Hyperopia and Presbyopia - part 6 potx

Among current corrective proce-dures undoubtedly laser-assisted in situ Keratomileusis LASIK and Ho:YAG laser ther-mal keratoplasty LTK are the most widespread.. CONTRAST SENSITIVITY IN

160 Chalita and Krueger

Figure 11 Spherical aberration after myopic treatment showing increased positive asphericity,

as represented by a sombrero hat

REFERENCES

1 Applegate RA, Thibos LN, Hilmantel G Optics of aberroscopy and super vision J CataractRefract Surg 2001; 27:1093–1107

2 Maeda N Wavefront technology in ophthalmology Curr Opin Ophthalmol 2001; 12:294–299

3 Huang D Physics of customized corneal ablation In: MacRae SM, Krueger RR, Applegate

RA, eds Customized Corneal Ablation: The Quest for Supervision Thorofare NJ: Slack, 2001:51–62

4 Mrochen M, Kaemmerer M, Seiler T Wavefront-guided laser in situ keratomileusis: earlyresults in three eyes J Refract Surg 2000; 16:116–121

5 Kaemmerer M, Mrochen M, Mierdel P, Krinke HE, Seiler T Clinical experience with theTscherning aberrometer J Refract Surg 2000; 16:S584–S587

6 Krueger RR, Mrochen M, Kaemmerer M, Seiler T Understanding refraction and tion through “retinal imaging” aberrometry Ophthalmology 2001; 108:674–678

accommoda-7 Artal P Understanding aberrations by using double-pass techniques J Refract Surg 2000; 16:S560–S562

8 Schwiegerling J Theoretical limits to visual performance Surv Ophthalmol 2000; 45(2):139–146

9 Applegate RA Limits to vision: Can we do better than nature? J Refract Surg 2000; 16:S547–S551

10 Williams D, Yoon GY, Porter J, Guirao A, Hofer H, Cox I Visual benefit of correcting higherorder aberrations of the eye J Refract Surg 2000; 16:S554–S559

11 Thibos LN The prospects for perfect vision J Refract Surg 2000; 16:S540–S546

12 Thibos L Wavefront data reporting and terminology J Refract Surg 2001; 17:S578–S583

13 Oshika T, Klyce SD, Applegate RA, Howland HC, Danasoury MAE Comparison of cornealwavefront aberrations after photorefractive keratectomy and laser in situ keratomileusis Am

J Ophthalmol 1999; 127:1–7

14 Mrochen M, Kaemmerer M, Mierdel P, Seiler T Increased higher-order optical aberrationsafter laser refractive surgery A problem of subclinical decentration J Cataract Refract Surg2001; 27:362–369

15 Mrochen M, Kaemmerer M, Seiler T Clinical results of wavefront-guided laser in situ ileusis 3 months after surgery J Cataract Refract Surg 2001; 27:201–207

keratom-16 Howland HC The history and methods of ophthalmic wavefront sensing J Refract Surg 2000;16:S552–S553

17 Mrochen M, Kaemmerer M, Mierdel P, Krinke HE, Seiler T Principles of Tscherning rometry J Refract Surg 2000; 16:S570–S571

aber-18 Platt BC, Shack R History and principles of Shack-Hartmann wavefront sensing J RefractSurg 2001; 17:S573–S577

19 Krueger RR Technology requirements for Summit-Autonomus CustomCornea J Refract Surg2000; 16:S592–S601

20 Thibos L Principles of Shack-Hartmann aberrometry J Refract Surg 2000; 16:S563–S565

21 Roberts C, Dupps Jr WJ Corneal biomechanics and their role in corneal ablative procedures.In: MacRae SM, Krueger RR, Applegate RA eds Customized Corneal Ablation: The Questfor Supervision Thorofare, NJ: Slack, 2001:109–131

22 Argento CJ, Consentino MJ Laser in situ keratomileusis for hyperopia J Cataract RefractSurg 1998; 24:1050–1058

23 McDonald M Summit—Autonomus CustomCornea Laser in situ keratomileusis outcomes J

J Refract Surg 2000; 16:S617–S618

24 Pettit GH, Campin J, Liedel K, Housand B Clinical experience with the CustomCornea surement device J Refract Surg 2000; 16:S581–S583

mea-Contrast Sensitivity Changes After

Hyperopia Surgery

LAVINIA C COBAN-STEFLEA

Bucharest University Hospital and Carol Davila University of Medicine and

Pharmacy, Bucharest, Romania

TOMMY S KORN

University of California–San Diego and Rees-Stealy Medical Group, San Diego,

California, U.S.A.

BRIAN S BOXER WACHLER

Boxer Wachler Vision Institute, Beverly Hills, California, U.S.A.

Understanding the importance of contrast sensitivity can be easier if we emphasize itsrelationship to spatial vision, which is the core of the visual perception (1) Spatial fre-quency theory of image processing is based on spatially extended patterns called sinusoidalgratings, which are characterized by four parameters: spatial frequency, orientation, ampli-tude, and phase The contrast sensitivity function is a measure of the observer’s sensitivity

to gratings at different frequencies and is determined by the lowest contrast at which thesinusoidal gratings can still be detected (2) Over 200 years ago, contrast sensitivity began

to be acknowledged as a clinical tool for doctors in studying visual disorders (3) In

1760 Bouguer defined and gave a value to the term light-difference threshold, the first

denomination of contrast threshold Since then other researchers have made a great number

of contributions to this field: Bjerrum (1884) with letter charts, the first low-contrast letteracuity tests, and Young (1918) with the ink spot test, an easy method to measure the light-difference threshold More recently Schade (1956) applied his knowledge of televisiontechnology to contrast sensitivity testing The work of Campbell and Green contributed

to a better understanding of the optical and neural mechanism of contrast sensitivity testingand inspired further studies regarding alterations of contrast sensitivity in ocular diseases

163

164 Coban-Steflea et al.

Correction of hyperopia has been a constant concern of ophthalmologists over thepast decades Some of the surgical procedures that have been developed—hexagonalkeratotomy (4,5), keratophakia, keratomileusis, and epikeratophakia (6–9)—have beenabandoned because of limited applicability or side effects Among current corrective proce-dures undoubtedly laser-assisted in situ Keratomileusis (LASIK) and Ho:YAG laser ther-mal keratoplasty (LTK) are the most widespread Recently published clinical results em-phasize the fact that LASIK is a procedure with good predictability, stability, efficacy,and safety for the correction of low to moderate spherical hyperopia (10) Long-termpredictability with occurrence of undercorrection is influenced by the preoperative kerato-metric values and ablation zone diameter (11) Other studies point out the importance ofcorneal thickness and width of the flap for LASIK feasibility (12) The effectiveness ofLASIK for severe hyperopia and hyperopic astigmatism is reduced (13,14) For treatmentsoverⳭ5.00 D, the incidence of loss of best-corrected visual acuity was increased Currentnomograms require the cut of a larger flap in order to enlarge the ablation zone and todecrease the risk of halos, glare, and night vision difficulties for patients with high hyper-opia and astigmatism (15) A lower predictability for astigmatic corrections was alsoreported after LASIK for myopia (16) in spite of in situ axis alignment (17,18) Encourag-ing results have been reported with respect to the safety, predictability, and stability ofLASIK correction, for small degrees of hyperopia that were secondary to previous radialkeratotomy (RK), and for automated lamellar keratoplasty (ALK) (19) The degree ofregression after H-LASIK was reported to be higher relative to myopic corrections butlower, even in high hyperopia, than with the PRK procedure (20) Flap irregularities,epithelium, infection, or nonspecific inflammation at the flap interface have been reportedcomplications of the LASIK procedure (21) Loss of vision can occur in cases of button-holes, free cap, or amputation of the flap (22)

Correction of hyperopia and astigmatism by thermal keratoplasty was reported morethan 100 years ago (23–25) The actual mechanism by which this procedure alters theanterior corneal curvature has been clarified with the discovery of shrinkage temperature

of corneal collagen by Stringer and Parr (26) In 1970s and 1980s, keratoconus was thefocus of theromokeratoplasty technology A number of clinical studies done have evaluatedthermal keratoplasty potential to replace penetrating keratoplasty in keratoconus treatment(27–30) In spite of the fact that initial flattening of the cone followed the procedure,regression occurred within a few weeks postoperatively It was not uncommon for thesekeratoconus treatments to be accompanied by complications such as corneal scarring,vascularization, and bullous keratopathy Additionally, poor predictability and stabilitycontributed to the withdrawing of the procedure from clinical use for keratoconus

A more recent approach to thermal keratoplasty is credited to Fyodorov, who oped a technique, using controlled thermal burns of corneal stroma with a retractable probetip heated to 600⬚C and applied in a radial pattern The procedure was eventually abandonedbecause of the high incidence of postoperative regression (31) In spite of repeated chal-lenges to achieve predictable and stable refractive outcomes, researchers did not give up

devel-on probe technology but took another avenue, which was the use of lasers to delivercontrollable amounts of energy to the stroma

Lasers such as continuous CO2 and cobalt magnesium fluoride have been used inexperimental studies on rabbit corneas, with transient results (32,33) Reports of clinicalstudies that used the erbium:glass laser (34) have shown good results for hyperopia higherthanⳭ3.00 D Over the past decade, ophthalmologists in the United States have directedtheir work at evaluating two Ho:YAG laser systems: the noncontact system (Sunrise Tech-

nologies, Fremont, CA) and the contact system (Summit Technologies, Waltham, MA).The Sunrise Ho:YAG is a pulsed laser that emits laser light at a wavelength of 2.13␮m.Other technical characteristics include pulse repetition frequency of 5 Hz and pulse energy

in the range of 226 to 258 in correlation with the amount of refractive correction required.The energy is applied to the cornea in a noncontact mode through a fiberoptic slit-lampsystem; the treatment pattern is represented by rings of spots concentric to the pupil (35).Sand, who was granted a patent for performing infrared LTK, was an important contributor

to the development of this technology Initial in vitro investigations have been made onswine and human cadaver eyes (36,37) in an attempt to establish a treatment protocol.Further studies done on human poorly sighted eyes showed a mean change in cornealcurvature of 1.10 D followed by some amounts of regression (38) Results of clinical trialsdone outside the United States, which used the eight-spot treatment pattern applied atdifferent diameters (6, 7, or 8 mm), had shown that the procedure works best up toⳭ3.00

D They also proposed a treatment algorithm adjusted to variables such as age and centralcorneal thickness (39) Other studies have demonstrated that the amount of refractivechange is increased when a two-ring treatment is applied at the 6- and 7-mm center line

in a radial instead of a staggered pattern (40,41) The U.S phase III study protocol hasdefined the efficacy criteria for the LTK procedure as improvement in distance UCVAand reduction in hyperopia manifest refraction spherical equvalent (MRSE) ⬎ 0.5 D.Evaluation at 2 years showed that 69.4% of patients had more than two lines of improve-ment in distance uncontrolled visual acuity (UCVA) and no eyes had lost more than twolines of best spectacle corrected visual acuity (BSCDVA) (35)

B CONTRAST SENSITIVITY IN LASIK AND LTK

In understanding the outcomes of contrast sensitivity, we conducted a study to evaluatethe quality of vision through its changes in LASIK and noncontact Ho:YAG LTK for thecorrection of low to moderate spherical hyperopia We analyzed the results of two groups

of patients who had LASIK and LTK, respectively, as primary procedures There was nohistory of ocular diseases or surgery We compared best-corrected contrast sensitivityvalues preoperatively and at 3 months postoperatively Contrast sensitivity was measuredwith the self-calibrated, internally luminated CSV-1000E Vector Vision (Dayton, OH) at

12 cycles per degree (cpd) spatial frequency The patient was instructed to identify whetherthe bars were in the top circle, bottom circle, or neither The last correct identificationhas been taken as the contrast sensitivity On the contrast sensitivity chart the numbersrepresent normalized ratios where values greater than 1.0 correspond to percent contrastssensitivity above the population average and values below 1.0 represent percent of theaverage contrast sensitivity below the population average (42) Visual acuity was measuredwith the Vector Vision acuity chart using a scoring method of the U.S Food and DrugAdministration for refractive surgery clinical trials (43) All visual function tests weredone with best spectacle-corrected visual acuity

Data were analyzed with the StatView (SAS Institute Inc., Cary, NC) statisticalpackage Visual acuity data were analyzed in logMAR values Normalized contrast sensi-tivity values were converted to log values and used for statistical analysis

The LASIK study group comprised 94 eyes of 49 patients, 21 men and 28 women.Mean patient age was 59.67 yearsⳲ7.95 SD, range 44 to 78 years Preoperatively, meandeviation from target manifest refraction was Ⳮ2.4 D Ⳳ1.2 D, SD, (range Ⳮ0.37 toⳭ5.60 D) LASIK procedures were performed by the same surgeon (B.B.W.) using the

was not statistically significantly different compared to preoperative levels (p⳱ 0.18) Themean best spectacle-corrected logMAR visual acuity value at 3 months was statistically

significantly worse relative to preoperative value (p⳱ 0.008) However, the change wasnot clinically significant, as the logMAR conversion was a loss of 1.5 letters on the acuitychart There was a statistically significant correlation between achieved refraction and

changes in log contrast sensitivity values (p ⳱ 0.006) (Fig 1) (r ⳱ 0.29, p ⳱ 0.006).

This indicated that higher amounts of hyperopic correction were associated with greaterloss of best-corrected contrast sensitivity No statistically significant correlation was ob-

Figure 1 Correlation between changes in log contrast sensitivity values and achieved refraction

in the H-LASIK group

Figure 2 Correlation between changes in best spectacle-corrected logMAR visual acuity valuesand achieved refraction in the H-LASIK group.

served between achieved refraction and changes in best spectacle-corrected logMAR visual

acuity (r ⳱ 0.05, p ⳱ 0.58)(Fig 2).

The LTK study group comprised 55 eyes of 35 patients, 16 males and 19 females.Mean patient age was 57.61 years Ⳳ7.35, SD, with a range of 39 to 71 years; meandeviation from target manifest refraction of treated eyes wasⳭ1.5 D Ⳳ0.59 D, SD, range

0 toⳭ3.00 D Noncontact Ho:YAG LTK treatments were performed by the same surgeon(B.B.W.) using the Sunrise Hyperion Holmium Laser Corneal Shaping System (SunriseTechnologies Inc., Fremont, CA) The treatment was centered on the corneal purkinjeimage of the patient fixation light The light reflex closely approximates the visual axis.Therefore, in cases of positive angle kappa, the treatment was not centered on the pupil.Laser parameters included wavelength, 2.13␮m; pulse duration, 250 ␮s; pulse repetitionfrequency, 5 Hz; pulse energy, adjustable from 226 to 258 mJ/pulse In the current study

we used a two concentric radial 8-spot ring treatment pattern centered around the fixationlight reflex on the cornea Postoperatively, results showed a mean deviation from targetmanifest refraction of ⳮ0.36 D Ⳳ0.84 D, SD, range ⳮ3.50 to Ⳮ1.25 D Mean log

contrast sensitivity value was not statistically significantly decreased (p⳱ 0.07) (Table2) and mean best spectacle-corrected logMAR visual acuity value was statistically signifi-

Table 2 LTK Group—Preoperative and Postoperative Log Contrast Sensitivity Values and BestSpectacle-Corrected LogMAR Visual Acuity Values

Mean Standard deviation Minimum Maximum

chart No statistically significant correlation (R ⳱ 0.16, p ⳱ 0.25) was found between

achieved refraction and changes in log contrast sensitivity values (Fig 3) Figure 4 showsthe lack of correlation between achieved refraction and best-spectacle corrected logMAR

visual acuity values (r ⳱ 0.15, p ⳱ 0.26).

Figure 4 Correlation between changes in best spectacle-corrected logMAR visual acuity valuesand achieved refraction in the LTK group

C DISCUSSION

As new surgical procedures are added to the refractive surgery armamentarium, assessingvisual outcome becomes more difficult Information regarding postoperative visual acuityand refractive changes is no longer satisfactory to evaluate the quality of the imageprojected on the retina (44) Contrast sensitivity, as a functional method, has been shown

to be directly affected by the distorted image following excimer laser surgery (45) Usingdigitized retroillumination, Vinciguerra has shown that corneal distortion arising fromprominent flap striae may be overlooked by the customary slit-lamp examination (46).Our results have shown a slight decrease in contrast sensitivity at 12 cpd spatial frequencypostoperatively after LASIK procedure However the difference was not statistically signif-

icantly different (p⳱ 0.18) Previous literature data that have demonstrated that spatialfrequency of 12 cpd is mostly affected by degradation in optics, such as aberration or blur(47) Other studies reported a loss of contrast sensitivity at 12 months after LASIK of up

to one line for low hyperopia and of more than two lines for high hyperopia with nostatistical significance (13) An interesting finding in the LASIK group was the significantcorrelation between achieved refraction and change in contrast sensitivity, demonstratingthat larger amounts of correction are accompanied by larger loss of contrast sensitivity.This indicates that with the Summit Apex Plus laser used for LASIK and centered on thepupil, higher degrees of hyperopic treatment as associated with a higher risk of loss ofbest-corrected contrast sensitivity

Contrast sensitivity showed little change after the LTK procedure The minimal

decrease observed was not statistically significant (p⳱ 0.07) Furthermore, contrast tivity changes showed no correlation with the amount of spherical correction attempted.Clinical trials at 1 and 2 years after LTK reported that mean contrast sensitivity increased

sensi-at all follow-up visits for the two-ring tresensi-atment group sensi-at Regan charts (40,48)

Postopera-tively visual acuity did not vary significantly (p ⳱ 0.0067) and was not influenced bythe amount of correction, although the amount of hyperopia corrected in the LTK groupwas less than that corrected in the LASIK group

We conclude that measuring contrast sensitivity after refractive surgical proceduresshould be encouraged and further developed in order to assess the limits of safety forgiven procedures and devices used for such procedures Studies should be directed atidentifying laser characteristics and treatment patterns that are able to optimize the opticalsystem of the eye, thus increasing safety

170 Coban-Steflea et al.

7 Barraquer JI Keratomileusis Int Surg 1967; 48:103–117

8 Morgan KS, Stephenson GS, McDonald MB, Kaufman HE Epikeratophakia in children thalmology 1984; 91:780–784

Oph-9 Anshutz T Laser correction of hyperopia and presbyopia In: ed International OphthalmologyClinics Refractive Surgery Boston: Little, Brown, 1994:107–137

10 Boxer Wachler BS, O’Brien TP, Tauber S Vision Correction—Seeing the Future CurrentLaser Refractive and Surgical Alternatives for the Correction of Hyperopia Oxford Institutefor Continuing Education, 2000:3–5

11 Esquenazi S, Mendoza A Two-year follow-up of laser in situ keratomileusis J Refract Surg1999; 15:648–652

12 Rosa JL, Febbraro DS Laser in situ keratomileusis for hyperopia J Refract Surg 1999; 5(2suppl):S212–S215

13 Arbelaez MC, Knorz MC Laser in situ keratomileusis for hyperopia and hyperopic tism J Refract Surg 1999; 15:406–414

astigma-14 Barraquer C, Gutierrez AM Results of laser in situ keratomileusis in hyperopic compoundastigmatism J Cataract Refract Surg 1999; 25:1198–1204

15 Lipner M Distant visions: how practitioners outside the United States are treating hyperopia.Eye World 1999; 4:17–18

16 Knorz MC, Wiesinger B, Liebermann A, Seiberth V, Liesenhoff H Laser in situ keratomileusisfor moderate and high myopia and myopic astigmatism Ophthalmology 1998; 105:932–940

17 Stevens JD Astigmatic excimer laser treatment: theoretical effects of axis misalignment Eur

J Implant Ref Surg 1994; 6:310–318

18 Vajpayee RB, McCarthy CA, Taylor HR Evaluation of axis alignment system for correction

of myopic astigmatism with the excimer laser J Cataract Refract Surg 1998; 24:911–916

19 Buzard KA, Fundingsland BR Excimer laser assisted in situ keratomileusis for hyperopia JCataract Refract Surg 1999; 25:197–204

20 Reviglio VE, Luna JD, Rodriguez ML, Garcia FE, Juarez CP Laser in situ keratomileusisusing the LaserSight 200 laser: results of 950 consecutive cases J Cataract Refract Surg 1999;25:1062–1068

21 Wilson SE LASIK: management of common complications (review) Cornea 1998; 17:459–467

22 Farah SG, Azar DT, Gurdal C, Wong J Laser in situ keratomileusis: literature review of adeveloping technique (review) J Cataract Refract Surg 1998; 24:989–1006

23 Lans LJ Experimentelle Untersuchungen uber die Entstehung von Astigmatismus durch perforierende Corneawunden Graefes Arch Clin Exp Ophthalmol 1898; 45:117–152

nicht-24 Wray C Case of 6 D of hypermetropic astigmatism cured by the cautery Trans OphthalmolSoc UK 1914; 34:109–110

25 O’Connor R Corneal cautery for high myopic astigmatism Am J Ophthalmol 1933; 16:337

26 Striger H, Parr J Shrinkage temperature of eye collagen Nature 1964; 204:1307

27 Gasset AR Thermokeratoplasty in the treatment of keratoconus Am J Ophthalmol 1975; 79:226–232

28 Aquavella JV, Buxton JN, Shaw EL Thermokeratoplasty in the treatment of persistent cornealhydrops Arch Ophthalmol 1977; 95:81–84

29 Itoi M Computer photokeratometry changes following thermokeratoplasty In: Schachar RA,Levy NS, Schachar L, eds Refractive Modulation of the Cornea Denison, TX LAL Publishers,1981

30 Rowsey JJ, Doss JD Preliminary report of Los Alamos keratoplasty techniques ogy 1981; 88:755–760

Ophthalmol-31 Caster AI The Fyodorov technique of hyperopia correction by thermal coagulation: a nary report J Refract Surg 1988; 4:105–108

prelimi-32 Peyman GA, Larson B, Raichand M, Andrews AH Modification of rabbit corneal curvaturewith use of carbon dioxide laser burns Ophthalmic Surg 1980; 11:325–329

33 Horn G, Spears KG, Lopez O, Lewicky A, Yang X, Riaz M, Wang R, Silva D, Serafin J.New refractive method for laser thermal keratoplasty with the Co: MgF2 laser J CataractRefract Surg 1990; 16:611–616.

34 Kanoda AN, Sorokin AS Laser correction of hypermetropic refraction In: Fyodorov SN, ed.Microsurgery of the Eye: Main Aspects Moscow: MIR Publishers, 1987:147–154

35 Aker AB, Boxer Wachler BS, Brown DC Vision Correction—Seeing the Future NoncontactHolmium:YAG Laser Thermal Keratoplasty for the Treatment of Hyperopia Oxford Institutefor Continuing Education, 2000:3–5

36 Koch DD, Berry MJ, Vassiliadis AJ, Abarca AA, Villarreal R, Haft EA Noncontact holmium:YAG laser thermal keratoplasy In: Salz JJ, ed Corneal Laser Surgery Philadelphia: Mosby,1995:247–254

37 Moreira H, Campos M, Sawusch MR, McDonnell JM, Sand B, McDonnell PJ Holmium laserthermokeratoplasty Ophthalmology 1993; 100:752–761

38 Ariayasu RG, Sand B, Menefee R, Hennings D, Rose C, Berry M, Garbus JJ, McDonnell PJ.Holmium laser thermal keratoplasty of 10 poorly sighted eyes Refract Surg 1995; 11:358–365

39 Alio JL, Ismail MM, Sanchez Pego JL Correction of hyperopia with noncontact Ho:YAGlaser thermal keratoplasty J Refract Surg 1997; 13:17–22

40 Koch DD, Kohnen T, McDonnell PJ, Menefee RF, Berry MJ Hyperopia correction by tact holmium:YAG laser thermal keratoplasty US phase IIA clinical study with a 1-yearfollow-up Ophthalmology 1996; 103:1525–1536

noncon-41 Vinciguerra P, Kohnen T, Azzolini M, Radice P, Epstein D, Koch DD Radial and staggeredpatterns to correct hyperopia using noncontact holmium:YAG laser thermal keratoplasty JCataract Refract Surg 1998; 24:21–30

42 Boxer Wachler BS, Kruger RR Normalized contrast sensitivity: a new notation for mainstreamcontrast sensitivity testing in refractive surgery Invest Ophthalmol Vis Sci 1997; 38:530

43 Boxer Wachler BS, Durrie DS, Assil KK, Kruger RR Role of clearance and treatment zones

in contrast sensitivity: significance in refractive surgery J Cataract Refract Surg 1999; 25:16–23

44 Pallikaris IG Quality of vision in refractive surgery J Refract Surg 1998; 14:551–557

45 Boxer Wachler BS, Frankel RA, Kruger RR, Durrie DS, Assil KK Contrast sensitivity andpatient satisfaction following photorefractive keratectomy and radial keratotomy Invest Oph-thalmol Vis Sci 1996; 37(suppl):S19

46 Vinciguerra P, Azzollini M, Radice P A new corneal analysis after excimer laser ablation:digitized retroillumination In: Pallikaris IG, Siganos DS, eds LASIK Thorofare, NJ: Slack,1997:331–337

47 Campbell FW, Green DS Optical and retinal factors affecting visual resolution J Physiol1965; 181:576–593

48 Koch D, Abarca A, Villarreal R, Menefee R, Kohnen T, Vassiliadis A, Berry M Hyperopiacorrection by noncontact holmium:YAG laser thermal keratoplasty Clinical study with two-year follow-up Ophthalmology 1996; 103:731–740

Wound Healing After Hyperopic

Corneal Surgery Why There Is Greater Regression in the

Treatment of Hyperopia

RENATO AMBRO ´ SIO, JR.

University of Washington, Seattle, Washington, U.S.A., University of Sa˜o Paolo, Sa˜o Paolo, and Clı´nica e Microcirurgia Oftalmolo´gica Renato Ambro´sio, Rio de

out-This response is very similar in different species, facilitating the creation of animalmodels for better characterization of the wound-healing response There are quantitativeand qualitative variations in specific processes that comprise the cascade There is alsovariability depending on the inciting injury within a species For example, thermal, inci-sional, lamellar, and surface scrape injuries are followed by wound-healing responses thatare similar in some respects but different in others

Corneal wound healing following correction of hyperopia may be more complexthan that associated with corrections of myopia (10) Steepening of the central cornea isrequired for hyperopic treatments This leads to the creation of a corneal contour with asteeper central area and a flatter paracentral area

173

174 Ambro ´ sio and Wilson

Refractive regression is defined as a gradual, partial, or total loss of the initialcorrection It limits the predictability of all refractive surgery procedures performed onthe cornea It has been hypothesized that changes occurring as a result of corneal woundhealing lead to addition of new tissue Epithelial hyperplasia and stromal remodeling arethe two mechanisms that are thought to underlie this phenomenon (3,11,12)

1 Keratocytes Disappear in Response to Epithelial

Injury—Keratocyte Apoptosis

One of the earliest observations that debunked the prior dogma regarding the quiescence

of keratocytes was detection of disappearance of superficial keratocytes following cornealepithelial scrape injury This observation was made first by Dohlman and coworkers in

1968 (16) Studies by later investigators confirmed that keratocytes in the anterior stromadisappear following corneal epithelial scrape injury (17–20) as well as thermokeratoplasty(21) The mechanism of disappearance of the keratocytes was not elucidated in thesestudies The authors of these studies suggested that the disappearance of the keratocyteswas attributable to several factors, such as osmotic changes from the loss of epithelium,exposure to the atmosphere, or even artifact

In 1996, Wilson and coworkers (20) first demonstrated that the early disappearance

of keratocytes that follows epithelial injury is mediated by apoptosis (13–15,22–29) Cellshrinkage, blebbing with formation of membrane bound bodies, condensation, fragmenta-tion of the chromatin, and DNA fragmentation consistent with apoptosis were detected

in anterior stromal keratocytes after epithelial scrape wounds by transmission electronmicroscopy Nuclear DNA fragmentation was confirmed by the TUNEL assay for 3′-hydroxyl DNA ends

Apoptosis is a programmed form of cell death that occurs without the release oflysosomal enzymes or other intracellular components that could damage the surroundingtissue or cells Uncontrolled release of cellular contents is characteristic of necrotic celldeath (26) Studies have suggested that apoptosis is mediated by cytokines released fromthe injured epithelium, such as interleukin 1 (IL-1) (22), the Fas/Fas ligand system (27),bone morphogenic proteins (BMP) 2 and 4 (28), or tumor necrosis factor (TNF) alpha(29)

Virtually any type of epithelial injury induces keratocyte apoptosis These includemechanical scrapes (22–25), corneal surgical procedures like PRK and LASIK (24), herpessimplex keratitis (14), incisions (25), and even a plastic ring pressed firmly against theepithelial surface (24)

Keratocytes undergo apoptosis after epithelial injury to a depth of third to half the stromal thickness, depending on the species and the type of injury Cellular pro-cesses, known as gap junctions, connect keratocytes in the unwounded cornea to form asyncytium (31,32) It is possible that signals transmitted by cytokines to the most superficialkeratocytes are relayed to deeper keratocytes via these intercellular communication chan-nels Alternatively, the proapoptotic cytokines may penetrate into the stroma after injury.The keratocyte apoptosis response in the stroma varies with the type of cornealepithelial injury (25) Thus, injuries such as scraping of the epithelium (25) or viral infec-tion of the epithelium (14) triggers keratocyte apoptosis in the superficial stroma A lamel-lar cut across the cornea produced by a microkeratome also induces keratocyte apoptosis.This can be detected at the site of epithelial injury and along the lamellar interface (Figure

one-Figure 1 (A) Apoptosis detected along the lamellar interface by TUNEL assay in rabbit eye thathad LASIK and (B) on the surface in rabbit eye that had PRK.

1) Localization of keratocyte apoptosis in LASIK is thought to be attributable to tracking

of epithelial material, including proapoptotic cytokines, into the interface by the tome blade (22–25) Alternatively, cytokines from the injured peripheral epithelium coulddiffuse along the lamellar interface and into the central stroma (22–25)

microkera-Apoptosis has also been correlated with severe complications Meitz et al (33)reported a severe case of acute corneal necrosis following PRK for hyperopia that requiredpenetrating keratoplasty Histopathological studies of the excised tissue were negative formicro-organisms Utilizing light microscopy, an anterior zone of corneal necrosis wasfound to be present, with a moderate amount of acute inflammation at the interface betweennecrotic and viable corneal stroma; in addition, keratocytes with typical features ofapoptosis were detected by TUNEL assay and electron microscopy (Figure 2)

2 Keratocyte Proliferation and Migration: Myofibroblasts

After the loss of keratocytes caused by apoptosis within the first few hours of cornealepithelial injury, there will be an area of stroma devoid of keratocytes Zieske and cowork-ers (34) demonstrated that remaining keratocytes in the posterior and peripheral corneabegin to undergo mitosis about 12 to 24 hours after the injury (34) Keratocyte mitosiscan be detected using bromodeoxyuridine incorporation or immunocytochemical stainingfor a mitosis-specific antigen called Ki-67 (34)

176 Ambro ´ sio and Wilson

Figure 2 Transmission electron microscopy (TEM) of rabbit cornea, 24 hours after Hi PRK(ⳮ9.0D): Keratocyte apoptosis and a PMN

The cell types derived from the keratocytes that undergo mitosis following cornealepithelial injury remain to be completely characterized Studies have suggested that myofi-broblasts are an important cell type generated following injury (38–41) These studies,however, are primarily in vitro tissue culture-based investigations Little information isavailable regarding the fate of the cells that undergo mitosis following PRK (41) Nothinghas been reported about the status of these cells following LASIK

3 Resolution of The Wound-Healing Response—Return to

“Normalcy”

In the months following injury to the cornea, the wound-healing response is completedand there is a return to normal morphology and function This process is associated withelimination of some of the cells associated with wound healing and remodeling of disor-dered collagen that was produced by myofibroblasts or keratocytes during the wound-healing process (54–55) This process begins within a few weeks after injury and cancontinue for years following severe injury

The corneal epithelium may undergo hyperplasia following corneal injury (1,56)

as well as refractive surgery (11,12,21,57–59) as a part of the wound-healing response.Hyperplasia may vary between individuals, the eyes of a single individual, and with differ-ent types and levels of refractive correction This is thought to be an important mechanismfor regression of many keratorefractive procedures (1,12,56–59) There may be a return

to a normal epithelial thickness over a period of months to years, and this may result ininstability of the refractive effect of PRK or LASIK The regulatory mechanisms thatmodulate this return to normal corneal epithelial morphology have not been characterized

THEY DIFFERENT FROM MYOPIC CORRECTIONS?

The surgical correction of hyperopia remains challenging, especially for corrections greaterthan 4 to 5 D While corneal surgery for myopia requires flattening the cornea with an