ARTICLE

Subbasal nerve fiber regenerationafter LASIK and LASEK assessed by noncontactesthesiometry and in vivo confocal microscopy:

Prospective studyTaym Darwish, MD, MSc, PhD, Arun Brahma, MD, FRCOphth,

Clare O’Donnell, PhD, MCOptom, FAAO, Nathan Efron, PhD, DSc

PURPOSE: To evaluate recovery of the corneal subbasal nerve plexus and corneal sensitivity aftermyopic laser in situ keratomileusis (LASIK) and laser-assisted subepithelial keratectomy (LASEK).

SETTING: Manchester Centre for Vision, Royal Eye Hospital, Manchester, United Kingdom.

METHODS: Thirty LASEK patients and 20 LASIK patients had slit-scanning confocal microscopy andnoncontact corneal esthesiometry preoperatively and 1, 3, and 6 months after surgery. Images ofthe subbasal nerve plexus were analyzed using customized software to evaluate nerve regeneration.

RESULTS: Central corneal sensitivity decreased significantly 1 month after LASEK and LASIK andreturned to normal levels after 3 months. Corneal subbasal nerve fiber density, nerve branch den-sity, nerve fiber length, and nerve fiber width decreased significantly 1 month after LASIK and hadnot returned to the preoperative levels by 6 months. Nerve fiber tortuosity decreased significantly 1month after LASEK and returned to the preoperative levels 3 months after surgery. There were nosignificant differences in nerve fiber tortuosity before and after LASIK. Neither corneal sensitivitynor nerve fiber morphology was different between the 2 groups at any postoperative visit.

CONCLUSIONS: Corneal sensitivity and subbasal nerve morphology were adversely affected byLASEK and LASIK. Corneal sensitivity recovered 3 months after the procedure, but subbasal nerveswere still abnormal after 6 months. Despite the different forms of surgical trauma to corneal nerveswith LASIK and LASEK, there was no apparent difference in the time course of recovery of cornealstructure and function.

J Cataract Refract Surg 2007; 33:1515–1521 Q 2007 ASCRS and ESCRS

Over the past decade, laser-based refractive surgeryhas become a mainstream ophthalmic procedure forthe correction of refractive error. At present, the mostpopular technique worldwide is laser in situ keratomi-leusis (LASIK); however, laser-assisted subepithelialkeratectomy (LASEK) may be the preferred procedurefor patients with thinner corneas, certain anatomic ab-normalities, or occupations that predispose them to oc-ular trauma.1 Although the clinically observed ocularand visual outcomes of these 2 procedures are broadlysimilar,1 significant differences in subclinical nerve fi-ber morphology might be expected in view of the dif-ferent ways in which corneal nerves are cut and/orablated.

Interference of corneal nerves during refractive sur-gery is of considerable significance to corneal healthbecause corneal innervation (1) provides protective

Q 2007 ASCRS and ESCRS

Published by Elsevier Inc.

mechanisms (eg, the aversion response) to preventdamage to the cornea,2 (2) has a trophic effect on themaintenance of corneal structure and function,2 and(3) provides neural feedback for regulation of the se-cretion of the preocular tear film.3 Impaired innerva-tion results in decreased corneal sensitivity and cancause impairment of epithelial cell function, increasedepithelial permeability, decreased cell migration, andreduced cell mitosis.4,5 Moreover, from a clinical per-spective, denervated corneas are prone to epithelialor stromal abnormalities, recurrent erosion, impairedwound healing, infection, and inflammation.2

New clinical investigative techniques are availablethat facilitate alternative approaches for examiningthe structure and function of the living human cornea.Corneal sensitivity can now be measured using an‘‘air-puff’’ noncontact corneal esthesiometer.6 This

0886-3350/07/$dsee front matter 1515doi:10.1016/j.jcrs.2007.05.023

1516 NERVE REGENERATION AFTER LASIK AND LASEK

instrument is thought to stimulate different types ofnerve endings, thus offering an alternative approachto determining sensitivity thresholds. Also, this ap-proach obviates patient apprehension as nothingphysically touches the eye.6 Corneal confocal micros-copy allows clinicians and researchers to investigatethe cornea in vivo at a cellular level, and structuressuch as the subbasal nerve plexus, which previouslycould not be observedwith the slitlamp biomicroscopeor other clinical techniques, can now be seen.7,8

Tavakoli et al.9 recently found a strong correlationbetween the integrity of the subbasal nerve plexusand corneal sensitivity in diabetic patients with vari-ous levels of severity of neuropathy. This finding sug-gests that the integrity of the subbasal nerve plexus isa primary determinant of corneal sensitivity. If this isthe case, differences in the surgical procedures inLASIK and LASEK and consequent differences in thenature of interference with corneal nerves might beexpected to lead to differences in postsurgical cornealstructure and function. The aim of this study was totest the above hypothesis by monitoring corneal nervemorphology and sensitivity using the techniques ofcorneal confocal microscopy7,8 and noncontact cornealesthesiometry6 in a 6-month longitudinal evaluation ofthe effects of LASIK and LASEK.

PATIENTS AND METHODS

General Approach

The goal was to recruit as many patients as possible whowere scheduled for LASIK and LASEK at the Royal Eye Hos-pital, Manchester, United Kingdom, between May 2004 andMay 2005. It was previously demonstrated that a cohort of 18subjects is sufficient to demonstrate statistically significantand clinically meaningful differences in subbasal nerve fibermorphology10; thus, a minimum recruitment target of 18 pa-tients per group was set.

The study was approved by the Manchester Local Re-search Ethics Committee. Informed consent was obtainedfrom all participants after the nature and possible conse-quences of taking part were explained.

The inclusion criteria were scheduled for myopic LASIKor LASEK, willing to participate in the study, and willing

Accepted for publication May 25, 2007.

From the Royal Eye Hospital (Darwish, Brahma), Manchester, andthe Faculty of Life Sciences (Darwish, O’Donnell), University ofManchester, Manchester, United Kingdom; the Faculty of Medicine(Darwish), Tishreen University, Lattakia, Syria; the Institute ofHealth and Biomedical Innovation (Efron) and School of Optometry,Queensland University of Technology, Kelvin Grove, Australia.

No author has a financial or proprietary interest in any material ormethod mentioned.

Corresponding author: Dr. Taym Darwish, PO Box 305, Lattakia,Syria. E-mail: taym@scs-net.org.

J CATARACT REFRACT SURG

and able to give informed consent. Exclusion criteria wereprevious corneal or intraocular surgery, history of significantocular trauma, previous corneal infection that could perma-nently affect corneal sensitivity, and history of diabetes mel-litus or other systemic disease known to affect cornealsensitivity.

Patients who wore contact lenses were instructed not towear soft or rigid lenses for 1week and 4weeks, respectively,before the presurgical visit. Corneal esthesiometry and con-focal microscopy were performed in 1 eye (right eye unlesspatient preferred left eye) of each patient preoperativelyand 1, 3, and 6 months after surgery. The same investigator(T.D.) performed all investigations.

Surgical Technique

A single surgeon (A.B.) performed all LASIK and LASEKprocedures.

Laser In Situ Keratomileusis The same standard (non-wavefront) LASIK treatment was used in all patients. Theeye was anesthetized topically with 3 drops of proxymeta-caine 0.5%. An M2 microkeratome (Moria SA) was used tocreate a superior flap with a depth of 130 mm. The opticalzone diameter varied between 6.5 mm and 7.5 mm, andthe total treatment zone was 9.0 mm. An Allegretto Waveexcimer laser (WaveLight Technology) was used forphotoablation.

Laser-Assisted Subepithelial Keratectomy All patientsreceived the same LASEK treatment. The eye was anesthe-tized topically by 3 drops of proxymetacaine 0.5%. A superi-orly hinged flap of 9.0mmdiameter was created by applying15% to 20% ethanol to the cornea for 20 to 30 seconds. An Al-legrettoWave excimer laser was used for ablation. A siliconehydrogel bandage contact lens was placed on the cornea af-ter the procedure.

Noncontact Corneal Esthesiometry

A custom-made noncontact corneal esthesiometer wasused to measure corneal sensitivity. This instrument wasconstructed as per the design of Murphy et al.6 Noncontactcorneal esthesiometers can assess the corneal sensationthreshold in an accurate and repeatable manner.11 Murphyet al.11 also determined that there is no difference in reliabil-ity between noncontact corneal esthesiometry and Cochet-Bonnet esthesiometry.

The instrument contains a 2.0 mm diameter air-puff jetprobe positioned 1 cm in front of the center of the cornea;this arrangement propels a jet of air from the surrounding at-mosphere toward the cornea at a known and variable force.11

The forced-choice double-staircase method of limits is usedto determine the threshold of corneal sensitivity. This tech-nique involves repeatedly applying the stimulus and askingpatients to indicate each time whether they can feela ‘‘breeze’’ or a ‘‘cold’’ sensation on the eye. At first, the stim-ulus is presented at a level well below the expected thresholdand this is increased gradually until the patient notices a sen-sation (the crossover point). This point is recorded, and thestimulus is progressively decreased from a suprathresholdintensity until the subject can no longer feel any sensation.This process is repeated twice, and the mean of the crossoverpoints is taken to be the corneal sensitivity threshold.

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Confocal Microscopy

Slit-scanning confocal microscopy was performed witha ConfoScan P4 (Tomey), according to a previously de-scribed technique.12 In brief, the 40�/0.75NA objective ofthe microscope is disinfected with a swab saturated with iso-propyl alcohol BP 70% v/v and the cornea is anesthetizedwith 1 drop of benoxinate hydrochloride 0.4%. A drop ofcarbomer liquid gel (Viscotears Liquid Gel) is applied tothe tip of the objective. The patient is positioned in the chinand forehead rests and instructed to look straight ahead.The objective lens is moved toward the eye until the gel con-tacts the central cornea. When an image of the epitheliumappears on the monitor of the confocal microscope, therecording button is pressed. The objective lens is moved for-ward and backward to record several scans of the entiredepth of the cornea.

The most representative image of the subbasal nerve fiberlayer in each patient was selected for further image analysis.Parameters were assessed according to previously describedtechniques12,13 that were adopted in subsequent studies.14,15

The parameters were nerve fiber density: the total number ofmajor nerve fibers per square millimeter of corneal tissue;nerve branch density: the number of branches emanatingfrommajor nerve trunks per square millimeter of corneal tis-sue; nerve fiber length: the total length of all nerve fibers andbranches per square millimeter of corneal tissue; nerve fiberwidth: the average width taken at 3 points on all major nervefibers visible in the image frame (microns); and nerve fibertortuosity: a dimensionless coefficient between 0 (straightline) to 100 (infinitely tortuous).

Nerve fiber density and branch density were determinedusing morphometric software incorporated within the To-mey instrument (Confocommander 2.7.1). Nerve fiber lengthand width were determined using third-party image-analy-sis software (Scion Image for Windows, Scion Corp.). Nervefiber tortuosity was determined using a previously devel-oped mathematical paradigm.13

Statistical Analysis

Data were analyzed using WinSTAT software (MicrosoftCorp.), an analysis tool pack for Microsoft Excel XP (Micro-soft Corp.), SPSS 11.5 (SPSS Inc.), and GraphPad Prism(GraphPad Software).

All data sets were tested for normality using the Kolmo-gorov-Smirnov test. For data that were not normally distrib-uted, Friedman tests (for paired groups) or Kruskal-Wallistests (for nonpaired groups) were used to look for differencesin each parameter between visits or groups. If differenceswere found, the Dunn post hoc test was used to establishwhich specific visit pairs displayed significant differencesin that parameter.

For data that were normally distributed, 1-way between-groups analysis of variance (ANOVA) tests or 1-way re-peated-measures ANOVA tests were used to determinewhether there were differences in each parameter betweenvisits or between groups. If significant differences werefound, the Bonferroni post hoc test was used to establishwhich specific visit pairs had significant differences for thatparameter. A P value of 0.05 was taken as the threshold ofstatistical significance.

A series of nonpaired t tests were performed to establishwhether there were significant differences between theLASIK results and LASEK results. Because 24 such t testswere performed, a P value of 0.002 (ie, 0.05/24) was taken

J CATARACT REFRACT SURG

as the threshold of statistical significance for thesecomparisons.

RESULTS

Twenty patients had myopic LASIK. Their mean agewas 41 years G 11 (SD). There were 10 men (meanage 41 G 13 years) and 10 women (mean age 40 G10 years). Preoperatively, the mean spherical equiva-lent (SE) refraction was �3.63 G 1.56 diopters (D).Subbasal nerves (Figure 1) were imaged in all corneaspreoperatively and in 69%, 80%, and 100% of corneas1, 3, and 6 months postoperatively, respectively. Themean ablation depth was 68 G 24 mm and the meantreatment diameter, 8.5 G 0.8 mm. Given that theflap thickness was 130 mm, the ‘‘true ablation depth’’was approximately 198 mm.

Thirty patients had myopic LASEK. Their mean agewas 41 G 13 years. This group comprised 14 men(mean age 35 G 12 years) and 16 women (mean age45 G12 years). Preoperatively, the mean SE refractionwas �4.45 G 2.43 D. Subbasal nerves (Figure 2) wereimaged in all patients preoperatively and in 55%,83%, and 100% of corneas 1, 3, and 6months postoper-atively, respectively. The mean ablation depth was91 G 37 mm and the mean treatment diameter, 8.8 G0.4 mm. Thus, the depth of stromal ablation resultingfrom LASEK was about half the true ablation depthresulting from LASIK.

Corneal Sensitivity

Central corneal sensitivity decreased significantly 1month after LASIK and LASEK.At 3 and 6months, the

Figure 1. In vivo confocal microscopic images of corneal subbasalnerves regenerating after myopic LASIK (Images represent typicalfindings at each visit.) A: Three nerves (arrows) before LASIK.B: Fine nerve (arrow) 1 month after LASIK with subepithelial hyper-reflectivity in the upper right of the field. C: Two nerves 3 monthsafter LASIK. D: Two nerves 6 months after LASIK.

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preoperative and postoperative sensitivities were notsignificantly different (Table 1). There was no differ-ence in corneal sensitivity between the 2 groups atthe preoperative or any postoperative visit.

Subbasal Nerves

Nerve fiber density, nerve branch density, nervefiber length, and nerve fiber width were significantlyreduced 1 month after LASIK and LASEK and didnot return to the preoperative level by 6 months aftersurgery (Table 2). Therewere no significant differencesin nerve fiber tortuosity before and after LASIK. Nervefibers were significantly less tortuous 1 month afterLASEK and returned to preoperative levels 3 monthsafter surgery.

Figure 2. In vivo confocal microscopic images of corneal subbasalnerves regenerating after myopic LASEK. (Images represent typicalfinding at each visit.) A: Nerves (arrows) before LASEK. B: Shortnerve (arrow) 1 month after LASEK with subepithelial hyperreflec-tivity to the right of the field. C: Long nerve 3 months after LASEK,with areas of hyperreflectivity to the right of the field.D: Two nerves6 months after LASEK, with areas of hyperreflectivity to the upperright of the field.

J CATARACT REFRACT SURG -

There was no difference in any morphometric mea-sure of subbasal nerves between the 2 groups preoper-atively or at any postoperative visit.

DISCUSSION

Changes in corneal sensitivity and nerve morphologyafter LASIK and LASEKmust be considered in relationto the different forms of incision and ablation of thecornea that occur in the course of performing thesesurgical procedures. In LASIK, the microkeratome,which creates the flap, cuts the subbasal nerve fibersand superficial stromal nerves in the flap margin butspares the nerves within the hinge of the flap. Midstro-mal nerves beneath the flap are destroyed by photo-ablation. In LASEK, all subbasal and subepithelialnerves in the region of treatment are destroyed bythe photoablation. In both procedures, the nerves be-neath the ablation base and beyond the lateral marginof the treatment zone are unaffected.

Corneal Sensitivity

In the present study, corneal sensitivity decreasedsignificantly 1 month after LASIK and LASEK. Three

Table 1. Corneal sensitivity before and after refractive surgery.

Mean CornealSensitivity (mbars) G SD

Visit LASIK LASEK P Value

Preop 0.78 G 0.31 0.74 G 0.31 .66Postop1 mo 1.09 G 0.55* 0.96 G 0.34* .313 mo 0.93 G 0.39 0.83 G 0.94 .666 mo 0.72 G 0.27 0.71 G 0.27 .90

P value 0.04 0.008 –

LASEK Z laser-assisted subepithelial keratectomy; LASIK Z laser in situkeratomileusis*Significant difference compared with preoperative value

Table 2. Subbasal nerve parameters before and after refractive surgery.

Nerve Fiber Density (Number/mm2) Nerve Branch Density (Number/mm2) Nerve Fiber Length (mm/mm2)

Visit LASIK LASEK P LASIK LASEK P LASIK LASEK P

Preop 43 G 20 45 G 14 .68 56 G 27 45 G 22 .12 7897 G 3098 8438 G 3177 .55Postop

1 mo 10 G 8* 9 G 10* .76 8 G 17* 1 G 5* .11 2245 G 1813* 1645 G 1585* .333 mo 19 G 14* 12 G 5* .23 9 G 19* 3 G 9* .18 3774 G 3288* 2194 G 1199* .036 mo 26 G 15* 22 G 9* .24 20 G 19* 14 G 15* .22 4182 G 1885* 3402 G 1304* .09

P value !.0001 !.0001 d !.0001 !.0001 d !.0001 !.0001 d

Note: All data but P values are mean G SD.LASEK Z laser-assisted subepithelial keratectomy; LASIK Z laser in situ keratomileusis; P Z P value*Significant difference compared with preoperative value

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months after both procedures, sensitivity was not sig-nificantly different from the preoperative value. Usingnoncontact corneal esthesiometry, Patel et al.16 foundthat corneal sensitivity did not return to normal by14 weeks after surgery. This difference might havearisen because they treated higher degrees of myopia(mean �6.30 G 2.70 D versus �3.63 G 1.56 D in thepresent study). Using a Belmonte gas esthesiometer,De Paiva and Pflugfelder17 found that corneal sensitiv-ity returned to the preoperative levels 6 months aftersurgery. Stapleton et al.18 found no difference in pre-operative and postoperative corneal chemical sensitiv-ity, which suggests this is an insensitive approach toassessing the effects of refractive surgery on cornealfunction.

Many studies have used Cochet-Bonnet esthesiome-try to measure the recovery of corneal sensitivity afterrefractive surgery. Recovery times of 3 weeks19 and3,20 6,21 and 12 months22–25 have been suggested afterLASIK and of 1,26 3,27,28 and 622 months after LASEK.Comparison of the findings between all these studies isconfounded by differences in, or lack of informationrelating to, the ranges of myopia treated, diameterand thickness of the flap, and location and width ofthe flap hinge.

Differences in results using the Cochet-Bonnet es-thesiometer versus the noncontact esthesiometer maybe attributed to these instruments stimulating differ-ent types of nerve endings. Myelinated Ad fibers arelarge-diameter, straight nerve fibers that run parallelto the corneal surface within the epithelial subbasalplexus. Unmyelinated C fibers are small-diameter,beaded nerves that pass a short distance along the sub-basal plexus and turn upward, terminating justbeneath the surface of the epithelium.29 Ad fibersrespond primarily to mechanical stimuli, whereas C fi-bers respond to thermal and chemical stimuli.30 It islikely, therefore, that the direct physical pressure ofthe nylon thread against the cornea when using the

J CATARACT REFRACT SURG

Cochet-Bonnet esthesiometer results in stimulation ofAd fibers.6 The puff of air that constitutes the stimulusin the noncontact esthesiometer has been shown topossess a significant thermal element.6 This could re-sult in stimulation of C fibers, with Ad fibers beingstimulated to a lesser extent as a result of a smallamount of physical pressure from the air puff.6

Subbasal Nerves

Perez-Gomez and Efron31 found that subbasal nervefiber length did not recover within 6 months afterLASIK. One month postoperatively, they were unableto image subbasal nerves, whereas we could imagethese nerves in 69% of corneas. This might be becausethe patients examined by Perez-Gomez and Efron31

had higher myopia (mean �5.00 G 3.00 D) thanpatients in our study (mean �3.50 G 1.56 D). Similarresults for nerve fiber length were found in both stud-ies preoperatively and at the third and sixth monthpostoperatively.

Various studies report the time for subbasal nervefiber density to recover after LASIK to be 1,24,32 2,33

and 534 years. Such protracted recovery periods arenot surprising in view of the recent demonstrationby Niederer et al.15 that abnormalities of stromalnerves are still identified up to 40 years after penetrat-ing keratoplasty, in which all stromal nerves are sev-ered. Lee et al.32 and Calvillo et al.33 report lowersubbasal nerve fiber densities than in the present study1, 3, and 6 months after LASIK. Differences in refrac-tive characteristics and surgical techniques betweenthe various studies may explain these discrepancies.Also, using microscopes of different resolution andlight intensity gives images of different quality, whichcould be a factor.7,8

Qualitative studies found varying results as well.Linna et al.21 observed subbasal nerve fibers in 5% to41%, 33% to 59%, and 44% to 100% of corneas 1, 3,

Nerve Fiber Width (mm) Nerve Fiber Tortuosity (Coefficient)

LASIK LASEK P LASIK LASEK P

2.1 G 0.3 2.1 G 0.4 1.00 21.8 G 7.3 22.1 G 6.7 .88

1.7 G 0.2* 1.4 G 0.3* .003 20.1 G 7.1 16.0 G 7.5* .131.4 G 0.3* 1.3 G 0.4* .40 24.7 G 11.6 18.9 G 11.1 .111.3 G 0.3* 1.3 G 0.4* 1.00 21.7 G 9.2 18.0 G 11.0 .22

!.0001 !.0001 d .67 .03 d

Table 2 (cont.)

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1520 NERVE REGENERATION AFTER LASIK AND LASEK

and 6 months after LASIK, respectively. In our study,the subbasal nerves were visible in 69%, 80%, and100% of corneas in the corresponding time frame.The greater visibility of subbasal nerves in our studymight result from the lower degrees of myopia treated.Higher degrees of myopia require deeper ablationdepths, which result in more injury to deeper stromalnerve trunks.24

Lee et al.22 found that the density of the subbasalnerves decreased significantly after LASEK and didnot recover to preoperative levels by 6 months aftersurgery. This is in agreement with our results.

As LASEK could be considered a modification ofphotorefractive keratectomy (PRK), our results canbe compared with those in studies of subbasal nerveregeneration after PRK. In PRK, the epithelium is re-moved by mechanical scraping and a laser is appliedto the stroma. The subbasal and subepithelial nervesare destroyed by the photoablation. As with LASEK,the nerves beneath the ablation base and beyond thelateral margin of the treatment zone are unaffected.

Linna and Tervo35 and Frueh et al.36 detected regen-erating subbasal nerve fibers 1 week and 4 weeks afterPRK, respectively. Erie37 detected subbasal nervefibers in 17%, 58%, and 100% of eyes at 1, 3, and 6months after PRK, respectively, and found that 2 yearsafter surgery, nerve fiber density and length returnedto preoperative levels. Erie also observed that regener-ated subbasal nerve fibers appeared thinner thanbefore surgery but did not report quantitative data.Our nerve fiber width measurements substantiateErie’s observation.

The disagreement between the results of Erie37 andthose in the present study 1 and 3months after surgerymight be related to the use of an objective of highernumerical aperture in the present study, which givesimages of higher resolution,magnification, and bright-ness. This might enable our microscope to image thin-ner nerve fibers.

Kauffmann et al.38 report that 6 to 8 months is re-quired for complete recovery of subepithelial innerva-tion after PRK.

No difference in the rate of recovery of cornealsensitivity or subbasal nerve morphology was ob-served in this study of LASIK and LASEK; however,Wu et al.39 and Lee et al.22 report that LASIK causedgreater reduction in corneal sensitivity and subbasalnerve fiber density, respectively, than LASEK. Thisdisagreement may be due to different surgical ap-proaches. (Lee et al. did not specify ablation depth ortreatment zone diameter.)

The lack of difference between LASIK and LASEK inthe pattern of recovery of corneal structure and func-tion could be interpreted as a more rapid recoveryfrom LASIK given the greater true ablation depth.

J CATARACT REFRACT SURG

From a theoretical standpoint, however, the compet-ing influences of sparing nerves in the hinge of theflap and a greater true ablation depth in LASIK, versusthe total ablation of subbasal and subepithelial nervesin LASEK, make it difficult, if not impossible, to pre-dict the rate of structural and functional neural regen-eration after these procedures.

The mismatch between the recovery of corneal sen-sitivity by 3 months and the failure of subbasal nervesto recover by 6months might be explained by the pres-ence of intraepithelial nerves or individual subbasalnerve fibers, whichmay be responsible for corneal sen-sation but are too fine to be imaged by the confocalmicroscope. Certainly, animal models30 suggest thatregenerating nerves are thinner than normal nerves.

Interpretation of the findings in our study should beconstrained to the effects of LASIK and LASEK for thecorrection of moderate degrees of myopia. Also, as isevident from the above discussion, results should beconsidered in the context of the surgical approacheswe applied. Future studies of the effects of LASIKand LASEK on corneal nerve morphology will be as-sisted by the recent introduction of laser scanning con-focal microscopy, which can image subbasal nerveswith greater clarity, contrast, and resolution7,8 andview the subbasal nerve plexus over a large expanseof corneal area via the construction of nerve maps.40

The latter facility, coupled with pan-corneal esthesi-ometry, could provide useful insights into regionalcorneal changes, such as those relating to the inwardpattern of nerve regeneration from the flap marginand the role of the flap hinge in preserving cornealneurology.

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First Author:Taym Darwish, MD, MSc, PhD

Royal Eye Hospital and Faculty of LifeSciences, University of Manchester,Manchester, United Kingdom, and Facultyof Medicine, Tishreen University, Lattakia,Syria

VOL 33, SEPTEMBER 2007