- Email: [email protected]
Recurrent Corneal Erosions Treated with Anterior Stromal Puncture by Neodymium: Yttrium–Aluminum–Garnet Laser
Recurrent Corneal Erosions Treated with Anterior Stromal Puncture by Neodymium: Yttrium–Aluminum–Garnet Laser Tzu-Yun Tsai, MD, Tzu-Hsun Tsai, MD, Fung-Rong Hu, MD, Yu-Chih Hou, MD Purpose: To evaluate the clinical outcomes in patients with recurrent corneal erosions who received anterior stromal puncture by use of neodymium:yttrium–aluminum– garnet (Nd:YAG) laser. Design: Retrospective, nonrandomized, consecutive case series. Participants: From 2000 to 2005, 33 eyes of 33 patients with unilaterally recurrent macroform corneal erosions showing poor response to conservative management who were treated with Nd:YAG laser were studied. Intervention: Anterior corneal stromal puncture with Nd:YAG laser was performed in the loosened epithelium or epithelial defect area. The causes and frequency of corneal erosions and the spot numbers and total energy of the Nd:YAG laser were recorded. Slit-lamp biomicroscopic examination, refraction, corneal topography, and times of laser were reviewed. A questionnaire regarding the preoperative and postoperative difference in the intensity of pain and frequency of corneal erosion was provided. Main Outcome Measures: Rate of recurrence and pain assessment by numerical rating scale. Results: Sixteen eyes were completely symptom free and 12 eyes had mild pain but no evidence of recurrent corneal erosion after operation. Five eyes had repeated episodes of recurrent corneal erosion. Eyes with a traumatic cause responded better to Nd:YAG laser therapy than those without. The frequency of corneal erosions and the severity of pain significantly improved in eyes with macroform and symptom-only recurrence. There was no significant change in refraction, but corneal surface regularity slightly improved after surgery. No adverse reaction was observed during follow-up. Conclusions: Anterior stromal puncture by Nd:YAG laser is an effective and simple procedure to treat recurrent corneal erosion. It can ameliorate the frequency of attacks and the intensity of pain. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:1296 –1300 © 2009 by the American Academy of Ophthalmology.
Recurrent corneal erosion is a relatively common condition and is characterized by repeated episodes of corneal epithelium breakdown resulting from a defect in adhesion to the basement membrane.1,2 This disorder usually is associated with superficial corneal trauma, but in some cases, it may be secondary to anterior corneal dystrophy or even may be idiopathic in origin.3 Most patients experience a sudden onset of severe eye pain, often at night or on first awakening, accompanied by redness, photophobia, and tearing. Individual episodes vary in severity and duration. Chandler4 classified recurrent corneal erosion into 2 main forms. Minor episodes (Chandler’s microform erosions) usually last from a few minutes to several hours and show no obvious epithelial defect at the time of slit-lamp examination. More severe episodes (Chandler’s macroform erosions) may persist over several days and are associated with intolerable pain, eyelid swelling, decreased vision, and photophobia. On slit-lamp examination, a frank epithelial defect or a loosened epithelium is noted. To date, a variety of treatment choices are available for recurrent corneal erosions, but none of them are definitive. Corneal abrasion often responds to conservative treatment with topical lubricants, pressure patching, or therapeutic bandage contact lens in the acute stage.5–7 However, approximately 5%
1296
© 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
of patients fail to achieve resolution of the acute episode,3 and approximately 60% of patients continue to have persistent symptoms.8 In these patients, more aggressive interventions are necessary, including simple epithelial debridement, alcohol delamination of the corneal epithelium,9 anterior stromal puncture with a needle,10,11 neodymium:yttrium–aluminum– garnet (Nd:YAG) laser treatment,12,13 superficial keratectomy with diamond burr,14 –16 or excimer laser phototherapeutic keratectomy.17–19 As compared with other treatment options, anterior stromal puncture with Nd:YAG laser is relatively simple and less painful. However, little has been documented in the literature regarding the efficacy of Nd:YAG laser on recurrent corneal erosions. One report demonstrated some success with Nd:YAG laser in 3 cases of recalcitrant recurrent corneal erosions.13 The present study aimed to evaluate the clinical outcomes after anterior stromal puncture with Nd:YAG laser in a consecutive series of 33 eyes of 33 patients with unilaterally recurrent corneal erosion.
Patients and Methods After institutional review board approval was obtained, a retrospective and nonrandomized study was carried out that included a total of 33 eyes of 33 patients with recurrent corneal erosions who ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.01.037
Tsai et al 䡠 Anterior Stromal Puncture for Recurrent Corneal Erosions received Nd:YAG laser treatment at the Department of Ophthalmology, National Taiwan University Hospital, from 2000 through 2005. Twenty patients were male and 13 patients were female, and the average age was 41.9 years (range, 20 –71 years). All patients occurred unilaterally and had documented macroform erosions and a history of more than 2 recurrences after conservative management with topical lubricants, patching, or therapeutic bandage contact lenses. All eyes were evaluated for the causes and frequency of corneal erosion and for presenting symptoms and underwent ophthalmologic examinations. Slit-lamp biomicroscopic examination in both eyes of each patient showed no evidence of anterior basement membrane dystrophy during the follow-up. All patients were asked to grade the pain retrospectively on a numerical rating scale before and after treatments. The intensity of pain was scored from 0 to 10 points, representing the spectrum of severity from no pain to very severe pain. The pain scales that best represented the severity of pain of every episode they were experiencing were recorded. Ophthalmologic examinations consisted of visual acuity, intraocular pressure, refraction, and slit-lamp biomicroscopic examination. Computerized videokeratographic examination (TMS-4; Tomey Corporation, Nagoya, Japan) was performed to evaluate corneal surface regularity in some of the cases. Anterior stromal puncture by Nd:YAG laser was performed in the loosened epithelial area or epithelial defect area without epithelial debridement after application of topical 0.5% proparacaine. Energy setting of Nd:YAG laser was 0.3 to 0.6 mJ per shot and was focused in corneal subepithelium or superficial stroma. After surgery, topical lubricant, sulfamethoxazole, and 0.1% fluorometholone 4 times daily and tetracycline ointment before sleep were used. Oral acetaminophen was used as necessary; however, most patients had only a mild foreign body sensation and did not require oral medication. The number of spots applied was dependent on the surface area of the loosening epithelium, ranging from 9 to 121 spots in these 33 eyes. After operation, all patients were followed up regularly at the outpatient clinic at 1 week, 4 weeks, 3 months, and 6 months. During postoperative visits, slit-lamp biomicroscopic examination and refraction were performed, and pertinent data were obtained from each patient. For those who were lost to follow-up after 6 months, information about their postoperative condition was acquired by telephone questionnaire. Recurrence was defined as the appearance of clinical symptoms accompanied by epithelial defects in the same area affected before treatments. Symptom free was defined as the absence of symptoms after surgery within the follow-up period. Based on their postoperative condition, the eyes were classified as being symptom free, with symptoms only, or with macroerosion recurrence. If corneal macroerosion recurred, conservative treatment or repeated Nd: YAG laser was administered, depending on the severity of the epithelial defect. Efficacy of the operation was evaluated by analyzing the recurrence rate in the cohort, the frequency of attacks, the amelioration of subjective pain, and the improvement of objective corneal surface regularity after surgery. Factors that may affect the recurrence of corneal erosion, including age, cause, preoperative attack frequency, and laser dosage, also were compared among the 3 groups. Statistical analyses were carried out using SPSS for Windows software version 11.0.1 (SPSS, Inc., Chicago, IL). The 2-tailed paired t test, Fisher exact test, and Wilcoxon signed-ranks test were used to compare difference between 2 groups. A 1-way analysis of variance was used to make comparisons among the 3 groups. A difference was significant if the P value was less than 0.05.
Results The demographic characteristics, clinical features, and causes of recurrent corneal erosion in the 33 eyes are summarized in Table 1. In 24 (73%) eyes, recurrent corneal erosion was attributed to trauma, whereas the underlying causes could not be identified in the other 9 (27%) eyes. The preoperative frequency of symptoms of corneal erosion ranged from 1.5 to 96 episodes per year. Clinical outcomes for all eyes are presented in Table 2. Sixteen (49%) eyes were completely symptom free after operation, and 12 (36%) eyes had subjectively mild symptoms but in the absence of macroform erosion (symptom-only group). The remaining 5 (15%) eyes had obvious symptoms with recurrence of documented corneal epithelial defects on the slit-lamp examination. Age did not differ significantly among the 3 groups (P⬎0.05, analysis of variance). A trauma history was recalled in 15 (94%) eyes in the symptom-free group, but was reported in 9 (52%) eyes in the symptom-only group and the with macroerosion group. There was a significant difference between the 2 groups (P⬍0.05, Fisher exact test). Preoperative attack frequency and Nd:YAG energy were not significantly different among the 3 groups (both P⬎0.05, analysis of variance). In both the symptoms only and with macroerosion recurrence groups, there was a significant difference between the preoperative and postoperative attack frequencies (P⬍0.05, paired t test). Likewise, a decrease in frequency was observed in the 5 eyes with concomitant recurrent macroerosion (P⬍0.05, paired t test). In these 17 eyes in the with symptoms only and with macroerosion recurrence groups, the preoperative pain score was compared with the highest score at the time of postoperative recurrence individually, and the subjective pain scores were all decreased as compared with preoperative status (P⬍0.01, Wilcoxon signed-ranks test). The subjective intensity of pain during the recurrence of symptom attacks significantly diminished with the mean pain score from 8 before surgery to 2 after surgery. Four of the 5 eyes in the with macroerosion recurrence group received further Nd:YAG laser treatment after recurrence. Further Nd:YAG laser enhancement ameliorated the symptoms both in terms of the frequency of the attacks and the intensity of the pain. The remaining 1 eye had a low-grade myopia and received photorefractive keratectomy for myopic correction. After photorefractive keratectomy, this eye was symptom free and had no further recurrence.
Table 1. Demographic Characteristics and Clinical Features of the 33 Eyes
Variables Age (mean⫾SD), yrs Range Gender (male:female) Cause, no. (%) Trauma Unknown Preoperative frequency, episodes/yr Mean⫾SD Range YAG pulse, spots YAG total energy, mJ Follow-up, mos
Cases Receiving Neodymium:Yttrium–Aluminum–Garnet Laser Treatment (n ⴝ 33) 41.9⫾12.8 20–71 20:13 24 (73%) 9 (27%)
13.5⫾17.5 1.5–96 9–121 3–60 18–48
SD ⫽ standard deviation; YAG ⫽ yttrium–aluminum– garnet.
1297
Ophthalmology Volume 116, Number 7, July 2009 Table 2. Outcome of Neodymium:Yttrium–Aluminum–Garnet Laser Treatment
Age (yrs) Cause (traumatic:unknown) Preoperative frequency (episodes/yr) YAG energy (mJ) Postoperative frequency (episodes/yr)
Eyes without Recurrence* (n ⴝ 16)
Eyes with Symptom Only (n ⴝ 12)
Eyes with Macroerosion Recurrence (n ⴝ 5)
45.5⫾14.1 15:1† 9.8⫾8.7 0.33⫾0.10 0
38.8⫾10.6 6:6† 18.9⫾26.7‡ 0.35⫾0.08 2.0⫾1.1‡
38.0⫾12.2 3:2 12.2⫾7.9‡ 0.35⫾0.10 1.9⫾0.9‡
YAG ⫽ neodymium:yttrium–aluminum– garnet. *No recurrence during at least 1.5 years of follow-up. † P⬍0.05, Fisher exact test. ‡ P⬍0.05, paired t test.
Corneal epithelium consists of nearly 7 layers of epithelial cells that lie above the basement membrane. In recurrent corneal erosion, the presumptive cause is failure of the wounded epithelial cells to adhere to the underlying stroma, probably because of weak hemidesmosomal attachment,20 reduplication of the basement membrane, the action of metalloproteinases,21 and disruption of type VII collagen
fibrils.22 Therefore, the aim of anterior stromal puncture is to induce a localized subepithelial fibrosis and to increase adhesion of the epithelium. Anterior stromal puncture is a well-accepted treatment for recurrent corneal erosions.10,11,23,24 Initially, early pioneers of this approach used a microdiathermy needle,25 a large-bore 20-gauge needle,24 and a specially designed 25or 27-gauge needle10 to perform anterior stromal puncture. The corresponding success rates in these series, as calculated by no recurrence of macroerosion of the cornea, ranged from 76% to 94%. The Nd:YAG laser was later introduced in the 1990s. In comparison with previous instruments, the Nd:YAG laser has the advantages of a minute and uniform wound with less corneal scarring, so the procedure could be repeated whenever necessary.12,13 In the present study, among the 33 consecutive subjects who received Nd:YAG laser anterior stromal puncture, macroerosion of the cornea developed again in only 5 (15%) of the eyes. The success rate of 85% is comparable with that of previous anterior stromal puncture reports. Furthermore, whether eyes had history of trauma was a significant factor associated with the success of treatment, rather than age, preoperative attack frequency, or
Figure 1. Graph showing the percentage of eyes without recurrence as a function of follow-up.
Figure 2. Graph showing the percentage of eyes without macroerosion recurrence as a function of follow-up.
The percentage of eyes without symptoms as a function of follow-up time is demonstrated in Figure 1, and those without macroerosion recurrence are depicted in Figure 2. Although symptoms developed again in many after anterior stromal puncture by Nd:YAG laser, obvious corneal erosion recurred in only approximately 15% of eyes after 15 months of follow-up. After surgery, refractions did not change significantly from before surgery with treatment (Table 3). Corneal topography was performed in 6 eyes, and the results showed a slight improvement in surface regularity after the operation but without statistical significance. No adverse reaction, such as corneal haze or endothelium or lens damage, was observed during follow-up.
Discussion
1298
Tsai et al 䡠 Anterior Stromal Puncture for Recurrent Corneal Erosions Table 3. Comparison between Preoperative and Postoperative Pain, Refraction, and Topographic Modeling System
Pain scores (n ⫽ 17) Median (range) Refraction, diopters (n ⫽ 33) Range SRI with TMS‡ Mean⫾SD Range
Preoperative
Postoperative
P Value
8 (6–10)
2 (1–5)
⬍0.01*
1.25 to ⫺9.5
1.0 to ⫺9.5
0.80†
2.39⫾1.80 0.56–4.56
0.68⫾0.16 0.57–1.0
0.06†
SD ⫽ standard deviation; SRI ⫽ surface regularity index; TMS ⫽ topographic modeling system. *Wilcoxon signed-rank test. † Paired t test. ‡ Comparison feasible in 6 patients.
the amount of laser energy. Eyes with traumatic history were inferred to have had limited damage and relatively normal microstructure of corneal basement membrane; therefore, those eyes could respond better to the laser treatment. The Nd:YAG laser may be less effective in treating corneal erosions caused by pathologically abnormal basement membrane. Further long-term follow-up, in vivo confocal microscopic studies, and possible ultrastructural studies of corneal specimens may help to investigate the different responses in the cause of trauma. In accordance with previous reports, symptoms may recur in some patients. In this study, 17 (51%) eyes experienced recurrent pain again after operation, but the frequency of the corneal erosion attacks, as well as the severity of pain improved significantly. Although Nd:YAG therapy did not completely cure corneal erosion in these patients, it apparently reduced the frequency of recurrence and the severity of discomfort. Previous studies regarding the management of recurrent corneal erosions have reported 50%5 to 95%3 success rates by conservative treatment. However, using a 4-year telephone questionnaire for follow-up, Heyworth et al8 found that 59% of the patients initially treated with topical lubricants were still symptomatic. Over the following decades, other alternative strategies were advocated. Positive results using diamond burr superficial keratectomy16 and alcohol delamination of corneal epithelium9 have been reported. In 1983, Buxton and Fox15 reported an 85% success rate with total superficial keratectomy, and an expanded study published in 1987 showed promising results with 97% successful outcomes.14 However, superficial keratectomy procedure requires removal of a loosening epithelial sheet, which may lead to more severe pain and may take a longer time for complete reepithelialization. The current procedure maintained the loose epithelial sheet and used Nd:YAG laser to perform anterior stromal puncture under the loose epithelial sheet. In most of the patients, pain was not increased and disappeared in 1 or 2 days. Incidentally, anterior stromal puncture was performed with an invisible Nd:YAG laser energy pulse instead of a visible needle, which may terrify some of patients. Phototherapeutic keratectomy is another well-known treatment option, with success rates ranging from 50% to 100%.17–19,26 However, phototherapeutic ker-
atectomy may induce hyperopic shift, especially after deep ablation and corneal haziness. Phototherapeutic keratectomy may not be performed easily in the peripheral areas of cornea and can induce irregular astigmatism if the treated depth is too deep. Surgery-associated disadvantages such as its time-consuming nature, increased postoperative pain, and higher risk of postoperative change in refraction status should be of concern. Furthermore, phototherapeutic keratectomy requires expensive and highly sophisticated equipment—an excimer laser—and costs more than superficial keratectomy and anterior stromal puncture. In this series, the refraction status of the patients remained stable after the treatment, and computerized videokeratographic examination revealed improved corneal regularity. The procedure was not painful and could be executed quickly. In conclusion, anterior stromal puncture by Nd:YAG laser is an effective and simple procedure to treat recurrent corneal erosion. The success rate was 85%. Patients with a traumatic cause showed a better response than those with an unknown cause. In those with microform or macroform recurrence after operation, the Nd:YAG laser ameliorated the symptoms both in terms of the frequency of the attacks and the intensity of the pain. It could be performed easily in the outpatient setting without serious adverse complications.
References 1. Aitken DA, Beirouty ZA, Lee WR. Ultrastructural study of the corneal epithelium in the recurrent erosion syndrome. Br J Ophthalmol 1995;79:282–9. 2. Goldman JN, Dohlman CH, Kravitt BA. The basement membrane of the human cornea in recurrent epithelial erosion syndrome. Trans Am Acad Ophthalmol Otolaryngol 1969;73: 471– 81. 3. Hykin PG, Foss AE, Pavesio C, Dart JK. The natural history and management of recurrent corneal erosion: a prospective randomised trial. Eye 1994;8:35– 40. 4. Chandler PA. Recurrent erosion of the cornea. Trans Am Ophthalmol Soc 1944;42:355–71. 5. Reidy JJ, Paulus MP, Gona S. Recurrent erosions of the cornea: epidemiology and treatment. Cornea 2000;19:767–71. 6. Kenyon KR. Recurrent corneal erosion: pathogenesis and therapy. Int Ophthalmol Clin 1979;19:169 –95. 7. Brown N, Bron A. Recurrent erosion of the cornea. Br J Ophthalmol 1976;60:84 –96. 8. Heyworth P, Morlet N, Rayner S, et al. Natural history of recurrent erosion syndrome—a 4 year review of 117 patients. Br J Ophthalmol 1998;82:26 – 8. 9. Dua HS, Lagnado R, Raj D, et al. Alcohol delamination of the corneal epithelium: an alternative in the management of recurrent corneal erosions. Ophthalmology 2006;113:404 –11. 10. Rubinfeld RS, Laibson PR, Cohen EJ, et al. Anterior stromal puncture for recurrent erosion: further experience and new instrumentation. Ophthalmic Surg 1990;21:318 –26. 11. McLean EN, MacRae SM, Rich LF. Recurrent erosion: treatment by anterior stromal puncture. Ophthalmology 1986;93:784 – 8. 12. Geggel HS, Maza CE. Anterior stromal puncture with the Nd:YAG laser. Invest Ophthalmol Vis Sci 1990;31:1555–9. 13. Geggel HS. Successful treatment of recurrent corneal erosion with Nd:YAG anterior stromal puncture. Am J Ophthalmol 1990;110:404 –7.
1299
Ophthalmology Volume 116, Number 7, July 2009 14. Buxton JN, Constad WH. Superficial epithelial keratectomy in the treatment of epithelial basement membrane dystrophy. Ann Ophthalmol 1987;19:92– 6. 15. Buxton JN, Fox ML. Superficial epithelial keratectomy in the treatment of epithelial basement membrane dystrophy: a preliminary report. Arch Ophthalmol 1983;101:392–5. 16. Soong HK, Farjo Q, Meyer RF, Sugar A. Diamond burr superficial keratectomy for recurrent corneal erosions. Br J Ophthalmol 2002;86:296 – 8. 17. Holzer MP, Auffarth GU, Specht H, Kruse FE. Combination of transepithelial phototherapeutic keratectomy and autologous serum eyedrops for treatment of recurrent corneal erosions. J Cataract Refract Surg 2005;31:1603– 6. 18. Ardjomand N, Fellner P, Vidic B. Phototherapeutic keratectomy with an epithelial flap for recurrent erosion syndrome. J Cataract Refract Surg 2004;30:543–5. 19. Maini R, Loughnan MS. Phototherapeutic keratectomy retreatment for recurrent corneal erosion syndrome. Br J Ophthalmol 2002;86:270 –2.
20. Tripathi RC, Bron AJ. Ultrastructural study of nontraumatic recurrent corneal erosion. Br J Ophthalmol 1972; 56:73– 85. 21. Garrana RM, Zieske JD, Assouline M, Gipson IK. Matrix metalloproteinases in epithelia from human recurrent corneal erosion. Invest Ophthalmol Vis Sci 1999;40:1266 –70. 22. Chen YT, Huang CW, Huang FC, et al. The cleavage plane of corneal epithelial adhesion complex in traumatic recurrent corneal erosion. Mol Vis 2006;12:196 –204. 23. Malecha MA. Anterior stromal puncture for recurrent corneal erosion after laser in situ keratomileusis. J Cataract Refract Surg 2004;30:496 – 8. 24. McLean EN. Update on stromal puncture technique [letter]. Ophthalmology 1990;97:1245. 25. Wood TO. Recurrent erosion. Trans Am Ophthalmol Soc 1984;82:850 –98. 26. Ohman L, Fagerholm P, Tengroth B. Treatment of recurrent corneal erosions with the excimer laser. Acta Ophthalmol (Cophenh) 1994;72:461–3.
Footnotes and Financial Disclosures Originally received: September 5, 2008. Final revision: January 23, 2009. Accepted: January 26, 2009. Available online: May 8, 2009.
Supported by the Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Manuscript no. 2008-1066.
Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
1300
Correspondence: Yu-Chih Hou, MD, Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei 10002, Taiwan. E-mail: ychou51@ntu. edu.tw.
Recurrent corneal erosion is a relatively common condition and is characterized by repeated episodes of corneal epithelium breakdown resulting from a defect in adhesion to the basement membrane.1,2 This disorder usually is associated with superficial corneal trauma, but in some cases, it may be secondary to anterior corneal dystrophy or even may be idiopathic in origin.3 Most patients experience a sudden onset of severe eye pain, often at night or on first awakening, accompanied by redness, photophobia, and tearing. Individual episodes vary in severity and duration. Chandler4 classified recurrent corneal erosion into 2 main forms. Minor episodes (Chandler’s microform erosions) usually last from a few minutes to several hours and show no obvious epithelial defect at the time of slit-lamp examination. More severe episodes (Chandler’s macroform erosions) may persist over several days and are associated with intolerable pain, eyelid swelling, decreased vision, and photophobia. On slit-lamp examination, a frank epithelial defect or a loosened epithelium is noted. To date, a variety of treatment choices are available for recurrent corneal erosions, but none of them are definitive. Corneal abrasion often responds to conservative treatment with topical lubricants, pressure patching, or therapeutic bandage contact lens in the acute stage.5–7 However, approximately 5%
1296
© 2009 by the American Academy of Ophthalmology Published by Elsevier Inc.
of patients fail to achieve resolution of the acute episode,3 and approximately 60% of patients continue to have persistent symptoms.8 In these patients, more aggressive interventions are necessary, including simple epithelial debridement, alcohol delamination of the corneal epithelium,9 anterior stromal puncture with a needle,10,11 neodymium:yttrium–aluminum– garnet (Nd:YAG) laser treatment,12,13 superficial keratectomy with diamond burr,14 –16 or excimer laser phototherapeutic keratectomy.17–19 As compared with other treatment options, anterior stromal puncture with Nd:YAG laser is relatively simple and less painful. However, little has been documented in the literature regarding the efficacy of Nd:YAG laser on recurrent corneal erosions. One report demonstrated some success with Nd:YAG laser in 3 cases of recalcitrant recurrent corneal erosions.13 The present study aimed to evaluate the clinical outcomes after anterior stromal puncture with Nd:YAG laser in a consecutive series of 33 eyes of 33 patients with unilaterally recurrent corneal erosion.
Patients and Methods After institutional review board approval was obtained, a retrospective and nonrandomized study was carried out that included a total of 33 eyes of 33 patients with recurrent corneal erosions who ISSN 0161-6420/09/$–see front matter doi:10.1016/j.ophtha.2009.01.037
Tsai et al 䡠 Anterior Stromal Puncture for Recurrent Corneal Erosions received Nd:YAG laser treatment at the Department of Ophthalmology, National Taiwan University Hospital, from 2000 through 2005. Twenty patients were male and 13 patients were female, and the average age was 41.9 years (range, 20 –71 years). All patients occurred unilaterally and had documented macroform erosions and a history of more than 2 recurrences after conservative management with topical lubricants, patching, or therapeutic bandage contact lenses. All eyes were evaluated for the causes and frequency of corneal erosion and for presenting symptoms and underwent ophthalmologic examinations. Slit-lamp biomicroscopic examination in both eyes of each patient showed no evidence of anterior basement membrane dystrophy during the follow-up. All patients were asked to grade the pain retrospectively on a numerical rating scale before and after treatments. The intensity of pain was scored from 0 to 10 points, representing the spectrum of severity from no pain to very severe pain. The pain scales that best represented the severity of pain of every episode they were experiencing were recorded. Ophthalmologic examinations consisted of visual acuity, intraocular pressure, refraction, and slit-lamp biomicroscopic examination. Computerized videokeratographic examination (TMS-4; Tomey Corporation, Nagoya, Japan) was performed to evaluate corneal surface regularity in some of the cases. Anterior stromal puncture by Nd:YAG laser was performed in the loosened epithelial area or epithelial defect area without epithelial debridement after application of topical 0.5% proparacaine. Energy setting of Nd:YAG laser was 0.3 to 0.6 mJ per shot and was focused in corneal subepithelium or superficial stroma. After surgery, topical lubricant, sulfamethoxazole, and 0.1% fluorometholone 4 times daily and tetracycline ointment before sleep were used. Oral acetaminophen was used as necessary; however, most patients had only a mild foreign body sensation and did not require oral medication. The number of spots applied was dependent on the surface area of the loosening epithelium, ranging from 9 to 121 spots in these 33 eyes. After operation, all patients were followed up regularly at the outpatient clinic at 1 week, 4 weeks, 3 months, and 6 months. During postoperative visits, slit-lamp biomicroscopic examination and refraction were performed, and pertinent data were obtained from each patient. For those who were lost to follow-up after 6 months, information about their postoperative condition was acquired by telephone questionnaire. Recurrence was defined as the appearance of clinical symptoms accompanied by epithelial defects in the same area affected before treatments. Symptom free was defined as the absence of symptoms after surgery within the follow-up period. Based on their postoperative condition, the eyes were classified as being symptom free, with symptoms only, or with macroerosion recurrence. If corneal macroerosion recurred, conservative treatment or repeated Nd: YAG laser was administered, depending on the severity of the epithelial defect. Efficacy of the operation was evaluated by analyzing the recurrence rate in the cohort, the frequency of attacks, the amelioration of subjective pain, and the improvement of objective corneal surface regularity after surgery. Factors that may affect the recurrence of corneal erosion, including age, cause, preoperative attack frequency, and laser dosage, also were compared among the 3 groups. Statistical analyses were carried out using SPSS for Windows software version 11.0.1 (SPSS, Inc., Chicago, IL). The 2-tailed paired t test, Fisher exact test, and Wilcoxon signed-ranks test were used to compare difference between 2 groups. A 1-way analysis of variance was used to make comparisons among the 3 groups. A difference was significant if the P value was less than 0.05.
Results The demographic characteristics, clinical features, and causes of recurrent corneal erosion in the 33 eyes are summarized in Table 1. In 24 (73%) eyes, recurrent corneal erosion was attributed to trauma, whereas the underlying causes could not be identified in the other 9 (27%) eyes. The preoperative frequency of symptoms of corneal erosion ranged from 1.5 to 96 episodes per year. Clinical outcomes for all eyes are presented in Table 2. Sixteen (49%) eyes were completely symptom free after operation, and 12 (36%) eyes had subjectively mild symptoms but in the absence of macroform erosion (symptom-only group). The remaining 5 (15%) eyes had obvious symptoms with recurrence of documented corneal epithelial defects on the slit-lamp examination. Age did not differ significantly among the 3 groups (P⬎0.05, analysis of variance). A trauma history was recalled in 15 (94%) eyes in the symptom-free group, but was reported in 9 (52%) eyes in the symptom-only group and the with macroerosion group. There was a significant difference between the 2 groups (P⬍0.05, Fisher exact test). Preoperative attack frequency and Nd:YAG energy were not significantly different among the 3 groups (both P⬎0.05, analysis of variance). In both the symptoms only and with macroerosion recurrence groups, there was a significant difference between the preoperative and postoperative attack frequencies (P⬍0.05, paired t test). Likewise, a decrease in frequency was observed in the 5 eyes with concomitant recurrent macroerosion (P⬍0.05, paired t test). In these 17 eyes in the with symptoms only and with macroerosion recurrence groups, the preoperative pain score was compared with the highest score at the time of postoperative recurrence individually, and the subjective pain scores were all decreased as compared with preoperative status (P⬍0.01, Wilcoxon signed-ranks test). The subjective intensity of pain during the recurrence of symptom attacks significantly diminished with the mean pain score from 8 before surgery to 2 after surgery. Four of the 5 eyes in the with macroerosion recurrence group received further Nd:YAG laser treatment after recurrence. Further Nd:YAG laser enhancement ameliorated the symptoms both in terms of the frequency of the attacks and the intensity of the pain. The remaining 1 eye had a low-grade myopia and received photorefractive keratectomy for myopic correction. After photorefractive keratectomy, this eye was symptom free and had no further recurrence.
Table 1. Demographic Characteristics and Clinical Features of the 33 Eyes
Variables Age (mean⫾SD), yrs Range Gender (male:female) Cause, no. (%) Trauma Unknown Preoperative frequency, episodes/yr Mean⫾SD Range YAG pulse, spots YAG total energy, mJ Follow-up, mos
Cases Receiving Neodymium:Yttrium–Aluminum–Garnet Laser Treatment (n ⴝ 33) 41.9⫾12.8 20–71 20:13 24 (73%) 9 (27%)
13.5⫾17.5 1.5–96 9–121 3–60 18–48
SD ⫽ standard deviation; YAG ⫽ yttrium–aluminum– garnet.
1297
Ophthalmology Volume 116, Number 7, July 2009 Table 2. Outcome of Neodymium:Yttrium–Aluminum–Garnet Laser Treatment
Age (yrs) Cause (traumatic:unknown) Preoperative frequency (episodes/yr) YAG energy (mJ) Postoperative frequency (episodes/yr)
Eyes without Recurrence* (n ⴝ 16)
Eyes with Symptom Only (n ⴝ 12)
Eyes with Macroerosion Recurrence (n ⴝ 5)
45.5⫾14.1 15:1† 9.8⫾8.7 0.33⫾0.10 0
38.8⫾10.6 6:6† 18.9⫾26.7‡ 0.35⫾0.08 2.0⫾1.1‡
38.0⫾12.2 3:2 12.2⫾7.9‡ 0.35⫾0.10 1.9⫾0.9‡
YAG ⫽ neodymium:yttrium–aluminum– garnet. *No recurrence during at least 1.5 years of follow-up. † P⬍0.05, Fisher exact test. ‡ P⬍0.05, paired t test.
Corneal epithelium consists of nearly 7 layers of epithelial cells that lie above the basement membrane. In recurrent corneal erosion, the presumptive cause is failure of the wounded epithelial cells to adhere to the underlying stroma, probably because of weak hemidesmosomal attachment,20 reduplication of the basement membrane, the action of metalloproteinases,21 and disruption of type VII collagen
fibrils.22 Therefore, the aim of anterior stromal puncture is to induce a localized subepithelial fibrosis and to increase adhesion of the epithelium. Anterior stromal puncture is a well-accepted treatment for recurrent corneal erosions.10,11,23,24 Initially, early pioneers of this approach used a microdiathermy needle,25 a large-bore 20-gauge needle,24 and a specially designed 25or 27-gauge needle10 to perform anterior stromal puncture. The corresponding success rates in these series, as calculated by no recurrence of macroerosion of the cornea, ranged from 76% to 94%. The Nd:YAG laser was later introduced in the 1990s. In comparison with previous instruments, the Nd:YAG laser has the advantages of a minute and uniform wound with less corneal scarring, so the procedure could be repeated whenever necessary.12,13 In the present study, among the 33 consecutive subjects who received Nd:YAG laser anterior stromal puncture, macroerosion of the cornea developed again in only 5 (15%) of the eyes. The success rate of 85% is comparable with that of previous anterior stromal puncture reports. Furthermore, whether eyes had history of trauma was a significant factor associated with the success of treatment, rather than age, preoperative attack frequency, or
Figure 1. Graph showing the percentage of eyes without recurrence as a function of follow-up.
Figure 2. Graph showing the percentage of eyes without macroerosion recurrence as a function of follow-up.
The percentage of eyes without symptoms as a function of follow-up time is demonstrated in Figure 1, and those without macroerosion recurrence are depicted in Figure 2. Although symptoms developed again in many after anterior stromal puncture by Nd:YAG laser, obvious corneal erosion recurred in only approximately 15% of eyes after 15 months of follow-up. After surgery, refractions did not change significantly from before surgery with treatment (Table 3). Corneal topography was performed in 6 eyes, and the results showed a slight improvement in surface regularity after the operation but without statistical significance. No adverse reaction, such as corneal haze or endothelium or lens damage, was observed during follow-up.
Discussion
1298
Tsai et al 䡠 Anterior Stromal Puncture for Recurrent Corneal Erosions Table 3. Comparison between Preoperative and Postoperative Pain, Refraction, and Topographic Modeling System
Pain scores (n ⫽ 17) Median (range) Refraction, diopters (n ⫽ 33) Range SRI with TMS‡ Mean⫾SD Range
Preoperative
Postoperative
P Value
8 (6–10)
2 (1–5)
⬍0.01*
1.25 to ⫺9.5
1.0 to ⫺9.5
0.80†
2.39⫾1.80 0.56–4.56
0.68⫾0.16 0.57–1.0
0.06†
SD ⫽ standard deviation; SRI ⫽ surface regularity index; TMS ⫽ topographic modeling system. *Wilcoxon signed-rank test. † Paired t test. ‡ Comparison feasible in 6 patients.
the amount of laser energy. Eyes with traumatic history were inferred to have had limited damage and relatively normal microstructure of corneal basement membrane; therefore, those eyes could respond better to the laser treatment. The Nd:YAG laser may be less effective in treating corneal erosions caused by pathologically abnormal basement membrane. Further long-term follow-up, in vivo confocal microscopic studies, and possible ultrastructural studies of corneal specimens may help to investigate the different responses in the cause of trauma. In accordance with previous reports, symptoms may recur in some patients. In this study, 17 (51%) eyes experienced recurrent pain again after operation, but the frequency of the corneal erosion attacks, as well as the severity of pain improved significantly. Although Nd:YAG therapy did not completely cure corneal erosion in these patients, it apparently reduced the frequency of recurrence and the severity of discomfort. Previous studies regarding the management of recurrent corneal erosions have reported 50%5 to 95%3 success rates by conservative treatment. However, using a 4-year telephone questionnaire for follow-up, Heyworth et al8 found that 59% of the patients initially treated with topical lubricants were still symptomatic. Over the following decades, other alternative strategies were advocated. Positive results using diamond burr superficial keratectomy16 and alcohol delamination of corneal epithelium9 have been reported. In 1983, Buxton and Fox15 reported an 85% success rate with total superficial keratectomy, and an expanded study published in 1987 showed promising results with 97% successful outcomes.14 However, superficial keratectomy procedure requires removal of a loosening epithelial sheet, which may lead to more severe pain and may take a longer time for complete reepithelialization. The current procedure maintained the loose epithelial sheet and used Nd:YAG laser to perform anterior stromal puncture under the loose epithelial sheet. In most of the patients, pain was not increased and disappeared in 1 or 2 days. Incidentally, anterior stromal puncture was performed with an invisible Nd:YAG laser energy pulse instead of a visible needle, which may terrify some of patients. Phototherapeutic keratectomy is another well-known treatment option, with success rates ranging from 50% to 100%.17–19,26 However, phototherapeutic ker-
atectomy may induce hyperopic shift, especially after deep ablation and corneal haziness. Phototherapeutic keratectomy may not be performed easily in the peripheral areas of cornea and can induce irregular astigmatism if the treated depth is too deep. Surgery-associated disadvantages such as its time-consuming nature, increased postoperative pain, and higher risk of postoperative change in refraction status should be of concern. Furthermore, phototherapeutic keratectomy requires expensive and highly sophisticated equipment—an excimer laser—and costs more than superficial keratectomy and anterior stromal puncture. In this series, the refraction status of the patients remained stable after the treatment, and computerized videokeratographic examination revealed improved corneal regularity. The procedure was not painful and could be executed quickly. In conclusion, anterior stromal puncture by Nd:YAG laser is an effective and simple procedure to treat recurrent corneal erosion. The success rate was 85%. Patients with a traumatic cause showed a better response than those with an unknown cause. In those with microform or macroform recurrence after operation, the Nd:YAG laser ameliorated the symptoms both in terms of the frequency of the attacks and the intensity of the pain. It could be performed easily in the outpatient setting without serious adverse complications.
References 1. Aitken DA, Beirouty ZA, Lee WR. Ultrastructural study of the corneal epithelium in the recurrent erosion syndrome. Br J Ophthalmol 1995;79:282–9. 2. Goldman JN, Dohlman CH, Kravitt BA. The basement membrane of the human cornea in recurrent epithelial erosion syndrome. Trans Am Acad Ophthalmol Otolaryngol 1969;73: 471– 81. 3. Hykin PG, Foss AE, Pavesio C, Dart JK. The natural history and management of recurrent corneal erosion: a prospective randomised trial. Eye 1994;8:35– 40. 4. Chandler PA. Recurrent erosion of the cornea. Trans Am Ophthalmol Soc 1944;42:355–71. 5. Reidy JJ, Paulus MP, Gona S. Recurrent erosions of the cornea: epidemiology and treatment. Cornea 2000;19:767–71. 6. Kenyon KR. Recurrent corneal erosion: pathogenesis and therapy. Int Ophthalmol Clin 1979;19:169 –95. 7. Brown N, Bron A. Recurrent erosion of the cornea. Br J Ophthalmol 1976;60:84 –96. 8. Heyworth P, Morlet N, Rayner S, et al. Natural history of recurrent erosion syndrome—a 4 year review of 117 patients. Br J Ophthalmol 1998;82:26 – 8. 9. Dua HS, Lagnado R, Raj D, et al. Alcohol delamination of the corneal epithelium: an alternative in the management of recurrent corneal erosions. Ophthalmology 2006;113:404 –11. 10. Rubinfeld RS, Laibson PR, Cohen EJ, et al. Anterior stromal puncture for recurrent erosion: further experience and new instrumentation. Ophthalmic Surg 1990;21:318 –26. 11. McLean EN, MacRae SM, Rich LF. Recurrent erosion: treatment by anterior stromal puncture. Ophthalmology 1986;93:784 – 8. 12. Geggel HS, Maza CE. Anterior stromal puncture with the Nd:YAG laser. Invest Ophthalmol Vis Sci 1990;31:1555–9. 13. Geggel HS. Successful treatment of recurrent corneal erosion with Nd:YAG anterior stromal puncture. Am J Ophthalmol 1990;110:404 –7.
1299
Ophthalmology Volume 116, Number 7, July 2009 14. Buxton JN, Constad WH. Superficial epithelial keratectomy in the treatment of epithelial basement membrane dystrophy. Ann Ophthalmol 1987;19:92– 6. 15. Buxton JN, Fox ML. Superficial epithelial keratectomy in the treatment of epithelial basement membrane dystrophy: a preliminary report. Arch Ophthalmol 1983;101:392–5. 16. Soong HK, Farjo Q, Meyer RF, Sugar A. Diamond burr superficial keratectomy for recurrent corneal erosions. Br J Ophthalmol 2002;86:296 – 8. 17. Holzer MP, Auffarth GU, Specht H, Kruse FE. Combination of transepithelial phototherapeutic keratectomy and autologous serum eyedrops for treatment of recurrent corneal erosions. J Cataract Refract Surg 2005;31:1603– 6. 18. Ardjomand N, Fellner P, Vidic B. Phototherapeutic keratectomy with an epithelial flap for recurrent erosion syndrome. J Cataract Refract Surg 2004;30:543–5. 19. Maini R, Loughnan MS. Phototherapeutic keratectomy retreatment for recurrent corneal erosion syndrome. Br J Ophthalmol 2002;86:270 –2.
20. Tripathi RC, Bron AJ. Ultrastructural study of nontraumatic recurrent corneal erosion. Br J Ophthalmol 1972; 56:73– 85. 21. Garrana RM, Zieske JD, Assouline M, Gipson IK. Matrix metalloproteinases in epithelia from human recurrent corneal erosion. Invest Ophthalmol Vis Sci 1999;40:1266 –70. 22. Chen YT, Huang CW, Huang FC, et al. The cleavage plane of corneal epithelial adhesion complex in traumatic recurrent corneal erosion. Mol Vis 2006;12:196 –204. 23. Malecha MA. Anterior stromal puncture for recurrent corneal erosion after laser in situ keratomileusis. J Cataract Refract Surg 2004;30:496 – 8. 24. McLean EN. Update on stromal puncture technique [letter]. Ophthalmology 1990;97:1245. 25. Wood TO. Recurrent erosion. Trans Am Ophthalmol Soc 1984;82:850 –98. 26. Ohman L, Fagerholm P, Tengroth B. Treatment of recurrent corneal erosions with the excimer laser. Acta Ophthalmol (Cophenh) 1994;72:461–3.
Footnotes and Financial Disclosures Originally received: September 5, 2008. Final revision: January 23, 2009. Accepted: January 26, 2009. Available online: May 8, 2009.
Supported by the Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Manuscript no. 2008-1066.
Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
1300
Correspondence: Yu-Chih Hou, MD, Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei 10002, Taiwan. E-mail: ychou51@ntu. edu.tw.