SURGICAL PROCEDURE

Our technique may be considered representative of the standard SMILE procedure and is
described as follows; Preoperative preparation is similar to that of patients undergoing LASIK
surgery. Topical anaesthetic (BNX, Benoxinate Minims, Chauvin Pharmaceuticals, England),
antibiotic (Ciloxan, ciprofloxacin, Alcon Inc, Ft Worth, Texas, USA) and anti-inflammatory
drops (Maxidex, dexamethasone, Alcon Inc) are instilled prior to entering the laser theatre. The
lids are swabbed with povidone-iodine solution (betadine, PDI, Orangeburg, NewYork,USA)
immediately prior to surgery.

The procedure is performed in several steps. When ready, the patient is brought underneath the
femtosecond laser (Visumax, Carl Zeiss, Erlangen, Germany). The patient is centred under the
operating microscope, as the surgeon orientates the docking mechanism. The patient interface
consists of a cone and curved contact glass interface. A speculum is placedin the eye to maintain
adequate exposure before the suction ring is placed onto the eye. During the docking procedure
the patient is able to maintain fixation on the internal fixation target to reduce the risk of
decentration. The suction ring is applied to the eye prior to the patient interface being moved in
to position. Once the surgeon is satisfied with the centration of the interface the laser may be
initiated. The laser first creates the posterior lenticule surface, which represents the refractive
correction. The anterior lenticule surface is then ablated, followed by vertical edge incisions at
the perimeter of the refractive zone. Finally the peripheral corneal incisions are created to allow
for the lenticule extraction (Figure 1).

Figure 1. Intra-operative compilation of SMILE surgical procedure. Top left; Showing the docking and laser
ablation. Topright: Immediately following the laser ablation. The spatula enters through the sidecut. Bottom
left:The spatula is moved across the anterior and then posterior lenticule surface. Bottom right: The lenticule
is removed.
 The laser parameters required willvary between centres and individual surgeons.
Typically our parameters are as follows; pulse energy 120 to 195 nJ, spot distance 4.5 mm,
lenticule side-cut angle 90 degrees, optical zone diameter 6.5 mm, cap thickness 120 mm and
side-cut circumferential length 3.0 mm. The procedure takes approximately 30 seconds in most
cases. The mean intra-operative intraocular pressure (IOP) is estimated at around 85mmHg in
comparison to standard LASIK parameters of between 150 and 250 mmHg (Zeissdataon file).
This suggests that the procedure remains more comfortable and that patient fixation maybe
retained during the laser procedure. Once the lenticule has been created, the suction ring and
interface are removed. The patient remains under the laser and a manual spatula is inserted to
separate the lenticule from the surrounding stroma, first within the anterior lamellar plane and
then within the posterior plane. Once the lenticule has been separated, forceps are used to extract
the intra-stromal lenticule. Unlike LASIK, fluid is not required to wash the corneal bed in the
majority of cases.

Bandage contact lenses may be required in cases with significant epithelial defects at the entry
site how ever this is rare in our experience. Topical antibiotics and anti-inflammatory drops are
placed on the eye and the speculum is removed. Asthere is no risk of corneal flap displacement,
an eye shield is not required; however, our practice routinely provides tinted glasses to protect
the eye in the immediate short-term period. Ciloxan and Maxidex are prescribed for one week
following surgery. Flourometholone (FML, Allergan, California, USA) is then prescribed on a
titrating basis for a further two weeks. Artificial lubricants are provided with insistence for use
over the initial month following surgery. The patient is instructed to avoid make-up, swimming
and body contact sports for only one week following the SMILE procedure (Figure 2).

Figure 2. Slitlamp image at day 1. Red arrow indicates side cut blue arrow indicates edge of optical zone. The
demarcation of the optical zone disappears over time.
CONTRAINDICATIONS

As discussed previously, the majority of contraindications for laser refractive surgery remain
similar for prospective SMILE patients; however, there remain several points of difference
(Table 1). The relative contraindications for SMILE are discussed in further detail below.

1. Dry eye

The SMILE procedure has been shown to have a less pronounced impact up on the ocular
surface and corneal innervation compared with LASIK. Although Denoyer et al demonstrated a
high incidence of mild to moderate dry eye in comparative LASIK and SMILE cohorts, the
incidence was significantly higher in the LASIK group at one month, an effect continuing
through six months. Corneal sensitivity similarly remained statistically better in the SMILE
group. Nerve fibre density, as measured with confocal microscopy was also better in SMILE
patients. These results are replicated in further studies and provide consistent evidence that both
the corneal flap and subsequent excimer laser ablation are significant contributing factors to dry
eye in laser refractive surgery patients. Against this several studies have failed to show a
statistical difference across dry eye parameters, such as tear film osmolarity, tear break-up time
or Schirmer’s tests. Moderate to severe dry eye remains a contraindication to SMILE surgery
with patients at risk of poor visual and safety outcomes; however, patients with mild dry eye or
those at increased risk of post-operative dry eye symptoms may present as more appropriate
candidates for SMILE surgery compared to LASIK. Employing established therapies such as
non-preserved artificial tear or nutritional supplements will further increase post-operative
patient satisfaction.

2. Suspect keratoconus

Suspect keratoconus suggests a mild corneal irregularity that may not have presented
clinically in terms of reduced visual acuity or biomicroscopic signs. A number of tomographic
units serve to display the parameters of keratoconus that help to objectively diagnose these cases.
Despite these programs, there remains no clear, reproducible set of parameters that enables the
practitioner to confirm suspect or forme fruste keratoconus. These patients remain at risk for
progression following kerato refractive surgery and therefore, they represent a significant
concern for treating specialists. The proposed retention of biomechanical strength following
SMILE may suggest the risk of corneal ectasia following surgery, particularly in subtle cases of
irregularity, will be reduced. Due to the current lack of long-term available data, this remains as
trictly the oretical proposal. Wang et al recently describe a 19year-old patient with suspect
keratoconus, who showed evidence of ectatic progression at six months following the SMILE
procedure. The patient age, lack of refractive stability and irregular tomography suggest the
presence of a number of surgical contraindications, which have undoubtedly contributed to the
post-operative complication in this case and confirm the need for preoperative vigilance. Ivarsen,
Asp and Hjortdal2 did not report ectasia cases in their cohort of 1,500 patients after 12 months.
Similarly, we have not seen any cases at our clinic suggesting that vigilance at the screening visit
will help minimize the risk of ectasia following surgery. Further long-term follow-up will serve
to confirm the relative incidence as well as to better define the potential for patients with subtle
corneal irregularities to safely undergo the SMILE procedure.

3. Corneal scarring

Corneal scarring may represent a physical barrier to visual acuity, depending on the
origin, significant and location of the s carring; however, it may not necessarily preclude patient
from undergoing laser refractive surgery. Surface ablation can represent the most appropriate
option, if the scarring is superficial in nature. LASIK has been used in cases with deeper or more
pronounced scarring with femtosecond laser energy parameters manipulated to ensure the cornea
scarring does not interfere intra-operatively; however, this may represent a more significant issue
with SMILE patients. To maximise efficiency in terms of refractive accuracy and the recovery
process, SMILE laser parameters have been progressively reduced.37 Currently, SMILE
parameters are represented in nanojoules rather than microjoules as required for LASIK
flapcreation. This effectively reduces the ability of the laser to pass through existing scar tissue
therefore, reducing the ability to treat even mild cases of scarring with this technique. The
suitability for the SMILE surgery will represent an individual decision undertaken at the
consultation.
COMPLICATIONS

A. Intra-operative complications

Early evidence suggests that the SMILE procedure is safe. Intra-operative complications may
occur; however, these are not likely to be sight threatening. Suction loss can occur albeit the
literature suggests an incidence of between 0.9 to 4.4 per cent of patients. If suction loss occurs
prior to the laser ablation, the patient can be re-engaged and the procedure can continue
immediately. If suction is lost once the laser has begun, the post-operative course will be
determined by the amount of laser completed. Early suction loss may represent an opportunity to
re-engage and complete without complication, whereas suction loss at the middle of the surgery
may require the procedure to be aborted in favour of later surface ablation. Epithelial
disturbances may occur due to the docking procedure or by the manual removal of the lenticule
through the laser created channel. A bandage contact lens is rarely required in our experience;
however, it may aid the post-operative comfort and healing process for some patients. The
difficulty of extracting the lenticule may vary depending on the laser energy settings. This is
usually resolved quickly following installation. It is possible that the lenticule may be partially
torn during the procedure. Further attempts to remove the remaining lenticule should be
undertaken. Dong and Zhou reported a case of irregular astigmatism following the SMILE
procedure, possibly related to incomplete dissection and subsequent residual lenticule left within
the pocket.

B. Post-operative complications

The absence of a corneal flap, as in the LASIK procedure, removes the risk of related concerns
such as flap displacement or striae. Otherwise, the SMILE procedure maintains a similar risk
profile following surgery with alternate laser refractive procedures. Reported post-operative
complications include; epithelial ingrowth, diffuse lamellar keratitis, corneal haze, irregular
astigmatism, increased aberrations, ectasia, punctate corneal staining and mild dry eye

1. EPITHELIAL INGROWTH

Ingrowth may be caused by epithelial cells displaced at the time of the procedure or
through cells invading the SMILE incision site. As per LASIK surgery, not reatment is often
required for mild cases. The risk for the progression of irregular astigmatism or corneal melt
increases significantly, if the ingrowth is considered severe. Surgical intervention is warranted in
these cases. The risk of epithelial ingrowth in LASIK procedures has been estimated to range
from 0.01to 6.1percent.The relative potential risk for ingrowth in SMILE cases should be less as
the entry point for epithelial cells is negligible compared to the full LASIK flap. Furthermore,
minimal washout is typically required, there by diminishing the risko f cells or debris being
introduced. A recent review of existing literature on the safety and efficacy of SMILE revealed
an accumulative risk of epithelial ingrowth of 0.5 per cent.37 Ivarsen, Asp and Hjortdal2
describe10eyes (outof1,500) with islands of epithelial cells seen near the incision site. No
progression was seen over three months and in 5 cases the cells spontaneously disappeared by
one year. Our current experience reflects this with only one case requiring secondary treatment.
The patient was returned to surgery and the cells removed. Visual acuity was 6/6 at day 1 with
no pain or photophobic symptoms.

2. DIFFUSE LAMELLAR KERATITIS

Diffuse lamellar keratitis (DLK) was first described in 1998 in conjunction with the
LASIK procedure. Representing an acute inflammatory response, the patient usually presents
with increasing discomfort, photophobia and a reduction in visual acuity. Biomicroscopic signs
have been described,50 briefly small white, granular cells may be seen under slitlamp
investigation increasing with the severity of the condition. Severe cases may lead to stromal
necrosis without furthert reatment. Typically, cases present during the immediate post-operative
period. A definitive cause of diffuse lamellar keratitis remains unclear; however, the condition
has variously been attributed to the introduction no f bacteria, surgical debris, meibomian gland
secretions and immune infiltrates. The existence of epithelial defects has been shown to
significantly increase the risk of diffuse lamellar keratitis. The incidence of diffuse lamellar
keratitis following SMILE has been reported as between 0.04 and1.6 percent. Of particular
interest, Zhaoetal 50 found that diffuse lamellar keratitis was associated with larger lenticule
diameter and thinner lenticules. The authors proposed that gas bubble accumulation in cases of
thin lenticules may induce a greater inflammatory response given the anterior and posterior poles
may accordingly be under more significant compressive force

Alternatively the thin nerlenticules may represent a greater technical challenge increasing the
intra-operative manipulation and the reby possible inflammatory response. Zhao et al 50 suggest
that the proximity to the limbus and limbal vasculature of the larger diameter lenticules may
further give rise to inflammatory cells. Further studies are required to elucidate the causes. It
should be noted that all cases resolved without sequellae following treatment with topical
corticosteroids.

3. CORNEAL HAZE AND OEDEMA

Up to eight per cent of patients in a study by Ivarsen, Asp and Hjortdal were found to have
trace haze at the initial post-operative visit. This did not impact upon visual acuity and
subsequently subsided. Yao et al describe micro-distortions in Bowman’s layer of up to 88.5 per
cent of SMILE cases. This was in comparison to only 42.1 per cent per cent of LASIK
comparable cases. These micro-distortions were diagnosed through optical coherence
tomography (OCT). There was no additional evidence of corneal striae under biomicroscopy and
the micro-distortions appeared to stabilise at 1 week suggesting minimal impact upon visual
acuity or quality. Similarly Moshifar et al37 reported only 0.2 per cent of patients in the
combined review with mild corneal oedema. In summary, corneal distortion does not appear to
represent a significant clinical issue in SMILE patients. Miao et al 52 describe the optical quality
and intraocular scattering after the SMILE procedure. The authors found that SMILE had little
impact upon the retinal image and further that the objective scatter index quickly returned to
normal following a temporary increase at three weeks. As corneal haze and anterior keratocyte
loss have been indicated as the main cause of a decrease in both parameters following excimer
laser procedures, these results would appear to confirm the lack of corneal distortion in SMILE
patients. Riau et al describe a statistically significant increase in inflammatory cells in patients
undergoing LASIK as compared to lenticule extraction. All patients observed had moderate to
high myopia (-6.00 to -9.00 D) suggesting a possible further benefit for the SMILE procedure in
reducing the incidence of corneal inflammation post-surgery.

4. IRREGULAR ASTIGMATISM AND INCREASED HIGHER-ORDER ABERRATIONS

Irregular astigmatism may result in ghost images or loss of visual acuity. Ivarsen, Asp
andHjortdal2 describe six eyes of five patients with monocular ghosting following surgery. In all
cases, corneal to pography showed irregular astigmatism. Interestingly, only one eye could be
directly attributed to a peri-operative complication (suction loss and attempted re-treatment). All
cases showed irregular Bowman’s layer with compensatory epithelial hyperplasia on OCT.48
Due to the epithelial hyperplasia, topography-guided surface ablation was undertaken in these
patients with a reduction in visual complaints and subsequent improvement in visual acuity in
most cases. Two eyes developed grade 2 corneal haze following surface treatment resulting in
worsening of symptoms. Both cases did not use mitomycin C during surgery suggesting this may
be beneficial in these cases. Li et al54 describe decentration following the SMILE procedure in a
cohort of 100 patients. The mean decentred displacement was 0.17 ± 0.09 mm. Although 99 per
cent of patients had post-operative uncorrected visionof6/6orbetter, fifteen eyes lost one line of
visual acuity and two eyes lost two lines at the final post-operative visit. Vertical coma showed
the greatest increase in magnitude possibly contributing to the decrease in visual acuity.

5. ECTASIA

Ectasia remains a significant concern for refractive surgeons. As discussed previously, one of
the proposed benefits of SMILE over LASIK in particular is the minimisation of biomechanical
changes following surgery. This would suggest a reduction in the risk fore ctatic changes
following the surgical l procedure. Through mid-2015, only one case of ectasia related to a
SMILE procedure has been reported in the peer-reviewed literature. In this case report, the
patient appeared to have pre-existing keratoconus.36 Although this is like ly to correspond with
the proposed biomechanical benefits of SMILE, it is likely also a consideration of our greater
understanding of potential risk factors for ectasia. Longer term data, with corresponding data
sets, will provide confirmation of the potential benefits of SMILE over LASIK surgery in
particular.
 6. INFECTIOUS KERATITIS

Infectious keratitis remains a potentially devastating complication of corneal refractive

surgery. Fortunately, the incidence is rare with published rates as low as 0.011 per cent in
LASIK cases and 0.066 per cent following surface ablation. Patients may complain of significant
loss of vision accompanied by pain, photophobia and epiphora. The condition usually presents in
the early post-operative period and may appear similar to diffuse lamellar keratitis or epithelial
ingrowth. Biomicroscopic signs should distinguish keratitis from these conditions. Initial
treatment is with broad-spectrum antibiotics and amended depending on the resolution of signs.
Ivarsen, Asp and Hjortdal2 noted five eyes with interface infiltrates and ocular irritation
following SMILE (0.33 per cent). Samples were taken for microbiological investigation how
ever no specific antigens could be identified. Patients were treated topically in four cases with the
further case requiring the interface to be flushed with cefuroxime. All eyes cleared without
sequellae by three months. There are no further reports in the current literature.

7. DRY EYE

The majority of literature relates the presence of significant dry eye symptoms with the
transection of corneal nerves during surgery. This may lead to the suppression of tear secretion
from the lacrima lgl and, mucin expression on the corneal epithelium and blink rate changes,
which impact upon the corneal surface. Further risk factors for post-surgery dry eye, include pre-
existing dry eye disease, deeper laser ablations, LASIK flap size, thickness and position albeit
evidence remains variable. As described earlier, results suggest that SMILE patients recover
more quickly and have less significant symptoms than patients undergoing the LASIK procedure.
These findings have clinical significance. Li et al30 describe significantly less corneal fluorescein
staining on slit lamp investigation; however, no significant differences in Schirmer test results
were found between corresponding SMILE and LASIK groups. Subjective patient satisfaction
remains increased in SMILE patients in comparison to LASIK groups. An ecdotally, this is what
we have experienced in our clinical practice, namely, despite the longer visual recovery of
SMILE patients compared to LASIK, the patients themselves report being more comfortable and
happier during the post-operative recovery period.