Review Article - Clinical

Refractive surgery and dry eye ‑ An update

Sridevi Nair, Manpreet Kaur, Namrata Sharma, Jeewan S Titiyal

Dry eye disease is the most common complication and a frequent cause of patient dissatisfaction after Access this article online
corneal laser refractive surgery, which includes laser‑assisted in situ keratomileusis (LASIK), small‑incision Website:
lenticule extraction (SMILE), and photorefractive keratectomy (PRK). It has a complex, multifactorial [Link]
etiology and is characterized by a highly variable clinical presentation. A detailed preoperative screening DOI:
and optimization of the ocular surface prior to refractive surgery are the key to minimizing the incidence 10.4103/IJO.IJO_3406_22
and severity of postoperative dry eye. Diagnosis of postrefractive surgery dry eye remains a challenge
as no single symptom or clinical parameter is confirmative of the condition, and the symptoms and
signs may not correlate well in many cases. A thorough understanding of the pathomechanism of the Quick Response Code:
disease and its manifestations is essential to facilitate a treatment approach that is individualized for each
patient. This article reviews various aspects of postrefractive surgery dry eye including its epidemiology,
etiopathogenesis, risk factors, diagnosis, and management.

Key words: Dry, eye, laser, LASIK, PRK, refractive, SMILE, surgery

Modern corneal refractive surgery offers a choice of procedures Etiopathogenesis

such as laser‑assisted in situ keratomileusis (LASIK),
small‑incision lenticule extraction (SMILE), and photorefractive Dry eye disease after corneal refractive surgery has a
keratectomy (PRK), all of which are associated with a high multifactorial etiology. The primary mechanism is the
index of efficacy and safety. Despite its overwhelming transection of the corneal nerves which impacts the cornea‑blink
popularity among surgeons and patients alike, it is not reflex and ocular surface‑lacrimal gland neural loop resulting in
free of complications. Dry eye disease is the most common reduced tear secretion and increased tear film instability. It also
complication observed after corneal laser refractive surgery causes a disruption of the neurotrophic factors released from
and one of the leading causes of patient dissatisfaction.[1] the corneal nerves. Reduced blinking may also adversely affect
It can significantly impact the patient’s quality of life with the meibomian gland function.[5‑7] The degree of corneal nerve
even mild dry eye resulting in utility scores equivalent to damage varies depending on the type of refractive surgery.
severe migraine.[2] Postoperative dry eye also predisposes In cornea, the stromal nerve fiber bundles run centripetally
to potentially vision threatening complications such as flap and toward the surface, perforating the Bowman layer to
folds, flap displacement, refractive regression, and microbial form the sub‑basal nerve plexus. Corneal flap creation during
keratitis. [3,4] In this review, we shall elaborate upon the LASIK results in transection of all sub‑basal fibers throughout
etiopathogenesis, epidemiology, predisposing factors, clinical the flap side cut extending 300–310 degrees. Subsequent
manifestations, and management of postcorneal refractive excimer laser ablation of stroma damages the deeper central
surgery dry eye disease. corneal stromal nerves.[8] SMILE does not entail a large flap
cut and the peripheral nerve fibers are resected only where
Methods of Literature Search the 25–50 degrees incision is placed. In addition, fibers that
perforate the Bowman layer within the area of refractive
A systematic literature search was undertaken using PubMed, lenticule are also resected; however, the fibers that had
Google Scholar, and Cochrane Library database. The following penetrated the Bowman layer outside the lenticule area may
keywords were used; “dry,” “eye,” “refractive,” “surgery,” run undisturbed as sub‑basal nerve plexus.[8] PRK does not
“laser,” “LASIK,” “SMILE,” and “PRK.” All relevant review require a flap creation at all. The smaller side cut in SMILE and
articles, original articles, case series, and case reports were absence of flap creation in PRK would theoretically result in
reviewed. The search was conducted in October 2022. We better preservation of sub‑basal nerve plexus.[8] This theory is
limited our search to articles that were published from 1995 supported by the less severe nerve damage and faster corneal
to 2022 and were written in English. re‑innervation observed after PRK[9] and SMILE[8,10] [Fig. 1].

This is an open access journal, and articles are distributed under the terms of
the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License,
Cornea, Cataract and Refractive Surgery Services, Dr. R. P. Centre,
which allows others to remix, tweak, and build upon the work non‑commercially,
All India Institute of Medical Sciences, New Delhi, India as long as appropriate credit is given and the new creations are licensed under
Correspondence to: Dr. Jeewan S Titiyal, Prof. of Ophthalmology ‑ Cornea, the identical terms.
Cataract and Refractive Surgery Services, Dr. R. P. Centre for
Ophthalmic Sciences, All India Institute of Medical Sciences, For reprints contact: WKHLRPMedknow_reprints@[Link]
New Delhi, India. E‑mail: titiyal@[Link]
Received: 31-Dec-2022 Revision: 16-Feb-2023 Cite this article as: Nair S, Kaur M, Sharma N, Titiyal JS. Refractive surgery
and dry eye‑ An update. Indian J Ophthalmol 2023;71:1105-14.
Accepted: 19-Feb-2023 Published: 05-Apr-2023

© 2023 Indian Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

1106 Indian Journal of Ophthalmology Volume 71 Issue 4

a b c

d e f
Figure 1: Confocal microscopy images of preoperative and postoperative sub‑basal corneal nerve fiber layer at 1 year after PRK (a and d),
LASIK (b and e), and SMILE (c and f), respectively

Postoperative inflammatory response associated with peak during the first week after surgery following which it
wound healing after laser refractive surgery also contributes gradually recovers over 6–12 months. About 8–48% continue
to development of dry eye. This neurogenic inflammatory to be affected up to 6 months after LASIK.[4,5,24] The variability
response is postulated to be distinct from that of other etiologies in the incidence rates reported by various studies appears to
of dry eye[11,12] as evidenced by the raised proinflammatory be due to use of different diagnostic criteria. The incidence of
tear mediator levels (IL‑6, MMP‑9), neuropeptides dry eye after SMILE is lower, less severe, and recovers faster
(Substance P and calcitonin gene‑related peptide), and than LASIK.[25‑32] Denoyer et al.[8] reported that 80% of SMILE
neuromediators (nerve growth factor).[12‑15] The upregulation is patients did not require any tear supplements at 6 months
less and recovery faster with SMILE as compared to LASIK.[12,16] postoperatively versus 57% of LASIK patients. Few studies
Direct damage to conjunctival goblet cells by the suction device have evaluated the incidence of dry eye post‑PRK; Hong
during LASIK and SMILE could lead to subsequent mucin et al.[33] reported that 37% of their patients complained of dry
deficiency and tear film instability.[17] Greater loss of goblet eye symptoms after PRK.
cells was reported with femtosecond (FS) LASIK as compared
with the use of microkeratome for LASIK.[18] In addition to Predisposing Factors
these factors, the change in corneal curvature induced by
Identifying patients at risk for development of dry eye after
laser refractive surgery can cause an abnormal distribution
refractive surgery allows the surgeon to adopt requisite
and instability of tear film. The central corneal flattening may
measures to optimize the ocular surface before surgery or
cause an incongruent interaction between ocular surface and
even plan alternative procedures in the more severe cases.
posterior lid margin to adversely affect the meibomian gland
Several preoperative and intraoperative factors can predispose
function.[19] Frequent instillation of preservative containing eye
the patients to develop postoperative dry eye after corneal
drops may also induce a toxic effect on the conjunctiva and
refractive surgery.
cornea further compounding postoperative dry eye disease.[7]
Preoperative factors
Incidence Pre‑existing dry eye is the most important risk factor for
Dry eye disease is the most common complication after development of dry eye after refractive surgery.[34]About 8–55%
any corneal laser refractive surgery. Although the reported of the patients being planned for refractive surgery reportedly
prevalence of post‑LASIK dry eye ranges from 36–75%,[20,21] suffer from dry eye disease.[4,22,35,36] Schallhorn et al.[37] reported
almost all patients experience some degree of dry eye in the that about one‑fifth of their patients with mild symptoms
immediate postoperative period.[22] The Patient‑Reported preoperatively progressed to develop moderate or severe
Outcomes with LASIK (PROWL) studies reported that symptoms after LASIK. Patients with poor tear function and
nearly one third of patients with normal Ocular Surface stability have higher odds of developing chronic dry eye after
Disease Index (OSDI) score before surgery complained of dry excimer laser surgery.[9,17] Interestingly, a low TBUT among
eye‑related symptoms 3 months after LASIK and 4% of them patients being planned for SMILE did not as such increase the
had severe symptoms.[23] The symptoms and signs typically likelihood of developing dry eye symptoms after surgery.[38]
 Nair, et al.: Refractive surgery and dry eye
April 2023 1107

Higher preoperative refractive error has been associated o’clock positions. The difference, however, was not evident on
with an increased risk of dry eye after LASIK, possibly due to long‑term follow‑up at 6 months.[54] Narrower hinge has also
the increased stromal ablation in these patients.[4,21,24,39] Tuisko been associated with a greater loss of corneal sensation and
et al.[40] reported that more than half of the patients undergoing more dry eye symptoms.[62] Interestingly, the incision size in
LASIK for high myopia complained of subjective dry eye SMILE (2 mm, 3 mm, or 4 mm) did not impact the incidence
symptoms even 2–5 years after surgery. One recent study, of postoperative dry eye.[63] Further studies are required to
however, reported that lower preoperative refractive error was explore the influence of factors such as lenticule thickness or
associated with greater risk of dry eye; the authors attributed diameter on the incidence of dry after SMILE.
this to the greater postoperative expectations making these
patients more sensitive to the symptoms.[41] Higher refractive Clinical Manifestations
correction with SMILE has been associated with greater tear
Postcorneal refractive surgery dry eye is a spectrum of disease
film instability, evidenced by decreased TBUT and abnormal
that includes tear dysfunction, neurotrophic epitheliopathy,
tear lipid layer thickness (LLT).[42]
and dysesthetic cornea.[64] The manifestations are typically
Demographic factors such as gender, age, and race may more severe and prolonged after LASIK as compared to SMILE
also influence the development of dry eye postsurgery. Female or PRK.
patients are at an increased risk[4,24,37,41] and have greater odds
Clinical symptoms
of developing more severe and chronic symptoms.[37,43] Older
age has been reported as a risk factor by some authors[24,41] Patients may present with symptoms such as ocular dryness,
while others found no such association[4,21,37,39] Asian patients pain, stinging, photophobia, redness, and visual fatigue.[5,22,43,58]
are at greater risk for developing chronic dry eye post‑LASIK Complaints of fluctuating vision and impaired functional
as compared with Caucasians.[44] Contact lens users also have vision due to irregular astigmatism induced by an unstable
a higher risk of developing postrefractive surgery dry eye.[39,45] tear film are not uncommon.[65] The intensity and duration
of these symptoms are highly variable due to the complex,
Intraoperative factors multifactorial etiology with an often poor correlation between
Surgery‑related factors which can influence corneal denervation subjective symptoms and objective signs.[7] The symptoms
and hence the development of postoperative dry eye include are most bothersome during the first month, following
the surgical technique, amount of stromal ablation or which they gradually improve over 3–12 months.[5] Various
tissue removal, ablation profile, flap diameter, thickness, questionnaires such as Ocular Surface Disease Index (OSDI),
and hinge position. SMILE has been found to have a more Impact of Dry Eye on Everyday Living (IDEEL), and Dry Eye
favorable response in terms of corneal sensitivity and dry Questionnaire (DEQ‑5) may be used to quantify the symptom
eye manifestations as compared to LASIK.[10,30,31,46] Surface severity in these patients.[66]
ablative procedures such as laser‑assisted subepithelial
keratectomy (LASEK) and PRK have also been found to be Ocular surface pain that variably overlaps with the dry
associated with less tear dysfunction and dry eye symptoms eye symptoms is another important manifestation of dry eye
as compared to LASIK.[19,41,47,48] Schallhorn et al.,[37] however, disease after laser ablative surgery.[67] A subset of patients
observed that PRK patients complained of more dry eye‑related complain of persistent and disabling pain which may be
symptoms as compared to LASIK at 3 months. The authors accompanied by hyperalgesia and allodynia and is termed
attributed this to the more severe neurotrophic effect induced as neuropathic ocular pain or corneal neuralgia. It attributed
by LASIK resulting in reduced corneal sensitivity and hence, to the dysfunctional recovery of trigeminal nerve after
greater comfort among the patients. Postoperative dry eye surgery‑induced damage, but the typical clinical signs of dry
incidence following SMILE was found to be comparable with eye are often lacking.[43] Levitt et al. reported that 20–55% of
PRK at 3 months[49] and higher than LASEK at 6 months.[50] their LASIK patients had at least mild symptoms of dry eye
or persistent ocular pain, whereas Moshirfar et al. reported
In LASIK patients, flap size, thickness, hinge location as well that only one patient per 900 undergoing LASIK developed
as the ablation profile and depth can impact the incidence of dry corneal neuralgia.[64,68] Among post refractive surgery patients
eye. Larger flaps and greater depth of ablation are associated with persistent dry eye, ocular pain was reported by up to
with higher risk of postoperative dry. [21,24] Furthermore, 78.8% patients, of which 63.5% was neuropathic in origin.[43]
hyperopic ablation leads to greater denervation due to the Onset of neuropathic ocular pain may be observed in the
increased nerve density in the periphery as compared to central immediate postoperative period in nearly half of the patients
cornea.[51] Thinner flaps are associated with faster recovery while others may show a later presentation.[43,64] Risk factors
of dry eye symptoms[52] and corneal sensation,[53] possibly identified for developing neuropathic pain after refractive
because shallower lamellar dissection results in a less volume surgery include neuropsychiatric conditions and central
of tissue through which the corneal nerves must regenerate.[54] sensitization syndromes. The proparacaine challenge test can
FS lasers allow creation of thinner flaps with more consistent help distinguish between central or peripheral pain origins for
dimensions which results in less damage to anterior stromal ocular neuropathic pain.[43]
nerves.[55] Salomão et al.[56] reported a lower incidence of dry
eye with FS LASIK as compared to LASIK with microkeratome Clinical signs
(9% vs 46%). Other studies found no such difference.[57‑59] Nasal Postrefractive surgery dry eye patients exhibit signs of
hinge flap has been reported to produce less dry eye symptoms dysfunctional tear syndrome with decreased tear film stability
in early postoperative period[60] and faster recovery of corneal and reduced tear secretion evidenced by positive vital staining
sensation,[60,61] possibly due to better preservation of the long of ocular surface, reduced TBUT, and decreased Schirmer test
ciliary nerves which enter the cornea at the 3 o’clock and 9 values.[5,7] Laser‑induced neurotrophic epitheliopathy (LINE),
1108 Indian Journal of Ophthalmology Volume 71 Issue 4

first described by Wilson, [69] is a dry eye like condition Table 1: Clinical manifestations after corneal laser
that is primarily characterized by epithelial erosions with refractive surgery and their salient characteristics
normal tear production manifesting a few days to weeks
after surgery. Decreased supply of neurotrophic factors to Clinical Salient Characteristics
epithelial cells, reduced tear production, and infrequent Manifestations
blinking may contribute to its development. It is observed in Vital staining of Positive vital staining at 1 week; predominantly
4–14% of cases and usually resolved within the first 6 months cornea involving the flap in LASIK, less severe in
of surgery. Various objective parameters such as the ocular SMILE
surface staining score, TBUT, Schirmer test, and tear meniscus Symptoms less severe due to reduced
height assessment can help quantify the severity of disease. sensitivity
More advanced diagnostic modalities that may employed Resolves by 6‑12 months after LASIK[7]
Resolves by about 1‑3 months after SMILE[16]
for better characterization of the disease include in vivo
Resolves by about 3 months after PRK[9]
confocal microscopy, meibography, tear film interferometry,
Tear breakup Reduced; most severe at 1 week
and tear analysis for osmolarity and inflammatory mediator
time Normalizes by about 6‑12 months
measurement. Table 1 details the important clinical
post‑LASIK[16,27,70]
manifestations of dry eye disease and their course following Normalizes by about 3‑6 months after
corneal laser refractive surgeries.[7,9,16,25,27,33,42,51,52,59,70‑76] SMILE[42,70]
Normalizes by about 3 months after PRK[9]
Preoperative Considerations Schirmer test Reduced after surgery; maximally during first
Identifying patients with pre‑existing dry eye during the month
preoperative evaluation is crucial to ensure optimal outcomes Normalizes by 6‑9 months after LASIK[7,59]
after any corneal refractive procedure. A detailed history and Normalizes by about 3 months after SMILE[42]
Normalizes by about 3‑6 months after PRK[9,33]
meticulous ocular surface examination can help detect the
high‑risk cases who then require to be treated aggressively Corneal Greater reduction after LASIK; decreased
sensitivity maximally at 1‑2 weeks
to optimize the ocular surface.[77] Moreover, special attention
Recovers by about 12 months after LASIK[7]
should be paid to the possibility of co‑existent ocular allergies
Recovers faster, by 3‑6 months after
and systemic disorders such as diabetes or collagen vascular SMILE[16,71,72]
diseases. [7,78] Corneal refractive surgery should not be Recovers in 3‑12 months after PRK[51,73,74]
performed in patients with uncontrolled systemic disorders Lipid layer Reduced after SMILE by 1 week, recovers by 3
or active ocular involvement. Surgery in systemic conditions thickness months[16,42]
that are well controlled with a normal tear function has been No significant change reported by one study
found to be fairly safe without serious complications.[79‑81] after LASIK[76]
There are reports of severe refractory dry eye and necrotizing Tear osmolarity Increased; more after LASIK than PRK and
keratitis postrefractive surgery in well‑controlled Sjogren SMILE
syndrome and Crohn’s disease patients indicating that these Levels raised for up to 3‑6 months after LASIK
patients are not well suited for refractive surgery.[82,83] Ocular and SMILE[25]
allergies are a known risk factor for dry eye and both often Levels raised for up to 4 months after PRK[75]
co‑exist, which may complicate the outcomes of laser refractive Nerve Sub‑basal nerve density, stromal nerve
surgery. Chronic inflammation of the ocular surface in allergic morphology cells reduced after surgery; other features
disorders impairs the tear film stability, conjunctival goblet on confocal include nerve beading, irregular branching,
scanning microneuromas and increased dendritic cells.
cells, and meibomian gland function which contributes to dry
Microneuroma in post‑LASIK neuropathic
eye disease.[84] Moreover, ocular surface inflammation induced
corneal pain.[64]
by corneal laser refractive surgery may be exacerbated in atopic Recovery may take up to 24‑60 months after
patients.[85] Laser refractive surgery is contraindicated in cases LASIK[74]
with active ocular allergic disease but may be considered after Recovery by about 12 months after SMILE[25,51]
adequately treating the allergic condition. Recovery by about 24 months after PRK[51]
LASIK‑laser‑assisted in situ keratomileusis; SMILE‑ small‑incision lenticule
Management extraction; PRK‑photorefractive keratectomy
Management approach for postrefractive surgery dry eye aims
to stabilize the tear film, increase aqueous production, and surgery. They are routinely prescribed post surgery for
control ocular surface inflammation. Depending on the severity about 4–6 weeks and often suffice for the management of
and nature of manifestations various agents including topical transient dry eye in majority of patients. Non‑preserved
lubricants, anti‑inflammatory drugs, punctal plugs, mucin carboxymethylcellulose (CMC)‑based artificial tears have been
secretagogues, and autologous serum may be employed in a shown to be more effective in stabilizing the ocular surface
step ladder approach. Table 2 details the different management after laser refractive surgery as compared to saline drops
options and their outcomes in postcorneal refractive surgery or 0.3% hydroxypropyl methylcellulose owing to its greater
dry eye disease. muco‑adhesive properties.[104,105] Other formulations such as
hyaluronic acid (HA), polyvinyl alcohol, and polyethylene
Tear substitutes glycol may be used depending on the severity and type of
Tear substitutes, preferably preservative free, are the first dry eye.[86,87] Hyaluronic acid is available in preservative‑free
line of treatment for postoperative dry eye after refractive formulation and has intrinsic properties of water retention,
 Nair, et al.: Refractive surgery and dry eye
April 2023 1109

Table 2: Management options and outcomes of postcorneal refractive surgery dry eye disease
Tear Supplements

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Durrie et al. (2008)[86] Evaluated PEG + PPG vs 30 patients 1 month TBUT TBUT significantly longer in
placebo in a randomized Corneal & PEG+PPG group at 2 weeks,
comparative contralateral eye conjunctival but comparable at 1 month
study in post‑LASIK patients staining
Astakhov Evaluated 0.15% 54 patients 3 months Corneal Similar efficacy with both
et al. (2013)[87] hyaluronate (PF) vs PEG+PPG fluorescein medications; PF hyaluronate
in a randomized comparative staining showed a trend for more rapid
study in post‑LASIK patients improvement
Fouda PEG+PPG vs intraoperative 70 patients 6 months ST, TBUT, OSDI All parameters better for the
et al. (2017)[88] botulinum toxin A (BTA) score BTA and punctal plug group
injection below lower puncta vs than the tear substitute only
punctal plugs group up to 3 months after
surgery. Fewer complications in
BTA than plug group
Wallerstein Evaluated CMC+HA vs CMC 148 patients 3 months ST, TBUT, OSDI, CMC‑HA‑was non inferior to
et al. (2018)[89] in a randomized comparative corneal staining CMC alone, with incremental
study in post‑LASIK patients benefit in uncorrected vision
Topical Cyclosporin

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Hessert Topical cyclosporin (0.05%) 124 eyes 3 months Ocular No significant benefit observed
et al. (2013)[90] therapy after LASIK and PRK symptoms, tear with prophylactic topical
evaluated in a randomized inflammatory cyclosporin therapy
comparative study mediators
Salib et al. (2006)[91] Evaluated topical cyclosporin 42 eyes 6 months ST, OSDI, Cyclosporine offered significant
therapy in dry eye patients corneal staining improvements in tear volume at
undergoing LASIK in a more study visits than artificial
randomized clinical trial tears (statistically insignificant)
Better refractive predictability 3
and 6 months after surgery with
topical cyclosporine 0.05%
Kanellopoulos Evaluated topical 0.05% 145 eyes 12 months ST, TBUT, OSDI, A significant improve in all
(2019)[92] cyclosporine A therapy in corneal epithelial metrics observed at 12 months
post‑LASIK dry eye patients in a thickness
retrospective study
Mucin Secretagogoues

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Mori et al. (2014)[93] Evaluated topical diquafosol 15 patients 12 weeks ST, TBUT, Improvement in ocular surface
tetrasodium in persistent corneal and staining, TBUT, and symptom
post‑LASIK dry eye patients in a conjunctival score observed
prospective study staining,
symptom score
Toda et al. (2014)[94] Prospective randomized study 206 eyes 1 month ST, TBUT, Hyaluronate and diquafosol
compared artificial tears, 0.3% corneal and combination therapy was
sodium hyaluronate, diquafosol conjunctival beneficial for early stabilization
tetrasodium, and a combination staining, of visual performance, tear
of hyaluronate and diquafosol in symptom score, secretion, and improvement of
post‑LASIK patients corneal sensitivity subjective dry eye symptoms
Igarashi et al. Rebamipide ophthalmic 30 patients 4 weeks ST, TBUT, Rebamipide therapy significantly
(2015)[95] suspension in post‑LASIK/ corneal staining, improved dry eye parameters
ReLEx dry eye patients in a subjective such as tear volume, TBUT,
randomized comparative study symptoms, fluorescein score, and subjective
objective symptoms while reducing the
scattering index intraocular scattering of light

Contd...
1110 Indian Journal of Ophthalmology Volume 71 Issue 4

Table 2: Contd...
Autologous Serum

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Noda‑Tsuruya, Randomized study evaluated 27 patients 6 months ST, TBUT, Autologous serum group
et al. (2006)[96] topical autologous serum corneal showed prolongation of TBUT
therapy in post‑LASIK patients staining scores, and reduction in rose bengal
subjective staining score
symptom score
Javaloy et al. Prospective randomized 108 eyes 3 months Corneal PRP drops promoted epithelial
(2013)[97] study evaluated the effect of sensitivity status but had no positive effect
platelet‑rich plasma (PRP) on Corneal staining on corneal sensitivity or nerve
corneal nerve regeneration and Sub‑basal nerve regeneration
sensitivity after LASIK density
Lin et al. (2015)[98] Retrospective review evaluated 10 patients 8.26±11.87 Corneal and Autologous serum was effective
the efficacy of autologous weeks conjunctival in improving corneal surface
serum eye drops in recalcitrant staining, conditions and postoperative
LASIK‑induced neurotrophic Schirmer, TBUT, visual acuity
epitheliopathy TMH,
Alio et al. (2017)[99] Prospective study evaluated 156 eyes 6 weeks Corneal Improvement in dry eye
PRP in post‑LASIK staining, OSDI, symptoms (85%), corneal
moderate–severe persistent dry conjunctival staining (90%), and conjunctival
eye patients unresponsive to hyperemia hyperemia (94%)
artificial tears
Punctal Plugs

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Yung et al. (2012)[100] Randomized comparative 25 eyes 2 months ST, TBUT, ocular Punctal plugs significantly
study evaluated punctal plus in surface staining, improved the symptoms, tear
post‑LASIK dry eye patients symptom score, function, and quality of vision
FVA, SRI
Nemet Retrospective comparative 345 eyes 3‑6 Presence of dry Preventive temporary punctal
et al. (2020)[101] study evaluated the effect months eye disease, plug placement reduced dry
of preventive intraoperative superficial eye symptoms by 13%, reduced
punctal plug implantation during punctate keratitis SPK by 12%, and delayed
LASIK dry eye disease by more than
30 days
Oral Supplements

Author/Year Study Details n Duration Outcomes Results

of therapy Measures
Goyal Evaluated ω3FA 60 eyes 3 months ST, TBUT, OSDI, Supplementation with ω3FA
et al. (2017)[102] supplementation in post‑LASIK corneal staining had a positive influence on
patients in a randomized scores tear secretion (Schirmer);
controlled study tear film stability remained
unaffected
Lin et al. (2022)[103] Oral Vitamin 90 patients 3 months ST, TBUT, Significantly better OSDI score,
D3 supplementation in OSDI, tear , tear production and TBUT in
post‑LASIK dry eye in a inflammatory study group
randomized controlled study mediators
LASIK‑laser‑assisted in situ keratomileusis; SMILE‑ small‑incision lenticule extraction; PRK‑photorefractive keratectomy; ReLEx‑refractive lenticule
extraction; PPG‑Polypropylene glycol; PEG‑Polyethylene glycol, TBUT‑tear breakup time, OSDI‑Ocular Surface Disease Index, FVA‑functional visual
acuity; SRI‑surface regularity index; CMC‑carboxymethyl cellulose; HA‑hyaluronic acid; ω3FA‑omega‑3‑fatty acid; TMH‑tear meniscus height; ST‑Schirmer
test

viscoelasticity, and promotion of corneal epithelial wound Topical anti‑inflammatory therapy

healing.[87] More recently, a multi‑ingredient formulation Postoperative inflammation is an important contributor
containing CMC 0.5% and HA 0.1% was found to promote to development of dry eye and can be controlled using
visual recovery faster after LASIK as compared to CMC alone anti‑inflammatory agents such as topical steroids and
possibly due to the HA‑mediated epithelium recovery which cyclosporin. Topical steroids are a part of routine postoperative
improved the surface optics.[89] regimen, tapered over 4–6 weeks. Topical cyclosporin
 Nair, et al.: Refractive surgery and dry eye
April 2023 1111

is effective in optimizing dry eye patients before laser a significant positive effect on corneal nerve regeneration and
refractive surgery as well the treatment of new onset dry eye recovery of corneal sensitivity after surgery.[97] Limitations of
postsurgery.[91,106] It is effective in improving the tear secretion autologous serum or plasma drops include the need for its
and stability for up to 1 year in patients with symptomatic preparation from the patient’s own blood and a limited shelf
dry eye after LASIK[92] Several weeks of treatment may be life of up to a week when stored at 40 C and 3 months when
required before any effect is apparent, with a maximum effect stored at ‑200 C.
reached at about 6 months.[92] The benefit of incorporating
Punctal plugs
topical cyclosporin in the routine postoperative regimen;
however, remains unclear. While one study reported improved Punctal plugs help in retaining patient’s own tears as well
visual outcomes with reduced recovery time when topical as instilled tear supplements for longer time. Preventive
cyclosporine was prescribed in routine post‑LASIK patients,[107] implantation of punctal plugs during LASIK was found
another found no significant benefit in terms of improving to reduce dry eye symptoms, improves tear function, and
the dry eye‑related signs, symptoms, and tear inflammatory decreases the need for frequent lubricant instillation during
mediators.[90] Topical cyclosporine has also been reported to the early postoperative period and may be considered in
enhance corneal nerve regeneration and improving corneal high‑risk cases.[88,101,113] Yung et al.[100] observed that punctal
sensitivity in post‑LASIK patients.[108] More recently, a newer occlusion with silicone plugs was effective in treating refractory
formulation of Cyclosporin A Cationic Emulsion 0.1% has post‑LASIK dry eye for up to 3 months after surgery. Loss of
shown promising results in moderate to severe dry eye patients plugs, epiphora, and granuloma formation are some of the
with improvement in clinical signs evident as early as 4 weeks, complications associated with use of punctal plugs.[88]
though, up to 12 months of treatment is recommended for more Other measures
sustained effects.[109] Further studies are required to assess its
Supportive measures such as lid hygiene, heated eye mask,
efficacy in postrefractive surgery dry eye patients.
eyelid thermal pulsation therapy, and oral doxycycline
Mucin secretagogues therapy should be prescribed to treat co‑existing anterior
Tear mucin plays an important role in maintaining tear film blepharitis or meibomian gland dysfunction which can
stability owing to its hydrophilicity and lubricating properties. contribute to postoperative dry eye.[114,115] Oral Omega‑3 fatty
Diquafosol tetrasodium (DQS) is a P2Y2 receptor agonist acid and vitamin D3 supplementation may also have role in
that facilitates mucin production and tear secretion from improving tear secretion and visual quality in post‑LASIK
conjunctival epithelial cells and goblet cells.[110] Addition of patients.[102,103] Newer treatment agents such as topical nerve
DQS 3% solution improved tear film stability and alleviated growth factor (NGF) have been found to stimulate corneal
symptoms in post‑LASIK dry eye patients who were sensitivity, nerve regeneration, and tear film stability in animal
unresponsive to artificial tears and topical sodium hyaluronate studies, making it a promising option for postrefractive surgery
therapy.[93] Combination therapy with DQS and hyaluronate dry eye patients in future.[116]
after LASIK has been found to act synergistically and improve
functional visual acuity, tear secretion, and dry eye symptoms Conclusion
faster than monotherapy with either agent. [94] However, Postoperative dry eye has a high prevalence among post corneal
it remains unclear if these improvements are maintained refractive surgery patients and can significantly impact their
after termination of the DQS treatment. Another mucin quality of life. The severity and duration of disease may be
secretagogue, Rebamipide 2% solution, has been reported highly variable and is determined by factors including but
to alleviate dry eye‑related signs and symptoms, as well as not limited to surgical variables, presence of pre‑existing dry
improve the optical quality in post‑LASIK dry eye patients.[95] eye, and magnitude of refractive error. Proper preoperative
evaluation and counseling can help detect the high‑risk cases
Autologous serum
and minimize postoperative dissatisfaction. The management
Autologous serum is rich in neurotrophic and epitheliotropic of postrefractive surgery dry eye follows a step ladder approach
factors such as nerve growth factor and substance P, epidermal and comprises tear supplements, topical anti‑inflammatory
growth factor (EGF), transforming growth factor (TGF), agents, mucin secretagogues, punctal plugs, and autologous
vitamin A as well as anti‑inflammatory factors and matrix serum drops in the more refractory cases. While most cases
metalloproteinase inhibitors. [111] It has been reported to resolve within the first year, a small subset may progress to
improve tear film stability demonstrated by prolongation of chronic dry eye warranting more aggressive therapy.
TBUT and reduction of ocular surface staining in post‑LASIK
patients.[96] Recalcitrant cases of LASIK‑induced neurotrophic Financial support and sponsorship
epitheliopathy have been found to benefit from autologous Nil.
serum therapy with significant improvement in ocular surface
parameters and visual acuity.[98] Platelet‑rich plasma (PRP) Conflicts of interest
and plasma rich in growth factors (PRGF) are considered There are no conflicts of interest.
to have advantages over autologous serum due to a higher
concentration of growth factors, anti‑inflammatory cytokines, References
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