ReLEx Technological Summary ESCRS 2013: Course IC-80 Reinstein DZ

ESCRS 2013; Course IC-80: Small incision lenticule extraction for

myopia and astigmatism

“Scientific rationale for why femtorefractive

keratomileusis is the future of corneal refractive
surgery”
Dan Z Reinstein, MD MA(Cantab) FRCSC DABO FRCOphth FEBO1,2,3

1. London Vision Clinic, London, UK

2. Department of Ophthalmology, Columbia University Medical College, NY, USA
3. Centre Hospitalier National d’Ophtalmologie, Paris, France

Financial disclosure: Dr Reinstein is a consultant for Carl Zeiss Meditec (Jena, Germany)
and has a proprietary interest in the Artemis technology (ArcScan Inc, Morrison, Colorado)
through patents administered by the Cornell Research Foundation, New York, NY.

Correspondence: Dan Z Reinstein, MD MA(Cantab) FRCSC FRCOphth

London Vision Clinic, 138 Harley Street, London W1G 7LA, United Kingdom. Tel +44 207 224
1005, Fax +44 207 224 1055, email dzr@londonvisionclinic.com

History of Intrastromal Refractive Surgery

Ever since femtosecond lasers were first introduced into refractive surgery, the ultimate goal
has been to create an intrastromal lenticule that can then be removed in one piece manually,
thereby circumventing the need for incremental photoablation by an excimer laser. A
precursor to modern ReLEx was first described in 1996 using a picosecond laser to generate
an intrastromal lenticule that was removed manually after lifting the flap,1, 2 however
significant manual dissection was required leading to an irregular surface. The switch to
femtosecond improved the precision3 and studies were performed in rabbit eyes in 19984 and
in partially sighted eyes in 2003,5 however these initial studies were not followed up with
further clinical trials.

Following the introduction of the VisuMax femtosecond laser (Carl Zeiss Meditec, Jena,
Germany) in 2007,6 the intrastromal lenticule method was reintroduced in a procedure called
Femtosecond Lenticule Extraction (FLEx). The 6 month results of the first 10 fully seeing eyes
treated was published in 20087 and results of a larger population have since been reported.8, 9
The refractive results were similar to those observed in LASIK, but visual recovery time was
longer due to the lack of optimization in energy parameters and scan modes; further
refinements have led to much improved visual recovery times.10

Following the successful implementation of FLEx, a new procedure called Small Incision
Lenticule Extraction (SMILE) was developed. This procedure involves passing a dissector
through a small 2-3mm incision to separate the lenticular interfaces and allow the lenticule to
be removed, thus eliminating the need to create a flap. The results of the first prospective

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trials of SMILE have been reported11-13 and there are now more than 50 surgeons routinely
performing this procedure worldwide.

VisuMax Design Elements Enabling Refractive Lenticule Surgery

A number of femtosecond lasers

exist on the market today, but
none possess the constellation of
elements that appear to be
required for the 3D geometric
cutting precision of refractive
lenticules within the body of the
stroma. It is out of the scope of
this document to provide all the
details in VisuMax design which
make it superior in this regard, but
in short these can be summarized
as follows: The VisuMax system is
designed for coupling of the femtosecond laser source to the cornea with minimal tissue
distortion and rapid high precision femtosecond pulse placement. Elements of this system are
summarized below:

1. The VisuMax coupling contact glass interface with the cornea is curved, thus leading to
very little corneal distortion when securing full corneal surface contact.
2. Corneal coupling of the contact glass is achieved with very low suction force applied
though specifically designed suction ports that are applied to the peripheral
cornea/limbus, but not the corneal conjunctiva/sclera. This low suction coupling force
minimizes corneal distortion.
3. Each contact glass is individually calibrated by a built in confocal imaging system thus
compensating for individual differences in contact glass geometry that are inevitable in
serial production.
4. The optical beam path system coupled to the contact glass is suspended on a fulcrum.
The fulcrum together with a continuous force-feedback servo control for patient bed
height produces a system delivering a constant force of the contact glass onto the
cornea. This constant force minimizes changes in corneal distortion that may occur with
patient head movement during the femtosecond cutting process.
5. The optical system delivering the femtosecond beam is designed with very high numerical
aperture optics thus allowing for very tight concentration of femtosecond energy, very little
collateral energy dissipation and high femtosecond spot placement accuracy.
6. The laser-tissue interaction dynamics are optimized for speed with a repetition rate of
500 kHz which minimizes treatment time and achieves the critical refractive cuts in a
short enough time to reduce the chances of eye or patient movements during this phase
of the cutting.

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Advantages of ReLEx SMILE over LASIK

These new femtosecond intrastromal lenticule procedures offer a number of potential

advantages.

1. More accurate and repeatable tissue removal independent of prescription treated

2. Increased biomechanical integrity of the postoperative cornea
3. Reduction in postoperative dry eye symptoms and recovery

1. More accurate and repeatable tissue removal

Intrastromal lenticule procedures may bring advantages over LASIK as all of the potential
errors associated with excimer laser ablation are avoided, such as stromal hydration,14 laser
fluence projection and reflection losses,15, 16 and other environmental factors.17 In ReLEx, the
tissue removal is defined only by the accuracy of the femtosecond laser, which is not affected
by any changes in environmental conditions. Therefore, it is likely that there will less need for
personalized nomograms to be used for different machines, locations or surgeons.

2. Increased biomechanical integrity

Another potential benefit of SMILE is increased biomechanical stability due to the absence of
a flap. There are two main reasons for this:

a. Anterior stromal lamellae are stronger than posterior stromal lamellae

b. Vertical cuts (e.g. flap sidecut) have more biomechanical impact than horizontal cuts

2.1 Anterior stromal lamellae are stronger than posterior stromal lamellae

Randleman et al18 published a study in 2008 in which they measured the tensile strength of
strips of stromal lamellae cut from different depths within the cornea. They found a strong
negative correlation between stromal depth and tensile strength as demonstrated in figure 1.
The anterior 40% of the central corneal stroma was found to be the strongest region of the
cornea, whereas the posterior 60% of the stroma was at least 50% weaker.

Figure 1: scatter plot of the tensile

strength against stromal depth showing
that the anterior stroma is about 50%
stronger than the posterior stroma.

(Reproduced from: Randleman JB,

Dawson DG, Grossniklaus HE, McCarey
BE, Edelhauser HF. Depth-dependent
cohesive tensile strength in human donor
corneas: implications for refractive
surgery. J Refract Surg. 2008
Jan;24(1):S85-9)

As we are so used to calculating the residual stromal thickness in LASIK as the amount of
stromal tissue left under the flap, the first instinct is to apply this rule to SMILE. However,
because there is no flap created in SMILE, the anterior stromal lamellae remain intact
everywhere except for the small areas of the incisions. Therefore, the actual residual stromal

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thickness in SMILE should be calculated as the stromal thickness below the posterior
lenticule interface plus the stromal thickness between the anterior lenticule interface and
Bowman’s layer. Moreover, because anterior stroma is 50% stronger than posterior stroma, a
further 50% of the untouched anterior stromal thickness can be added to get a residual
stromal thickness value that can be compared to a LASIK residual stromal thickness. This can
be summarized by the following RST equation for SMILE (1) compared to the well-known
equation for LASIK (2).

(1) RST = CCT – Cap Thickness (CT) – Lenticule Thickness

+ 1.5 * (Cap Thickness – Epithelial Thickness)

(2) RST = CCT – Flap Thickness – Ablation Depth

CCT=Central Corneal Thickness, RST=Residual Stromal Thickness

If these equations are applied to an example case, the significant difference in biomechanical
strength can be appreciated. Consider an eye with a spherical equivalent refraction of -8.00 D
and a central corneal pachymetry of 500 μm. We will assume that the epithelial thickness is
50 μm, that the LASIK excimer laser ablation depth and SMILE lenticule thickness are both
100 μm, and that a 120 μm LASIK flap was created and the SMILE cap thickness was 120
μm (anterior lenticule interface). The RST calculations are demonstrated in figure 2.

Using equation (2), the LASIK RST would be 500 – 120 – 100 = 280 μm

Using equation (1), the SMILE RST would be 500 – 120 – 100 + 1.5 * (120 – 50) = 385 μm

Figure 2: diagrams of the intact stromal lamellae after LASIK (top) and SMILE (bottom) highlighting the anterior
lamellae that remain intact after SMILE. The RST calculations are shown for a 500 μm cornea with a 100 μm
ablation/lenticule and 120 μm flap/cap thickness. The LASIK RST of 280 μm consists only of posterior stroma. On the
other hand, the SMILE RST has the same 280 μm of posterior stroma, but also has 70 μm of anterior stroma, which
makes a total of 350 μm of stroma. However, since the anterior stroma is 50% stronger than posterior stroma, a
further 35 μm (50% of the 70 μm of anterior stroma) can be added to make an effective total of 385 μm.

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2.2 Vertical cuts have more biomechanical impact than horizontal cuts

In 2000, we published a paper showing that the peripheral stroma actually thickens after
LASIK, as shown in figure 3.19 This biomechanical change seems to be true cause for the
majority of spherical aberration induction (probably about 85%) rather than the more
commonly discussed reasons of laser fluence projection and reflection errors in the periphery
due to the curvature of the cornea. In the same issue of JRS, Cynthia Roberts proposed a
model to explain this finding in an editorial.20 Briefly, the cornea is made of layers of collagen
lamellae running from limbus to limbus are oriented at precise angles with respect to adjacent
lamellae, contributing to corneal transparency and strength. Stromal collagen lamellae are
surrounded by several proteoglycans responsible for proper spacing of collagen and stromal
hydration. The creation of a flap and stromal tissue ablation severs the anterior corneal
lamellae, which means that the peripheral anterior lamellae are no longer under tension and
therefore relax and spread out resulting in stromal thickening. The consequence of this
expansion of peripheral anterior lamellae is to exert a pulling force on the posterior lamellae,
which causes central flattening. However, the posterior lamellae also have to contend with an
unchanged IOP, which can result in some forward bowing of the cornea.

Figure 3: Artemis very high-frequency digital ultrasound maps of stromal thickness before and 3 months after a -9.00
D LASIK procedure. The change map shows the central stromal tissue that was removed by the ablation, but it also
shows an annulus outside the 6-mm ablation zone where the stroma has actually thickened.

Recently, Knox Cartwright et al21 performed a study on human cadaver eyes that compared
the corneal strain produced by a LASIK flap, a sidecut only, and a delamination cut only, with
each incision type performed at both 90 μm and 160 μm. The table below summarizes the
results, which found that the sidecut resulted in a similar increase in strain to that found after
a whole flap with a significantly greater increase for the 160 μm depth, whereas the increase
in strain was the same at both depths when the delamination cut only was performed.

Table 1: Percentage increase in central corneal

strain (to an intraocular pressure change from 90 μm 160 μm
15mmHg to 15.5mmHg) after the creation of a LASIK Flap 9% 32%
LASIK flap, a sidecut or delamination at both 90 Sidecut Only 9% 33%
21
μm and 160 μm. Delamination Only 5% 5%

Applying this finding to SMILE, since no anterior corneal sidecut is created, there will be
slightly less increase in corneal strain in SMILE compared to thin flap LASIK and a significant
difference in corneal strain compared to LASIK with a thicker flap.

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Also, given the finding that the increase in corneal strain with a delamination cut only is
independent of the depth, this means that the SMILE lenticule can be created at any depth
within the stroma. Therefore, putting this finding together in context of the varying tensile
strength of stroma at different depths as described above, the effective postoperative corneal
strength will increase as the lenticule is moved deeper. As there is no flap, the total stroma
left intact is the same regardless of the depth from which the lenticule is removed. In effect, as
the lenticule is moved deeper, for every micron of “RST” lost (in the LASIK sense), we would
be gaining 1.5 microns worth of tensile strength of relative ‘posterior stroma’. Taking this
concept to its logical end, if we know that 250 μm of posterior stroma is sufficient after LASIK,
then it may be possible to perform SMILE and leave 167 μm of anterior stroma (with, say 50
μm of posterior stroma to eliminate the chance of crossing Descemet’s) as this is equivalent
in strength to 250 μm of posterior stroma. This demonstrates how SMILE might be used to
extend the range of myopia that can be corrected by corneal laser refractive surgery. Also,
the true RST limit for LASIK is almost certainly less than 250 μm (e.g. a probability model we
developed predicted that the true limit was 191 μm22), which means that this concept might be
taken even further.

2.3 Biomechanics model – comparing SMILE to PRK and LASIK

We have now developed a mathematical model based directly on the

Randleman18 depth-dependent tensile strength data to calculate the
postoperative tensile strength and compare this between PRK, LASIK
and SMILE and put these ideas to the test.23 We performed non-linear
regression analysis on this data and found that a fourth order curve
maximized the fit to the data with the R2 of 0.930 demonstrating the very
high correlation achieved by a non-linear fit. The total tensile strength of
the untreated cornea was then calculated as the area under the
regression line by integration (see figure 4). The total tensile strength of
the cornea after LASIK was derived by calculating the area under the
regression line for all depths below the residual stromal bed thickness
(assuming the flap does not contribute to the tensile strength of the
postoperative cornea24). This value was divided by the total tensile
strength of the untreated cornea to represent the relative total tensile
strength as a percentage. Similarly, the total tensile strength of the
cornea after PRK was derived by calculating the area under the
regression line for all depths below the stromal thickness after ablation.
Finally, the total tensile strength of the cornea after SMILE was
calculated as the area under the regression line for all depths below the
lower lenticule interface added to the area under the regression line for
all depths above the upper lenticule interface or within the stromal cap. Figure 4

The model was then applied to a variety of different scenarios and a number of conclusions
could be drawn from the analyses:
1. The postoperative tensile strength was greater after SMILE than after PRK – in
SMILE, the refractive stromal tissue removal takes place in deeper and relatively
weaker stroma, leaving the stronger anterior stroma intact, meaning that for any given
refractive correction SMILE will leave the cornea with greater tensile strength than
PRK.

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2. The postoperative tensile strength was greater after SMILE than after LASIK –
because the anterior stroma is left intact, SMILE will (by definition) leave the cornea
with greater tensile strength than LASIK for any given refractive correction.
3. The postoperative tensile strength increased for SMILE with increasing cap thickness
– if SMILE is performed deeper in the cornea, more of the stronger anterior stroma
will remain and hence the postoperative tensile strength will be greater; this is in
contrast to LASIK, where deeper ablation results in lower postoperative tensile
strength given the minimal contribution of the flap to corneal biomechanics after
healing.

These results can be quantified in the example scenario represented in Figure 5 which shows
the relative total tensile strength after LASIK (purple), photorefractive keratectomy (PRK)
(blue), and small incision lenticule extraction (SMILE) (green) plotted against a range of
ablation depths for a fixed central corneal thickness of 550 μm, a LASIK flap thickness of 110
μm, and a SMILE cap thickness of 130 μm. The orange lines indicate that the postoperative
relative total tensile strength reached 60% for an ablation depth of 73 μm in LASIK
(approximately -5.75 diopters [D]), 132 μm in PRK (approximately -10.00 D), and 175 μm in
SMILE (approximately -13.50 D), translating to a 7.75 D difference between LASIK and
SMILE for a cornea of the same postoperative relative total tensile strength. The red lines
indicate that the postoperative relative total tensile strength after a 100 μm tissue removal
would be 54% in LASIK, 68% in PRK, and 75% in SMILE.

Figure 5: postoperative tensile strength after PRK, LASIK and SMILE

Considering the safety of subtractive corneal refractive surgical procedures in terms of tensile
strength represents a paradigm shift away from classical residual stromal thickness limits.

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The residual thickness based safety of corneal laser refractive surgery should be thought of at
least in terms of total residual uncut stroma. Ideally, a parameter such as total tensile
strength, which takes the nonlinearity of the strength of the stroma into account, seems more
appropriate. For example, the residual stromal bed thickness under the interface in SMILE
could easily be less than 250 μm due to the additional strength provided by the untouched
stromal lamellae in the cap, as long as the total remaining corneal tensile strength is
comparable to that of the postoperative LASIK 250 μm residual stromal bed thickness
standard. In this new case of using remaining total tensile strength, the minimum would
evidently be defined as the total tensile strength remaining after LASIK with a residual stromal
bed thickness of 250 μm.

3. Reduction in postoperative dry eye

The other major potential advantage of the flapless ReLEx SMILE procedure is the reduction
in postoperative dry eye compared with that observed after PRK and LASIK.

The cornea is one of the most densely innervated peripheral tissues in humans. Nerve
bundles within the anterior stroma grow radially in from the periphery towards the central
cornea. The nerves then penetrate Bowman’s layer and create a network of nerve fibers,
known as the subbasal nerve plexus, by branching both vertically and horizontally between
Bowman’s layer and basal epithelial cells.

Figure 6: diagrams demonstrating the difference Figure 7: mean corneal sensation for 39 eyes after
between SMILE (top) and LASIK (bottom) in how the SMILE compared with the corneal sensation after LASIK
25-33
two procedures affect the anterior corneal nerve plexus. averaged over nine published studies.

In LASIK (as shown in figure 4), subbasal nerve bundles and superficial stromal nerve
bundles in the flap interface are cut by the microkeratome or femtosecond laser, with only
nerves entering the flap through the hinge region being spared. Subsequent excimer laser
ablation severs stromal nerve fiber bundles. Postoperatively, this means that the patient may
have dry eye symptoms and decreased corneal sensitivity while the nerves regenerate. A
number of studies have reported the recovery of corneal sensation after LASIK and show that
recovery to normal levels takes on average 6 months.25-33 Studies have also shown that
corneal sensation recovery takes longer after higher corrections25, 28 and after a hyperopic
ablation.28 Figure 5 shows the average corneal sensation across these nine studies.

In ReLEx SMILE on the other hand, the anterior corneal anatomy is preserved and the
anterior stromal nerve plexus is disrupted significantly less since there are no sidecuts
created – no flap is created; this should result in fewer dry eye symptoms and a faster
recovery of postoperative patient comfort. Early results seem to support this hypothesis. We

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have measured corneal sensation in 39 eyes after SMILE and the results compare favorably
with the average data taken from the LASIK studies. Corneal sensation had recovered to the
baseline level by 3 months after SMILE compared with 6-12 months after LASIK. Also, there
was some corneal sensation measured in the majority of eyes after SMILE at the day one
postoperative visit, whereas corneal sensation was found to be 0 in the studies that reported
one-day data. Also, the mean spherical equivalent refraction was -6.72 D in our SMILE
population compared with -5.30 D in the LASIK studies, which means that the difference
might be even greater since it has been shown that corneal sensation is reduced more for
higher corrections.25, 28 Similar results have been reported by Wei and Wang.34

In summary, with the introduction of the VisuMax femtosecond laser technology it has
become clinically feasible to now create refractive lenticules of proper regularity with sufficient
accuracy to meet and probably exceed the accuracy of excimer laser tissue ablation for
corneal refractive corrections. This enables Jose Ignacio Barraquer’s original concept of
keratomileusis to be effectuated through a minimally invasive pocket incision with maximal
retention of anterior corneal innervational and structural integrity. It is undoubtedly the final
frontier in the realization of the perfect refractive surgical technique for both patients and
surgeons alike.

Retreatment Options after ReLEx SMILE

As there ReLEx SMILE is a flapless procedure, retreatment is not as straight forward as with
LASIK where the flap can simply be lifted. However, there are a number of different options
depending on each individual scenario.

1. Photorefractive Keratectomy (PRK)

PRK is always an option for retreatment although this obviously brings the associated
disadvantages of slow visual recovery, pain management and risk of haze.

2. Sidecut only / Circle

Carl Zeiss Meditec have developed a number of different options for using the VisuMax to
convert the existing SMILE cap interface into a LASIK flap. These have been described and
studied in rabbits by Riau et al.35 The sidecut only option is an effective way of easily
converting a SMILE cap into a LASIK flap, however, the flap diameter is limited to the
diameter of the cap. Given that the cap diameter is usually about 7.5mm, a LASIK flap with
7.5mm diameter limits the optical zone that can safely be used for an excimer laser ablation,
especially for a hyperopic ablation that would requires a large optical zone.

Riau et al35 investigated the ease of lifting the flap using

three different Circle options as shown in figure 7 (right) that
are designed to create a LASIK flap with a larger diameter
than the original cap. It was found that the “junction cut” was
the easiest to lift as the flap bed extension is intended to be
at the same depth as the original cap. Also, they found that
the flap bed was undisrupted with smooth transition between
Figure 7: Different Circle options
the Circle interface and the original cap interface.

However, as described earlier, it is the sidecut that is responsible for virtually all of the
biomechanical changes due to the creation of a LASIK flap,21 so a Circle procedure will

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negate the biomechanical advantage gained by the original SMILE procedure. A Circle
procedure is also forced to create a flap with the same thickness as the original cap, plus the
additional depth for the sidecuts required to ensure a cross-over with the cap interface.

It has been demonstrated that Circle represents a viable and straight forward method of
performing a retreatment after SMILE. It seems to be a good option for cases where the cap
thickness was thin (although, given the benefits of a thicker cap, these cases should be rare).
Ideally, the actual achieved cap thickness would be measured directly by OCT36 or VHF
digital ultrasound.6 prior to the procedure.

3. Thin flap LASIK

The third retreatment option is to perform a standard LASIK procedure with a thin flap. The
limiting factor for this option is whether a new LASIK interface can be safely created (a)
without crossing the existing cap interface and potentially creating slivers that are difficult to
handle, and (b) avoiding the creation of a cryptic buttonhole (also known as gas
breakthrough) by the interface crossing into the epithelium.

It is known that the epithelium increases in thickness centrally after a myopic excimer laser
ablation37 and the same is true after SMILE. Ideally, the epithelial thickness would be
measured directly (e.g. by VHF digital ultrasound37, 38 or OCT39) so that the flap thickness
could be chosen to eliminate the possibility of a cryptic buttonhole. In the absence of a direct
measurement of the epithelial thickness, some assumptions can be made based on previous
studies. In an earlier study, we have found that the epithelium thickened by about 2 μm per
diopter treated. Therefore, given that the preoperative epithelium is rarely greater than 60
μm,38 the postoperative epithelium will rarely be greater than 80 μm.

In a previous study using VHF digital ultrasound, we have found that the reproducibility of
SMILE cap thickness is 4.4 μm.40 In order to minimize the risk of a cryptic buttonhole, the flap
thickness should be chosen to be 4 standard deviations more than the maximum epithelial
thickness – i.e. 18 μm, meaning an intended flap thickness of 98 μm.

A further 4 standard deviations then need to be added to simulate the risk of the flap crossing
the existing cap interface – i.e. 98 + 18 = 116 μm. As long as this potential maximum flap
thickness is less than the existing cap interface, then it is safe to proceed with a thin flap
LASIK procedure. However, this relies on knowledge of the actual cap thickness, which would
ideally be measured by OCT36 or VHF digital ultrasound.6 In the absence of a direct
measurement of the actual cap thickness, then a further 4 standard deviations should be
added to simulate the possibility that the original cap was thinner than intended – i.e. 116 +
18 = 134 μm. Therefore, given the above analysis, a thin flap LASIK procedure with a 98 μm
flap will always be possible if a cap thickness of 135 μm or greater had been used.

Figure 8: Simulation of the safety of a 98 μm LASIK flap after SMILE with a 135 μm cap

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Given the advantages of using a thicker cap (less dry eye, increased tensile strength), this
seems to represent an excellent protocol for SMILE as thin flap LASIK becomes the most
straight forward method for retreatments. Interestingly, this protocol is actually safer than a
LASIK flap lift retreatment because there is a much lower risk of epithelial ingrowth with a flap
creation compared to flap lift.

4. Re-SMILE above the original cap interface

As long as there is sufficient room between the bottom of the epithelium and the cap interface
(see above), it may be possible to perform a second SMILE procedure above the existing cap
interface. However, this option is probably limited to treating very small refractions and there
may be increased difficulty in handling the very thin lenticules. Also, performing SMILE in the
anterior-most stroma negates the benefits of SMILE of reduced dry eye and increased tensile
strength. Finally, it is more likely to experience OBL or more difficult dissections with thinner
caps.

5. Re-SMILE below the original cap interface

Another alternative option is to perform a second SMILE procedure below the existing cap
interface, which retains the dry eye and biomechanical benefits of leaving the anterior stroma
intact. The limiting factor for this technique is the thickness of the lenticule as a very thin
lenticule might be difficult to handle, as opposed to thin flap LASIK where low corrections and
small optical zones can be used without any issues. Therefore, re-SMILE might not be a
viable option for cases where the available stroma is limited, although the safety calculation
should be done based on tensile strength as described earlier.

6. Intra-stromal keratotomy incisions

Finally, very small corrections might be corrected using keratotomy incisions, which would be
a good option for cases with limited remaining stromal tissue. Although this is not currently
available with the VisuMax, it will be possible to create these incision intra-stromally leaving
Bowman’s layer intact (similar to the intra-stromal incision in IntraCor41), which might improve
the accuracy of this method compared to corneal surface incisions.

In summary, there are a number of different options for retreatment after SMILE, which have
advantages and disadvantages in different situations depending on cap thickness and
remaining stromal tissue. While it was initially thought that a retreatment would have to be
done by PRK, we have shown these other options to be feasible in almost all cases meaning
that retreatment by PRK should be extremely rare. Similarly, the relative complexity of the
Circle option, as well as the negation of the anterior stroma related benefits, means that Circle
is really only an option in cases where the original cap thickness was thin. The sensible
approach would seem to be to use a cap thickness of at least 135 μm for the primary SMILE
procedure which brings the advantages of leaving the anterior stroma intact, while also
allowing for retreatments to be performed as a straight forward thin flap LASIK procedure.

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6. Reinstein DZ, Archer TJ, Gobbe M, Johnson N. Accuracy and Reproducibility of Artemis Central Flap
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Excimer Laser Platforms. J Refract Surg. 2010;26:107-119.
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Cataract Refract Surg. 2008;34:1513-1520.
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