- Email: [email protected]
Recovery of corneal sensitivity after laser-assisted subepithelial keratectomy
J CATARACT REFRACT SURG - VOL 32, MAY 2006
Recovery of corneal sensitivity after laser-assisted subepithelial keratectomy Ying Wu, MD, Ren Y. Chu, MD, Xing T. Zhou, MD, Jin H. Dai, MD, Xiao M. Qu, MD, Srinivas Rao, MD, Dennis Lam, MD
PURPOSE: To evaluate the recovery of corneal sensitivity after laser-assisted subepithelial keratectomy (LASEK) for myopia. SETTING: Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China. METHODS: In this prospective interventional case series, central corneal sensitivity (CCS) was measured using a Cochet-Bonnet esthesiometer (Luneau Ophthalmologie) in 85 eyes of 50 patients before and 2 weeks, 1 month, 3 months, and 6 months after LASEK for the treatment of myopia. For analysis, the eyes were divided into 2 groupsdthe low–moderate myopia group (spherical equivalent [SE] ÿ1.0 to ÿ6.0 diopters [D]) and the high myopia group (SE ÿ6.0 to ÿ16.0 D)dand the correlation between ablation depth and CCS was evaluated. RESULTS: In both groups, a significant decrease in CCS was present at 2 weeks and 1 month. In the low–moderate myopia group, the CCS recovered to preoperative values at 3 months. In the high myopia group, recovery of CCS was slower and preoperative values were reached only at the 6-month follow-up. Measured CCS was significantly correlated with the ablation depth used at the 3-month and 6-month examinations (r Z ÿ0.262 and r Z ÿ0.264, respectively; P<.05). CONCLUSION: Recovery of corneal sensitivity began 1 month after LASEK and was completed by 3 months in eyes treated for low–moderate myopia and at 6 months in eyes with high myopia. The depth of ablation during surgery affected the recovery of corneal sensitivity. J Cataract Refract Surg 2006; 32:785–788 Q 2006 ASCRS and ESCRS
Corneal innervation is essential for the maintenance of normal structure and function.1,2 Conditions such as viral keratitis and diabetic keratopathy affect the integrity of the corneal nerves and can result in significant corneal morbidity. Damage to corneal nerves can also be iatrogenic,
Accepted for publication August 6, 2005. From the Eye and ENT Hospital (Wu, Chu, Zhou, Dai, Qu), Fudan University, Shanghai, and the Department of Ophthalmology and Visual Science (Rao, Lam), the Chinese University of Hong Kong, Hong Kong, China. Supported by a grant (NO. 30371506) from the National Natural Science Foundation of China. No author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Ren.Y Chu, MD, 83 Fenyang Road, Shanghai, China. E-mail: [email protected]. Q 2006 ASCRS and ESCRS Published by Elsevier Inc.
resulting from surgical procedures. Knowledge of these effects is important to improve our understanding of corneal healing in these situations and can improve surgical outcomes. Corneal refractive surgery using the excimer laser is currently the most popular approach for the treatment of refractive errors. Laser in situ keratomileusis (LASIK) allows quick recovery of visual acuity with minimal or no postoperative pain and is the preferred procedure. These advantages of LASIK are due to the removal of corneal stromal tissue under a flap of superficial corneal tissue. Creation of the corneal flap, however, results in transsection of the nerves in the anterior cornea, and subsequent laser ablation can result in further damage to the stromal nerves. This can result in marked reduction of corneal sensitivity after LASIK, especially in the central cornea.3–5 Studies report that recovery of central corneal sensitivity (CCS) in these eyes may take 6 to 12 months.2–5 One of the important 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.01.066
785
CORNEAL SENSITIVITY RECOVERY AFTER LASEK
consequences of decreased CCS is the occurrence of a temporary tear dysfunction state following LASIK. Laser-assisted subepithelial keratectomy (LASEK), a recent variant of excimer refractive surgery, requires the creation of an epithelial flap using chemodisruption of corneal epithelial attachment complexes. Compared with photorefractive keratectomy (PRK), LASEK results in less pain and corneal haze. Because a flap of stromal tissue is not created, it may preserve corneal integrity better than LASIK and the availablilty of more stromal tissue for remodeling allows the safe treatment of refractive errors in eyes with thin corneas. A recent clinical study reported that recovery of CCS and tear-film function after LASEK may occur as early as 1 month after surgery.6 The preoperative mean spherical equivalent (SE) among patients in the study was ÿ4.0 diopters (D). Because LASEK is currently used in the treatment of high myopia and it is likely that greater nerve damage can result from deeper ablations, we evaluated the recovery of CCS in eyes with low–moderate and high myopic LASEK. PATIENTS AND METHODS The prospective interventional case series comprised 50 patients (85 eyes) who had LASEK for myopic correction from June to July 2004. Exclusion criteria included a history of corneal trauma or past surgery, viral keratitis, and systemic diseases such as diabetes or connective-tissue diseases. The washout period for long-term contact lens users (more than 5 years) was at least 2 weeks. Informed consent was obtained from all patients. During LASEK, an incision in the epithelium was made using a special microtrephine (Kangning Medical Electronic Equipment Development Co.). After ethanol 20% was applied for 10 to 20 seconds (mean 15 seconds), a superior hinged epithelial flap was created. All laser ablations were performed with the Carl Zeiss Meditec MEL 80 laser system, and the ablation diameter was chosen based on the scotopic pupil diameter. After laser ablation, the stromal surface was irrigated with balanced salt solution and the epithelial flap was repositioned. A 14 mm soft contact lens was used as a bandage for 3 to 7 days until epithelial healing was completed. Postoperatively, ofloxicin 0.3% eyedrops were used for 2 weeks and fluorometholone 0.1% eyedrops were used for 2 to 3 months. Central corneal sensitivity was examined preoperatively and 2 weeks, 1 month, 3 months, and 6 months postoperatively by the same observer using a Cochet & Bonnet esthesiometer (Luneau
Ophthalmologie). The maximal filament length of 60 mm, which corresponds to the lowest possible pressure, was used first, and length was subsequently decreased in 5 mm steps until the patient could perceive the sensation. The results were expressed as filament lengths (millimeters). Three measurements were performed at each filament length. Data are presented as mean G SD. Corneal haze levels were evaluated at 3 and 6 months using slitlamp biomicroscopy and were graded from 0 to 4.7 Continuous variables were evaluated using the paired t test. Between-group differences were assessed using the independent t test. The relationship between CCS and ablation depth was assessed by Spearman rank correlation analysis. All statistical analyses were performed using the SPSS software package. A 2-tailed P value less than 0.05 was considered statistically significant. RESULTS
The patient demographics and the myopic status of the eyes are shown in Table 1. For analysis, eyes were divided into 2 groups according to the preoperative SE refraction: the low–moderate myopia group (SE ÿ1.0 to ÿ6.0 D) and the high myopia group (SE ÿ6.0 to ÿ16.0 D). There was no difference in time of ethanol application and ablation diameters between the 2 groups (PO.05) (Table 1). The corneal haze levels in the 2 groups at 3 and 6 months are shown in Table 2. Most eyes in the low–moderate myopia group had no haze throughout the study period. In the high myopia group, 12.96% of eyes had grade 1 haze and 3.71% had grade 2 haze at 3 months and this increased slightly to 16.67% and 5.56%, respectively, at the 6-month visit. No eye had greater than grade 2 haze during the study. Central corneal sensitivity scores are shown in Table 3. In the low–moderate myopia group, a significant decrease in CCS was seen at 2 weeks and 1 month (t Z 3.85 and t Z 4.85, respectively; P!.05). At 3 months, the CCS was not significantly different from the preoperative value, but a slight further improvement was noted at the 6-month visit. In the high myopia group, a significant decrease was noted at the 2-week and 1-month visits (t Z 7.05 and t Z 7.51, respectively; P!.05). Unlike in the low–moderate myopia group, this difference was still significantly lower at 3 months (t Z 4.40, P!.05). At the 6-month visit, although the CCS value was less than the preoperative value, the difference was not statistically significant (Figure 1). In 3 eyes
Table 1. Patient and ocular characteristics.
Myopia Group
Number of Patients (M/F)
Low–moderate
22 (12/10)
High
28 (13/15)
Age (Y)
Preoperative SE (D)
23.61 G 6.59 ÿ3.68 G 1.56 (18 to 32) (ÿ1.25 to ÿ6.0) 28.57 G 7.43 ÿ10.70 G 3.81 (23 to 38) (ÿ6.25 to ÿ16.0)
Preoperative Pachymetry (mm)
Ablation Depth (mm)
539.74 G 35.26 (487 to 583) 525.18 G 33.96 (482 to 597)
72.36 G 23.30 (33 to 112) 128.98 G 20.28 (96 to 162)
Mean G SD (range) SE Z spherical equivalent
786
J CATARACT REFRACT SURG - VOL 32, MAY 2006
Ablation Time of Ethanol Diameter (mm) Application (s) 6.02 G 0.13 (5.75 to 6.25) 5.87 G 0.18 (5.5 to 6.0)
13.73 G 3.10 (8 to 18) 13.58 G 3.04 (8 to 20)
CORNEAL SENSITIVITY RECOVERY AFTER LASEK
Table 2. Corneal haze levels after LASEK.
Months After Surgery (% of eyes) 3
6
Corneal Haze Low–Moderate
High
Low–Moderate
High
0 0.5 1 2 3 4
38.89 44.44 12.96 3.71 0 0
93.55 6.45 0 0 0 0
35.18 42.59 16.67 5.56 0 0
90.32 9.68 0 0 0 0
central corneal sensitivity (mm)
60
50
40
30 low-moderate high
with a corneal haze of grade 2, the CCS remained decreased at the 6-month visit. A significant correlation between the CCS and ablation depth was present at 3 and 6 months (r Z ÿ0.262, P Z.013; r Z ÿ0.264, P Z.012) (Figure 2). DISCUSSION
The cornea is 1 of the most densely innervated tissues in the body. Most corneal nerve fibers are sensory and derived from the trigeminal nerve. Nerve bundles enter the cornea at the 3 o’clock and 9 o’clock peripheries in the anterior third of the stroma. Normal corneal sensitivity is essential to normal corneal structure and function, and corneal hypesthesia can compromise the protective blink reflex, reduce epithelial mitosis, delay wound healing, and result in decreased tear flow.8,9 Because corneal refractive procedures can damage nerve fibers, it is important to understand the effects of such alterations on corneal recovery after these procedures. In PRK, the nerve endings and fibers in the anterior stroma are destroyed in the area of laser ablation, and in the acute phase after PRK (0 to 4 weeks), corneal sensitivity is decreased. In the intermediate phase (4 to 6 weeks), the epithelium remodels to a normal structure and nerve fibers regenerate inside the ablated area. However, corneal sensitivity is still decreased and a large number of fibroblasts populate the anterior stroma, which may result in corneal haze and regression.10 Reports show that the recovery of CCS after PRK is achieved between 3 and 12 months after surgery. Recovery is generally faster after low myopic correction,11,12 and it is postulated that the slower recovery after high myopic correction could be due to the formation of
20
before
2w
1m
3m
6m
Figure 1. Changes in CCS after low–moderate and high myopic LASEK.
corneal haze and also the greater nerve destruction from the deeper ablation.13 In LASIK, nerve fiber damage occurs from 2 causes. First, a microkeratome is used to cut a superficial corneal stromal flap and severs superficial nerve fibers in the area of the flap. Fibers entering the corneal stroma in the region of the flap hinge tend to be spared. However, if the hinge is positioned superiorly, considerable damage can result since most of the fibers enter the corneal stroma at 3 o’clock and 9 o’clock. Second, laser ablation of the exposed stroma results in damage to the deeper nerve fibers. The flap is usually 75 to 160 mm thick, and the additional ablation depth is dependent on the myopic correction. Because most stromal nerves run in the anterior third of the stroma (approximately 200 mm from the surface), significant sensory deprivation of the cornea can result from the refractive procedure.11 Using in vivo confocal microscopy, Perez-Gomez and Efron14 noted a total disappearance of the subepithelial nerve fiber bundle 1 month after LASIK and a return to a normal appearance at 6 months. Other reports indicate that clinical recovery of CCS after LASIK may take 6 to 12 months.11–13 Laser-assisted subepithelial keratectomy, a modication of PRK, combines the advantages of PRK and LASIK. Experimental studies have shown that treatment with alcohol 20% for 30 seconds preserves the viability of most of the treated corneal epithelium.15,16 In our study, we used an even shorter time of 10 to 20 seconds to create the epithelial flap. Horwath-Winter et al.6 report that LASEK for the
Table 3. Central corneal sensitivity before and after surgery.
Central Corneal Sensitivity, Mean (Range) (mm) Group
Preoperative
2 Weeks
1 Month
3 Months
6 Months
Low–moderate 58.78 G 2.2 (55–60) 50.28 G 8.82* (25–55) 50.93 G 6.36* (40–60) 56.07 G 4.16 (50–60) 58.33 G 2.42 (55–60) High 58.90 G 2.1 (55–60) 48.80 G 9.79* (30–55) 48.17 G 8.17* (40–60) 54.50 G 5.65* (40–60) 55.45 G 10.63 (50–60) *Paired t test P!0.05
J CATARACT REFRACT SURG - VOL 32, MAY 2006
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CORNEAL SENSITIVITY RECOVERY AFTER LASEK
180
REFERENCES
160
1. Mu¨ller LJ, Marfurt CF, Kruse F, Tervo TMT. Corneal nerves: structure, contents, and function. Exp Eye Res 2003; 76:521–542; errata 2003; 77:253 2. Davis EA, Dohlman CH. Neurotrophic keratitis. Int Ophthalmol Clin 2001; 41:1–11 3. Donnenfeld ED, Solomon K, Perry HD, et al. The effect of hinge position on corneal sensation and dry eye after LASIK. Ophthalmology 2003; 110:1023–1029; discussion by CJ Rapuano, 1029– 1030 4. Donnenfeld ED, Ehrenhaus M, Solomon R, et al. Effect of hinge width on corneal sensation and dry eye after laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:790–797 5. Nassaralla BA, McLeod SD, Nassaralla JJ Jr. Effect of myopic LASIK on human corneal sensitivity. Ophthalmology 2003; 110:497–502 6. Horwath-Winter J, Vidic B, Schwantzer G, Schmut O. Early changes in corneal sensation, ocular surface integrity, and tear-film function after laser-assisted subepithelial keratectomy. J Cataract Refract Surg 2004; 30:2316–2321 7. Fantes FE, Hanna KD, Waring GO III, et al. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch Ophthalmol 1990; 108:665–675 8. Martin XY, Safran AB. Corneal hypoesthesia. Surv Ophthalmol 1988; 33:28–40; see notes, 217 9. Beuerman RW, Schimmelpfennig B. Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol 1980; 69: 196–201 10. Kohlhaas M. Corneal sensation after cataract and refractive surgery. J Cataract Refract Surg 1998; 24:1399–1409 11. Pe´rez-Santonja JJ, Sakla HF, Cardona C, et al. Corneal sensitivity after photorefractive keratectomy and laser in situ keratomileusis for low myopia. Am J Ophthalmol 1999; 127:497–504 12. Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, et al. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 1997; 23:34–38 13. Kohlhaas M, Klemm M, Bo¨hm A, et al. Corneal sensitivity after refractive surgery. Eur J Implant Refract Surg 1994; 6:319–323 14. Perez-Gomez I, Efron N. Change to corneal morphology after refractive surgery (myopic laser in situ keratomileusis) as viewed with a confocal microscope. Optom Vis Sci 2003; 80:690–697 15. Kim S-Y, Sah W-J, Lim Y-W, Hahn T-W. Twenty percent alcohol toxicity on rabbit corneal epithelial cells: electron microscopic study. Cornea 2002; 21:388–392 16. Song I-K, Joo C-K. Morphological and functional changes in the rat cornea with an ethanol-mediated epithelial flap. Invest Ophthalmol Vis Sci 2004; 45:423–428
ablation depth (µm)
140 120 100 80 60 DEEP sensitivity-6m
40 20 2.5
DEEP sensitivity-3m
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
central corneal sensitivity (Cm) Figure 2. Correlation between ablation depth and CCS 3 and 6 months after surgery.
correction of a low myopic error resulted in a short-term reduction in CCS of 1 month. The recovery of CCS after LASEK for low to moderate myopia in our study was slightly slower than that reported by Horwath-Winter et al.6 The recovery of CCS after LASEK for high myopic correction was even slower, especially in eyes with corneal haze of more than grade 1. Despite this, however, the CCS recovery after high myopic correction in our study was faster than that reported after PRK. We postulate that this could be due to the reduced corneal haze after LASEK, which may influence the regrowth of nerve fibers. In conclusion, our study indicates that the degree of myopic correction influences the speed of recovery of CCS after LASEK for the correction of myopia. Because there is a significant correlation between the occurrence of posttreatment corneal haze and the recovery of CCS, it appears that in addition to the depth of ablation, the occurrence of corneal scarring after LASEK may influence the recovery of CCS.
788
J CATARACT REFRACT SURG - VOL 32, MAY 2006
Recovery of corneal sensitivity after laser-assisted subepithelial keratectomy Ying Wu, MD, Ren Y. Chu, MD, Xing T. Zhou, MD, Jin H. Dai, MD, Xiao M. Qu, MD, Srinivas Rao, MD, Dennis Lam, MD
PURPOSE: To evaluate the recovery of corneal sensitivity after laser-assisted subepithelial keratectomy (LASEK) for myopia. SETTING: Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China. METHODS: In this prospective interventional case series, central corneal sensitivity (CCS) was measured using a Cochet-Bonnet esthesiometer (Luneau Ophthalmologie) in 85 eyes of 50 patients before and 2 weeks, 1 month, 3 months, and 6 months after LASEK for the treatment of myopia. For analysis, the eyes were divided into 2 groupsdthe low–moderate myopia group (spherical equivalent [SE] ÿ1.0 to ÿ6.0 diopters [D]) and the high myopia group (SE ÿ6.0 to ÿ16.0 D)dand the correlation between ablation depth and CCS was evaluated. RESULTS: In both groups, a significant decrease in CCS was present at 2 weeks and 1 month. In the low–moderate myopia group, the CCS recovered to preoperative values at 3 months. In the high myopia group, recovery of CCS was slower and preoperative values were reached only at the 6-month follow-up. Measured CCS was significantly correlated with the ablation depth used at the 3-month and 6-month examinations (r Z ÿ0.262 and r Z ÿ0.264, respectively; P<.05). CONCLUSION: Recovery of corneal sensitivity began 1 month after LASEK and was completed by 3 months in eyes treated for low–moderate myopia and at 6 months in eyes with high myopia. The depth of ablation during surgery affected the recovery of corneal sensitivity. J Cataract Refract Surg 2006; 32:785–788 Q 2006 ASCRS and ESCRS
Corneal innervation is essential for the maintenance of normal structure and function.1,2 Conditions such as viral keratitis and diabetic keratopathy affect the integrity of the corneal nerves and can result in significant corneal morbidity. Damage to corneal nerves can also be iatrogenic,
Accepted for publication August 6, 2005. From the Eye and ENT Hospital (Wu, Chu, Zhou, Dai, Qu), Fudan University, Shanghai, and the Department of Ophthalmology and Visual Science (Rao, Lam), the Chinese University of Hong Kong, Hong Kong, China. Supported by a grant (NO. 30371506) from the National Natural Science Foundation of China. No author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Ren.Y Chu, MD, 83 Fenyang Road, Shanghai, China. E-mail: [email protected]. Q 2006 ASCRS and ESCRS Published by Elsevier Inc.
resulting from surgical procedures. Knowledge of these effects is important to improve our understanding of corneal healing in these situations and can improve surgical outcomes. Corneal refractive surgery using the excimer laser is currently the most popular approach for the treatment of refractive errors. Laser in situ keratomileusis (LASIK) allows quick recovery of visual acuity with minimal or no postoperative pain and is the preferred procedure. These advantages of LASIK are due to the removal of corneal stromal tissue under a flap of superficial corneal tissue. Creation of the corneal flap, however, results in transsection of the nerves in the anterior cornea, and subsequent laser ablation can result in further damage to the stromal nerves. This can result in marked reduction of corneal sensitivity after LASIK, especially in the central cornea.3–5 Studies report that recovery of central corneal sensitivity (CCS) in these eyes may take 6 to 12 months.2–5 One of the important 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.01.066
785
CORNEAL SENSITIVITY RECOVERY AFTER LASEK
consequences of decreased CCS is the occurrence of a temporary tear dysfunction state following LASIK. Laser-assisted subepithelial keratectomy (LASEK), a recent variant of excimer refractive surgery, requires the creation of an epithelial flap using chemodisruption of corneal epithelial attachment complexes. Compared with photorefractive keratectomy (PRK), LASEK results in less pain and corneal haze. Because a flap of stromal tissue is not created, it may preserve corneal integrity better than LASIK and the availablilty of more stromal tissue for remodeling allows the safe treatment of refractive errors in eyes with thin corneas. A recent clinical study reported that recovery of CCS and tear-film function after LASEK may occur as early as 1 month after surgery.6 The preoperative mean spherical equivalent (SE) among patients in the study was ÿ4.0 diopters (D). Because LASEK is currently used in the treatment of high myopia and it is likely that greater nerve damage can result from deeper ablations, we evaluated the recovery of CCS in eyes with low–moderate and high myopic LASEK. PATIENTS AND METHODS The prospective interventional case series comprised 50 patients (85 eyes) who had LASEK for myopic correction from June to July 2004. Exclusion criteria included a history of corneal trauma or past surgery, viral keratitis, and systemic diseases such as diabetes or connective-tissue diseases. The washout period for long-term contact lens users (more than 5 years) was at least 2 weeks. Informed consent was obtained from all patients. During LASEK, an incision in the epithelium was made using a special microtrephine (Kangning Medical Electronic Equipment Development Co.). After ethanol 20% was applied for 10 to 20 seconds (mean 15 seconds), a superior hinged epithelial flap was created. All laser ablations were performed with the Carl Zeiss Meditec MEL 80 laser system, and the ablation diameter was chosen based on the scotopic pupil diameter. After laser ablation, the stromal surface was irrigated with balanced salt solution and the epithelial flap was repositioned. A 14 mm soft contact lens was used as a bandage for 3 to 7 days until epithelial healing was completed. Postoperatively, ofloxicin 0.3% eyedrops were used for 2 weeks and fluorometholone 0.1% eyedrops were used for 2 to 3 months. Central corneal sensitivity was examined preoperatively and 2 weeks, 1 month, 3 months, and 6 months postoperatively by the same observer using a Cochet & Bonnet esthesiometer (Luneau
Ophthalmologie). The maximal filament length of 60 mm, which corresponds to the lowest possible pressure, was used first, and length was subsequently decreased in 5 mm steps until the patient could perceive the sensation. The results were expressed as filament lengths (millimeters). Three measurements were performed at each filament length. Data are presented as mean G SD. Corneal haze levels were evaluated at 3 and 6 months using slitlamp biomicroscopy and were graded from 0 to 4.7 Continuous variables were evaluated using the paired t test. Between-group differences were assessed using the independent t test. The relationship between CCS and ablation depth was assessed by Spearman rank correlation analysis. All statistical analyses were performed using the SPSS software package. A 2-tailed P value less than 0.05 was considered statistically significant. RESULTS
The patient demographics and the myopic status of the eyes are shown in Table 1. For analysis, eyes were divided into 2 groups according to the preoperative SE refraction: the low–moderate myopia group (SE ÿ1.0 to ÿ6.0 D) and the high myopia group (SE ÿ6.0 to ÿ16.0 D). There was no difference in time of ethanol application and ablation diameters between the 2 groups (PO.05) (Table 1). The corneal haze levels in the 2 groups at 3 and 6 months are shown in Table 2. Most eyes in the low–moderate myopia group had no haze throughout the study period. In the high myopia group, 12.96% of eyes had grade 1 haze and 3.71% had grade 2 haze at 3 months and this increased slightly to 16.67% and 5.56%, respectively, at the 6-month visit. No eye had greater than grade 2 haze during the study. Central corneal sensitivity scores are shown in Table 3. In the low–moderate myopia group, a significant decrease in CCS was seen at 2 weeks and 1 month (t Z 3.85 and t Z 4.85, respectively; P!.05). At 3 months, the CCS was not significantly different from the preoperative value, but a slight further improvement was noted at the 6-month visit. In the high myopia group, a significant decrease was noted at the 2-week and 1-month visits (t Z 7.05 and t Z 7.51, respectively; P!.05). Unlike in the low–moderate myopia group, this difference was still significantly lower at 3 months (t Z 4.40, P!.05). At the 6-month visit, although the CCS value was less than the preoperative value, the difference was not statistically significant (Figure 1). In 3 eyes
Table 1. Patient and ocular characteristics.
Myopia Group
Number of Patients (M/F)
Low–moderate
22 (12/10)
High
28 (13/15)
Age (Y)
Preoperative SE (D)
23.61 G 6.59 ÿ3.68 G 1.56 (18 to 32) (ÿ1.25 to ÿ6.0) 28.57 G 7.43 ÿ10.70 G 3.81 (23 to 38) (ÿ6.25 to ÿ16.0)
Preoperative Pachymetry (mm)
Ablation Depth (mm)
539.74 G 35.26 (487 to 583) 525.18 G 33.96 (482 to 597)
72.36 G 23.30 (33 to 112) 128.98 G 20.28 (96 to 162)
Mean G SD (range) SE Z spherical equivalent
786
J CATARACT REFRACT SURG - VOL 32, MAY 2006
Ablation Time of Ethanol Diameter (mm) Application (s) 6.02 G 0.13 (5.75 to 6.25) 5.87 G 0.18 (5.5 to 6.0)
13.73 G 3.10 (8 to 18) 13.58 G 3.04 (8 to 20)
CORNEAL SENSITIVITY RECOVERY AFTER LASEK
Table 2. Corneal haze levels after LASEK.
Months After Surgery (% of eyes) 3
6
Corneal Haze Low–Moderate
High
Low–Moderate
High
0 0.5 1 2 3 4
38.89 44.44 12.96 3.71 0 0
93.55 6.45 0 0 0 0
35.18 42.59 16.67 5.56 0 0
90.32 9.68 0 0 0 0
central corneal sensitivity (mm)
60
50
40
30 low-moderate high
with a corneal haze of grade 2, the CCS remained decreased at the 6-month visit. A significant correlation between the CCS and ablation depth was present at 3 and 6 months (r Z ÿ0.262, P Z.013; r Z ÿ0.264, P Z.012) (Figure 2). DISCUSSION
The cornea is 1 of the most densely innervated tissues in the body. Most corneal nerve fibers are sensory and derived from the trigeminal nerve. Nerve bundles enter the cornea at the 3 o’clock and 9 o’clock peripheries in the anterior third of the stroma. Normal corneal sensitivity is essential to normal corneal structure and function, and corneal hypesthesia can compromise the protective blink reflex, reduce epithelial mitosis, delay wound healing, and result in decreased tear flow.8,9 Because corneal refractive procedures can damage nerve fibers, it is important to understand the effects of such alterations on corneal recovery after these procedures. In PRK, the nerve endings and fibers in the anterior stroma are destroyed in the area of laser ablation, and in the acute phase after PRK (0 to 4 weeks), corneal sensitivity is decreased. In the intermediate phase (4 to 6 weeks), the epithelium remodels to a normal structure and nerve fibers regenerate inside the ablated area. However, corneal sensitivity is still decreased and a large number of fibroblasts populate the anterior stroma, which may result in corneal haze and regression.10 Reports show that the recovery of CCS after PRK is achieved between 3 and 12 months after surgery. Recovery is generally faster after low myopic correction,11,12 and it is postulated that the slower recovery after high myopic correction could be due to the formation of
20
before
2w
1m
3m
6m
Figure 1. Changes in CCS after low–moderate and high myopic LASEK.
corneal haze and also the greater nerve destruction from the deeper ablation.13 In LASIK, nerve fiber damage occurs from 2 causes. First, a microkeratome is used to cut a superficial corneal stromal flap and severs superficial nerve fibers in the area of the flap. Fibers entering the corneal stroma in the region of the flap hinge tend to be spared. However, if the hinge is positioned superiorly, considerable damage can result since most of the fibers enter the corneal stroma at 3 o’clock and 9 o’clock. Second, laser ablation of the exposed stroma results in damage to the deeper nerve fibers. The flap is usually 75 to 160 mm thick, and the additional ablation depth is dependent on the myopic correction. Because most stromal nerves run in the anterior third of the stroma (approximately 200 mm from the surface), significant sensory deprivation of the cornea can result from the refractive procedure.11 Using in vivo confocal microscopy, Perez-Gomez and Efron14 noted a total disappearance of the subepithelial nerve fiber bundle 1 month after LASIK and a return to a normal appearance at 6 months. Other reports indicate that clinical recovery of CCS after LASIK may take 6 to 12 months.11–13 Laser-assisted subepithelial keratectomy, a modication of PRK, combines the advantages of PRK and LASIK. Experimental studies have shown that treatment with alcohol 20% for 30 seconds preserves the viability of most of the treated corneal epithelium.15,16 In our study, we used an even shorter time of 10 to 20 seconds to create the epithelial flap. Horwath-Winter et al.6 report that LASEK for the
Table 3. Central corneal sensitivity before and after surgery.
Central Corneal Sensitivity, Mean (Range) (mm) Group
Preoperative
2 Weeks
1 Month
3 Months
6 Months
Low–moderate 58.78 G 2.2 (55–60) 50.28 G 8.82* (25–55) 50.93 G 6.36* (40–60) 56.07 G 4.16 (50–60) 58.33 G 2.42 (55–60) High 58.90 G 2.1 (55–60) 48.80 G 9.79* (30–55) 48.17 G 8.17* (40–60) 54.50 G 5.65* (40–60) 55.45 G 10.63 (50–60) *Paired t test P!0.05
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CORNEAL SENSITIVITY RECOVERY AFTER LASEK
180
REFERENCES
160
1. Mu¨ller LJ, Marfurt CF, Kruse F, Tervo TMT. Corneal nerves: structure, contents, and function. Exp Eye Res 2003; 76:521–542; errata 2003; 77:253 2. Davis EA, Dohlman CH. Neurotrophic keratitis. Int Ophthalmol Clin 2001; 41:1–11 3. Donnenfeld ED, Solomon K, Perry HD, et al. The effect of hinge position on corneal sensation and dry eye after LASIK. Ophthalmology 2003; 110:1023–1029; discussion by CJ Rapuano, 1029– 1030 4. Donnenfeld ED, Ehrenhaus M, Solomon R, et al. Effect of hinge width on corneal sensation and dry eye after laser in situ keratomileusis. J Cataract Refract Surg 2004; 30:790–797 5. Nassaralla BA, McLeod SD, Nassaralla JJ Jr. Effect of myopic LASIK on human corneal sensitivity. Ophthalmology 2003; 110:497–502 6. Horwath-Winter J, Vidic B, Schwantzer G, Schmut O. Early changes in corneal sensation, ocular surface integrity, and tear-film function after laser-assisted subepithelial keratectomy. J Cataract Refract Surg 2004; 30:2316–2321 7. Fantes FE, Hanna KD, Waring GO III, et al. Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys. Arch Ophthalmol 1990; 108:665–675 8. Martin XY, Safran AB. Corneal hypoesthesia. Surv Ophthalmol 1988; 33:28–40; see notes, 217 9. Beuerman RW, Schimmelpfennig B. Sensory denervation of the rabbit cornea affects epithelial properties. Exp Neurol 1980; 69: 196–201 10. Kohlhaas M. Corneal sensation after cataract and refractive surgery. J Cataract Refract Surg 1998; 24:1399–1409 11. Pe´rez-Santonja JJ, Sakla HF, Cardona C, et al. Corneal sensitivity after photorefractive keratectomy and laser in situ keratomileusis for low myopia. Am J Ophthalmol 1999; 127:497–504 12. Kanellopoulos AJ, Pallikaris IG, Donnenfeld ED, et al. Comparison of corneal sensation following photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 1997; 23:34–38 13. Kohlhaas M, Klemm M, Bo¨hm A, et al. Corneal sensitivity after refractive surgery. Eur J Implant Refract Surg 1994; 6:319–323 14. Perez-Gomez I, Efron N. Change to corneal morphology after refractive surgery (myopic laser in situ keratomileusis) as viewed with a confocal microscope. Optom Vis Sci 2003; 80:690–697 15. Kim S-Y, Sah W-J, Lim Y-W, Hahn T-W. Twenty percent alcohol toxicity on rabbit corneal epithelial cells: electron microscopic study. Cornea 2002; 21:388–392 16. Song I-K, Joo C-K. Morphological and functional changes in the rat cornea with an ethanol-mediated epithelial flap. Invest Ophthalmol Vis Sci 2004; 45:423–428
ablation depth (µm)
140 120 100 80 60 DEEP sensitivity-6m
40 20 2.5
DEEP sensitivity-3m
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
central corneal sensitivity (Cm) Figure 2. Correlation between ablation depth and CCS 3 and 6 months after surgery.
correction of a low myopic error resulted in a short-term reduction in CCS of 1 month. The recovery of CCS after LASEK for low to moderate myopia in our study was slightly slower than that reported by Horwath-Winter et al.6 The recovery of CCS after LASEK for high myopic correction was even slower, especially in eyes with corneal haze of more than grade 1. Despite this, however, the CCS recovery after high myopic correction in our study was faster than that reported after PRK. We postulate that this could be due to the reduced corneal haze after LASEK, which may influence the regrowth of nerve fibers. In conclusion, our study indicates that the degree of myopic correction influences the speed of recovery of CCS after LASEK for the correction of myopia. Because there is a significant correlation between the occurrence of posttreatment corneal haze and the recovery of CCS, it appears that in addition to the depth of ablation, the occurrence of corneal scarring after LASEK may influence the recovery of CCS.
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