nonsignificant re-
p value duction from a baseline value of 0.096 (SD 0.114) to a final
post-treatment value of 0.083 (SD 0.109). Regarding the
OSDI 52.97±21.66 31.13±11.92 0.000*
BCVA 0.096±0.114 0.083±0.109 0.060
ocular symptoms measured by the VAS score regarding
VAS frequency 74.21±22.50 46.05±22.12 0.000* frequency and severity, a significant decrease (p < 0.05)
VAS severity 73.42±22.21 45.79±21.64 0.000* was measured ranging from a baseline value of 74.21 (SD
Schirmer test 4.10±1.78 7.06±2.34 0.000* 22.50) and 73.42 (SD 22.21) to a final post-treatment val-
TBUT 4.10±1.11 6.74±1.65 0.000* ue of 46.05 (SD 22.12) and 45.79 (SD 21.64), respectively.
IOP 11.76±2.12 10.83±1.78 0.007* This represents a statistically significant (p < 0.05) reduc-
Sphere –0.36±0.94 –0.23±0.69 0.448
Cylinder –0.62±0.76 –0.15±0.47
tion of both variables of 41.89 and 42.47%, respectively.
0.001*
Axis 61.32±66.85 39.34±55.83 0.106 Furthermore, patients treated with PRGF eye drops
showed a significant increase (p < 0.05) in tear volume
Values are means ± standard deviations. PRGF, plasma rich in measured by the Schirmer test and in tear film stability
growth factors; OSDI, Ocular Surface Disease Index; BCVA, best- evaluated by TBUT. The Schirmer test increased from a
corrected visual acuity; VAS, visual analogue scale; TBUT, tear
breakup time; IOP, intraocular pressure. * Statistically significant dif-
baseline value of 4.10 mm (SD 1.78) to a final post-treat-
ference (p < 0.05) before versus after treatment with PRGF therapy. ment value of 7.06 mm (SD 2.34), showing a statistically
significant increase of 88.98%. Likewise, TBUT increased
significantly by 71.14% from 4.10 s (SD 1.11) to a final
follow-up value of 6.74 s (SD 1.65). Finally, although this
Table 3. Comparative analysis of percentage changes (before and
after treatment) between standard (control) and PRGF therapy for is clinically irrelevant, PRGF treatment also significantly
the different analyzed outcome variables reduced (p < 0.05) IOP values by 5.32%, ranging from a
baseline value of 11.76 (SD 2.12) to a final post-treatment
Control group PRGF group Wilcoxon value of 10.83 (SD 1.78).
test
p value
Finally, differential changes obtained before and after
follow-up for each outcome variable were compared be-
OSDI –6.40±47.73 –38.13±14.20 0.000* tween both treatment groups (control vs. PRGF) (Table
BCVA 15.27±97.82 19.60±68.75 0.481 3). In summary, significant differences between both
VAS frequency 17.47±146.38 –41.89±26.61 0.001* groups were found for different outcome variables, in-
VAS severity –16.10±42.77 –42.47±24.60 0.000*
cluding OSDI, VAS frequency, VAS severity, Schirmer
Schirmer test 4.06±14.81 88.98±82.95 0.000*
TBUT 7.79±10.81 71.14±42.87 0.000* test, TBUT, sphere, and cylinder. Results showed that
IOP –0.06±23.51 –10.58±24.64 0.695 PRGF treatment significantly reduced (p < 0.05) the OSDI
Sphere 5.11±75.70 –33.15±49.32 0.042* score by 38.12% in comparison to the control group
Cylinder –7.16±64.17 –49.15±60.33 0.001* (6.40%). Regarding the frequency and severity of dry eye
Axis 16.66±179.79 –32.62±46.98 0.070 symptoms measured by the VAS, significant differences
Values are means ± standard deviations. PRGF, plasma rich in
(p < 0.05) were found in both variables after PRGF treat-
growth factors; OSDI, Ocular Surface Disease Index; BCVA, best- ment compared to conventional therapy, showing a re-
corrected visual acuity; VAS, visual analogue scale; TBUT, tear duction of 41.89 and 42.74%, respectively, in the PRGF
breakup time; IOP, intraocular pressure. * Statistically significant dif- group and an increase of 17.47% for VAS frequency and
ference (p < 0.05) between PRGF and control group for the differen- a reduction of 16.10% for VAS severity in the control
tial changes of each outcome variable before and after follow-up.
group. Finally, patients treated with PRGF eye drops also
showed a significant improvement (p < 0.05) of outcome
variables that measure the production and quality of the
However, the group of patients treated with PRGF eye tear film (Schirmer test and TBUT) in comparison to the
drops showed significant changes (p < 0.05) in most of the control group. The Schirmer test showed a significant in-
variables included in the study, except for BCVA and crease of 88.98% in the tear film production after PRGF
sphere and axis refractive variables (Table 2). A signifi- treatment compared to the control group, the latter show-
cant reduction in the OSDI scale was observed from a ing an increase of only 4.06%. In addition, PRGF treat-
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4 Ophthalmic Res Sanchez-Avila et al.


DOI: 10.1159/000487951
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ment also significantly improved the TBUT values in which leads to dry eye [9, 25]. Therefore, an early recovery
contrast to the control group showing an increase of 71.14 of corneal nerves may attenuate the dry eye symptoms
and 7.79%, respectively. after LASIK surgery by restoring tear secretion and the
normal blinking reflex.
NGF plays an essential role in the development, dif-
Discussion ferentiation, and survival of nerves [26]. NGF is synthe-
sized and secreted by different corneal cells, including
To our knowledge, this is the first reported study fo- epithelial and endothelial cells and keratocytes, and it can
cusing specifically on the outcome of postoperative be taken up by the sympathetic or sensory nerve ending,
LASIK patients using PRGF therapy. This retrospective promoting nerve regeneration. Topical recombinant
and descriptive study was performed between January NGF treatment has been shown to promote corneal rein-
2012 and June 2015 in patients who underwent bilateral nervation after mechanical corneal nerve injury [10, 11].
LASIK and were treated postoperatively with PRGF or However, its use is limited as recombinant growth factors
with conventional treatment. are still not cost-efficient. Furthermore, there are several
In the present study, we assessed the ocular surface neuropeptides involved in nerve regeneration, such as
conditions after LASIK in patients who were prescribed NGF, substance P, and calcitonin gene-related peptide,
PRGF eye drops or artificial tears. Tear function was eval- which are altered in tear films after refractive surgery,
uated by the Schirmer test and TBUT, while ocular sur- suggesting that they may be key factors in the dry eye after
face symptoms were measured by OSDI scores, VAS, and LASIK surgery [27, 28].
by BCVA. The results show that, except for BCVA, all These and other proteins and growth factors involved
clinical variables measured were significantly improved in tissue regeneration are stored in the alpha granules of
after LASIK in the PRGF eye drop group, whereas no platelets [14]. These proteins are secreted by exocytosis
change was noted in the control group, except for TBUT. after platelet activation, allowing the release of their con-
These findings suggest that PRGF eye drops could be ef- tents to the milieu [29]. The use of blood-derived eye
fective for the prevention of postoperative dry eye in- drops has been proposed as another option for treatment
duced by LASIK compared to treatment with conven- of dry eye caused by LASIK surgery. A recent study
tional eye drops. In our study, the addition of topical showed that AS treatment improved some ocular signs of
PRGF eye drops to the standard postoperative regimen dry eye, but no differences were observed in the scores for
provided a statistically significant improvement in most dryness in patients treated with AS in comparison to the
of the clinical variables analyzed in 71% of patients after artificial tears group [13]. In contrast to the latter study,
12 weeks (1 cycle of PRGF treatment). in the present study PRGF eye drops significantly im-
LASIK surgery has been developed rapidly in the re- proved the different ocular symptoms of dry eye analyzed
cent years due to its safety, efficacy, and predictability. compared to conventional therapy (control group). These
However, some complications associated with this sur- differences between PRGF and AS eye drops for the treat-
gery have attracted wide attention. Dry eye is the most ment of several ocular surface pathologies were also pre-
common complication and leads to patient dissatisfac- viously observed [30, 31].
tion, with up to 50% of patients who underwent LASIK Moreover, it has been widely demonstrated that dry
surgery experiencing symptoms of dry eyes 6 months af- eye disease is the result of an underlying cytokine and
ter corneal refractive surgery [2, 23]. Several treatments, receptor-mediated inflammatory process. Although
such as artificial tears, punctal plugs, and botulinum tox- some studies have shown beneficial effects of topical anti-
in, have been used to treat dry eye syndrome after LASIK inflammatory drugs, such as cyclosporine A and corti-
surgery. However, these therapies are associated with coids, for the treatment of dry eye after LASIK [32], their
some complications, including eye irritation, extrusion, use is limited due to several side effects, such as increase
or decreasing blinking power [24]. in IOP, cataract, and glaucoma [33, 34]. Subsequently,
In the last years, several studies have demonstrated recent studies have demonstrated the anti-inflammatory
that the main reason for dry eye in LASIK surgery is de- potential of PRGF eye drops for different ocular surface
rived from the mechanical nerve injury as a result of cor- disorders, including dry eye disease [20, 22, 35].
neal flap formation. The corneal flap cuts off all the nerves The manufacture of PRGF eye drops has a standard-
outside the pedicle, leading to a significant reduction in ized protocol; a closed technique is used for its production
corneal sensitivity and blocking the reflex tear secretion, and storage; it has been classified as a medicine for human
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PRGF in LASIK Surgery Ophthalmic Res 5


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use, it also has anti-inflammatory, bacteriostatic, and re- In conclusion, these results suggest that PRGF eye
generative properties, and is supported by solid evidence drops are effective for the improvement of dry eye symp-
in preclinical and clinical research [18–22, 30, 31]. We be- toms in patients who underwent LASIK surgery. Further-
lieve that therapy with autologous PRGF in patients with more, these results have demonstrated that PRGF is much
dry eye after LASIK could be initiated as soon as there is more effective in the improvement of dry eye syndrome
evidence of the diagnosis, given the potential for the con- than conventional treatment, suggesting PRGF eye drop
trol of symptoms and the regenerative properties of PRGF. treatment as an alternative for the patients who suffer
The results concerning improvement of the sphere from postoperative dry eye.
and cylinder could suggest that the regenerative effect of
PRGF on the cornea is involved in the remodeling of the
corneal curvature, due to modulation in healing, associ- Acknowledgments
ated with anti-inflammatory properties. This opens an
The authors thank Virginia Cuadrado for her support with the
important path for experimentation which should be English grammar.
confirmed by other preclinical and clinical studies.
There are some limitations to the design of this study.
First, this is an open-label retrospective evaluation with all Disclosure Statement
shortcomings inherent in this type of design. Another lim-
itation of the study is the small sample size. On the other The authors declare the following competing financial
hand, the age of the patients presents a wide range (28–81 interest(s): E.A. is the scientific director of and G.O and F.M. are
scientists at BTI Biotechnology Institute, a dental implant com-
years), which could influence the complaints and clinical pany that investigates in the fields of oral implantology and PRGF
recovery of patients. Future randomized clinical studies Endoret technology. For all other authors, no competing financial
will be necessary to properly confirm these initial results. interests exist.

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