can diminish the long-term efficacy of trabeculectomysurgery.

Data from experimental animals and humans suggestthat bimatoprost may have less inflammatory effect on theocular surface than other medications. No histologic find-ings of ocular inflammation were observed in chronictoxicity studies in rabbits and monkeys given daily oculardoses that achieved exposures of at least 50 to 60 timeshigher than those occurring in humans receiving 0.03%bimatoprost once daily.1

As Dr. Fellenbaum states, ocular surface inflammationhas been associated with latanoprost. A controlled maskedclinical study comparing latanoprost with unpreservedartificial tears showed that latanoprost increased the ex-pression of HLA-DR on conjunctival epithelium consis-tent with a subclinical inflammatory response.2 In aseparate study in New Zealand white rabbits, conjunctivalsurface inflammation was evaluated for several glaucomamedications (including bimatoprost and latanoprost).Mean lymphocyte scores in conjunctival biopsies werehighest for latanoprost compared with controls. Lympho-cyte counts in eyes receiving bimatoprost were not signif-icantly different from controls.3 In a clinical study,latanoprost, timolol, and betaxolol were evaluated forinflammation using impression cytology specimens frompatients. A clinical study showed a significant increase inHLA-DR on conjunctival epithelial cells, using impressioncytology in patients receiving latanoprost, timolol, orbetaxolol. Timolol and betaxolol are preserved with 0.01%benzalkonium chloride (BAK); latanoprost is preservedwith 0.02% BAK. The authors concluded that BAK maybe a contributing factor to the subclinical inflammation ofthe conjunctiva.4 The concentration of BAK in latano-prost is fourfold higher and in timolol and betaxolol istwofold higher than the concentration used to preservebimatoprost (0.005%).

Fibroblast stimulation by glaucoma medications is an-other potential cause of bleb failure in glaucoma surgery.Mitomycin-C and 5-fluorouracil have been used to inhibitfibroblast proliferation. Researchers have now demon-strated that F-type prostaglandins, such as PGF2alpha andfluprostenol (travoprost-acid), stimulate fibroblasts via ac-tivation of FP receptors. Data show that while latanoprostand travoprost stimulate fibroblasts,5,6 bimatoprost is de-void of any proliferative effects on fibroblasts.7

Finally, in addition to considering the inflammatoryeffects on the ocular surface, it is important to also makesure that medications are not associated with intraocularinflammation. Flare photometry studies that assess proteinconcentration in the anterior chamber of the eye, showedno increased inflammation in eyes receiving bimatoprost.8

In summary, we agree with Dr. Fellenbaum that poten-tial inflammatory effects of glaucoma medications can havea negative impact on the success of glaucoma surgery. As aresult of the lack of a proliferative effect of bimatoprost onfibroblasts, and the extremely low BAK concentration in

the ophthalmic formulation, topical application of bimato-prost has not been associated with significant inflammatoryeffects on the ocular surface. As suggested by Dr. Fellen-baum, additional studies will contribute to our betterunderstanding of the effects of glaucoma medications onthe ocular surface.

ROBERT S. NOECKER, MD

Tucson, ArizonaMONTE S. DIRKS, MD

Rapid City, South DakotaNEIL T. CHOPLIN, MD

San Diego, CaliforniaPAULA BERNSTEIN, MD

AMY L. BATOOSINGH

SCOTT M. WHITCUP, MD

Irvine, California

REFERENCES

1. Summary basis of approval for LUMIGAN, on the Food andDrug Administration website. Available at: http://www.fda.gov/cder/foi/nda/2001/21275Lumigan.htm. Accessed on 14February 2003.

2. Guglielminetti E, Barabino S, Monaco M, Mantero S, Ro-lando M. HLA-DR expression in conjunctival cells afterlatanoprost. J Ocul Pharmacol Ther 2002;18:1–9.

3. Noecker R, Herrygers, L, Anwaruddin R. Comparison ofconjunctival inflammation and corneal damage caused bycommonly used glaucoma medications. Abstract presented atthe American Glaucoma Society meeting in 2002. AmericanGlaucoma Society website. Available at: http://www.glaucomaweb.org/abs2002/poster19.php.

4. Cvenkel B, Ihan A. Ocular surface changes induced by topicalantiglaucoma monotherapy. Ophthalmologica 2002;216:175–179.

5. Woodward DF, Lawrence RA. Identification of a single (FP)receptor associated with prostanoid-induced Ca2� signals inSwiss 3T3 cells. Biochem Pharmacol 1994;47:1567–1574.

6. Woodward DF, Kraus AH-P, Chen J, et al. The pharmacologyof bimatoprost (Lumigan). Surv Opthalmol 2001;45(Suppl4):S337–S345.

7. Woodward DF, Kraus AH-P, Chen J, et al. Pharmacologicalcharacterization of a novel antiglaucoma agent, bimatoprost(AGN 192024). J Pharmacol Exp Ther 2003. Forthcoming.

8. Higginbotham EJ, Schuman JS, Goldberg I, et al. One-year,randomized study comparing bimatoprost and timolol inglaucoma and ocular hypertension. Arch Ophthalmol 2002;120:1286–1293.

Risk Factors for IntraoperativeEpithelial Defect in Laser In SituKeratomileusis

EDITOR:

REGARDING THE ARTICLE ON RISK FACTORS FOR INTRA-

operative epithelial defects in laser in situ keratomileusis

CORRESPONDENCEVOL. 136, NO. 2 393

(LASIK) surgery by Tekwani and Huang (Am J Ophthal-mol 2002;134:311–316), we commend the authors for awell-researched article. We were interested to note that 24of 247 eyes (9.7%) developed intraoperative epithelialdefects (IED).

We use the Chiron Technolas 217 (Baush and LombSurgicals GmBh, Dornach, Germany) LASIK machinewith a Hansatome microkeratome (Baush and LombSurgicals). All surgeries were performed by experiencedsurgeons. In bilateral cases we routinely perform LASIKsurgery in the right eye followed by the left eye. Pre-operatively, topical 0.5% proparacaine eye drops are in-stilled once or twice a few minutes before the surgery. Forlubrication of the microkeratome, distilled water is usedafter the application of the suction ring and the suction iskept on while doing the reverse pass.

As compared with the authors, in our experiencefrom 1999 to 2002, only 1.3% (27/2,056) of the eyesdeveloped intraoperative epithelial defects. Of these, 10were in the right eye and 17 in the left eye. Thepreponderance of intraepithelial defects in the left eyecould be possibly due to the fact that we use the same bladefor both the eyes of one patient. In view of our experiencewe think that the instillation of topical phenylephrine andtropicamide 30 minutes (contact period) before surgerycould be an important cause for the development of IEDin all three regimen groups. Topical proparacaine inregimen one and two also could be a cause. We do not usemydriatics, as a dilated pupil is not required in ourmachine.

Our patient group was younger (23.7 � 5.39 years vs40.3 � 10.3 years) than the study group. This could also beresponsible for a lower incidence due to better epithelialadhesion in the younger group and thinner corneas devel-oping lesser appositional force against the applanatingsurface of microkeratome.

Use of balanced salt solution for gear track lubricationmay lead to precipitation on the gear track, so theexcursion of the microkeratome on the dovetail may notbe smooth, leading to a corkscrew type of epithelial defect.

Also, we would like to know the fate of patients inwhom the epithelial defect developed; that is, if there wasdevelopment of any epithelial ingrowth, diffuse lamellarkeratitis, and the final uncorrected and best-correctedvisual acuity. Shah and coauthors1 have reported that therisk of diffuse lamellar keratitis was 24 times greater if anyepithelial defect of any size occurred. Moreover, there arereports of development of diffuse lamellar keratitis with useof carboxymethylcellulose 1% before keratotomy2 (in24/30 eyes, 80%).

NAMRATA SHARMA, MD

MAYANK S. PANGTEY, MD

RASIK B. VAJPAYEE, MBBS, MD

New Delhi, India

REFERENCES

1. Shah M, Misra M, Wilhelmus KR, Koch DD. Diffuse lamellarkeratitis associated with epithelial defects after laser in situkeratomileusis. J Cataract Refract Surg 2000;26:1312–318.

2. Samuel MA, Kaufman SC, Ahee JA, Wee C, Bogorad D.Diffuse lamellar keratitis associated with carboxymethycellu-lose sodium 1% after laser in situ keratomileusis. J CataractRefract Surg 2002;28:1409–1411.

AUTHOR REPLY

WE THANK DRS. SHARMA, PANGTEY, AND VAJPAYEE FOR

sharing their experience regarding laser in situ kerato-mileusis (LASIK)-related epithelial defect. We must takecare in comparing our results with that of Dr. Sharma’sgroup because the demographics are very different. Thereis evidence that the risk of intraoperative epithelial defect(IED) is two or three times greater in lighter pigmentedpersons (our patients in Cleveland) compared with moredarkly pigmented persons.1 Even if we ignore the racialdifference, the age difference alone would more thanaccount for the different rates of IED. Using the riskestimation equation (Figure 1) in our article,2 we estimatethat the average patient in Dr. Sharma’s series, who is 24years old, received anesthetic just prior to LASIK (our eyedrop regimen 3), and had suction maintained on thereverse pass of the Hansatome, would have an IED risk ofabout 0.7%, which is even lower than the incidence of1.3% in Dr. Sharma’s series. Therefore, we cannot draw aconclusion regarding another factor (such as mydriatic eyedrops) in our study as causing a higher IED risk comparedwith Dr. Sharma’s series.

We are performing a case-control study on the sequelaeof IED to be published later. In short, complication rateswere low or visual outcomes were good in both groups,with no significant difference between them. The rate ofdiffuse lamellar keratitis in our control LASIK series isbelow 2%, even with the use of carboxymethocellulose andbalanced saline solution as lubricants. Some aspects of mysurgical technique may have reduced the possibility ofcarboxymethocellulose-incited DLK. I only paint a thinlayer of lubricant on the cornea. With reverse-pass suctionon, I generally do not see any fluid on the stromal bed afterreflecting the flap. I also irrigate of the flap interfacevigorously with balanced salt solution for a few secondsafter replacing the flap.

DAVID HUANG, MD, PHD

Cleveland, Ohio

REFERENCES

1. Bashour M. Risk factors for epithelial erosions in laser in situkeratomileusis. J Cataract Refract Surg 2002;28:1780–1788.

2. Tekwani NH, Huang D. Risk factors for intraoperative epi-

AMERICAN JOURNAL OF OPHTHALMOLOGY394 AUGUST 2003