Laser in situ keratomileusis in patients with corneal guttata and family history of Fuchs endothelial dystrophy

Transcription

1 J CATARACT REFRACT SURG - VOL 31, DECEMBER 2005 Laser in situ keratomileusis in patients with corneal guttata and family history of Fuchs endothelial dystrophy Majid Moshirfar, MD, Vahid Feiz, MD, Michael R. Feilmeier, Paul C. Kang, MD PURPOSE: To report 1-year results of laser in situ keratomileusis (LASIK) in 7 eyes with corneal endothelial guttata and a family history of Fuchs endothelial dystrophy. SETTING: John Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: A retrospective chart review was performed of 4 patients (7 eyes) who had trace to 1C endothelial guttata and a family history of Fuchs dystrophy and then had uneventful LASIK for the correction of myopia and myopic astigmatism. Preoperative and postoperative measurements included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), corneal pachymetry, endothelial cell density (ECD), manifest refraction, and spherical equivalent. The changes in ECD, pachymetry, and spherical equivalent after LASIK were subjected to statistical analysis using a paired Student t test to determine significance. RESULTS: Transient corneal edema was noted in the early postoperative period in 3 eyes of 2 patients. At 1 year, 6 of the 7 (86%) eyes had lost R2 lines of BSCVA. A statistically significant decrease in ECD of 12.4% G 2.7% was observed at 1 year compared with baseline (P<.001). An increase in corneal thickness (P Z.006) and a statistically significant myopic shift in spherical equivalent (P Z.017) was also noted at 1 year compared with 3 months. CONCLUSIONS: Patients with mild corneal guttata and a family history of Fuchs dystrophy are prone to transient corneal edema, loss of BSCVA, endothelial cell loss, and myopic regression after uneventful LASIK for correction of myopia and myopic astigmatism. J Cataract Refract Surg 2005; 31: Q 2005 ASCRS and ESCRS Fuchs endothelial dystrophy is a member of the family of posterior dystrophies initially described by Ernst Fuchs in 1910 with a clinical presentation of bilateral corneal edema in the elderly. 1 The disease is a disorder of the endothelial pump mechanism characterized clinically by guttata or excrescences of Descemet s membrane. With the advent of biomicroscopy, pathological changes in the central corneal endothelium were observed to precede the development of edema. 2 Fuchs dystrophy follows an autosomal dominant inheritance pattern with variable expressivity and has a 3:1 female preponderance. 3,4 It characteristically has a late onset and is slowly progressive, rarely becoming symptomatic before 50 years of age. Studies indicate that cornea guttata are fairly common, with an estimated prevalence of 10% to 70% in people older than 40 years. 2,3 The lack of a universal classification system for grading cornea guttata accounts for the large variability in these estimates. Laser in situ keratomileusis (LASIK) has become the most widespread surgical technique used in the United States to treat refractive errors. 5 When screening potential candidates for LASIK, it is important to understand how dystrophic corneas will respond to the procedure. Although several studies have documented the safety of myopic LASIK in patients with a healthy endothelium, 6 10 experience with LASIK in corneas with abnormal endothelium is limited. 11,12 In this study, the outcomes of LASIK in 4 patients (7 eyes) who had preoperative trace to 1C guttata and a family history of Fuchs dystrophy were reviewed. PATIENTS AND METHODS From July 2001 through July 2003, all patients with corneal guttata noted during refractive surgery consultation at the Moran Eye Center were asked about a possible family history of Fuchs dystrophy. Diagnosis was confirmed by slitlamp Q 2005 ASCRS and ESCRS Published by Elsevier Inc /05/$-see front matter doi: /j.jcrs

2 examination or documentation of previous examination of family members. Four patients (7 eyes) elected to proceed with LASIK for correction of myopia and myopic astigmatism. The patients gave their consent with the understanding that having guttata and a positive family history of Fuchs dystrophy might make LASIK in their eyes less predictable and place them at increased risk for corneal decompensation. All patients had a complete ocular examination including uncorrected (UCVA) and best spectacle-corrected (BSCVA) visual acuities, manifest and cycloplegic refractions, tonometry, slitlamp examination, and a dilated fundus evaluation. Optical pachymetry was performed using the Orbscan (Bausch & Lomb). All corneas showed trace to 1C central cornea guttata, defined as 1 or many ungrouped guttata scattered about the middle two-thirds of the cornea. No eye had signs of corneal folds or stromal edema. Because of the corneal findings, all eyes also had specular microcopy using a Topcon SP2000 noncontact specular microscope to determine baseline endothelial cell density (ECD). This system automatically selects a central corneal window for analysis. Three central corneal images were captured from each eye and ECD was calculated using Topcon Imagenet, version 2.13 cell analysis software. All images included guttata in the central window used for calculation. The 3 densities were then averaged. Patients were instructed to discontinue soft contact lens use 2 weeks before surgery and rigid gas-permeable lens use 8 weeks before surgery. All eyes had standard LASIK under topical anesthesia by 1 surgeon (M.M.) in the following manner: A Hansatome microkeratome (Bausch & Lomb Surgical, Inc.) with a 180 mm depth plate was used to create a superiorly hinged flap. Excimer laser ablation of the stromal bed was performed using a Visx Star S2 laser system with an energy fluence of 160 mj/cm 2, a frequency of 7 to 8 Hz, and a 6.0 mm ablation zone. After ablation, the flap was replaced and the interface was irrigated with balanced salt solution. All patients received 5 minutes of drying time. All eyes were checked at the slitlamp 30 to 60 minutes postoperatively to ensure adequate flap position and lack of gross striae. All patients were then prescribed Ocuflox and Pred-Forte 4 times a day for 1 week. The refractive goal in all eyes was plano. Postoperative BSCVA, UCVA, and manifest refraction (MR) were measured at follow-up visits at 1 day, 1 month, 3 months, and 1 year. Optical pachymetry was obtained for all eyes at 1 month, 3 months, and 1 year. In addition, 4 eyes had pachymetry values measured at 1 day and 1 week. Endothelial cell density Accepted for publication May 18, From the John A. Moran Eye Center (Moshirfar, Feilmeier), University of Utah, Salt Lake City, Utah, Department of Ophthalmology (Feiz), University of California Davis Medical Center, Sacramento, California, and University Ophthalmic Consultants of Washington (Kang), Chevy Chase, Maryland, USA. Supported in part by a grant from Research to Prevent Blindness to the Department of Ophthalmology, University of Utah, Salt Lake City, and the Department of Ophthalmology, University of California, Davis, USA. No author has a financial or proprietary interest in any materials or methods mentioned. Reprint requests to Majid Moshirfar, MD, John A. Moran Eye Center, University of Utah, 50 North Medical Drive, Salt Lake City, Utah 84132, USA. majid.moshirfar@hsc.utah.edu. was measured at 1 week in 2 eyes, 3 months in 4 eyes, and 1 year in all eyes. RESULTS The characteristics of the 4 patients are shown in Table 1. There was 1 man and 3 women and 4 right eyes and 3 left eyes. The mean age was 46 years (range 39 to 51 years). No patient had an ocular history or symptoms other than refractive error. All patients denied worse vision upon awakening or other vision fluctuations. One patient was contact lens intolerant, 2 patients wore rigid gas-permeable lenses, and 1 patient wore soft contact lenses for refractive correction. Uncorrected Visual Acuity All eyes had a UCVA worse than or equal to 20/100 prior to LASIK (range 20/100 to 20/400). At 1 year, all 7 eyes had UCVA of 20/50 or better, 5 eyes (71%) had UCVA of 20/40 or better, 2 eyes (29%) had UCVA of 20/30, and no eye had UCVA of better than 20/30 (Table 1). Best Spectacle-Corrected Visual Acuity Before surgery, all eyes had a BSCVA of 20/25 or better. At 1 year, 6 of 7 (86%) eyes had a BSCVA of 20/40. No eye had BSCVA of 20/25 or better. All eyes had lost 2 or more lines of BSCVA from preoperative levels (Table 1). Refractive Error Table 2 shows the spherical equivalent (SE) in all eyes at baseline and 1 month, 3 months, and 1 year after LASIK. For patient 3, the 1-month refraction was not available due to lack of follow-up. The mean SE at baseline, 1 month, 3 months, and 1 year were ÿ3.54 diopters (D) (range ÿ1.50 to ÿ5.63 D), ÿ0.10 D (range C0.25 to ÿ0.50 D), ÿ0.71 D (range ÿ0.50 to ÿ1.00 D), and ÿ0.91 D (range ÿ0.50 to ÿ1.13 D). The difference in SE at 1 month and 1 year was found to be statistically significant using a paired Student t test (P Z.017). Pachymetry Mean corneal thickness before LASIK was 635 G 48 mm (range 575 to 689 mm). Mean laser corneal ablation depth was 45 mm (range 19.5 to 70.0 mm). Mean calculated residual stromal bed thickness was 410 mm (range to mm). Postoperatively, mean central corneal thickness was 598 G 46 mm, 608 G 44 mm, and 610 G 51 mm at 1 month, 3 months, and 1 year, respectively (Table 3). The difference in central pachymetry at 1 month versus 1 year, although small, was found to be statistically significant using a paired Student t test (P Z.006) J CATARACT REFRACT SURG - VOL 31, DECEMBER 2005

3 Table 1. Patient characteristics, baseline MR, SE, UCVA, BSCVA. At Baseline At 1 Year Patient Eye Age (Y) MR (D) SE (D) UCVA BSCVA UCVA BSCVA 1 OD 39 ÿ2.75 C ÿ /200 20/20 20/30 20/30 OS ÿ3.25 C ÿ /200 20/20 20/30 20/30 2 OD 48 ÿ4.75 C ÿ /400 20/25 20/50 20/40 OS ÿ4.50 C ÿ /400 20/25 20/50 20/50 3 OD 46 ÿ5.75 C ÿ /400 20/25 20/40 20/40 OS ÿ5.00 C ÿ /400 20/25 20/40 20/40 4 OD 51 ÿ1.75 C ÿ /100 20/25 20/40 20/40 BSCVA Z best spectacle-corrected visual acuity; MR Z manifest refraction; OD Z right eye; OS Z left eye; SE Z spherical equivalent; UCVA Z uncorrected visual acuity Corneal Endothelial Cell Density Specular microscopy was done in all eyes preoperatively and 1 year postoperatively. Mean ECD before LASIK was 1591 G 156 cells/mm 2 (range 1415 to 1876 cells/mm 2 ). One year postoperatively, mean ECD was 1393 G 128 cells/mm 2 (range 1287 to 1630 cells/mm 2 ). This represents a 12.4% G 2.7% loss of central ECD (range 7.9% to 16.9%). Using a paired Student t test to compare baseline ECD with 1-year post-lasik ECD, the difference was highly statistically significant (P!.001). The same analysis was used to compare the ECD at 3 months and 1 year post LASIK in patients who had 3 month data and the difference was not statistically significant (P Z.91) (Table 4). both eyes, and moderate epithelial cystic changes were noted. Corneal pachymetry was greater than preoperatively on day 1 and week 1 (Table 3). One week after LASIK, there was a 23% decrease in ECD in the right eye and a 28% decrease in ECD in the left eye (Table 4). Examination at that point showed mild stromal edema with resolution of the epithelial cystic findings. Examination of the patient 1 month after LASIK did not reveal any overt corneal abnormalities. Slitlamp examination of patient 4 on postoperative day 1 revealed minimal corneal flap edema with minimal cystic epithelial change. Repeat examination of this patient s cornea 1 week after LASIK was normal. Complications and Adverse Reactions All surgery was uneventful, and no intraoperative complications were noted. Two patients (cases 2 and 4) experienced clinically significant corneal edema on postoperative day 1. Slitlamp examination of Patient 2 on postoperative day 1 revealed anterior stromal edema with flap involvement. The flap margins were clearly elevated in Table 2. Spherical equivalent at baseline and 1 month, 3 months, and 1 year after LASIK. SE (D) Patient Eye (Baseline) (1 Month) (3 Months) (1 Year) 1 OD ÿ2.38 ÿ0.25 ÿ0.75 ÿ0.50 OS ÿ2.63 ÿ0.50 ÿ1.00 ÿ OD ÿ4.25 C0.25 ÿ0.62 ÿ1.13 OS ÿ3.75 Plano ÿ0.60 ÿ OD ÿ5.63 N/A ÿ0.75 ÿ0.75 OS ÿ4.63 N/A ÿ0.50 ÿ OD ÿ1.50 Plano ÿ0.75 ÿ0.75 Mean ÿ3.54 ÿ0.10 ÿ0.71 ÿ0.91 N/A Z not available; OD Z right eye; OS Z left eye; SE Z spherical equivalent DISCUSSION Laser in situ keratomileusis has generally been accepted as predictable, effective, and safe for the treatment of low to moderate myopia Specifically, the 193 nm wavelength excimer laser has a tissue penetration of less than a cell diameter 17 and is reportedly safe for healthy endothelium. With the exception of 2 studies 11,12 reporting ECD loss after high myopic correction, LASIK has not been associated with a significant loss of central corneal endothelial cells 2 weeks to 3 years postoperatively in healthy eyes The response of the peripheral endothelium to excimer keratectomy may be less predictable. Stulting and coauthors 18 found a significant decrease in peripheral ECD related to the level of treatment 3 months and 1 year after photorefractive keratectomy; no significant decrease was reported centrally. This may suggest that healthy corneas experience central endothelial cell loss following laser ablation, but it may go unnoticed because of the rapid centripetal migration of healthy endothelium. Kim et al. 19,20 and Carones and coauthors 21 report diffuse corneal endothelial swelling following excimer keratectomy in J CATARACT REFRACT SURG - VOL 31, DECEMBER

4 Table 3. Corneal pachymetry before and after LASIK. Mean Corneal Pachymetry (mm) Post LASIK Patient Eye Pre LASIK 1 Day 1 Week 1 Month 3 Months 1 Year 1 OD 575 d d OS 567 d d OD OS OD 650 d d OS 630 d d OD 689 d Mean 635 G 48 d d 598 G G G 51 LASIK Z laser in situ keratomileusis; OD Z right eye; OS Z left eye. healthy eyes that resolved in 24 hours without a significant decrease in ECD. While these findings appear significant, in clinical settings healthy endothelium appears to tolerate LASIK without long-term detriment This may not be true for compromised endothelium, which may be prone to damage and cell loss and may result in a decreased ability to maintain corneal deturgescence and transparency. In our study, the observed cell loss of 12.4% 1 year after LASIK appears significant compared with the anticipated 0.6% annual decrease in ECD in healthy aging individuals. 22 Multiple mechanisms of endothelial damage secondary to laser treatment have been hypothesized, including mechanical trauma from shock waves. 23 Moreover, changes in intraocular pressure (IOP) during LASIK may play a role. Transient, acute rise in IOP is associated with significant endothelial damage correlating to the duration of increased pressure. 24,25 While the period of increased IOP during LASIK on application of the suction ring is minimal, in cases of marginal endothelial function, this transient spike may have the potential to induce stromal edema and cellular damage. Kim et al. 19 reported morphological changes in a patient who had application of the suction ring only, suggesting that even transient increases in pressure may have an effect on the endothelium. Stromal bed irrigation during LASIK results in corneal hydration and may induce cellular damage by creating additional endothelial stress. The normal endothelial response including cellular remodeling, maintenance of tight junctions, and upregulation of metabolic pump sites may overcome this load. 26 However, the lack of this capacity may lead to accelerated endothelial cell loss and a compromised barrier. 27,28 Both Vroman et al. 11 and Dastjerdi and Sugar 12 have reported cases of endothelial cell loss after LASIK in patients with Fuchs dystrophy. While these studies support our observations, it is difficult to separate the effect of the refractive surgery on endothelial cells from the natural course of the disease. We observed a 12.4% endothelial cell loss, which is certainly higher than cell loss in nondystrophic Table 4. Endothelial cell density before and after LASIK. Mean ECD (cells/mm 2 ) Post LASIK Patient Eye Pre LASIK 1 Week 3 Months 1 Year Change (%) 1 OD 1876 G 306 d 1653 G G 299 ÿ13.1 OS 1706 G 321 d 1682 G G 311 ÿ OD 1486 G G G G 484 ÿ11.9 OS 1501 G G G G 387 ÿ OD 1549 G 305 d d 1287 G 378 ÿ16.9 OS 1607 G 495 d d 1396 G 365 ÿ OD 1415 G 339 d d 1303 G 323 ÿ7.9 Mean 1591 G 156 d d 1393 G 128 ÿ12.4 G 2.7 ECD Z endothelial cell density; LASIK Z laser in situ keratomileusis; OD Z right eye; OS Z left eye 2284 J CATARACT REFRACT SURG - VOL 31, DECEMBER 2005

5 corneas. 22 However, it may not be abnormal in corneas with endothelial disease. Our literature search failed to find any report of rate of endothelial cell loss in patients with silent guttata who had not had ocular surgery. The endothelial cell count between baseline and 1 year was significant (P!.001), but the difference between cell count at 3 months and 1 year was not (P Z.91). This may suggest most cell loss occurs in the immediate postoperative period, followed by a return to the baseline rate, and may support a causal relationship. Further research exploring the individual effect of laser ablation, acute increased IOP, and stromal irrigation on corneas with normal versus compromised endothelium is needed. Two of our patents experienced flap edema in the immediate postoperative period. While transient, this raises the possibility of poor flap adherence and higher likelihood of early dislocation. Poor endothelial function was found to cause poor flap adhesion in animal models 29 and should be considered during lamellar surgery in patients with compromised endothelium. We acknowledge that ECD was not consistently measured in all patients immediately postoperatively and 1 day, 1 week, and 1 month after LASIK. These measurements would have provided us with a better understanding of the nature and time course of endothelial cell loss. Corneal pachymetry measurements 1 day and 1 week following surgery would have been helpful in following endothelial function. The refractive and visual outcomes in these small case series were also suboptimal. All patients lost 2 lines of BSCVA. In addition, most patients experienced a significant myopic shift in the SE. The exact etiology for this myopic shift is unknown. Cataracts were not detected, but subtle changes could be present. Changes in stromal hydration of the cornea secondary to decreased endothelial cell function may have changed the refractive index of the cornea. The myopic shift may also represent regression after LASIK. However, the high rate of regression in this group makes that less likely. While no patient in this study developed corneal decompensation after 1 year, the long-term effect of the procedure remains uncertain. The possibility of accelerating the natural course of the disease has been reported following other intraocular procedures, and predisposing these patients to corneal transplantation a decade or more sooner is concerning. It is difficult to determine precisely which patients are at risk for clinically significant damage. This case series demonstrates that patients with cornea guttata and a family history of Fuchs endothelial dystrophy may experience unfavorable outcomes, including loss of BSCVA, myopic regression, and accelerated loss of endothelial cells after LASIK. Refractive surgeons may consider avoiding LASIK in patients with evidence of corneal endothelial abnormalities and a known family history of Fuchs endothelial dystrophy until further studies define more appropriate and specific guidelines. REFERENCES 1. Fuchs E. Dystrophia epithelialis corneae. Albrecht von Graefes Arch Klin Ophthalmol 1910; 76: Adamis AP, Filatov V, Tripathi BJ, Tripathi RC. Fuchs endothelial dystrophy of the cornea. Surv Opthalmol 1993; 38: Wilson SE, Bourne WM. Fuchs Dystrophy. Cornea 1988; 7: Waring GO, Bourne WM, Edelhauser HF, Kenyon KR. The corneal endothelium. Normal and pathologic structure and function. Ophthalmology 1982; 89: Duffey RJ, Leaming D. Trends in refractive surgery in the United States. J Cataract Refract Surg 2004; 30: Perez-Santonja JJ, Sakla HF, Alio JL. Evaluation of endothelial cell changes 1 year after excimer laser in situ keratomileusis. Arch Ophthalmol 1997; 115: Perez-Santonja JJ, Sakla HF, Gobbi F, Alio JL. 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