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Abstract
Dry eye is the most common post-operative complication in patients who undergo
laser-assisted in situ keratomileusis and other photorefractive procedures.
Epidemiological studies have found that almost all patients experience some form of
dry-eye-related discomfort in the post-operative period. This review seeks primarily
to identify patient factors, which predispose to this complication, as well as outline
the possible interventions clinicians can consider to avoid, prevent and treat this
complication. Numerous pre-, intra- and post-operative guidelines are provided. The
ideal method of post-laser-assisted in situ keratomileusis dry eye prevention is a
meticulous peri-operative management plan, as opposed to post-operative
management alone. Newer modalities of photorefractive surgery may have differing
effects on the ocular surface.
Introduction
Dry eye disease is defined as a multifactorial disease of the ocular surface and tear
film that results in symptoms of discomfort, visual disturbance and tear film
instability. It is characterized by hyperosmolarity of the tear film and inflammation of
the ocular surface.[1]
Photorefractive surgery induces dry eye or exacerbates pre-existing dry eye by
causing increased tear osmolarity and inflammation of the ocular surface via various
mechanisms.[2] The three predominant techniques of photorefractive surgery now
used in clinical practice are laser-assisted in-situkeratomileusis (LASIK),
photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK).
LASIK continues to be the most commonly performed surgery of the three. [3] This
discussion is hence centered upon LASIK, but still includes a study of some recent
variants of laser corneal refractive procedures. While it is acknowledged that this
topic has been extensively reviewed previously,[4] this article focuses on providing
concise, evidence-based guidelines to clinicians on how best to prevent or treat
post-LASIK dry eye. This begins from a process of prudent patient selection
combined with peri-operative treatment of the condition
Epidemiology
Pathophysiology
The pathophysiologic mechanisms behind post-LASIK dry eye have been previously
reviewed,[2,10] and are summarized below with updates included:
corneal innervation have also been identified after LASIK, more specifically
decreased length, width and tortuosity of sub-basal nerve fibers. [13] In this study,
tortuosity returned to a pre-operative state by 3 months post-operatively, while
decreases in length and width persisted even after 6 months of follow-up. The time
required for sub-basal nerves to recover to its pre-operative length and width is
unknown.
Decreased afferent input can also cause decreased blink frequency and increases
the inter-blink interval. There are also previous reviews that have explored the fact
that LASIK can cause incomplete blinking, leading to exposure keratopathy.
[14]
Overall, the increased exposure time of the ocular surface to the environment
leads to greater evaporative loss of the tear film, contributing to dryness. [10]
Dry eyes are associated with minute punctate epithelial erosions of the cornea,
usually detected by fluorescein or Rose Bengal staining of the ocular surface. This is
seen in post-LASIK patients due to impaired healing of the epithelium.
Numerous small peptides released by sensory nerve endings play a role in
supporting overlying epithelium.[15] Beyond the anesthetic effect caused by sensory
nerve damage, disruption of corneal innervation also deprives the epithelium of
epitheliotrophic factors such as substance P and insulin-like growth factor-1 that play
a role in maintaining a healthy epithelium and wound healing. [16] Studies in mice have
shown that innervation is important in maintaining limbal corneal stem cells. [17]
Nerve growth factor (NGF) has been highlighted as a major factor in promoting
epithelial healing by promoting cell migration via the upregulation of matrix
metalloproteinase-9 and cleavage of beta4 integrins. [18] It has been found to be
elevated in post-PRK and LASIK eyes and is likely to be the predominant
neuropeptide in promoting epithelial healing after the procedure. [19] Lower levels of
post-operative NGF are associated with poorer post-operative tear function.
[19]
Deficiency of NGF expression may hence be the pathophysiologic basis of LASIKinduced neurotrophic epitheliopathy (LNE),[20] in which a persistent corneal epithelial
defect forms, regardless of tear production status.
The healing process after photorefractive surgery is initiated by epithelial migration,
followed by epithelial proliferation and stromal regeneration. [21] Expression of
cytokines involved in wound-healing such as TNF-, PDGF, VEGF and TGF-1 is
part of the keratocyte's innate response to insult. After LASIK, the expression of
these cytokines was not impaired.[2225] This seems to support LNE as the primary
cause of poor epithelial healing in post-LASIK corneas.
Unlike keratocyte-derived growth factors, lacrimal secreted glycoproteins and
cytokines may be impaired after LASIK. Lacritin for instance is produced almost
exclusively by the lacrimal gland.[26] After secretion, it can drive further lacrimal
secretion and acinar proliferation. Post-LASIK hyposecretion of tears leads to
decreased delivery of lacritin to the ocular surface. This may contribute to poor
epithelial healing or dry eye, though this has to be confirmed by studies. There have
been no studies investigating transferrin or lactoferrin levels in post-LASIK eyes.
The threshold for detection of painful stimuli may have been altered after the LASIK
surgery. The neuropeptides mentioned above have been implicated in lowering
nociceptive thresholds, possibly contributing to more readily perceived symptoms of
inflammation such as dryness and discomfort after LASIK. [34]
Laser-induced inflammation of the cornea occurs due to excimer laser ablation of
the corneal stroma, and femtosecond laser flap creation. In such cases, a sequential
cascade of keratocyte apoptosis, activation and differentiation into myofibroblasts
occurs.[35] The pattern of inflammation has been found to be significantly different
between LASIK and PRK, first in the type of cytokine responses elicited, and second
in the intensity and site of inflammatory response. Laser-induced inflammation
associated with PRK occurs predominantly at the corneal sub-epithelial layer and
anterior stroma, while laser-induced inflammation in LASIK is more confined to the
deeper stroma.[36]
Cytokines such as IL-1, IL-6, IL-8 and monocyte chemotactic protein-1 were
expressed by human corneal fibroblasts at 24 h after exposure to the excimer laser.
[37]
They contribute to polymorphonuclear leukocyte and monocyte/macrophages
recruitment to the ocular surface and inflammatory changes. The inflammatory
cytokines can contribute to corneal scarring and haze, [38] particularly in PRK.[39]
Other morphological changes include a decreased nuclear-cytoplasmic ratio of nongoblet conjunctival epithelial cells,[42] but the significance of this alteration is not
known.
Photorefractive surgery involves excising stromal tissue that results in flattening of
the central cornea post-surgery. This is postulated to be detrimental to the eyelid's
interaction with the ocular surface as well as surface tension of the tear film. [29,43] This
in turn leads to incongruent interaction between the posterior lid margin and the
cornea surface during blinking.
Irregularities in the corneal surface have also been found after photorefractive
surgery. Striae detectable by slit-lamp examination and microfolds detectable by
confocal microscopy have both been documented in the Bowman's layer after
LASIK.[44] Some cases of corneal striae are severe enough to cause refractive error
and were persistent even at 15 months after LASIK. [45] Microfolds are also
consistently found in almost all post-LASIK eyes, with some being discovered 2
years after LASIK.[44,46]It is postulated that these irregularities contributes to impaired
tear spreading with tear instability and resultant post-LASIK dry eye. [47]
In a separate study, age and gender were not found to predispose to post-LASIK dry
eye, but this study diagnosed dry eye purely on corneal fluorescein staining.
[8]
Ethnicity as a risk factor may be confounded by other factors. These include racial
differences in lid and orbital anatomy, blinking dynamics; higher pre-operative
myopia and attempted refractive correction; and poorer pre-existing tear film
parameters in East Asians. The effects of age, gender and race have been reviewed
elsewhere and similar conclusions were obtained. [8,50,51]
History of contact lens wear is also important. Patients with contact lens intolerance
may have underlying dry eye. Long duration of contact lens use is a risk factor for
otherwise normal individuals to develop dry eye [2,52] and similarly predisposes postLASIK patients to chronic dry eye defined as dry eye persisting beyond 6 months.
[49]
The duration of contact lens wear in this study ranged from 3 to 23 years.
Cigarette smoking should also be considered. A study published in 2013 discovered
that contact lens wear and chronic cigarette smoking positively correlate with TGF1 and VEGF tear levels and delayed corneal re-epithelialization. [53] There is no
evidence that smoking cessation improves the tear outcome after LASIK.
artificial tears, topical autologous serum, punctal occlusion, etc. Consultation with
the rheumatologist is also necessary to assess the severity and stability of the
patient's condition.
While no studies have been conducted to assess the risk of post-LASIK dry eye in
patients with a history of blepharoplasty, we believe patients who have had previous
blepharoplasty should be stringently assessed before proceeding with LASIK, as dry
eye may be a common complication after blepharoplasty.[61]
In the lateral view, a vertical line dropped from the supraorbital rim to the infraorbital
rim is usually in tangent with the corneal surface. If the corneal surface protrudes
beyond this line, it is termed a negative vector.[62] Looking out for a negative vector of
the orbit may also be helpful in assessing risk of dry eye. A negative vector is
associated with greater incidence of scleral show and lower lid descent after lower
lid blepharoplasty. Nocturnal lagophthalmos can occur after blepharoplasty [63] and
should also be assessed in patients.
demonstrated to be relevant risk factors for chronic post-LASIK dry eye. [48] Among
these, the pre-LASIK Schirmer score is of particular importance and its pre-operative
value is significantly correlated with post-operative TBUT (r = 0.504, p = 0.02) for up
to 9 months in a study.[42] Schirmers I of less than 10 mm (at 5 min) was associated
with increased risk (relative risk: 1.58; 95% CI: 1.102.26) of post-operative dry eye
at one month post-operatively.[64] There has been no study using a receiving
operating curve approach to examine the optimal Schirmer test threshold to detect
post-LASIK dry eye.
Certain groups performed Rose Bengal dye staining of the conjunctiva. [20,27,42,59,67] This
has not proven to be mandatory for the purpose of routine assessment. It is also a
potential source of ocular irritation, and hence its use does not seem warranted.
Corneal sensitivity, although not a routine component of dry eye diagnosis, is
valuable because of its role in the pathogenesis of LASIK-induced dry eye as
previously mentioned. Assessment is performed using the Cochet-Bonnet
esthesiometer. Three studies used non-contact gas esthesiometers for corneal
sensitivity assessment.[6870] Though these are proven to give results that are
consistent with those of Cochet-Bonnet esthesiometry, the gas esthesiometers may
not be widely available for use in LASIK clinics due to their cost. There have been
no studies that found correlation between pre-operative corneal sensitivity and postoperative tear function.
InflammaDry, a rapid point-of-care diagnostic test to detect elevated matrix
metalloproteinase 9 levels, has shown good sensitivity (85%) and specificity (94%),
in detecting dry eye.[71] However, it should be noted that the diagnostic criteria for dry
eye were strict in this study, and required positive OSDI, TBUT, Schirmer's test and
corneal staining findings for dry eye. In the context of post-LASIK dry eye,
InflammaDry may have a role in patient selection for pre-operative ocular surface
optimization and for anti-inflammatory dry eye treatment. [72]
Other diagnostic aids to consider include tear osmolarity testing with the TearLab
Osmolarity System. Use of this device to diagnose and assess dry eye has been
reviewed favorably,[73] and has been found to be useful in assessment of LASIK-related
dry eye.[31]
Intra-operative Factors
longest follow-up period, and showed that hinge position had no effect on corneal
sensitivity or dry eye outcomes at any given time point after LASIK.
A narrow hinge width (3.005.50 mm) was also reported to be associated with
slower recovery and greater severity of post-operative loss of corneal sensitivity, and
more severe dry eye symptoms than a wider hinge width (6.007.50 mm). [66,81]
Differences in hinge angle[79] and flap thickness[79,82] were not found to affect postoperative corneal sensitivity and dry eye at any given time point within 12 months.
Enhancement surgeries with flap lifting at a mean of 1 year after the initial
procedure, which could damage healed corneal nerves, also did not lead to an
increased incidence of post-operative dry eye. [83]
As elaborated in the 'Pathophysiology' section, intra-operative application of a
suction ring on the ocular surface would reduce goblet cell density in the conjunctiva
for up to 1 month after LASIK.[41]
Variations of LASIK
Different modalities of flap creation, namely microkeratome and different platforms of
femtosecond lasers, have also been investigated for their effects on post-operative
dry eye.
One study (which included 183 eyes) reported that compared with microkeratome
LASIK, femtosecond laser LASIK led to lower incidence and severity of punctate
epithelial erosion and dry eye symptoms, as well as lesser use of cyclosporine A for
post-LASIK dry eye treatment at 1 month post-operatively.[5]
In contrast, two other studies, with sample sizes of 102 and 274, reported no
significant difference in both tear function and symptoms between microkeratome or
femtosecond laser procedures.[84,85]These two studies had longer follow-up times (12
months and 3 months). Some clinicians may favor the use of femtosecond lasers
over the microkeratome, but the difference in dry eye outcomes is once again
unlikely to be substantial regardless of modality used, especially beyond the first
month of post-LASIK recovery.
Among femtosecond laser flap-creation systems, there was no association between
the types of femtosecond lasers, namely lasers of frequency (500 vs 60 kHz) and
machines (VisuMax vs Intralase), and post-operative dry eye. [86]
Use of different ablation laser platforms also had no effect on post-LASIK dry eye
(summarized in Table 2), though more research has to be done to draw any
meaningful conclusions.[87,88]
Alternatives to LASIK
PRK, LASEK and epipolis laser in-situ keratomileusis (Epi-LASIK) are common
alternatives to LASIK for corneal refractive surgeries. Literature has reported
different risk profiles for these alternatives, and they are summarized below:
Photorefractive keratectomy PRK patients have better post-operative tear
function, but suffer more severe dry eye symptoms and poorer wound healing.
Available studies revealed that PRK offered better post-operative tear function, in
terms of higher Schirmer score and TBUT, and lower tear osmolarity, than LASIK at
up to 3 months following surgery.[29,89] Symptoms were not investigated in these
studies.
However, symptomatic dry eye seemed to be worse in patients who have undergone
PRK rather than LASIK. One study assessed dry-eye symptoms in post-LASIK and
PRK patients by using a questionnaire, which enquired about major symptoms such
as frequency of dryness, tenderness of the eyelid and the sensation of eyelid
stickiness. It reported a higher frequency of dry-eye symptoms in patients who
underwent PRK as compared with LASIK, for at least 6 months post-operatively.[9] In
another randomized trial, while symptoms of dryness and foreign body sensation
were not significantly different between procedures, patients with PRK reported a
higher frequency of visual fluctuation at 1 month after operation. [90]
The reason behind this discrepancy between signs and symptoms can be explained
by the differing effects PRK and LASIK have on corneal sensitivity, and the greater
degree of wound healing necessary in PRK. A study that compared PRK and LASIK
patients for up to 3 months post-operatively found that corneal sensitivity was more
significantly impaired in LASIK patients.[91] Hence, while patients may have poorer
tear function after LASIK, their corneas are less sensitive to irritating or painful
stimuli, hence they suffer less symptoms. Moreover, due to the stripping of the
corneal epithelium during the PRK procedure, re-epithelialization of the cornea to
pre-operative thickness requires about 6 months. [92] In contrast, this process of reepithelialization is not required after LASIK due to replacement of the flap. This
prolonged period of post-operative wound healing may contribute greatly to postPRK dry eye.
Laser epithelial keratomileusis LASEK has very similar effects on post-operative
dry eye as LASIK.
LASEK, compared with LASIK, has shown better post-operative tear secretion in
patients[89] and was found in a separate study to lead to earlier recovery of corneal
sensitivity, which was shown to be correlated with the sub-basal nerve fiber and
keratocyte density at time of measurement.[93] However, dry eye symptomology was
not investigated in these studies.
Four other studies[9396] have demonstrated contrasting results. In particular,
Dooley et al. [94] took the most holistic approach of investigating both signs and
symptoms of dry eye in a prospective controlled cross-sectional study. This study of
85 eyes over a 12-month period showed no differences between LASEK and LASIK
in dry eye symptoms (ocular surface disease index score), tear function (Schirmer
score and tear osmolarity) and incidence of dry eye.
EpiLASIK EpiLASIK seems to be intermediate between LASIK and PRK in terms of
induction of dry eye.
The mechanics of the EpiLASIK procedure (creation of a sub-epithelial flap, ablation
of the superficial stroma) is a combination of elements from both LASIK and PRK. Its
post-operative effects on the ocular surface are also likely to be that between the
profiles of LASIK and PRK.
In a rabbit model, early post-operative increase in NGF was found to be higher in the
EpiLASIK group than the LASIK group,[97] implying that corneal nerve regeneration is
faster in EpiLASIK. This is consistent with research in human eyes, where on-flap
EpiLASIK was shown to offer faster recovery of corneal sensitivity over a 6-month
period.[98] Tear function, which was assessed by TBUT and Schirmer II, was also
found to be superior in EpiLASIK in the same study.
Another human study found no significant differences in incidence of post-operative
dry eye between patients who underwent either LASIK, LASEK or EpiLASIK.
[96]
However, this study only assessed their patients up to 1 week post-operatively.
(Enlarge Image)
Figure 1.
The relationship between different photorefractive modalities and its patient outcomes.
(A)Photorefractive procedures ranked by length of time before relief in pain or dry eye symptoms, in
ascending order. (B) Photorefractive procedures ranked by severity of tear dysfunction, in ascending
order.
Solomon also recommended that patients kept their eyes closed for 4 h postoperatively. While it may be beneficial for the patients to do so, it is impractical given
the day surgery setting of all photorefractive procedures. We hence recommend;
Instruct the patient to close their eyes for the duration of observation after surgery,
and to avoid strenuous activity of the eye for the rest of the day.
HPMC artificial tears, such as Bion tears (Alcon). These conclusions were made
by an unmasked, randomized study, which monitored dry eye symptoms and signs
in 18 eyes of 10 patients for a period of 1 month. [108]
If there are additional contributing factors such as MGD or aqueous tear deficiency,
additional treatment modalities targeting the specific pathology can be administered.
To date, no study has looked specifically at how pre-operative MGD contributes to
post-LASIK dry eye, but it can be assumed that these patients will have more severe
tear film dysfunction after surgery. Hence, it will be best to address MGD and
observe for improvement in the patient's condition before proceeding to
photorefractive surgery.
In MGD, the use of lid hygiene, warm compress and lid warming, nutritional
supplement, topical azithromycin and oral doxycycline have been described by
various authors for post-LASIK patients.[4,51,109] In particular, a lid warming device,
Eyefeel (Kao, Inc.), was shown to improve post-operative symptoms (OSDI), tear
film stability (TBUT) and tear lipid layer thickness (interferometry). [110] In this study,
these post-LASIK patients were not examined for MGD before operation, but only 16
out of 17 of them had dry eye symptoms before LASIK. They all presented with
persistent dry eyes for more than one year post-operatively with signs of lipid layer
deficiency. Their condition responded well to lid warming therapy, with a reduction of
symptoms and increase in thickness of the lipid layer, suggesting that MGD was the
underlying cause of their dry eyes.
In aqueous tear deficiency, post-operative use of punctal plugs has showed faster
recovery toward a stable tear film and symptom relief, as well as the improvement of
both quantitative and functional visual acuity.[111113] In dry eye, irregularity of the tear
film induces wavefront aberrations. Patients with high amounts of wavefront
aberrations pre-operatively continue to have aberrations, which were not caused by
the refractive procedure. The aberrations experienced by such patients, measured
by a Shack-Hartmann wavefront sensor (Zywave, Bausch and Lomb), were reduced
with the use of post-operative punctal plug insertion at day 1. [111] However, a case
report warned that plug insertion after LASIK carries the risk of causing canaliculitis,
even among the new generation SmartPLUG (Medennium Inc.). [114]
Findings from a rabbit study showed that autologous serum inhibited cytokine
release and migration of inflammatory cells. It also decreased keratocyte apoptosis
and promoted migration of fibroblast and myofibroblast to the wound site following
surgery.[115] Topical autologous serum was shown in a trial of 27 men to reduce
corneal epithelial erosions and improve post-operative tear film stability more
effectively than artificial tears at up to 3 and 6 months, respectively.[116] However the
high cost and limited availability of this modality continues to limit its clinical use.
Topical cyclosporine A (CsA) given twice a day may be incorporated into standard
treatment [104,106,117119]. A randomized controlled trial comprising 21 patients
with pre-existing dry eyes showed that CsA, given at 1 month before operation,
discontinued for 48 h post-operatively then continued for another 3 months in
addition to artificial tears as needed, showed greater tear secretion in patients
between 1 and 6 months post-operatively compared with artificial tears alone.
[106]
This is supported by a retrospective study of 45 patients, in which addition of CsA
to standard treatment improved recovery of post-operative uncorrected visual acuity
and better predictability of refractive correction. [118] Disappointingly, the benefits of
CsA were not replicated in a prospective randomized controlled trial by Hessert et
al.,[117] which had a larger sample size of 124 patients as compared with all previously
quoted studies in CsA. Improvements in visual acuity, mesopic contrast acuity, dry
eye symptoms and tear film inflammatory mediator levels were found to be similar
compared with standard treatment without CsA at all time-points up to 3 months for
both LASIK and PRK.
Tacrolimus is an immunosuppressive agent similar to cyclosporine. In a noncontrolled trial, tacrolimus eye drops were shown to improve tear film function and
reduce corneal epitheliopathy in eight dry eye patients with Sjogren syndrome. Tear
secretion and tear stability improved only at day 90 and day 28 of treatment while
corneal staining was reduced by day 14 of treatment. [120] However, patients should be
warned that tacrolimus can cause an uncomfortable stinging sensation.
fibers in the stroma is limited.[121] Given its low cost and its lack of known adverse
events,[123] it may one day become a standard treatment.
Ophthalmic gels consisting of protein-free calf blood extract and recombinant bovine
basic fibroblast growth factor (r-bFGF) have been studied clinically for the treatment
of LASIK-induced dry eye and have shown clinical efficacy.[124,125] However, the longterm safety profile of these bovine-derived products has not been reported.
Finally, several compounds are still being put through basic research and their
potential may be better understood in the future. Their common mechanism of action
is through stimulating corneal nerve regeneration. Both the NGF [126] and the bioactive
N-terminal peptide from adenylate cyclase-activating polypeptide (PACAP27)
[127]
have demonstrated that they increased the speed of recovery of corneal
sensitivity and induced growth of neurite extensions. However, the tear NGF is
usually already raised after LASIK. Theoretically, this treatment modality may only
be effective in patients with deficient NGF expression.
FK962 (N-[1-acetylpiperidin-4-yl]-4-fluorobenzamide) has also shown increased
corneal nerve regeneration in rat trigeminal ganglion cells and recovery of corneal
sensitivity in rabbits[128] and its mechanism using the rat trigeminal ganglion cell
model is shown to likely involve glial derived neurotrophic factor that induces neurite
elongation but is independent of NGF.[129]
Another compound, leukemia inhibitory factor (LIF), when compared with balanced
saline, showed accelerated corneal nerve regeneration and better post-operative
tear function (Schirmer I and TBUT) for at least 3 months in rabbits. [130]
Expert Commentary
Prevention of dry eye lies clearly in the identification of patients at risk of such a
complication, using the risk factors outlined earlier in this review. From there, a
proper post-operative management of the patient can be planned, such as the use
of cyclosporine A together with lubricant drops in patients with high risk of dry eye.
Patient counseling is a key component of pre-operative management. Patient
satisfaction will be less affected if patients are given a more accurate prognosis of
their post-operative discomfort. We also urge clinicians to extend the concept of
Five-year View
Current research findings suggest that post-LASIK dry eye is but a transient problem
after the procedure and will resolve with time. The proportion of patients that go on
to develop persistent, chronic dry eye problems years after surgery is poorly
investigated. Even if such studies have been done, given the delay between the
refractive procedure and onset of dry eyes in these patients, it is hard to prove that
the refractive procedure contributed to dry eye.
Of all the pathophysiologic mechanisms implicated in post-LASIK dry eye, most
resolve within one year after surgery and cannot seem to account for cases of
chronic, persistent post-LASIK dry eye. As mentioned earlier, however, nerve
morphology and corneal irregularities seem to be persistent defects that last beyond
one year after surgery, and should be investigated for its possible effects on dry eye.
Future research in neural influences of sub-basal nerves on the corneal surface may
consider investigating if nociceptive thresholds have been reduced in these cases of
chronic post-LASIK dry eye, or if subtle changes in the biochemical make-up of the
sub-basal nerves can account for the condition of these patients.
Advances in interferometry allow detection and localization of tear film breakup.
There have been previous studies implicating corneal irregularities as the focal point
for tear breakup and postulating it as a cause for post-LASIK dry eye, but more
studies have to be carried out in patients who have persistent post-LASIK dry eye to
establish this theory as an etiology of chronic dry eye after LASIK.
In the area of management, many novel therapeutic agents are currently in clinical
trials, with many holding great promise. Of note will be E-PRP that may see greater
acceptance and use in the years ahead due to its low cost and good safety profile.
ReLEx SMILE (small-incision lenticule extraction) is a new photorefractive
procedure, which is gaining popularity. This new procedure completely removes the
need for flap creation or epithelial stripping, achieving the desired refractive
correction by creating an intra-stromal lenticule with a femtosecond laser, and
removing the lenticule thereafter by a small incision made at the limbus.
Theoretically, this leaves most of the corneal nerves intact and should lead to
superior post-operative preservation of corneal sensitivity than previous
photorefractive procedures.
Two trials, one randomized[131] and one non-randomized[132] found SMILE to have
better dry eye outcomes to femtosecond LASIK (femto-LASIK). In one randomized
trial involving 28 patients (28 eyes underwent SMILE, contralateral eye underwent
femto-LASIK), SMILE was found to result in significantly higher corneal sensitivity for
up to 3 months when compared with femto-LASIK. In another non-randomized trial
involving 54 eyes for femto-LASIK and 61 eyes for SMILE, corneal sensitivity was
found to be superior in eyes, which have undergone SMILE compared with femtoLASIK for up to 3 months, and a complete recovery to baseline corneal sensitivity
was faster and could be achieved 3 months post-operatively.
SMILE was also superior to Femtosecond Lenticule Extraction (FLEx) in preserving
corneal sensitivity. Moreover, in a randomized self-controlled trial involving 35
patients,[133] sub-basal nerve density was better preserved in SMILE than FLEx at 6
months post-operatively. This corresponded to superior corneal sensitivity of SMILE
to FLEx at 6 months in the same study.
However, in both randomized trials, tear film parameters were not significantly
different between the surgical methods, despite differences in post-operative corneal
sensitivity. In the non-randomized trial, tear film parameters were not examined.
Sidebar
Key Issues
Dry eye is a common complication after photorefractive procedures, and most cases
spontaneously resolve a few months after surgery.
A subset of patients have persistent symptoms, and there is limited literature on this
group of patients.
It is best to avoid LASIK and other photorefractive procedures in patients with preoperative dry eye, collagen vascular diseases and allergies.
Most intra-operative factors such as hinge properties in LASIK, flap creation method and
differing ablation platforms do not seem to influence post-operative dry eye outcomes,
the exceptions being hinge width and ablation depth.
As a general rule, LASIK causes poorer tear function but less dry eye symptoms, while
PRK produces more severe symptoms related to dry eye or wound healing.
Numerous novel therapeutic agents for dry eye are currently in research, with eye
platelet-rich plasma showing the most promise of becoming a component of standard
treatment in future.
Future research should focus on investigating the prevalence of chronic dry eye lasting
more than one year post-LASIK, and finding the specific etiology of this form of dry eye.
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