BLOG

Dr. Melki Restores Vision to Vermont Woman Blinded by Lye in a Vicious Attack

Created on: Monday, October 20, 2014

Click here to read the full Boston Globe article and watch video

Baseball Hall of Famer Jim Rice Undergoes LASIK Surgery with Dr Melki

Created on: Monday, October 20, 2014

Dr. Melki recently performed LASIK surgery on Hall of Famer Jim Rice. Boston Laser congratulates Jim on this great accomplishment!

Dr. Melki in the U.K.

Created on: Monday, October 20, 2014

  • Dr. Melki recently took his US experience to the UK to become the first surgeon there to implant the Crystalens 5.0 Accomodating lens.
  • 2 New UK cataract Centers opened in November of 2009 with Dr. Melki as the Medical Director

Viscoelastic-Assisted DSAEK

Created on: Monday, October 20, 2014

Dear Editor: We describe a modification of Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK) where the button insertion was performed in a sodium hyaluronate-filled anterior chamber. Nine consecutive patients (9 eyes) underwent DSAEK with the following technique. Sodium hyaluronate 10 mg/ml (Healon, AMO, Abbott Park, IL), a cohesive ophthalmic viscosurgical device (OVD) was placed into the anterior chamber throughout the procedure.

A suture-pull technique was used for graft insertion. Bimanual irrigation and aspiration cannulae (Alcon, Fort Worth, TX) were used to clear the anterior chamber from residual viscoelastic. The cannulae were inserted through the preplaced side port incisions and the irrigation bottle was lowered to minimize turbulence. In the first instance, the aspiration cannula was placed between the donor and recipient stroma while the irrigation cannula was placed under the donor button. This was then switched until no viscoelastic material could be discerned in the anterior chamber. An air bubble was then injected through 1 side port incision using a 30-gauge cannula. The pupil was dilated using cyclopentolate and the patient kept in a supine position for at least 60 minutes prior to discharge home.

Growth Factors in Aqueous Humor

Created on: Monday, October 20, 2014

Dear Editor: The aqueous humor plays an important function in the health of the anterior segment of the eye, serving to both nourish the eye and maintain the structural integrity of the anterior chamber. Although aqueous humor production and outflow has been extensively studied, little has been done to investigate its nourishing effects. Prior studies have only quantified electrolytes and basic molecules in the aqueous humor of normal humans. Although the protein concentration in the aqueous humor is only 0.2 mg/ml, proteins play an important role in the health of the anterior segment. More specifically, the interactions of different growth factors regulate most living cells in the eye along with the rest of the human body.1 With the advent of multiplex-bead testing, such as Luminex (Austin, TX), it is now possible to simultaneously test multiple factors on a small volume sample such as aqueous humor tap.2,3 Quantification of the normal levels of growth factors is important when trying to determine growth factor imbalances. With this knowledge, the aqueous humor can be tested to determine its role in anterior segment diseases in the future.

Aqueous humor was collected (100–200 _l) from 25 healthy and 25 diabetic patients undergoing cataract extraction. Patients in this study were treated with concordance to Health Insurance Portability and Accountability Act standards. The study was approved by the Texas Tech University Health Sciences Center institutional review board. The samples were then processed using Luminex multiplex-bead technology and tested for platelet-derived growth factor, brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor, transforming growth factor _, epidermal growth factor, fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, tumor necrosis factor _, interferon _, interferon _, and interleukin 1, 2, 4, 5, 6, 8, and 10.

When tested for inflammatory markers, most of the samples showed undetectable levels of inflammation in both the control and the diabetic group. Growth factor testing did not show any statistically significant difference between the control group and the diabetic group. The results taken collectively did not reveal any obvious difference between the control and diabetic groups (P_0.47). None of the test for differences in individual growth factor was significant.

The advent of multiplex-bead technology provides a new tool in protein analysis. Recently, a few studies have used this technology to investigate intraocular disease states like Funding et al2 for inflammatory factors in failed penetrating grafts and Sato et al3 for 27 different factors in the vitreous of retinopathy of prematurity patients. Similarly, we had applied the same technology to investigate growth factors in diabetic eyes; however, there are some inherent shortcomings to this study due to the small sample size, sample dilutions, and the large number of factors tested. Despite these limitations, this study does provide some trends in the factors tested. As expected, inflammatory markers are not present in most eyes undergoing routine cataract surgery. Trends in growth factor levels in this study may be verified with a larger sampling size.4

This study provides the first quantification of a broad spectrum of growth factors and cytokines in the aqueous humor in patients undergoing cataract surgery in both diabetic and nondiabetic eyes. This information and technique will be useful for other future studies analyzing these aqueous components in various ocular disease states. Future studies utilizing multiplexbead technology will further elucidate the pathogenesis of ocular disease and allow more targeted therapies.

WILLIAM YANG, MD
Springfield, Illinois
JAY C. BRADLEY, MD
TED W. REID, PHD
DAVID L. MCCARTNEY, MD
Lubbock, Texas

References

1. Klenkler B, Sheardown H. Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology. Exp Eye Res 2004;79:677– 88.

2. Funding M, Hansen TK, Gjedsted J, Ehlers N. Simultaneous quantification of 17 immune mediators in aqueous humour from patients with corneal rejection. Acta Ophthalmol Scand 2006;84:759–65.

3. Sato T, Kusaka S, Shimojo H, Fujikado T. Simultaneous analyses of vitreous levels of 27 cytokines in eyes with retinopathy of prematurity. Ophthalmology 2009;116: 2165–9.

4. Wilson SE, Bourne WM, Maguire LJ, et al. Aqueous humor composition in Fuchs’ dystrophy. Invest Ophthalmol Vis Sci 1989;30:449 –53.

Risk Factors for the Development of Retroprosthetic Membranes with Boston Keratoprosthesis Type 1

Created on: Monday, October 20, 2014

Multicenter Study Results
Christopher J. Rudnisky, MD, MPH,1 Michael W. Belin, MD,2 Amit Todani, MD,3,4
Khalid Al-Arfaj, MD,3,4,5
Jared D. Ament, MD,3 Brian J. Zerbe, MD,4,6 Joseph B. Ciolino, MD,3,4 for the Boston
Type 1 Keratoprosthesis
Study Group*

Objective: The purpose of this study was to identify possible risk factors for retroprosthetic membrane (RPM) development in a large, multicenter cohort of patients receiving a Boston type 1 keratoprosthesis.

Design: Cohort study.

Participants: The final analysis included 265 eyes of 265 patients who underwent implantation of a Boston keratoprosthesis type I device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers.

Methods: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site.

Main Outcome Measures: The primary outcome was the presence or absence of an RPM during the follow-up period.

Results: The average age of patients was 63.3_19.1 years, 48.5% of the patients were female, and 52.5% of procedures were performed on the right eye. The mean follow-up time was 17.8_14.9 months. The majority (85.4%; n _ 222) had undergone an average of 2.2_1.2 (range, 1–8) penetrating keratoplasties before keratoprosthesis implantation, and 38 eyes (14.6%) received a primary keratoprosthesis. The overall RPM formation rate was 31.7% (n _ 84). The most significant risk factor for RPM development was infectious keratitis (as a surgical indication for keratoprosthesis surgery itself), resulting in a rate of RPM formation of 70.6%. As an independent risk factor, the hazard ratio (HR) of RPM development in these eyes was 3.20 (95% confidence interval, 1.66–6.17). Aniridia was also an independent risk factor for RPM development (HR, 3.13; 95% confidence interval, 1.10–8.89).

Conclusions: Formation of RPM is a common complication of keratoprosthesis surgery, occurring in approximately one-third of cases. Eyes at the highest risk of RPM development are those receiving corneal replacement for infectious keratitis and aniridia.

Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2012;119:951–955 © 2012 by the American Academy of Ophthalmology.
*Group members listed in Appendix 1.

The Boston keratoprosthesis, developed at the Massachusetts Eye and Ear Infirmary and approved by the US Food and Drug Administration in 1993, is used in eyes at high risk for penetrating keratoplasty (PK) failure. Over the years, the device underwent several modifications to improve retention and, subsequently, is now used by ophthalmologists worldwide. However, there are a number of significant complications that can occur in eyes that have received a keratoprosthesis, including retroprosthetic membrane (RPM),1–4 glaucoma,4,5 endophthalmitis,3,6 sterile vitritis, 4,7 and prosthetic failure.1–2,4,8 One of the most common complications is the development of RPM, reported to affect between 254 and 65%3 of cases. Although not every patient requires treatment for RPM, which includes Nd:YAG laser membranotomy, some require surgical removal because the RPM can become too thick and dense to treat with laser. Zerbe et al4 reported an RPM incidence of 25% (35/141 eyes); 74% (n _ 25) of the affected eyes were treated with ND:YAG laser, 11.4% (n _ 4) were treated surgically, and 17% were observed. The etiology of RPM is unknown; authors have reported that the performance of other intraocular surgery at the time

© 2012 by the American Academy of Ophthalmology ISSN 0161-6420/12/$–see front matter 951 Published by Elsevier Inc. doi:10.1016/j.ophtha.2011.11.030

Photochemical Keratodesmos Versus Sutures

Created on: Monday, October 20, 2014

The IOPL after PKD treatment was compared with that obtained using sutures. Two interrupted radial sutures of black monofilament 10-0 nylon (Ethilon suture; Ethicon, Piscataway, NJ) were used to close the keratome incision. The sutures were placed in a radial fashion at approximately 90% corneal depth. Preliminary experiments produced IOPLs of approximately 230 mm Hg. This pressure is similar for the incisions closed with PKD treatment. However, it was observed that the IOP was maintained even when there was leakage around the sutures. The leaks surrounding the sutures were reversible, whereas with PKD the damage was irreversible after the opening of the incision.

DISCUSSION

This study demonstrates the feasibility of using PKD treatment to close small incisions made in the cornea of rabbit eyes ex vivo. The results show that PKD produces a significant increase in the immediate IOPL of enucleated rabbit eyes after treatment of 3.5-mm corneal incisions.

The dose–response pattern observed for the PKD treatment, using RB as a photosensitizer, is not simple. Reduced IOPL and tissue shrinkage were observed consistently at the highest irradiance of 3.82 W/cm2 and occasionally at 2.55 W/cm2 for doses between 762 and 1524 J/cm2, which suggests contributions from both photochemical and photothermal processes. The ideal conditions to produce a clinically relevant IOPL with PKD are those that balance the shortest treatment time with the highest dose; the limitation is the thermal effects produced using high irradiances. In the cornea, photothermal effects may produce collagen contraction resulting in distortion of the patient’s vision. Therefore, higher irradiances that would allow a shorter treatment time are limited by thermal effects.

Other potential photosensitizers for PKD, chosen on the basis of suitable photochemistry, were investigated. PKD treatments using R-5-P and N-HPT produced increases in the IOPL. Relative efficiencies of the photosensitizers were evaluated by comparing the IOPLs produced by optically matched solutions of the photosensitizers at the same set of irradiances and doses. However, these comparisons do not take into account considerations such as the binding efficiency of the photosensitizers, which alters the dye concentration on the incision surface. All the photosensitizers generate singlet oxygen or reactive radicals that may be toxic to cells in the cornea. Future in vivo studies are needed to determine whether this effect is relevant and, if so, to evaluate possible protective agents. Our results using R-5-P are comparable with those found by Khadem et al.4–6 who used a photoactivated adhesive consisting of fibrinogen and R-5-P irradiated with argon ion laser light (488–514 nm) to close 5-mm penetrating central corneal incisions made in human cadaveric eyes. With this method of incision closure in a smaller sample size, a mean wound-bursting pressure of 154 mm Hg was found. The maximum mean IOPL observed in our study using R-5-P was 254 mm Hg. Our results suggest that the presence of fibrinogen is not necessary to obtain a good seal. Elimination of fibrinogen from the system removes the limitations imposed by using this protein, such as the limited tensile strength and the requirement that the fibrinogen be isolated from the patient to be treated, to avoid risk of infection from donor plasma.42 Other possible suture alternatives for use in ophthalmic surgery that have been investigated include chemical glues.1–3 Glues are limited by the requirement that they be nontoxic, noncarcinogenic, and biodegradable. In addition, glues do not generally provide a permanent closure; they are sloughed off within weeks of application.

Our results show that PKD treatment of small keratome incisions in rabbit cornea ex vivo produced IOPLs comparable with those incisions closed with sutures. The leaks associated with the sutures were reversible, but after the PKD-treated incision had been opened, the seal was completely lost. However, PKD treatment can easily and effectively be repeated on the previously treated incision.

PKD offers many potential advantages over the methods currently used to attach corneal tissue and close incisions in a variety of surgical procedures such as penetrating keratoplasty, laser in situ keratomileusis (LASIK), and cataract surgery and in the treatment of corneal lacerations. The sutures currently used in corneal transplants can induce postoperative astigmatism, neovascularization, and rejection of the donor cornea. Furthermore, loose or broken sutures can leave a patient vulnerable to microbial keratitis. The suturing procedures used are skill intensive and are mainly performed by corneal specialists. PKD offers a simple procedure to close wounds, spot seal LASIK flaps and attach donor cornea, reducing the operating and rehabilitation time.

Acknowledgments

The authors thank Norman Michaud and Thomas Flotte for collecting the confocal images and for useful discussion, Hans-Christian Luedemann and Dominic Bua for technical help, and Be�atrice M. Aveline for preparation of N-HPT.

References

1. Henrick A, Gaster RN, Silverstone PJ. Organic tissue glue in the closure of cataract incisions. J Cataract Refract Surg. 1987;13: 551–553.

2. Henrick A, Kalpakian B, Gaster RN, et al. Organic tissue glue in the closure of cataract incisions in rabbit eyes. J Cataract Refract Surg. 1991;17:551–555.

3. Shigemitsu T, Majima Y. The utilization of a biological adhesive for wound treatment: comparison of suture, self-sealing sutureless and cyanoacrylate closure in the tensile strength test. Int Ophthalmol. 1997;20:323–328.

4. Goins KM, Khadem J, Majmudar PA, et al. Photodynamic biological tissue glue to enhance corneal wound healing after radial keratotomy. J Cataract Refract Surg. 1997;23:1331–1338.

5. Goins KM, Khadem J, Majmudar PA. Relative strength of photodynamic biological tissue glue in penetrating keratoplasty in cadaver eyes. J Cataract Refract Surg. 1998;24:1566–1570.

6. Khadem J, Truong T, Ernest JT. Photodynamic biological tissue glue. Cornea. 1994;13:406–410.

7. Barak A, Eyal O, Rosner M, et al. Temperature controlled CO2 laser tissue welding of ocular tissues. Surv Ophthalmol. 1997; 42(suppl):S77– 81.

8. Bass LS, Treat MR. Laser tissue welding: a comprehensive review of current and future applications. Lasers Surg Med. 1995;17:315– 349.

9. Jain KK, Gorisch W. Repair of small blood vessels with the neodynium-YAG: a preliminary report. Surgery. 1979;85:684–688.

10. Oz MC, Bass LS, Popp HW, et al. In vitro comparison of thuliumholium- chromium: YAG and argon ion lasers for welding of biliary tissue. Lasers Surg Med. 1989;9:248 –253. IOVS, October 2000, Vol. 41, No. 11 Photochemical Keratodesmos for Corneal Incision Repair 3339

11. Poppas DP, Schlossberg SM. Laser tissue welding in urological surgery. Urology. 1994;43:143–148.

12. Sauer JS, Hinshaw JR, McGuire KP. The first sutureless, laser welded, end to end bowel anastomosis. Lasers Surg Med. 1989;9: 70–73.

13. Schober RF, Ulrich F, Sander T, et al. Laser-induced alteration of collagen substructure allows microsurgical tissue welding. Science. 1986;232:1421–1422.

14. Dubbleman TMAR, Goeij AFPMD, Stevenick JV. Photodynamic effects of protoporphyrin on human erythrocytes: nature of crosslinking of membrane proteins. Biochim Biophys Acta. 1981;511: 141–151.

15. Verweij H, Dubbelman TMAR, Steveninck JV. Photodynamic protein crosslinking. Photochem Photobiol. 1981;28:87–94.

16. Shen H, Spikes JD, Kopeckova P, et al. Photodynamic crosslinking of proteins, II: photocrosslinking of a model protein-ribonuclease. J Photochem Photobiol B. 1978;35:213–219.

17. Girotti AW. Photosensitized crosslinking of erythrocyte membrane proteins: evidence against participation of amino groups in the reaction. Biochim. Biophys Acta. 1980;602:45–56.

18. Judy MM, Matthews JL, Boriack RL, et al. Photochemical crosslinking of proteins with visible-light absorbing 1,8-naphthalimides. Proc SPIE Int Soc Opt Eng. 1993;1882:221–224.

19. Ramshaw JAM, Stephens LJ, Tulloch PA. Methylene blue sensitized photo-oxidation of collagen fibrils. Biochim Biophys Acta. 1994; 1206:225–230.

20. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66:97–103.

21. Judy MM, Fuh L, Matthews JL, et al. Gel electrophoretic studies of photochemical cross-linking of type I collagen with brominated 1,8-naphthalimide dyes and visible light. Proc SPIE Int Soc Opt Eng. 1994;2128:506–509.

22. Judy MM, Matthews JL, Boriack RL, et al. Heat-free photochemical tissue welding with 1,8-naphthalimide dyes using visible (420 nm) light. Proc SPIE Int Soc Opt Eng. 1993;1876:175–179.

23. Gollnick K, Schenck GO. Mechanism and stereoselectivity of photosensitized oxygen transfer reactions. Pure Appl Chem. 1964;9: 507–525.

24. Gandin E, Lion Y, Van de Worst A. Quantum yield of singlet oxygen production by xanthene derivatives. Photochem Photobiol. 1983;37:271–278.

25. Kato Y, Uchida K, Kawakishi S. Aggregation of collagen exposed to UVA in the presence of riboflavin: plausible role of tyrosine modification. Photochem Photobiol. 1994;59:343–349.

26. Hill T, Redmond RW, Kochevar IE. Photosensitized crosslinking of collagen: mechanistic approaches to improved tissue welding. In: First Internet Conference Photochemistry and Photobiology. 1997.

27. Aveline BM, Kochevar IE, Redmond RW. Photochemistry of the nonspecific hydroxyl radical generator, N-hydoxypyridine-2(1H)- thione. J Am Chem Soc. 1996;118:10113–10123.

28. Barton DHR, Jaszberenyi JC, Morrell AI. The generation and reactivity of oxygen centered radicals from the photolysis of derivatives of N-hydroxy-2-thiopyridone. Tetrahedron Lett. 1991;32: 311–314.

29. Boivin J, Crepon E, Zard SZ. N-hydroxy-2-pyridinethione: a mild and convenient source of hydroxyl radicals. Tetrahedron Lett. 1990;31:6869–6872.

30. Hess KM, Dix TA. Evaluation of N-hydroxy-2-thiopridone as a non-metal dependent source of the hydroxyradical in non-aqueous systems. Anal Biochem. 1992;206:309–314.

31. Abergel RP, Lyons RF, White RA. Skin closure by Nd: YAG laser welding. J Am Acad Dermatol. 1986;14:810–814.

32. Cilesiz I, Thomsen S, Welch AJ. Controlled temperature tissue fusion: argon laser welding of rat intestine in vivo. Parts 1 and 2. Lasers Surg Med. 1997;21:269–286.

33. Massicotte JM, Stewart RB, Poppas DP. Effects of endogenous absorption in human albumin solder for acute laser wound closure. Lasers Surg Med. 1998;23:18 –24.

34. Oz M, Johnson JP, Parangi S, et al. Tissue soldering by use of indocyanine green dye-enhanced fibrinogen with the near infrared diode laser. J Vasc Surg. 1990;11:718–725.

35. Poppas D, Stewart RB, Massicotte M, et al. Temperature-controlled laser photocoagulation of soft tissue: in vivo evaluation using a tissue welding model. Lasers Surg Med. 1996;18:335–344.

36. Poppas D, Massicotte JM, Stewart RB, et al. Human albumin solder supplemented with TGF-B1 accelerates healing following laser welded wound closure. Lasers Surg Med. 1996;19:360–368.

37. Stewart R, Benbrahim A, LaMuraglia GM, et al. Laser assisted vascular welding with real time temperature control. Lasers Surg Med. 1996;19:9 –16.

38. Wider T, Libutti SK, Greenwald DP, et al. Skin closure with dyeenhanced laser welding and fibrinogen. Plastic Reconstructr Surg. 1991;88:1018–1025.

39. Chuck R, Oz MC, Delohery TM, et al. Dye-enhanced laser tissue welding. Lasers Surg Med. 1989;9:471–477.

40. Lessing HE, Richardt D, Von Jena A. Quantitative triplet photophysics by picosecond photometry. J Mol Struct. 1982;84:281– 292.

41. Fleming GR, Knight AWE, Morris JM, et al. Picosecond fluorescence studies of xanthene dyes. J Am Chem Soc. 1977;99:4306– 4311.

42. Khodadoust A. Tissue adhesives in ophthalmology. In: Sears ML, Tarkkanen A, eds. Surgical Pharmacology of the Eye. New York: Raven Press; 1985:223–234. 3340 Mulroy et al. IOVS, October 2000, Vol. 41, No. 11

Photochemical Keratodesmos for Repair of Lamellar Corneal Incisions

Created on: Monday, October 20, 2014

Louise Mulroy,1 June Kim,1 Irene Wu,1 Philip Scharper,2 Samir A. Melki,2 Dimitri T. Azar,2 Robert W. Redmond,1 and Irene E. Kochevar1

PURPOSE. To determine the efficacy of photochemical keratodesmos (PKD) for closing surgical incisions in the cornea of enucleated rabbit eyes compared with that achieved using sutures and self-sealing incisions.

METHODS. A 3.5-mm incision, at an angle parallel to the iris, was made in the cornea of enucleated New Zealand White rabbit eyes. The intraocular pressure required to cause leakage (IOPL ) from the untreated incision was then recorded. Photochemical keratodesmos treatment was then performed by application of a dye, Rose Bengal (RB), in saline solution to the surfaces of the incision wound, followed by laser irradiation at 514 nm from an argon ion laser. Immediately after treatment, the IOPL was measured. Both dose and laser irradiance dependencies were studied in five or more eyes for each condition and appropriate control eyes. The IOPLs were compared with those obtained using conventional interrupted 10-0 nylon sutures. Other dyes were tested in a similar fashion.

RESULTS. The IOPL of 300 mm Hg was obtained using a fluence of 1270 J/cm2 with an irradiance of 1.27 W/cm2 (laser exposure time, 16 minutes 40 seconds). No sealing was observed using dye or light alone where control pressures of approximately 30 mm Hg were found. At higher dose (1524 J/cm2) and irradiance (3.82 W/cm2; 6 minutes 35 seconds), PKD was less effective, which may be attributable to thermal effects. PKD produced IOPLs similar to those in closure by sutures. Other dyes such as riboflavin-5-phosphate and N-hydroxy-pyridine thione also produced efficient bonding after PKD. Nonphotochemically active dyes did not produce significant increases in the IOPL at which leakage occurred.

CONCLUSIONS. The increase in IOPL after PKD treatment, comparable with that with sutures, in enucleated rabbit eyes demonstrates the feasibility of this technique ex vivo. (Invest Ophthalmol Vis Sci. 2000;41:3335–3340) The ideal technique for wound closure in the cornea would be simple and rapid and would produce a watertight seal without astigmatism or inflammation. Closure of corneal wounds is often associated with induced astigmatism, partly due to uneven suture tension. This is prevalent after penetrating keratoplasty in which numerous sutures are needed to hold the graft in place. Suturing techniques designed to evenly distribute tension across corneal grafts may still result in significant astigmatism. Although factors such as wound healing, host graft sizing, and trephination techniques also play a role in postoperative astigmatism, a method to hold the graft with equally distributed force could help reduce the postoperative astigmatism.

Possible alternatives to sutures include adhesives, such as fibrin1,2 and cyanoacrylate glue.3 Additionally, photodynamic tissue glue, composed of a riboflavin-5-phosphate and fibrinogen mixture, is reported to close cataract incisions and attach donor cornea in corneal transplants.4–6 Temperature-controlled tissue welding also has been attempted in the cornea.7 Photochemical keratodesmos (PKD) may offer an improved result using a relatively easy method. Unlike photothermal tissue welding,8–13 PKD can produce a tissue–tissue seal without collagen denaturation or heat-induced peripheral tissue damage. PKD involves the application of a photosensitizer to the wound surfaces followed by laser irradiation to seal the wound. Strong covalent cross-links are believed to form between collagen molecules on opposing surfaces to produce a tight seal. Photosensitization of proteins has been previously reported to produce intermolecular covalent cross-links.14–18 Light and photosensitizers also have been reported to cause collagen cross-links.19–21 However, there are few reports of PKD. Photochemical tissue welding of dura mater has been reported, using 1,8-naphthalimides irradiated with visible light.22

In this study, we have tested the efficiency of PKD for closing small keratome incisions in the cornea of enucleated rabbit eyes. Rose bengal (RB), riboflavin-5-phosphate (R-5-P), fluorescein (Fl), methylene blue (MB) and N-hydroxypyridine- 2-(1H)-thione (N-HPT) have been compared as photosensitizers. From the 1Massachusetts General Hospital, Wellman Laboratories of Photomedicine, Department of Dermatology, and 2Cornea and Refractive Services, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. Supported by the DoD Medical Free Electron Laser program, contract number N00014-94-10927, and the Center for Innovative Minimally Invasive Therapy, Massachusetts General Hospital, Boston. Submitted for publication February 2, 2000; revised April 27, 2000; accepted May 31, 2000. Commercial relationships policy: N. Corresponding author: Irene E. Kochevar, Wellman Laboratories of Photomedicine, Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, WEL-224, Boston, MA 02114. kochevar@helix.mgh.harvard.edu Investigative Ophthalmology & Visual Science, October 2000, Vol. 41, No. 11 Copyright © Association for Research in Vision and Ophthalmology 3335

MATERIALS AND METHODS

Young, albino rabbit eyes were received on ice (Pel-Freez, Rogers, AR) approximately 17 to 24 hours after death and enucleation. The eyes were kept on ice and used the same day. The eye to be studied was mounted on a plastic-covered polystyrene block and fixed in position by needles inserted through the extraocular muscles into the polystyrene. The eye was then placed under a dissecting microscope allowing visualization of the treated area during the entire procedure. A 27-gauge needle was inserted parallel to the iris, 2 mm anterior to the limbus into clear cornea, and positioned above the lens in the anterior chamber. The needle was connected to both a blood pressure transducer (Harvard Apparatus, Holliston, MA) and a miniinfuser (Bard 400; Harvard) through a T coupler. The pressure transducer consists of a transducer element that is hardwired to an amplifier box and uses a semidisposable dome with an integral silicone rubber membrane. Pressure inside the dome is transmitted through the membrane to a plastic button, the motion of which is translated to a voltage. The voltage generated by the transducer–amplifier combination is proportional to the lower limit of intraocular pressure (IOP). Signals from the transducer amplifier were recorded on a computer (Macintosh G3 Powerbook; Apple, Cupertino, CA, equipped with a PCMICA [Daqcard-1200] data acquisition card; National Instruments, Austin, TX). Data acquisition was controlled using programs written in commercial software (LabView 4; National Instruments). The voltage from the transducer and amplifier was converted to pressure by calibrating with a standing manometer.

Experiments on individual eyes were initiated by increasing the IOP to 30 to 40 mm Hg, using water infusion at a rate of 1 ml/min. An incision was made in the cornea, 1 mm anterior to the limbus (j) and parallel to the iris, using a 3.5-mm angled keratome (Becton Dickinson, Lincoln Park, NJ). For each eye, the IOP required to produce fluid leakage from the incision (IOPL ) was recorded before and after PKD treatment. The photosensitizer, dissolved in phosphate buffer solution (PBS [pH 7.2]; Gibco, Grand Island, NY) was applied to the walls of the incision using a gastight 50-ml syringe (Hamilton, Reno, NV) with a 27-gauge needle. Confocal fluorescence spectroscopy confirmed the location of RB on the incision walls and indicated that the photosensitizer penetrated approximately 100 mm laterally into the wall of the incision. The photosensitizers, their absorption maxima, and their absorption coefficients at the laser wavelength were: RB, 550 nm, 33,000 dm3/mol per centimeter at 514 nm; Fl, 490 nm, 88,300 dm3/mol per centimeter at 488 nm; MB, 664 nm, 15,600 dm3/mol per centimeter at 661 nm; R-5-P, 445 nm, 4330 dm3/mol per centimeter at 488 nm; and N-hydroxypyridine- 2-(1H)-thione (N-HPT), 314 nm, 2110 dm3/mol per centimeter at 351 nm. The photosensitizers were used as received, with the exception of N-HPT, which was recrystallized twice from aqueous ethanol before use. The concentrations of the photosensitizers were adjusted so that all the solutions had an absorbance of approximately 1.0 in a path length of 200 mm at the laser irradiation wavelength, with the exception of N-HPT for which the absorption was lower by approximately a factor of 10.

Irradiations used a continuous-wave (CW) argon-ion laser (Innova 100; Coherent, Palo Alto, CA) at 488 nm (for Fl and R-5-P), 514.5 nm (for RB), or 351 nm (for N-HPT). An argon-ion pumped-dye laser (CR-599; Coherent) with 4-dicyanomethylene- 2-methyl-6-( p-dimethylaminostyryl)-4H-pyran dye (Exciton, Dayton, OH) was used for irradiation at 661 nm (for MB). Laser light was coupled into a 1-mm diameter quartz fiber, and a 1- cm diameter spot on the tissue was created by using a combination of 1- and 2-in. focal length, S1-UV–grade fused silica, biconvex lenses (Esco Products, Oak Ridge, NJ), mounted in a cage assembly (SM1 series; ThorLabs, Newton, NJ). The 1-cm diameter circular spot was sufficient to cover the entire incision, and the optics were adjusted so that the laser light was incident on the cornea at an angle approximately 45o to the plane of the incision. Dose–response curves were obtained by varying the duration of the irradiation at a constant irradiance. In separate experiments, the effects of laser irradiance were investigated by comparison of the same delivered dose using different irradiances. The doses used ranged from 124 to 1524 J/cm2, and the irradiances used were 0.64, 1.27, 2.55, and 3.86 W/cm2. The laser exposure time varied from 33 seconds for the lowest dose using the highest irradiance to 26 minutes, 27 seconds for the highest dose using the lowest irradiance.

The IOPL was recorded immediately after treatment. Infusion was started (1 ml/min), and the IOP increased until a maximum was reached, followed by a sharp decrease, corresponding to the opening of the incision and leakage of fluid from the anterior chamber. A typical trace showing the changes in IOP with infusion time is shown in Figure 1. Five to 10 rabbit eyes were tested for each condition of dose and irradiance. Control experiments included: irradiation with no photosensitizer application, photosensitizer application only and no photosensitizer or laser irradiation. In the experiments using no photosensitizer, PBS was applied to the incision walls, using the same method as described for the photosensitizers. In control experiments with no laser irradiation, the eye was allowed to stand for the same period as the laser-treated samples.

FIGURE 1. Typical trace of increasing IOP with infusion time for aPKD-treated eye showing IOPL at 300 mm Hg.
3336 Mulroy et al. IOVS, October 2000, Vol. 41, No. 11
RESULTS Photochemical Keratodesmos with RB

Treatment of incisions with RB (1.5 mM) and 514-nm laser light resulted in an increase in posttreatment IOPL. Control experiments demonstrated that a significant increase (P , 0.005) in the IOPL after PKD treatment occurred only when both RB and laser irradiation were applied and not after either alone (Fig. 2). The mean IOPL of incisions treated with RB and 514-nm laser light was greater than 300 6 48 mm Hg, whereas laser irradiation alone or photosensitizer alone produced no significant increase between the pre- and posttreatment IOPLs. Dose response curves for IOPL are shown in Figure 3 for doses delivered at irradiances of 1.27, 2.55, and 3.82 W/cm2. A clear dose–response relationship was observed at the lowest irradiance (1.27 W/cm2) for doses between 508 and 1270 J/cm2 (Fig. 3A). No significant increase in the IOPL was observed for doses below 508 J/cm2 at any irradiance. PKD was most efficient at 1270 J/cm2 delivered at an irradiance of 1.27 W/cm2, All doses delivered at the two lower irradiances (1.27 and 2.55 W/cm2) gave IOPL greater than 100 mm Hg. Treatment using irradiances of 2.55 and 3.82 W/cm2 produced no obvious dose–response pattern. In general, for a selected dose the IOPL was lower at higher irradiances. For example, at 1270 J/cm2 the mean IOPLs are 274, 150, and 130 mm Hg for the irradiances 1.27, 2.55, and 3.86 W/cm2, respectively. In addition to reduced IOPL, thermal damage was consistently observed at doses of 762 to 1524 J/cm2 at the highest irradiance (3.82 W/cm2) and occasionally at 2.55 W/cm2. Tissue shrinkage and deformation around the wound site were taken as signs of thermal damage. Significant bleaching and color change of the photosensitizer were observed after irradiation. A seal was considered a failure if the IOPL after treatment was in the range of 30 to 40 mm Hg, the same range of pressures measured for pretreatment IOPLs. A mean failure rate of 40% was found for the PKD treatment of incisions with RB and light doses of 508 to 1524 J/cm2 for all irradiances. Failure of a treatment did not correlate with light dose or irradiance. However, high failure rates correlated with obvious deterioration of the enucleated eyes by the time of the experiment, as was evident from globes that were not firm and corneas that appeared milky. In addition, nonuniform application of the dye as determined by observation through the dissecting microscope, also appeared to correlate with treatment failure.

Investigation of Other Photosensitizers for PKD

RB was chosen for these studies, because it photosensitizes cross-linking of soluble collagen as detected by sodium dodecyl sulfate (SDS)– gel electrophoresis. RB is known to undergo reductive and oxidative electron transfer reactions as well as singlet oxygen production.23,24 With this in mind, additional dyes were evaluated that were also known to produce radicals after photoexcitation. R-5-P was selected for evaluation, because flavins undergo photoelectron transfer processes, in addition to singlet oxygen production. Riboflavin has been shown to photosensitize the formation of cross-linked collagen molecules25 and to increase the stiffness of the cornea through the induction of collagen cross-links.20 Our previous studies have shown that R-5-P and 355-nm light efficiently cross-link soluble collagen.26 The application of 11 mM R-5-P and irradiation using 488 nm light, at the same irradiances used for RB, and doses of 762 and 1016 J/cm2, significantly increased IOPL after PKD treatment (P , 0.05; Fig. 4). The IOPLs observed using R-5-P were of a magnitude similar to those for RB. However, the IOPLs observed for each dye at the same irradiance and dose were not comparable. Although the treatment produced significant increases in IOPL, no simple pattern between the two dyes was observed.

FIGURE 2. Mean IOPL values for PKD-treated eyes (n 5 5) using 514 nm light (2.55 W/cm2) and RB (1.5 mM) in PBS. Additional controls are incisions treated with RB or buffer but no laser light.

FIGURE 3. Mean IOPL before and after PKD using RB and 514-nm irradiation. RB (10 ml, 1.5 mM) was applied to the incision surfaces, which were then treated with the doses indicated using irradiances of (A) 1.27 W/cm2, (B) 2.55 W/cm2, and (C) 3.82 W/cm2. IOVS, October 2000, Vol. 41, No. 11 Photochemical Keratodesmos for Corneal Incision Repair 3337

Another photosensitizer, N-HPT, produces hydroxyl radicals and other reactive species after UV irradiation,27–30 and studies have shown it to be an efficient agent for cross-linking of soluble collagen.26 A 4.5-mM solution of N-HPT was applied to the walls of the incision and irradiated using 351 nm light (0.64 W/cm2) at doses ranging from 127 to 508 J/cm2. No significant increase in the IOPLs was observed at the lowest dose. However, mean IOPL values of 60 6 23 and 126 6 40 mm Hg were produced when using the doses of 254 and 508 J/cm2, respectively—lower doses than used for the other photosensitizers. MB is a frequently used dye in ophthalmic surgery that has been reported to photosensitize collagen cross-links in rat tail tendon.19 Our previous studies showed that MB and 355 nm light did not produce efficient cross-linking of soluble collagen, 26 and MB was therefore used as a control in these ex vivo studies. MB (3 mM) applied to the walls of the incision and irradiated with 0.64 W/cm2 of 661 nm light at doses of 508, 762, and 1016 J/cm2 did not increase the posttreatment IOPL. However, it was observed that MB did not stain the corneal tissue efficiently, explaining its low efficiency in PKD. Laser-activated tissue welding has been studied in a variety of tissues.8,31–38 In tissue welding, the laser radiation is used to heat the tissue to temperatures at which collagen denatures and, on cooling, the collagen molecules intertwine to form a weld. Additionally, dye-enhanced thermal welding has been investigated.8,39 In this method, the dye selectively absorbs the laser energy and then releases heat to the desired area, reducing peripheral tissue damage. These methods, however, are not appropriate for the cornea because of the potential reduction in visual acuity that would result from the corneal deformation produced by thermal tissue damage. When performing PKD on the cornea, heating must be avoided.

We evaluated the possibility that nonphotochemical processes contribute to wound closure by comparing PKD produced by RB with that produced by Fl, a dye with a similar structure but one that is not expected to induce protein crosslinks. RB and Fl are both xanthene dyes. However, RB is halogenated (four iodines and four chlorines), and the presence of these heavy atoms causes RB to be photochemically active.40 Fl has a high quantum yield of fluorescence41 and lower quantum yield of triplet state formation than RB40 and will, therefore, produce a lower proportion of active species with the potential to produce collagen cross-links. A solution of 0.6 mM Fl was applied and irradiated using 488-nm laser light at the same range of irradiances used for RB and at doses from 508 J/cm2 to 1016 J/cm2 (Fig. 5). No increase in IOPL was observed for the incisions treated with the two lowest doses using the two lowest irradiances studied. However, at the highest dose for all irradiances, an increase in IOPLs was observed with pressures ranging from 63 6 30 to 89 6 42 mm Hg, although this is much less efficient than RB (compare Figs. 3 and 5). These results suggest that PKD is indeed produced by photochemical processes. The IOPL of 116 6 40 mm Hg obtained using a dose of 762 J/cm2 at 3.82 W/cm2 (laser exposure time of 3 minutes, 10 seconds) is considerably higher than any other observed using Fl. The sealing observed at the highest irradiance (3.82 W/cm2) and dose (762 J/cm2) suggests that some other effect is operating, such as a thermal mechanism under these conditions.

FIGURE 4. Mean IOPL before and after PKD using R-5-P and 488-nm irradiation. R-5-P (40 ml, 11 mM) was applied to the incision surfaces, which were then treated with the doses indicated using irradiances of (A) 1.27 W/cm2, (B) 2.55 W/cm2, and (C) 3.82 W/cm2.

FIGURE 5. Mean IOPL before and after PKD using Fl and 488-nm irradiation. Fl (40 ml, 0.6 mM) was applied to the incision surfaces, which were then treated with the doses indicated using irradiances of (A) 1.27 W/cm2, (B) 2.55 W/cm2, and (C) 3.82 W/cm2.

3338 Mulroy et al. IOVS, October 2000, Vol. 41, No. 11

Late Traumatic Dislocation of Laser In Situ

Created on: Monday, October 20, 2014

Keratomileusis Corneal Flaps

Samir A. Melki, MD, PhD,1 Jonathan H. Talamo, MD,2 Anna-Maria Demetriades, BA,1 Nada S. Jabbur, MD,3 John P. Essepian, MD,4 Terrence P. O’Brien, MD,3 Dimitri T. Azar, MD1

Purpose: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps.

Design: Retrospective, observational case series.

Participants: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days–2 months) after the procedure.

Intervention: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases.

Main Outcome Measures: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored.

Results: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity.

Conclusions: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.

Ophthalmology 2000;107: 2136–2139 � 2000 by the American Academy of Ophthalmology.

Laser in situ keratomileusis (LASIK) is a relatively new ophthalmic procedure that represents a combination of previously used techniques in refractive surgery.1 It involves using a microkeratome to create a thin corneal flap, followed by excimer laser stromal ablation and repositioning of the flap.2 The creation of a corneal flap represents additional risks of intraoperative and postoperative complications as compared with laser ablation after epithelial removal alone, as in photorefractive keratectomy.3–5 These complications include incomplete, irregular, or buttonholed flaps; flap folds; epithelial ingrowth; and diffuse lamellar keratitis.6–8 Although early flap slippage has been reported in various studies, the vulnerability of the LASIK flap to late dislocation is still unclear.

In the first 24 hours after LASIK, flap dislodgment presumably occurs as a result of mechanical disruption (e.g., blinking, lid squeezing, eye rubbing). It is not known to what extent the flap is subject to traumatic dislocation later in the postoperative period. In this study, we report four cases of late-onset (.1 week after the surgery) traumatic LASIK flap displacement.

Patients and Methods

We performed a retrospective analysis of patients with flap dislodgment occurring more than 1 week after LASIK surgery between October 1996 and February 2000. Details of the mechanism of injury, repair, and postoperative follow-up were available on all patients. Follow-up ranged between 4 and 21 months.

Patient 1

A 28-year-old man with a cycloplegic refraction of 25.25 2 1.75 3 90 in the right eye and 24.00 2 2.25 3 115 in the left eye and best spectacle-corrected visual acuity (BSCVA) of 20/20 in the right eye and 20/25 in the left eye underwent uneventful bilateral simultaneous LASIK for full correction of myopia and astigmatism. On postoperative day 8, both uncorrected visual acuity (UCVA) and BSCVA were 20/20 in both eyes. Two days later, he was struck in the left eye with a basketball resulting in immediate decrease in vision. Slit-lamp evaluation revealed a radial tear of the LASIK flap at the nasal hinge with 50% of the hinge intact. The inferior portion of the flap was folded on itself with bare stroma exposed.

The patient was immediately taken to the operating room and the flap was refloated, irrigated, and flattened. Tobramycin and dexamethasone combination eyedrops (Tobradex, Alcon, Fort Worth, TX) were given four times daily for 1 week, followed by a tapering dose of fluorometholone 0.1% (FML, Allergan, Inc., Irvine, CA) for 1 month. After surgery, moderate striae and minimal epithelial ingrowth at the tear location were noted. The Originally received: May 9, 2000.

Accepted: July 5, 2000. Manuscript no. 200279. 1Massachusetts Eye & Ear Infirmary, Boston, Massachusetts. 2Cornea Consultants of Boston, Boston, Massachusetts. 3Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland. 4Private practice, Fairfax, Virginia. Presented in part at the American Academy of Ophthalmology annual meeting, Orlando, Florida, October 1999.

The authors have no proprietary interest in any aspect of this article. Reprint requests to Dimitri T. Azar, MD, Corneal and Refractive Surgery Services, Massachusetts Eye & Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114. 2136 � 2000 by the American Academy of Ophthalmology ISSN 0161-6420/00/$–see front matter Published by Elsevier Science Inc. PII S0161-6420(00)00405-X BSCVA steadily improved, reaching 20/20 (12.25 2 2.00 3 30) at 2 months after injury (UCVA, 20/30). There was no progression of the epithelial ingrowth, and the folds were not considered visually significant.

Patient 2

A 21-year-old white male with a manifest refraction of 28.25 2 3.25 3 020 in the right eye (BSCVA, 20/15) and 27.25 2 2.00 3 002 in the left eye (BSCVA, 20/15) underwent uneventful bilateral simultaneous LASIK for the correction of myopia and astigmatism. The corneal flap was created using a Hansatome (Bausch & Lomb) microkeratome (8.5-mm suction ring diameter, 160-mm thickness footplate). The UCVA was 20/25.

Twenty-four days after surgery he was injured in the right eye by a “finger flick.” He was examined 10 hours after the injury and had a UCVA of 4/200. Examination revealed a partially dislocated corneal flap with flap folds across the visual axis as well as epithelial migration over the exposed area of the stroma in the inferotemporal quadrant (Figs 1A–C). The flap was immediately repositioned after thorough scraping of the stromal bed and of the flap underside. A bandage contact lens was placed for additional protection. On postoperative day 1, his UCVA was 20/30. Mild diffuse lamellar keratitis subsequently developed and was treated with intensive topical prednisolone acetate 1% (Pred Forte, Allergan) as well as oral prednisone. One week later, the inflammation was resolved and his UCVA was 20/20.

Patient 3

A 61-year-old woman with a manifest refraction of 12.50 2 0.50 3 60 in the right eye and 12.50 2 0.75 3 160 in the left eye and BSCVA of 20/15 in both eyes underwent uneventful bilateral LASIK surgery resulting in BSCVA of 20/20 in the left eye (UCVA, 20/30). Six weeks after surgery she was struck in the left eye by a dog’s paw. She noted immediate decrease in vision, pain, and photophobia. Evaluation revealed counting fingers visual acuity (pinhole, 20/60), 21 conjunctival injection, and a dehisced corneal flap. The temporal 30% of the underlying stromal bed was exposed. The remaining portion of the nasal-hinged flap exhibited significant folds and debris. Centrally, vertical paw marks were noted with fluorescein staining.

Four hours after injury, the flap was refloated with scraping and irrigation of the underlying stromal bed. A bandage contact lens was placed and a regimen of trimethoprim sulfate and polymyxin B sulfate combination eyedrops (Polytrim, Allergan, Inc.) every 2 hours and prednisolone acetate 1% twice daily was instituted for 2 weeks. The BSCVA was 20/30 2 days after repair and returned to 20/20 at 5 weeks after the injury (UCVA, 20/20). At the 2-month follow-up, no other complications were noted except scattered inert debris in the flap interface.

Patient 4

A 38-year-old man with a preoperative manifest refraction of 28.50 2 1.00 3 130 in the right eye and 27.50 2 0.50 3 070 in the left eye underwent uneventful bilateral LASIK for full correction of myopia and astigmatism (nasal-hinged flap). Two months later his left eye was struck by a snowball. He noted eye pain and decrease in vision. A BSCVA of 20/60 was noted, and slit-lamp evaluation revealed an edematous dehisced corneal flap. The inferotemporal quarter of the underlying stromal bed was exposed. The central portion of the flap, however, did not exhibit significant folds.

Within hours of the injury, the flap was refloated with scraping and irrigation of the underlying stromal bed, a bandage contact lens was placed, and a regimen of ofloxacin 0.3% (Ocuflox, Allergan) four times daily for 5 days and tobramycin and dexamethasone combination eyedrops (Alcon) four times daily for 3 weeks was instituted. Spectacle-corrected and uncorrected visual acuity returned to the preinjury level of 20/20 2 weeks after repair. Visual acuity was 20/15 at 21 months after repair. No apparent flap abnormalities were noted.

Figure 1. A, B, C: color photograph of a dislocated laser in situ keratomileusis flap 24 days after surgery secondary to a “finger flick” to the right eye (patient 2). Note the severe folds across the visual axis (B) as well as the coverage of the exposed stroma by corneal epithelium (C) within 10 hours of the injury. Melki et al z Late Dislocation of LASIK Flaps 2137

Results

A summary of the relevant clinical findings is presented in Table 1. All cases reported in this series resulted in recovery of pretrauma BSCVA. Epithelial ingrowth was noted only in one case after flap repair (patient 1). Diffuse lamellar keratitis occurred in another patient who responded well to topical and systemic steroid treatment (patient 2).

Discussion

Keratorefractive surgery may be associated with a variety of complications.6,7 This includes loss of BSCVA, reduction in the quality of vision (secondary to glare, halos, and diminished contrast sensitivity), and other optical aberrations.9,10 The susceptibility of eyes undergoing refractive surgery to injury after blunt trauma deserves close attention, especially because one of the most common motivations for undergoing the procedure is to engage in sporting activities without the need for corrective (and protective) glasses.

Several studies reported early flap dislocation and most seem to be related to early postoperative slippage. Gimbel et al11 reported an incidence of 1.2% in a study of 1000 eyes. Lin and Maloney12 noted an overall incidence of 2.0% in 1017 eyes. Stutling et al13 documented an incidence of 1.1% in 1062 eyes. In the aforementioned studies, there are no reports of loss of BSCVA more than two lines from flap dehiscence. A recent report by Lam et al14 described management of four cases of flap slippage within the first 24 hours after the surgery.

The cases reported in this article indicate that the corneal flap remains susceptible to trauma as late as 2 months after LASIK. This is consistent with anecdotal and published reports relating the ease of lifting a LASIK corneal flap more than 1 year after the initial procedure. Other supporting evidence can be found in a case of partial flap infolding related to a bird’s peak injury as late as 11 months after uneventful LASIK.15 Similarly, LASIK and automated lamellar keratectomy (ALK) cap displacement has been reported as an intraoperative event during retinal surgery as late as 5 months after the procedure.16,17 Thus an eventual return of the corneal surface to its preoperative integrity may take years in certain patients.

The exact mechanism of long-term adhesion remains unclear. Postulated mechanisms of early flap adherence include endothelial pumping, capillarity, fiber interlacing, intracorneal suction, intracorneal molecular attraction, and ionic bonding.18–20 The relative strengths of such forces early in the postoperative period as compared with later in the postoperative period have yet to be elucidated. Wound healing occurring at the stromal interface is believed to be less than that of the surrounding epithelial rim, as evidenced by the surgical experience during retreatment. More difficulty is noted when lifting the flap at the time of enhancement in younger patients, presumably because of a faster healing rate (personal observation). It is not known if other factors such as race, amount of refractive error corrected, or underlying systemic diseases could influence the rate and strength of flap healing.

A displaced or subluxed flap should be regarded as an emergency. Immediate repositioning is crucial to prevent formation of fixed folds and epithelial ingrowth. Fixed folds probably occur secondary to epithelial hyperplasia within the fold crevices, rendering flap stretching more difficult. Initially, the flap should be reflected and the interface examined carefully for epithelial cells and debris. If present, we recommend aggressive scraping before repositioning of the flap. Application of a contact lens for a few days may provide added protection from further displacement. If a flap is completely detached from its bed, repositioning in the proper orientation becomes fairly difficult after the loss of surgical landmarks.21 Improper repositioning of the flap can result in irregular astigmatism and loss of BSCVA. Suturing of the flap may be necessary at times.22 In the event of a lost flap, the epithelium is simply allowed to heal. This, however, may lead to significant flattening, depending on the diameter and the thickness of the flap, and may induce a hyperopic shift. Despite appropriate surgical techniques, complications such as diffuse lamellar keratitis and epithelial ingrowth may still occur, as seen in two of our patients. In conclusion, traumatic displacement of corneal flaps after LASIK is a possible postoperative complication occurring weeks to months after the procedure. As more cases of late trauma emerge, we will learn more about the fragility of the attachment of the flap to the underlying stroma. At the same time, reports of cases of ocular trauma where the flap remains intact would provide additional information regarding the strength of the flap adhesion. Discussion of this potential complication should be included in the informed consent process, especially for patients at greater risk for blunt ocular trauma from occupational hazards (such as military or law enforcement personnel) or sporting activities.

References

1. Pallikaris IG, Papatzanaki ME, Stathi EZ, et al. Laser in situ keratomileusis. Lasers Surg Med 1990;10:463– 8.
2. Pallikaris IG, Papatzanaki ME, Siganos DS, Tsilimbaris MK. Table 1. Traumatic Laser In Situ Keratomileusis Flap Dislocation: Summary of Injury Characteristics and Outcomes

Patient No.
Age/
Gender
Mechanism of Injury
Time after Laser In Situ
Keratomileusis
Hinge
Location
Uncorrected Visual
Acuity before Trauma
Time of Repair
Final Uncorrected Visual
Acuity and Best Spectaclecorrected
Visual Acuity
Loss of Best
Spectacle-corrected
Visual Acuity

1 28/M Basketball 10 days Nasal 20/20 ,6 hrs 20/30, 20/20 No
2 21/M Finger 24 days Superior 20/25 12 hrs 20/20, 20/20 No
3 61/F Dog’s paw 6 wks Nasal 20/30 ,6 hrs 20/20, 20/20 No
4 38/M Snowball 2 mos Nasal 20/20 ,6 hrs 20/20, 20/20 No
Ophthalmology Volume 107, Number 12, December 2000 2138

A corneal flap technique for laser in situ keratomileusis. Human studies. Arch Ophthalmol 1991;109:1699 –702.

3. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol 1983;96:710 –5.

4. McDonald MB, Frantz JM, Klyce SD, et al. Central photorefractive keratectomy for myopia. The blind eye study. Arch Ophthalmol 1990;108:799–808.

5. Azar DT, Farah SG. Laser in situ keratomileusis versus photorefractive keratectomy: an update on indications and safety [editorial; review]. Ophthalmology 1998;105:1357– 8. Comment on: Ophthalmology 1998;105:1512–22; discussion 1522–3.

6. Farah SG, Azar DT, Gurdal C, Wong J. Laser in situ keratomileusis: literature review of a developing technique. J Cataract Refract Surg 1998;24:989 –1006.

7. Wilson SE. LASIK: management of common complications. Cornea 1998;17:459–67.

8. Smith RJ, Maloney RK. Diffuse lamellar keratitis. A new syndrome in lamellar refractive surgery. Ophthalmology 1998;105:1721– 6.

9. Pallikaris IG. Quality of vision in refractive surgery. Barraquer Lecture 1997. J Refract Surg 1998;14:549 –58.

10. Melki SA, Proano CE, Azar DT. Optical disturbances and their management after myopic laser in situ keratomileusis [review]. Int Ophthalmol Clin 2000;40:45–56.

11. Gimbel HV, Penno EEA, van Westenbrugge JA, et al. Incidence and management of intraoperative and early postoperative complications in 1000 consecutive laser in situ keratomileusis cases. Ophthalmology 1998;105:1839–47; discussion 1847–8.

12. Lin RT, Maloney RK. Flap complications associated with lamellar refractive surgery. Am J Ophthalmol 1999;127:129– 36.

13. Stulting RD, Carr JD, Thompson KP, et al. Complications of laser in situ keratomileusis for the correction of myopia. Ophthalmology 1999;106:13–20.

14. Lam DSC, Leung ATS, Wu JT, et al. Management of severe flap wrinkling or dislodgment after laser in situ keratomileusis. J Cataract Refract Surg 1999;25:1441–7.

15. Leung ATS, Rao SK, Lam DSC. Traumatic partial unfolding of laser in situ keratomileusis flap with severe epithelial ingrowth. J Cataract Refract Surg 2000;26:135–9.

16. Chaudhry NA, Smiddy WE. Displacement of corneal cap during vitrectomy in a post-LASIK eye. Retina 1998;18:554–5.

17. Shakin EP, Fastenberg DM, Udell IJ, et al. Late dislocation of a corneal cap after automated lamellar keratoplasty and epithelial debridement for retinal surgery [letter]. Arch Ophthalmol 1996;114:1420.

18. Perez EP, Viramontes B, Schor P, Miller D. Factors affecting corneal strip stroma-to-stroma adhesion. J Refract Surg 1998; 14:460 –2.

19. Maurice DM, Monroe F. Cohesive strength of corneal lamellae. Exp Eye Res 1990;50:59–63.

20. Holly FJ. Biophysical aspects of epithelial adhesion to stroma. Invest Ophthalmol Vis Sci 1978;17:552–7.

21. Kim EK, Choe CM, Kang SJ, Kim HB. Management of detached lenticule after in situ keratomileusis. J Refract Surg 1996;12:175–9.

22. Pannu JS. Incidence and treatment of wrinkled corneal flap following LASIK [letter]. J Cataract Refract Surg 1997;23: 695–6. Comment on: J Cataract Refract Surg 1996;22:1391. Melki et al z Late Dislocation of LASIK Flaps 2139

LASIK Interface Fluid

Created on: Monday, October 20, 2014

Letters to the Editor

Nonarteritic anterior ischemic optic neuropathy (NAION) and age- and refraction-matched controls.”1

Our finding that cup-to-disc (C/D) ratio increases in NAION eyes was in agreement with the report by Contreras et al.2 The reason for a more evident increase in C/D ratio in our study is most likely the longer length of observation period after the onset of NAION (3 months vs. an average of 48 months).

Contreras et al question the reason why we found a statistically significant difference in disc size between control normal eyes and NAION fellow eyes, whereas there was no difference found in their study.2 Data not included in their original manuscript,2 such as the inclusion criteria regarding refraction and the average refraction of the subjects have been presented in the letter. We believe that it is not unusual that different studies bring some different outcomes because the study designs, participants, or measurement methods are not identical. However, some plausible reasons for the difference include: (1) difference in measurement devices for disc area: as Contreras points out, Heidelberg Retina Tomograph (HRT) measurements are known to have inter-examiner variability.3 However, one experienced examiner (HS) outlined all normal and NAION subjects in this study, and although intra-examiner variability cannot be fully ignored, we did not consider the variability large enough to affect our results.

Furthermore, HRT measurements are corrected by refractive error and corneal curvature which would theoretically yield more accurate results than OCT. Leung et al4 have reported that, in subjects with refraction between _8.0D and _4.0D, disc area measured by HRT were independent of axial length, whereas measurements with OCT correlated with axial length and tended to overestimate disc area in myopic eyes4; (2) race: racial difference in optic disc morphology has been reported5 and this could cause some discordance between the studies; (3) small number of patients: there were 23 NAION patients included in the study by Contreras et al2 and 31 NAION patients in our study. Due to the fairly rare nature of the disease, both studies had to be based on relatively small numbers of subjects, which may have lead to a limitation on statistical power in both studies.

We agree with the authors that one of the main risk factors for NAION appears to be the crowded optic nerve and small C/D ratio. However, smaller disc size as a risk factor for NAION has also been reported by several investigators other than us. Mansour et al6 found a significantly smaller disc area in NAION eyes compared with their fellow eyes with fundus photographs. Because disc area shows no or minimal changes after the onset of NAION, comparison of disc area between affected NAION eyes and control normal eyes should be also valid. A study by Jonas et al7 using fundus photography and a study by Nagai-Kusuhara et al8 using HRT have reported smaller disc size in NAION affected eyes compared with control normal eyes. Taking these previous reports and our results into account, whether small disc area itself is a risk factor for NAION remains controversial and further study, preferably with a larger number of subjects, is needed.

HITOMI SAITO, MD
ATSUO TOMIDOKORO, MD
MAKOTO ARAIE, MD
Tokyo, Japan

References

1. Saito H, Tomidokoro A, Tomita G, et al. Optic disc and peripapillary morphology in unilateral nonarteritic anterior ischemic optic neuropathy and age- and refraction-matched controls. Ophthalmology 2008;115:1585–90.

2. Contreras I, Rebolleda G, Noval S, Muñoz-Negrete FJ. Optic disc evaluation by optical coherence tomography in nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 2007;48:4087–92.

3. Iester M, Mikelberg FS, Courtwright P, et al. Interobserver variability of optic disk variables measured by confocal scanning laser tomography. Am J Ophthalmol 2001;132:57– 62.

4. Leung CK, Cheng AC, Chong KK, et al. Optic disc measurements in myopia with optical coherence tomography and confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 2007;48:3178–83.

5. Racette L, Boden C, Kleinhandler SL, et al. Differences in visual function and optic nerve structure between healthy eyes of blacks and whites. Arch Ophthalmol 2005;123:1547–53.

6. Mansour AM, Shoch D, Logani S. Optic disk size in ischemic optic neuropathy. Am J Ophthalmol 1988;106:587–9.

7. Jonas JB, Xu L. Optic disc morphology in eyes after nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci 1993;34:2260 –5.

8. Nagai-Kusuhara A, Nakamura M, Kanamori A, et al. Evaluation of optic nerve head configuration in various types of optic neuropathy with Heidelberg retina tomograph. Eye 2008;22:1154–60.

Dear Editor:
Dawson et al1 elegantly described the causes and pathogenesis of interface fluid syndrome in human eye bank corneas after LASIK. In their discussion, they distinguish diffuse lamellar keratitis from interface fluid syndrome as being associated with pain and limbal vascular injection. This is based on the description by Linebarger et al.2 In our experience, the majority of diffuse lamellar keratitis cases are painless and not associated with a red eye. It is important not to use these 2 factors to differentiate diffuse lamellar keratitis from interface fluid syndrome because it may lead to misdiagnosis.
SAMIR MELKI, MD, PHD
AMIT TODANI, MD
Boston, Massachusetts

References

1. Dawson DG, Schmack I, Holley GP, et al. Interface fluid syndrome in human eye bank corneas after LASIK: causes and pathogenesis. Ophthalmology 2007;114:1848 –59.

2. Linebarger EJ, Hardten DR, Lindstrom RL. Diffuse lamellar keratitis: identification and management. Int Ophthalmol Clin 2000;40:77– 86.
Letters to the Editor
815

LASIK Complications: Etiology, Management, and Prevention

Created on: Monday, October 20, 2014

LASIK Complications: Etiology, Management, and Prevention Samir A. Melki, MD, PhD, and Dimitri T. Azar, MD

Cornea and Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, and Schepens Eye Research Institute, Harvard Medical School, and Boston Cornea Center, Boston, Massachusetts, USA

Abstract.

Laser in situ keratomileusis (LASIK) is a rapidly evolving ophthalmic surgical procedure. Several anatomic and refractive complications have been identified. Anatomic complications include corneal flap abnormalities, epithelial ingrowth, and corneal ectasia. Refractive complications include unexpected refractive outcomes, irregular astigmatism, decentration, visual aberrations, and loss of vision. Infectious keratitis, dry eyes, and diffuse lamellar keratitis may also occur following LASIK. By examining the etiology, management, and prevention of these complications, the refractive surgeon may be able to improve visual outcomes and prevent vision-threatening problems. Reporting outcomes and mishaps of LASIK surgery will help refine our approach to the management of emerging complications.

Laser in situ keratomileusis (LASIK) is a relatively new ophthalmic procedure that represents a combination of previously used techniques in refractive surgery. It involves the use of a microkeratome to create a thin corneal flap followed by excimer laser ablation of the corneal stroma and repositioning of the flap.

Corneal lamellar dissection was first described in 1949 by Jose I. Barraquer as part of keratomileusis surgery, and it was later modified to become an integral component of automated lamellar keratoplasty.

Corneal excimer laser ablation has been used in photorefractive keratectomy (PRK) since 1983. Further advances in excimer laser technology and the development of safer microkeratomes have allowed lamellar refractive surgery to expand from being a procedure that is performed by few experts to one that the general ophthalmic surgeon is now undertaking.

LASIK is now a widely performed refractive procedure with an estimated 1.5 million annual procedures performed worldwide.

New complications are bound to occur when a surgical procedure is performed with increasing frequency. Unforeseen events might be encountered as patients with yet unidentified contraindications undergo the surgery.

Effective means have emerged to manage several LASIK complications, whereas others are still subject to investigation. A thorough understanding of the potential complications of LASIK and the various strategies to manage them is essential for surgeons performing the procedure. This helps in improving surgical outcomes and in offering patients comprehensive informed consent. In this article, we review the currently known complications of LASIK as well as various strategies to prevent and manage them.

I. Anatomic Complications
A. THIN/IRREGULAR/BUTTONHOLED FLAP

The incidence of thin flaps after LASIK has been reported to vary between 0.3% and 0.75% in the three major studies.

Lamellar flap creation in LASIK should be deeper than Bowman’s layer, sparing it from laser ablation. A flap is considered thin when the keratome cuts within or above the 12m-thick Bowman’s layer. This is recognized by a shiny reflex on the stromal surface. The use of pachymetry before and after lifting the flap may be helpful in recognizing this occurrence. A measurement below 60m is suspicious, as the thickness of the corneal epithelium is approximately 50m.

The definition of an irregular flap varies according to the study. It can refer to a bi-leveled flap, a bisected flap, or a flap with a notch.

Its incidence is lower than that of thin flaps (Table 1). This can lead to scarring and irregular astigmatism.

A buttonholed flap occurs when the microkeratome blade travels more superficially than intended and enters the epithelium/Bowman’s complex.

This can provide a channel for epithelial cells to infiltrate the flap–stroma interface. Buttonholes may be partial thickness if they transect Bowman’s layer or full thickness if they exit through the epithelium. The incidence of buttonholes ranges between 0.2% and 0.56% (Table 1). This was the most common complication resulting in loss of best corrected visual acuity (BCVA) among 1062 eyes studied by Stulting et al.

A flap buttonhole is more likely to occur when LASIK is performed on eyes with previous incisional keratotomy. Thompson described a flap hydrodissection technique to minimize incision separation in this situation.

His technique involves placing a 27-gauge cannula under the flap, near the hinge to hydrodissect the flap. Once the flap floats on a bed of balanced salt solution, it can be lifted with minimal stress to the radial keratotomy (RK) incisions.

1. Etiology

Steep corneas have been compared to tennis balls that would buckle centrally upon applanating pressure. This results in a central dimple missed by the blade, leading to a buttonhole. Another theory is that higher keratometric values offer increased resistance to cutting when applanated, leading to upward movement of the blade. Leung et al reported six cases of buttonholed flaps with a mean keratometric value of 44.20 D.

Instead of high keratometric values, they believe that a lack of synchronization between translational flat keratome movement and oscillatory blade movement results in forward displacement of corneal tissue and stepped, thinned, or buttonholed flaps. Flat corneas may result in a thin and/or small flap, as they could be below the adequate cutting plane in certain locations locations (Table 2).

Irregular flaps (abnormal shape/diameter) or buttonholes with or without abnormal thickness may result from damaged microkeratome blades, irregular oscillation speed, or poor suction. The latter is more likely to occur in the setting of deep set eyes or small diameter corneas with inadequate suction ring placement or conjunctival incarceration in the suction port.

LASIK COMPLICATIONS

Blade positioning in the microkeratome and the preset space for the blade in the microkeratome may affect flap thickness in the absence of irregular flap shape. Blade damage may happen either during manufacturing or at the time of usage.

Another possible risk factor for flap buttonhole occurrence may be previous ocular surgery, as suggested by Stulting et al. However, this did not reach statistical significance (P 0.09).

2. Management

The safest way to proceed when a thin, irregular, or buttonholed flap is encountered is to reposition the flap and abort the procedure. A deeper flap may be recut (20–60 _ m deeper) approximately 10–12 weeks later with a different microkeratome or a larger diameter flap size. While some advocate proceeding with scraping the epithelium and performing a PRK laser ablation, this approach may not be feasible in higher myopes due to the appearance of subepithelial haze.

Kapadia and Wilson advocate using a no-touch transepithelial PRK within 2 weeks of the initial irregular cut to prevent irregular astigmatism formation from the uneven ablation profile resulting from any late scar formation.

The recommendation to perform PRK over a LASIK buttonholed flap to avoid scar formation is contradictory to the common belief that haze occurs following PRK treatment on top of a LASIK flap. A transepithelial PRK may prevent the development of a buttonhole-related scar. This is different from PRK after a normal LASIK flap because the scarring in the latter situation would not occur in the absence of PRK.

3. Prevention

The incidence of thin, irregular, and perforated flaps may be reduced if the surgeon ensures adequate suction, inspects the blades, adjusts the plate thickness according to corneal curvature, and pays attention to the following guidelines:
1. Avoid cutting the flap if the intraocular pressure (IOP) is low due to low suction. A pressure above 80 mm Hg may be essential for safest flap creation. Measurement is probably most valuable with a pneumotonometer, as other means may provide imprecise readings at times.

Care should be taken to avoid pseudosuction, often caused by conjunctival clogging of the suction port, which could lead to discrepancy between the intraocular pressure and the suction pressure recorded on the microkeratome vacuum console.

2. Set the microkeratome to a deeper cutting depth if keratometry readings show evidence of a steep cornea, assuming that the amount of intended myopic correction to be treated allows such modification. Most refractive surgeons follow such an approach, setting the cut-off point at 46–48 D, although no definitive supportive study exists in the literature.

3. Use larger suction rings in flat corneas to prevent small flaps.

4. Inspect the microkeratome blade under the operating microscope before engaging it in the suction ring in order to rule out manufacturing or other preoperative damage to the blade. Keep the microkeratome away from hard surfaces after assembly to avoid subsequent blade damage.

5. Inspect previous keratotomy incisions to ensure adequate healing and lack of epithelial plugs prior to proceeding with LASIK. This can prevent intraoperative separation of incisions.

B. INCOMPLETE FLAP

Incomplete
flaps are created when the microkeratome blade comes to a halt prior to reaching the intended location of the hinge. Visual aberrations are more likely to occur when the created hinge results in scarring in proximity to the visual axis (Fig. 2). The incidence of this complication reported in large series ranges between 0.3% and 1.2% (Table 1).

1. Etiology

Microkeratome jamming due to either electrical failure or mechanical obstacles may be the most common cause of incomplete flaps. Lashes, drape, loose epithelium, and precipitated salt from the irrigating solution have been recognized as possible impediments to smooth keratome head progression. Incomplete flaps also occur when the gear advancement mechanism jams or is inadequate.

Loss of adequate suction in some microkeratomes may lead to automatic abortion of the dissection or force the surgeon to premature arrest of the microkeratome head.

2. Management

Unless enough space exists for ablation, incomplete flaps are best managed by immediate repositioning and postponing the procedure. Resuming forward cutting after a stop may result in an irregular stromal bed and irregular astigmatism. It is advisable to achieve a deeper and more peripheral cut during the retreatment. If the created hinge is beyond the visual axis, some surgeons may instinctively consider manually extending the dissection with a blade. Caution is advised when attempting such a maneuver due to the risks of uneven bed creation and flap buttonhole formation. When the laser ablation is performed, the flap should be protected from laser exposure. This may be more important in hyperopic treatments, given the larger diameter ablations.

3. Prevention

Microkeratome jamming can be minimized by meticulous cleaning of its components and by inspection of its electrical connections. The manufacturer’s recommendations for cleaning procedures and solutions may differ over time as more is learned about a particular machine. A clear cutting path for the microkeratome can be achieved through adequate draping (to prevent lashes from getting into the cutting field), adjustable eye speculae (to provide as wide of an interpalpebral opening as tolerated by the patient) and gentle lifting of the globe after vacuum activation (to provide better exposure and unhindered gear progression). In addition, variable tilting of the suction ring and eye can be utilized to obtain a clear cutting path. This should be followed by the IOP measurement step to rule out inadvertent loss of suction pressure when lifting the globe.

Deep orbits may represent a challenge, as some keratome heads may not fit and may be stopped by the eyelid speculum. We believe that the risks and discomfort associated with more invasive techniques, such as retrobulbar saline injections and lateral canthotomies, may not be justified, given the elective nature of the procedure. Poor or loss of suction can be prevented through measures discussed in section IA.

C. DISLODGED FLAP

A dislodged flap is an emergency. It should be repositioned as soon as possible to prevent infection, fixed folds, and epithelial ingrowth. This displacement can occur as late as many months after the procedure. The incidence of perioperative flap dislocation has been reported to vary between 1.1% and 2.0% in large series.

The relative high rate of dislodged flaps after LASIK in earlier publications has prompted many investigators to refine their techniques of flap repositioning with resultant positive impact on lowering the incidence of this complication.

1. Etiology

Mechanical displacement by lid action is the main factor in the early period, especially if the ocular surface is dry. This may follow eyelid rubbing or squeezing. Larger diameter and thinner flaps are more prone to be displaced, especially if the hinge is small. The flap remains vulnerable to traumatic displacement several months after surgery.

Two reports described dislocation of a LASIK flap during vitrectomy surgery. LASIK corneal flaps can be lifted for retreatment even later than 12 months after the primary procedure. This is in agreement with histological studies showing minimal healing at the stromal interface after LASIK.

2. Management

The flap should first be reflected and the interface (stromal bed and stromal aspect of the flap) carefully examined for epithelial cells or other debris. It should be aggressively scraped prior to repositioning the flap. A contact lens can be applied to provide added protection from further displacement and to protect the flap from eyelid movement. Stromal scarring in an incomplete flap after an aborted LASIK.

LASIK COMPLICATIONS

Tecniques described below to flatten any associated folds should be used. This is important to prevent epithelial cell migration from the healing periphery toward the flap interface under the tented folds.

3. Prevention

Prevention of dislodged flaps rests mainly on the use of protective measures such as the superiorly hinged flaps, which were designed to circumvent upper flap edge displacement through blinking.

It is not clear yet whether they have achieved their intended purpose. Other preventive steps include applying a contact lens after the procedure, lid taping, and encouraging eyelid closure in the first few hours following surgery. We advise our patients not to apply eyedrops soon after surgery to avoid any early mechanical disturbances.

For 1–3 weeks after the procedure, a protective shield can be worn when sleeping to minimize traumatic displacement through unintentional rubbing or mechanical pressure on the eyelids. Patients involved in contact sports and similar activities should be thoroughly counseled about the added risk of late flap displacement with LASIK. PRK might be a better alternative, if judged feasible, in these situations.

D. FREE CAP

If the cap cannot be retrieved, attempts at fashioning a lamellar flap from a donor cap should not be attempted as a primary procedure. The corneal epithelium is allowed to heal as in PRK with possibly a more profound central applanation effect. The excimer laser treatment should be aborted and retreatment deferred until refractive stability is achieved.

3. Prevention

The same measures described to prevent thin and small flaps also will help avoid a free cap. We believe that presurgical fiducial marking may facilitate proper flap orientation during cap repositioning and avoid induced irregular astigmatism.

E. FLAP FOLDS

Flap folds can induce irregular astigmatism with optical aberrations and loss of BCVA, especially if they involve the visual axis.

Macrofolds are easily seen by slit-lamp examination and represent fullthickness flap tenting in a linear fashion. On the other hand, microfolds within the flap itself may represent wrinkles in Bowman’s layer or in the epithelial basement membrane. They are easily visualized as negative staining lines with sodium fluores- Fig. 3. Dislocation of a corneal flap 3 weeks post-LASIK secondary to trauma by finger to the eye. (Courtesy of Nada S. Jabbur, MD).

Carpel et al described 5 types of folds and striae in LASIK flaps. While confocal microscopy reveals microfolds at the Bowman’s layer in 97% of cases, the incidence of folds requiring intervention ranges between 0.2% and 1.5%.

It is not clear why some folds may adversely affect vision while others with similar appearance may be asymptomatic.

1. Etiology

Flap folds result from uneven alignment of the flap edge and the peripheral epithelial ring. Thinner and larger flaps tend to shift more readily with resultant surface wrinkling. Uneven sponge smoothing can result in radial (with centrifugal movement) or circumferential folds (with centripetal movement). A higher incidence of flap folds is usually found in higher myopes and hyperopes and is sometimes unavoidable. This is due to the altered central convexity and stromal support resulting in flap redundancy that may be quite difficult to flatten. The latter is referred to as the tenting effect.

2. Management

The management of flap folds ranges from stroking the flap with a moist microsponge at the slitlamp to simple lifting and refloating of the flap and to placement of sutures to stretch a recalcitrant flap into position.

It is likely that the earlier a flap is attended to, the higher the chances of quick resolution.

Fixed folds probably occur when epithelial hyperplasia has time to form in the crevices formed by the folds. Flattening should aim toward an even distribution of forces applied to the flap.

This can be performed with methylcellulose sponges or their equivalent. Instruments such as the Pineda LASIK Flap Iron (Asico, Westmont, IL) can also be used to flatten isolated flaps at the slit-lamp or under the operating microscope by gently pressing on them. Recalcitrant folds may respond well to placement of running antitorque sutures at the flap edge.

However, this may result in significant astigmatism. Another strategy is to make superficial epithelial incisions, phototherapeutic keratectomy (PTK), or frank epithelial debridement over the wrinkled area. This may relieve contractures that occur secondary to epithelial hyperplasia in longer standing folds. Probst et al described a technique using the red reflex as a way to better detect mild irregularities.

Other reported strategies include hydrating the flap with hypotonic saline (60–80%) or deionized water,153,188 which may facilitate flattening. In extreme cases, removal of the corneal cap has been reported to be successful.138 Suturing of the flap may be the procedure of choice for recalcitrant cases that do not respond to the measures listed here. The sutures, however, should be removed in the first few days after surgery, especially if suture-induced folds are evident postoperatively. We have noted few instances where mere flap ironing will result in refractive error shift of more than one diopter.

3. Prevention

Preplaced surgical landmarks straddling the flap edge permit accurate repositioning of the flap in the immediate operative and postoperative period. Examination at the slit-lamp 20 min after the procedure is useful to ensure adequate flap positioning. Care should be taken to ensure even distribution of the gap “gutter” between the flap edge and the peripheral epithelial ring. This is noted after the procedure and usually disappears by the first postoperative day. This gap is probably due to biomechanical retraction of the collagen lamellae or to flap dehydration and subsequent retraction. The dehydration effect alone may not explain the gutter formation as the gutter can be seen immediately after the cut where dehydration may not have yet occurred. Contraction of intercellular adhesion complexes secondary to mechanical trauma might also contribute to the retraction of the flap. There has been no histologic confirmation of these theories.

Placing a wet microsponge on the stromal aspect of the flap during long ablations might minimize the dehydration effect. However, this may introduce fibrils and debris in the interface. We currently favor spreading 1–2 drops of fluid on the stromal aspect of the reflected flap after lifting. Other surgeons prefer folding the flap while performing the laser ablation.

F. EPITHELIAL IMPLANTATION AND INGROWTH

Implantation of epithelial cells in the interface occurs either due to seeding during surgery or migration under the flap.88 Epithelial cells can be seen as tongues or pearls (Fig. 4). Connection to the outside epithelium might be conspicuous or undetectable at the slit-lamp. Most isolated nests of cells will disappear without consequences. More concerning is epithelial ingrowth that is contiguous with the flap edge. This can progress to involve the visual axis with irregular astigmatism and possible overlying flap melting.40 The epithelial cells at the interface may block aqueous diffusion, which may compromise the nutrition of the flap and result in corneal melting. The migrating epithelial cells may also produce proteolytic enzymes that may further contribute to stromal melting of the flap. Epithelial growth at the interface may be more common after enhancement procedures, as the lifting of the flap can induce adjacent epithelial abrasions with increased cell proliferation.

LASIK COMPLICATIONS

1. Etiology

Helena88 described four mechanisms by which epithelial cells could reach the lamellar interface. These include mechanical dragging by the keratome blade during keratectomy, backflow during irrigation carrying floating epithelial cells, outgrowth from epithelial plugs in eyes with previous incisional keratotomy, and ingrowth at the junction of the epithelium and keratotomy. The latter is believed to be the most frequent cause of epithelial ingrowth. Other mechanisms include:

1. Implantation of epithelial cells when the interface is manipulated with instruments that touch the surrounding epithelium.
2. Cell migration under a fold extending to the flap edge. This is more likely to occur if an epithelial defect is induced at the edge of the flap during the procedure, leading to greater mitotic activity.
3. Buttonholed flap epithelial infiltration at the edges of the perforation.278 Wang et al reported an incidence of 0.92% in a cohort of 3786 eyes that underwent primary LASIK.279 The incidence after enhancement was 1.7% (480 eyes). The authors hypothesize that epithelial ingrowth is secondary to postoperative invasion under the flap by surface epithelial cells rather than intraoperative implantation of epithelial cells.

2. Management

Epithelial cells under the LASIK flap should be managed aggressively if they progress toward the visual axis or induce stromal melting.150 The flap is lifted, the stromal bed and the flap undersurface are thoroughly irrigated and scraped, and the flap is repositioned. 278 Epithelial cell debridement can be achieved mechanically with a #15 Bard-Parker blade or with dedicated instruments such as the Yaghouti LASIK Polisher (Asico, Westmont, IL), or by using excimer laser bursts in phototherapeutic keratectomy (PTK) mode.16,88,260 Haw et al successfully treated aggressive epithelial ingrowth in four eyes with 50% ethanol.85 Nonprogressive isolated epithelial cells should be monitored. Hyperopic shift is an early indicator of possible underlying stromal melt. This may result in irregular astigmatism and loss of BCVA.

3. Prevention

Close inspection for epithelial ingrowth is essential for patients with surgically induced epithelial defects, especially when the defects are adjacent to the flap edge. Considering PRK rather than LASIK in patients with a history of poorly adherent epithelium (e.g., history of recurrent erosions) may help reduce epithelial defect formation.49 Other preventive measures include dedicating instruments for interface manipulation that do not come in contact with the surrounding epithelium. Similarly, meticulous attention should be paid to avoid flap folds, especially those extending toward the periphery, providing a conduit for cell infiltration. It is reasonable to speculate that the introduction of epithelial cells in the interface during LASIK enhancement may be significantly minimized by lifting the flap edge with a dedicated forceps rather than extensive edge dissection around the flap circumference. Alternatively, the gutter can be dissected with a Sinskey hook prior to separating the stromal lamellae. This may prevent large epithelial tears. Walker et al advocate the use of an aspirating lid speculum and a bandage contact lens for the first day after surgery during LASIK and LASIK enhancement.

G. INTERFACE DEBRIS

Interface debris should be distinguished from inflammatory or infectious reactions. This distinction may be difficult at times. An in vivo confocal microscopy study revealed corneal flap interface debris in 100% of 62 eyes that had undergone myopic LASIK. As a rule, debris is usually inert with no progression or deleterious effects on vision unless present in large quantities. Nevertheless, it must be kept in mind that some patients might be more susceptible than others and may present with an inflammatory response to a variety of debris.

1. Etiology

Several possible sources of debris have been identified at the LASIK flap interface.270 These include metallic fragments from blade shattering during the dissection,57 oil material from the microkeratome, meibomian gland secretions, powder from gloves,252 air bubbles, central interface opacification of unknown etiology,68 and lint fibers. Lint fibers settle on the stromal bed prior to flap repositioning. They can be released from clothes, eye patches used to cover the unoperated eye, and gauze close to the operative field. Hirst93 reported brown interface deposits from dry methylcellulose sponges used to protect the hinge during laser ablation.

2. Management

If an inflammatory reaction is suspected secondary to interface debris, the flap should be lifted and copious irrigation applied. We examine our patients 20 min after the procedure and proceed to early flap lifting and irrigation if debris or fibers are noted.

3. Prevention

Lint fibers may be minimized by the use of scrub suits by the surgical team and by having the patient wear a scrub-like cover over their clothes to minimize floating fibers in the atmosphere. Moistening any gauze material in the surgical field will achieve a similar result. Other measures include using powder- free gloves, draping the lashes, and applying a fibrocellulose ring (LASIK Eye Drain [Chayet], Visitec, FL) around the limbus to provide a barrier from surrounding ocular secretions. Oblique illumination under the operating microscope can reveal very small fibrils and other debris in the interface after flap repositioning, which can be removed with generous interface irrigation.

H. EPITHELIAL DEFECT

On postoperative day 1, dilute sodium fluorescein can aid in detecting epithelial defects that might have occurred during or after the procedure. Many patients will demonstrate mild staining at the edge of the flap. Larger defects are more worrisome, especially those with a connection to the flap edge. The incidence of epithelial defects with LASIK was reported to be around 5%.51 As mentioned above, the proliferating epithelial cells might migrate under the flap edge. Associated inflammation can also lead to melting of the surrounding flap tissue. We and others have observed an increased risk of diffuse lamellar keratitis in patients with epithelial defects.

1. Etiology

Patients with a history of recurrent erosions or anterior basement membrane dystrophy (ABMD) are at higher risk of developing epithelial abrasions, especially with LASIK, and would probably be better PRK candidates. In fact, surface excimer laser ablation is used to treat patients with recurrent erosion syndrome.

2. Management

If an epithelial defect is noted intraoperatively, a higher index of suspicion for epithelial ingrowth should be maintained. An attempt at repositioning the loose epithelium should be performed. Alternatively, the epithelium can be gently debrided and a contact lens applied. These measures help in pain control as well as improving flap adherence and preventing epithelial cell ingrowth. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) may also be useful to ease the associated discomfort, but they may be associated with the induction of sterile infiltrates.

3. Prevention

Candidates for LASIK surgery should be questioned for prior history or symptoms of recurrent erosion syndrome. Slit-lamp examination should include careful inspection of the epithelial surface for signs of ABMD. Even when the corneal surface appears clear, negative or asymmetric fluorescein staining should alert the observer to an abnormality in corneal surface integrity. Some investigators recommend touching the corneal epithelium at the slitlamp with a microsponge applicator in patients with suspected loose epithelium. If movable epithelium is noted, PRK may be a more appropriate procedure.

I. CORNEAL PERFORATION

This devastating complication occurs mainly as a result of faulty microkeratome assembly. A handful of studies in the literature report cases of anterior chamber penetration during lamellar dissection10,11,73 or through laser ablation.100,111 The original ACS microkeratome (Bausch & Lomb Surgical, Rochester, NY) keratome models require the placement of a thickness foot-plate to determine the depth of dissection. If it is left out, a full-thickness corneal incision with serious damage to anterior segment structures could ensue. This should be managed as any traumatic ruptured globe situation. Meticulous adherence to the instructions of keratome assembly to prevent this catastrophic event cannot be emphasized enough. In one published case, a thin preexisting keratoconic cornea was suspected as the etiology for the full-thickness laser ablation.

J. CORNEAL ECTASIA

Corneal ectasia is a devastating complication as it induces a keratoconus-like condition with all its attendant complications. Only a relatively small number of cases have been reported in the literature to date.Initially, patients may be managed with hard contact lens wear but many progress to require penetrating keratoplasty. The true incidence of this iatrogenic complication might not emerge until longer term follow-up studies are conducted. The safe limit of residual stromal bed thickness after refractive surgery remains subject to speculation. The current consensus is a minimum of 250m, while Barraquer has recommended a minimal thickness of 300m of stress-bearing corneal stroma.

1. Etiology

Although a thin stromal bed is suspected to be the culprit in all reported cases of corneal ectasia after LASIK, none of the cases had a reliable measurement of residual bed thickness. Other factors, such as late stromal melting, cannot be ruled out at this time. One report showed no underlying inflammation in an excised ectatic corneal button after LASIK, suggesting biomechanical corneal weakening as the cause of the ectasia. Patients who develop postoperative ectasia can be detected by conventional videokeratography or through slit-lamp findings. Orbscan technology (Bausch and Lomb, Rochester, NY) can image posterior corneal curvature and total corneal pachymetry, which may be useful in following patients after LASIK.

2. Prevention

Safeguarding 250m of stromal bed is the current standard of care to prevent this complication. The surgeon should, however, keep a high index of suspicion as this value could be proven inadequate when longer follow-up on better documented cases become available. Preoperatively, keratoconus suspects, may be detected by characteristic patterns on videokeratography such as inferior corneal steepening, and should be approached cautiously. Amoils et al recommend a preoperative corneal thickness of 500m, and Seiler believes that it is safer to use a percentage of the corneal thickness as a minimal residual stromal thickness rather than an absolute number. Orbscan topography can provide information on posterior corneal curvature before and after refractive surgery, as well as detailed pachymetry that can help detect forme fruste keratoconus. A combination of clinical and topographic criteria is currently used at the Massachusetts Eye and Ear Infirmary, which serves as the basis for diagnosing keratoconus and keratoconus suspects . High-frequency ultrasound corneal analysis may be able to resolve flap from residual stromal bed with a 2-micron precision. Similarly, optical coherence tomography may have some promise in providing detailed analysis of flap and stromal bed thickness postoperatively.These modalities could turn out to be useful tools in the analysis of cases with poor postoperative optical quality or unexpected ectasia.

Calculations should be made prior to surgery to determine if a safe corneal bed thickness can be achieved. It must be stressed that there can be considerable variation in the actual flap thickness, compared to the expected one (based on microkeratome manufacturer’s specifications).In high refractive error cases, pachymetry should be performed on the stromal bed after the flap is lifted. By factoring the amount of tissue removed by the laser, a more accurate assessment of residual bed thickness can be made. This can guide the surgeon later if enhancement is necessary. Establishing a registry of corneal ectasia cases could help collect much needed information on this concerning aspect of LASIK and prevent a late discovery of a potentially disastrous longterm outcome of the procedure. A safe approach would involve Orbscan videokeratography prior to enhancement ablations to differentiate between early ectasia versus regression due to stromal or epithelial remodeling.

II. Refractive Complications
A. CENTRAL ISLANDS

Patients with topographic central islands often report visual fluctuations, ghost images, and monocular diplopia. Both uncorrected and best-corrected vision may be affected. Wilson suspected that the incidence of central islands after LASIK is higher than that after PRK, but no data have been reported. Laser manufacturers have modified their software to allow additional central pulses, which appears to have minimized the incidence of this complication. Other factors, such as pattern of laser ablation and surgical technique, may also influence the development of central islands.

1. Etiology

No consensus exists about the true etiology of central islands after PRK or LASIK. They are thought to result from shielding of the central stroma by pulverized tissue plume or central collection of fluid as the ablation is performed. Degradation of the laser optics has also been implicated in causing central islands.

2. Management

Central islands in LASIK have less tendency to spontaneously resolve than in PRK. This is probably due to minimal epithelial remodeling after LASIK. Central island treatment is usually based on the last topography performed, as described by Rachid et al. Manche et al1 also described a technique to treat central islands after refractive surgery but cautioned against associated hyperopic shifts. Successful treatment protocols after PRK may not apply to LASIK patients.

Custom ablations solely based on videokeratography data might erroneously treat areas of overlying epithelial hyperplasia over areas of stromal depression, not achieving the intended stromal smoothness. In recalcitrant cases, hard contact lenses may be the only currently available means of regaining lost visual acuity and relieving visual aberrations.

3. Prevention

Both the Summit company (APEX, Waltham, MA) and the VISX Laser company (VISX, Sunnyvale, CA) have developed anti-island software for additional central ablation. There is growing evidence of minimal occurrence of this complication with scanningslit beam and flying spot lasers. Some surgeons believe that corneal fluid collects on the surface of the central stroma and suggest wiping the bed surface with a sponge or spatula every 40 to 50 laser bursts. Others only dry the surface when moisture is visible. To date, there are no studies to evaluate the benefit of these techniques.

B. DECENTRATION

Corneal surgical procedures should always be centered over the pupil. Astigmatism due to decentration of the ablation is probably the most difficult problem to correct. Although patient fixation might be more difficult under a dissected flap, Pallikaris et al reported similar centration between their LASIK and PRK groups.206 Decentration results in an uneven ablation area with the flatter treatment zone shifted peripherally, leaving the central area of the ablation zone with a higher corneal surface power difference. Consequently, the area of greatest flattening of tangential curvature is shifted away from the center of the ablation zone, resulting in uneven and undercorrected corneal surface over the pupillary axis. Decentration that involves laser application to the stromal side of the flap results in significant asymmetric flattening. This is translated into irregular astigmatism, causing glare, monocular diplopia, and halos. Decentration is best measured with tangential topography. Decentration not exceeding 0.3 mm is rarely visually significant.

1. Etiology

Decentration of excimer laser ablation may occur secondary to either treatment displacement (shift) or intraoperative drift. Shift refers to a decentered treatment throughout the ablation. This can occur due to poor fixation or surgeon’s error. Drift occurs when the eye moves involuntarily during treatment or when the surgeon attempts to correct apparent decentration during treatment. Azar and Yeh have shown that the visual outcomes of patients with treatment displacement were better than those with intraoperative drift.

2. Management

Theoretically, the flap can be lifted, and the patient retreated with decentration of the treatment in the opposite direction to the previous ablation, using a wide optical zone. This is more easily performed with decentered PRK after transepithelial PTK with the epithelium being used as a masking agent over the already ablated area. Such a technique yields quite satisfactory results. It is not clear whether other masking agents at the LASIK interface would be as effective. Currently developed modalities, such as wavefront or topography-guided ablations, may yield more accurate results. Miotics can be tried to constrict the pupillary axis to the central smooth ablation and minimize optical aberrations. This might be more useful if both the decentration and the pupil shift with pharmacological miosis are superonasal. A hard contact lens can alleviate the symptoms by neutralizing optical aberrations resulting from irregular astigmatism.

3. Prevention

The risk of decentration can be minimized by performing the ablation under the lowest illumination possible to improve the patient fixation. Meticulous attention should be directed toward adequate centration from the onset of ablation. Recentration should be avoided when possible, in view of the drift effect on visual outcome. When recentration is attempted early in the procedure, the drift effect might not be as significant as that in the late stages of the ablation. Continuous verbal encouragement can help patients maintain fixation, especially during deep ablations.

Lasers with a pupillary-tracking ability are designed to prevent decentered ablations (drift).17,264 The effects of the microsaccades of the eye may be abolished, in principle, with these lasers. Miotics or high illumination are preferably avoided. They can shift the pupil superonasally, resulting in decentered ablations that are apparent only after surgery.

C. OVER- AND UNDER-CORRECTION

Variations in corneal healing, atmospheric pressure, humidity, and ambient temperature are among the many factors that contribute to the relative unpredictability of refractive surgical procedures. Some patients develop unintentional refractive overor under-corrections following LASIK, often affecting uncorrected visual acuity (UCVA). Myopic patients with a hyperopic result can suffer from quite unsatisfactory UCVA both at near and distance, especially if they belong to the presbyopic age group.

1. Etiology

Surgical procedures based on inaccurate refractions could result in significant residual or induced postoperative refractive errors. These include erroneous refraction, relying on non-cycloplegic refraction in an accommodating patient, and wrong information input into the laser secondary to human error. Failing to reexamine a contact lens wearer until a stable and reproducible refraction is obtained may result in unexpected refractive outcomes. In the case of rigid or gas permeable contact lenses, it can take 5 weeks to achieve preoperative refractive stability. Planocylindrical corrections have been associated with a higher incidence of over-correction. This is probably due to the fact that flattening of the intended steep meridian is accompanied by the unintentional flattening of the flat meridian (but to a lesser degree).

2. Management

Over- or under-correction can be corrected by lifting the flap (even months after the surgery) and applying additional laser ablation. Multiple procedures have been developed to correct hyperopia, whether induced or native. The FDA-approved treatments in the USA at the time of this publication are hyperopic PRK and laser thermo-keratoplasty (LTK). The latter is approved only for the temporary reduction of low levels of hyperopia. In a study of 13 overcorrected eyes after LASIK, Ismail reported a mean increase of 4.1 D in central keratometric power with use of the noncontact holmuim:YAG (Ho:YAG) LTK (18-month follow-up). Goggin et al treated 11 eyes with induced hyperopia after myopic PRK and reported satisfactory results as late as 1 year after surgery. As mentioned above, a high level of suspicion for keractesia disguised as myopic regression is vital, especially in patients with higher levels of initial corneal ablation.

3. Prevention

Accurate preoperative manifest and cycloplegic refractions are essential for reliable assessment of the patient’s refractive error. Reexamination of patients with fluctuating or unstable refractions prior to performing primary or secondary treatments may help avoid unexpected outcomes. We advocate a conservative approach in treating plano-cylindrical errors, erring on the side of under-correction.

D. RESIDUAL/INDUCED ASTIGMATISM

Correction of preoperative astigmatism can result in incomplete resolution, worsening and/or shift in axis. Spherical corrections can also lead to postoperative cylindrical refractive errors.

1. Etiology

Inaccurate refraction and contact lens-induced corneal warpage can easily lead to unexpected cylindrical residual or induced errors. Similar errors may occur following rotational ocular shift or drift during laser ablation. A axis error results in loss of 50% of the cylindrical correction, while a axis error results in no change of the magnitude of the cylinder (but with a rotation in the axis of astigmatism). Other factors, such as cyclotorsion between the sitting and supine position and the lamellar cut, may contribute to astigmatism alteration.

2. Management

Depending on the amount of residual refractive error, an enhancement procedure can be contemplated. Some currently available software programs do not allow treatment of plano-cylindrical errors. Maneuvers to bypass the built-in software could lead to unexpected over-correction.

3. Prevention

As noted above, meticulous refractions and ensuring refractive stability improve the predictability of refractive outcomes. Marking of the cardinal meridians at the slit-lamp prior to the procedure and constant monitoring during the ablation to ensure proper globe orientation may help reduce the effect of ocular rotation.

E. REGRESSION

Regression seems to be reported with higher frequency after high-myopia correction and after hyperopic LASIK. Often the underlying stromal bed is too thin to permit additional laser ablation. Regression may be differentiated from natural progression of refractive error by analyzing difference maps by corneal topography. Hyperopic treatment has been plagued by regression due to peripheral epithelial hyperplasia counteracting the laser-induced corneal steepness. It must be noted that, in principle, an over-corrected myopic treatment may require less peripheral and hyperopic ablation for a specific desired long-term outcome than primary hyperopic treatments. This is because of the associated amelioration of the steep zone at the junction of the treated and untreated areas.

1. Etiology

Postoperative epithelial or subepithelial and stromal hyperplasia leading to postoperative corneal steepening have been implicated in the etiology of postoperative refractive regression. It is not clear yet which layer plays a more prominent role in this postoperative complication. Occasionally, patients whose refractive error is erroneously believed to have reached the plateau stage prior to the surgery will exhibit progressive refractive change even months after the procedure. This is more likely to occur in younger patients.

2. Management

It is not clear if regression after LASIK is as amenable to pharmacological manipulation as in PRK. There are no data to confirm the benefits of topical steroids for corneal steepening secondary to the healing response. Additional laser ablation must be guided by careful and conservative calculations of residual stromal bed thickness. Guell suggested treating regression after LASIK with intraepithelial PRK. The temptation of not disappointing a demanding patient should be tempered by the increased risk of excessive corneal thinning (see section IIJ). Sophisticated instruments, such as the very high-frequency ultrasound, might be able to accurately measure residual stromal thickness and better guide the surgeon in deciding whether or not to perform additional surgery.

3. Prevention

Development of surgeon-specific nomograms might allow better tailoring of ablations for higher correction. The variety of factors that influence the outcome (age, corneal hydration, ambient temperature, etc.) makes this task relatively imprecise.

F. HALOS AND GLARE

Visual aberrations have plagued most refractive procedures, sometimes permanently affecting the quality of vision. It is not clear to what extent pupil size plays a role in the pathogenesis of glare and halos. Generally, these symptoms abate over time. It is not clear if this is due to resolution of an underlying anatomic irregularity or to patient’s adaptation. A small subset of patients report no significant improvement and can be substantially incapacitated under various lighting situations, such as night driving, despite good uncorrected visual acuity at high contrast levels. This may be due to loss of contrast sensitivity and may pose a hazard for night driving.

1. Etiology

There is growing evidence that main reasons for higher order aberrations resulting in glare and halos are subclinical decentration (less than 1.0 mm) and/or wide-area laser ablation profiles solely based on Munnerlyn’s recommendation. Similarly, when pupils dilate to a diameter larger than the optical treatment zone, rays of light refracted by the untreated peripheral cornea are not focused at the same position as the central rays and result in blur circles (negative clearance phenomenon). These symptoms are more pronounced after treatment of cylindrical errors due to the oval shape of laser treatment with inherently smaller optical zone in the steep meridian. In addition, correction of higher refractive errors is associated with increased aberrations due to the larger refractive differential between the ablated and the intact cornea. Irregular astigmatism due to flap folds, topographic abnormalities, or simply residual myopia can also result in these symptoms. Other contributing factors include dry eyes and irregular epithelial surface.

2. Management

Optical aberrations after refractive surgery may be significantly reduced through enlargement of the ablation zone by means of the currently developed wavefront- or topography-guided lasers. Currently, conservative management, such as mild miotics, is prescribed, which can help for night activities, especially driving. Leaving the car dome’s light on when driving at night has also been reported to improve symptoms through pupillary constriction. Anecdotal evidence suggests a reduction in mesopic pupillary dilation with topical brimonidine (Alphagan; Allergan, Irvine, CA). Tinted contact lenses with artificial pupils and yellow-tinted eyeglasses might occasionally provide significant relief. Ocular surface lubrication with artificial tears or punctal plugs can occasionally result in dramatic improvement of symptoms related to ocular surface dryness. Other strategies include prescribing correcting spectacles, which can sometimes be the easiest solution to relieve poor night vision due to residual myopia. Similarly, a well-centered hard contact lens will enlarge the optical zone and could be helpful in select situations.

3. Prevention

Pupil size can be gauged with use of a Rosenbaum near card scale or an infrared Colvard infrared pupillometer. Room lights should be dimmed in both situations to replicate mesopic conditions en108 Surv Ophthalmol countered by the patient at night. Patients with pupil diameter of more than 6.0 mm should be informed of the significant risk of night vision disturbances after LASIK. Larger ablation zone diameters have been associated with decreased incidence of night glare. The development of software allowing effective larger ablation diameter with adequate preservation of stromal tissue could help lower the incidence of this problem. Measures discussed above to prevent decentration and central islands may also help diminish the incidence of these symptoms. Several investigators encourage their patients to look for symptoms of glare, halos, and starburst effects at night, prior to surgery. This may help reduce the possibility of attributing preexisting visual aberrations to the surgical procedure.

G. LOSS OF CONTRAST SENSITIVITY

Holladay et al recently showed worsening in functional vision as the target contrast diminishes and the pupil size increases. They concluded that the oblate shape of the cornea following LASIK is the predominant factor in the functional vision decrease. On the other hand, Perez-Santonja reported improvement in contrast sensitivity at certain frequencies 6 months after LASIK in eyes with moderate to high myopia. It is difficult to compare studies measuring contrast sensitivity due to the different methods used. It is unclear to what extent loss of contrast sensitivity overlaps with patients’ complaints of other optical disturbances, such as glare and halos.

III. Loss of Best Spectacle-Corrected
Visual Acuity (BSCVA)

The incidence of loss of 2 or more lines of best spectacle-corrected visual acuity (BSCVA) after LASIK is reported to be about 4.8%. It is more frequent with correction of larger refractive errors256 and with correction of compound astigmatism compared to spherical corrections. Comparing various studies could prove difficult, as some report BCVA while others only measure spectacle-corrected visual acuity. Lin et al reported less than two lines of loss of BSCVA, which were secondary to flap complications in lamellar surgery but did not mention other types of complications. Davidorf reported higher loss of BSCVA with hyperopic treatment.51 Most complications described in this report could potentially affect BSCVA either temporarily or permanently. Early recognition and heightened levels of suspicion are valuable for the prevention of unnecessary loss of vision in an otherwise healthy eye.

IV. Dry Eyes

A majority of patients complain of dry eye symptoms after LASIK. It is not known whether PRK patients report these symptoms as frequently. Many present with superficial punctate keratopathy.51 A recent study reported that 35 (42.2%) of 83 eyes displayed a distinctive brown-colored corneal iron line of variable density in a ring or patch configuration near the margin of the ablated zone in the overlying corneal flap epithelium after LASIK. The appearance of this iron line correlated positively with time after surgery (3 months) and preoperative spherical equivalent (4.5 D). This probably reflects an alteration in the surface tear dynamics due to the central corneal flattening. It can also be associated with central island formation.135 Similarly, an iron ring is usually noted after hyperopic excimer ablation.

1. Etiology

The dry eye condition after LASIK may be due to decreased corneal sensation, resulting from severing of corneal nerves, with subsequent decreased blinking rate. Another theory implicates suction ring damage to the keratolimbal area with subsequent damage to goblet cells.

2. Management

Most patients will notice an improvement in their symptoms a few weeks after the procedure. Meanwhile, surface lubrication will alleviate the sensation of ocular irritation. A recent report showed better results with carmellose-based artificial tears than with balanced salt solution. Temporary collagen plugs or longer lasting silicone lacrimal punctal plugs also provide symptomatic relief in the postoperative period after LASIK.

3. Prevention

Prophylactic placement of temporary lacrimal punctal plugs at the end of the procedure has been used by some surgeons to enhance the tear lake in the early postoperative period. A slow taper of the postoperative topical steroids may also provide relief from dry eye symptoms in the early postoperative period.

V. Infectious Keratitis and Sterile Infiltrates

Lin et al reported the incidence of bacterial keratitis after LASIK to be 0.1%. The low rate of infection may have encouraged some surgeons to abandon sterile techniques while performing the procedure. It is not known whether this has resulted in a higher rate of infection. Nevertheless, this approach is inherently risky from the medical and legal standpoints. LASIK should be approached in a manner similar to other surgical procedures, given that bilateral69,102,282 corneal infections and endophthalmitis have been reported.186 Similarly, cases of fungal47,251 and micobacterial keratitis have been repor ted. Karp et al reported two cases of delayed infectious keratitis (1 month and 3 months) after LASIK.115 Occasionally, sterile infiltrates may be seen at the edge of the flap. Blepharitis with or without rosacea, dry eyes, the use of topical NSAIDs, and undiagnosed connective tissue diseases may predispose to the formation of such infiltrates. These cannot be reliably differentiated solely by their appearance from infectious infiltrates; a high level of suspicion should be maintained.

1. Etiology

Sources of contamination include the ocular flora, any instruments or sponges used to manipulate the eye, the surgeon’s hands, or airborne contaminants. Several organisms have been implicated in post-LASIK infectious keratitis. A known history of herpes simplex virus (HSV) is a contraindication for LASIK50 especially in the presence of corneal findings because of the risk of virus reactivation.

2. Management

Treatment should be initiated promptly after corneal cultures are obtained whenever possible. Unique features to post-LASIK infectious keratitis include the possibility of lifting the flap and culturing/ irrigating the interface if deemed useful. In addition, the flap can be disinserted and excised in extreme cases of nonresponsive infections leading to severe flap melting.

3. Prevention

The following measures may help reduce the incidence of post-operative infectious keratitis:
1. Strict aseptic technique.
2. Using one microkeratome blade per eye in cases of simultaneous bilateral LASIK.
3. Warning patients about the possibility of recurrence if a questionable history of herpes infection is elicited and if signs of prior HSV keratitis are not seen. Anesthesiometry prior to surgery could help in assessing the risk of persistent epithelial defects. Systemic antiviral prophylaxis could also be considered to minimize the risk of surgically triggered reactivation.

VI. Diffuse Lamellar Keratitis

Diffuse lamellar keratitis (DLK) is a recently described syndrome117,152,249 characterized by proliferation of presumably inflammatory cells at the LASIK interface . It occurs in approximately 0.2– 3.2% of cases . It can lead to stromal corneal melting with induced hyperopia or hyperopic astigmatism. Additional symptoms include loss of BCVA with optical aberrations secondary to irregular astigmatism. Lyle et al reported a case associated with interface fluid accumulation and epithelial ingrowth. Other reported associations include corneal epithelial defects, micropannus hemorrhage, and concomitant contact dermatitis of the eyelids. In their initial report about DLK, Smith and Maloney noted several characteristics defining the infiltrate associated with this new syndrome. Since then, we and others have noted major differences as compared to the criteria described by Smith et al (in italics hereafter). Our patients include cases where the patients presented with DLK as early as the first postoperative day (day 2), asymptomatic (pain/photophobia), extending beyond the interface (confined to the interface), more prevalent with epithelial defects (no overlying epithelial defect), and associated with an inflamed conjunctiva (no ciliary flush). It has been anecdotally reported to happen sporadically or in clusters with primary procedures or in cases of LASIK enhancement. No single agent has been demonstrated to be responsible for this relatively rare but potentially serious complication. A relationship to endotoxins released from sterilizer reservoir biofilms has been described. Left: Diffuse lamellar keratitis, 2 days post-LASIK. Right: Diffuse lamellar keratitis, central coalescence with scarring and stromal melt, 5 days post-LASIK. The natural history of DLK appears to involve central coalescence of the inflammatory cells if not resolved by the 5th postoperative day (personal observations). This may lead to central stromal melting and scarring (Fig. 8, right). Our current protocol involves flap lift, scraping and irrigation by the 4th postoperative day at the latest if the inflammation is judged to progress despite hourly topical prednisolone acetate 1% with broad-spectrum topical antibiotic coverage. Any signs of stromal melting should prompt earlier surgical intervention. We have used intensive perioperative topical steroids when retreating at least 5 patients after an episode of DLK with no recurrence (unpublished observations). Peters et al propose the use of topical intrastromal steroid during LASIK to reduce the incidence and severity of DLK.

VII. Other Complications

Other complications include reports of increased risk of cataract formation, effect on endothelial cell count, unilateral or bilateral macular hemorrhage, difficulty in contact lens fitting, and difficulties in IOL power calculations in patients undergoing cataract extraction. A large study of eyes who have undergone LASIK showed a low incidence of vitreoretinal pathology (0.06%), confirming earlier reports of infrequent serious retinal complications.

VIII. Conclusions

LASIK refractive surgery is a relatively new technique with very high success rate. The demand for high standards of safety for this surgery is mandated by the fact that relatively healthy eyes are placed at risk every time the procedure is performed. These risks can be minimized by learning from our mistakes, analyzing outcomes, and prodding new territory thoughtfully and ethically. Investigators have helped advance our knowledge of unexpected results and prompted indepth procedural reviews of this relatively recent surgical procedure by reporting their complications and sharing their experience with the rest of the refractive community. This has allowed for continuous refinements in LASIK surgical technique and provided the basis for new and improved future vision correction strategies.

Method of Literature Search

In this review, we identified pertinent articles on LASIK published in the peer-reviewed journals through a multistaged, systematic approach. In the first stage, a computerized search of the PUBMED database (National Library of Medicine) was performed to identify all articles about LASIK published up to February 2000. The term laser in situ keratomileusis and the text word keratomileusis were used for a broad and sensitive search. In the second stage, all abstracts were carefully scanned to identify articles, written in English, that described either the complications of LASIK or the results of a clinical series. Non-English articles were included when deemed necessary. Copies of the entire articles were obtained. Bibliographies of the retrieved articles were manually searched with use of the same search guidelines. In the third stage, articles were reviewed and complications of LASIK were compiled and incorporated into the manuscript. We have derived the incidence of various LASIK complications primarily from three large studies (1000 eyes). Due to the rapid evolving nature of the subject, we included some information gathered from anecdotal reports, selected presentations at scientific meetings, and from our personal experience. Additionally, stages 1–3 were repeated upon final revision of the manuscript to include important articles published in the February 2000 to February 2001 interval.