CLINICAL SCIENCE
Impact of Intraoperative Topical Hydroxypropyl Methylcellulose 2% Versus Sodium Hyaluronate 1.2% on Corneal Reepithelialization After Intentional Epithelial Debridement During Vitrectomy Gian Marco Tosi, MD, PhD, Davide Marigliani, MD, Tommaso Bacci, MD, Angelo Balestrazzi, MD, PhD, Gianluca Martone, MD, PhD, and Maria Sole Polito, MD
Purpose: The aim of this study was to assess the impact of the intraoperative use of topical hydroxypropyl methylcellulose (HPMC) 2% versus sodium hyaluronate 1.2% on corneal reepithelialization time and final corneal status after intentional epithelial debridement during vitrectomy for proliferative vitreoretinopathy.
Methods: Forty eyes of 40 patients were included in the study, divided into 2 groups of 20 eyes. HPMC 2% and sodium hyaluronate 1.2% were used as corneal protectors in the first and second group, respectively. Patients’ charts were reviewed to determine any differences between the HPMC 2% and sodium hyaluronate 1.2% groups in relation to the preoperative, intraoperative, and postoperative factors that could impact postoperative corneal reepithelialization. Postoperative reepithelialization time and final corneal status were recorded. Results: No significant between-group differences in preoperative, intraoperative, and postoperative factors were found. Reepithelialization time was significantly shorter in the sodium hyaluronate 1.2% group than in the HPMC 2% group, although reepithelialization was eventually achieved in every patient in both groups. Corneal sequelae were significantly more frequent in the HPMC 2% group than in the sodium hyaluronate 1.2% group.
Conclusions: The choice of the ophthalmic viscosurgical device for intraoperative corneal protection may significantly influence the postoperative corneal status after complicated retinal detachment. Key Words: proliferative vitreoretinopathy, vitrectomy, postoperative complications, persistent corneal epithelial defect, viscosurgical devices (Cornea 2014;33:942–945)
Received for publication March 26, 2014; revision received June 9, 2014; accepted June 10, 2014. Published online ahead of print July 22, 2014. From the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. The authors have no funding or conflicts of interest to disclose. Reprints: Gian M. Tosi, MD, PhD, Department of Medicine, Surgery and Neuroscience (Ophthalmology Section), University of Siena, Siena, Italy (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
942
| www.corneajrnl.com
I
ntraoperative corneal clarity is critical for successful vitreoretinal surgery, especially in complicated cases that require extensive membrane peeling. Reduced corneal clarity makes intentional intraoperative epithelial debridement necessary. This is always followed by postoperative corneal epithelial defects that take time to repair, causing patient discomfort, requiring intensive care from physicians, and increasing the risk of infection and permanent corneal sequelae.1 Intraoperative corneal epithelial edema and clouding might be related to preoperative systemic disease (eg, diabetes) or ocular conditions (eg, ocular surface disease, previous vitreoretinal surgery, ocular trauma), or intraoperative factors (eg, duration of procedure, increased intraocular pressure).1–3 Concerning the intraoperative factors, the use of viscous surface lubricants for corneal protection4–6 and viewing systems1,7 during vitrectomy have been debated in the literature. Since the beginning of the vitrectomy era, the use of preservative-free ophthalmic viscosurgical devices (OVD) such as hyaluronic acid (HA) has been suggested to ensure intraoperative protection of the cornea.6 More recently, topical compounds containing 2.5% methylcellulose and 0.3% hydroxypropyl methylcellulose (HPMC),4 or HA 1.5%,5 together with noncontact and contact viewing systems for vitrectomy1,7 have been evaluated from the point of view of corneal clarity maintainance4,5 and the incidence of immediate postoperative corneal epithelial defects.1,7 The healing of postoperative corneal epithelial defects may require eye patching and bandage contact lens application; although in some cases, the defect still persists for several weeks, eventually developing into stromal opacity or infectious keratitis.1,8 In the present series, we assessed the impact of intraoperative topical HPMC 2% versus sodium hyaluronate 1.2% on postoperative corneal reepithelialization time and the final corneal status after intentional epithelial debridement during contact panoramic viewing system–assisted vitrectomy for proliferative vitreoretinopathy (PVR).
MATERIALS AND METHODS We reviewed the clinical records of consecutive patients affected by retinal detachment with PVR who underwent scleral buckling and vitrectomy at the Cornea Volume 33, Number 9, September 2014
Cornea Volume 33, Number 9, September 2014
Ophthalmology Section of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy, between January 2009 and August 2013. The research conformed to the provisions of the 1995 Declaration of Helsinki (as revised in Edinburgh in 2000), and the institutional review board approved the study. The inclusion criteria were: a PVR grade greater than CP-3 and CA-3 (updated PVR classification)9; the intraoperative use as a corneal lubricant of either HPMC 2% (Gel 4000, Bruschettini, Genoa, Italy)10 or sodium hyaluronate 1.2% (IAL; Bausch & Lomb Inc, Rochester, NY)10,11; use of the same contact panoramic viewing system during surgery (AVI lenses)12; and having undergone intentional corneal epithelial debridement during surgery. The exclusion criteria were: a history of diabetes mellitus; previous intraocular surgery, except cataract surgery; glaucoma; ocular traumas; anterior segment disease, including corneal dystrophies; and ocular surface disease. All patients were operated on under general or local anesthesia and subjected to scleral buckling and vitrectomy. Intraocular tamponade with silicone oil was applied in all patients. Cataract surgery through phacoemulsification and intraocular lens (IOL) implantation was performed in phakic patients, and IOL removal was performed when deemed necessary to achieve adequate posterior segment visualization. All patients, including those who were pseudophakic and those who were scheduled to have cataract surgery, were subjected to corneal endothelial cell count. Postoperatively the duration of the corneal epithelial defect was defined as the time to the first follow-up visit with no fluorescent staining. After intraoperative corneal epithelial debridement, patients were subjected to postoperative eye patching if no closure of the epithelial defect was obtained at 1-week follow-up; a bandage contact lens was applied if no closure was obtained at 2-week follow-up; and topical steroids and nonsteroidal antiinflammatory drugs were discontinued, whereas the bandage contact lens was maintained, if no closure had been obtained at 3-week follow-up. Patients’ charts were reviewed to determine any differences between the HPMC 2% and sodium hyaluronate 1.2% groups in relation to the preoperative, intraoperative, and postoperative factors that could impact postoperative corneal reepithelialization. Between-group difference in the number of topical postoperative medications and their frequency of application was evaluated. Follow-up visit charts at 1, 2, 3, 4, 6, 8, 10, 12, 14, and 16 weeks were reviewed in all patients. The main outcome measures were: postoperative reepithelialization time, including the need for eye patching, bandage contact lens application, or discontinuation of topical steroids and nonsteroidal antiinflammatory drugs; reopening of the corneal epithelial defect; and the final corneal status. Corneal haze was graded on a scale based on the visibility of iris details. Before performing any statistical comparisons, we verified that the quantitative variables studied followed a normal distribution for any follow-up period, using the Kolmogorov– Smirnov test. Quantitative variables were compared between groups using a 2-tailed Mann–Whitney test (95% confidence interval). Qualitative variables were compared between groups using Fisher exact test (95% confidence interval). A P value ,0.05 was considered significant. Ó 2014 Lippincott Williams & Wilkins
Impact of Topical HPMC Versus Sodium Hyaluronate
RESULTS Forty eyes of 40 patients were included in the study, divided into 2 groups of 20 eyes. No significant betweengroup differences were found regarding: age, sex, type of dilating drops, the use of betadine for surgical field preparation, preoperative intraocular pressure, preoperative endothelial cell count, performance of anterior segment procedures such as cataract surgery with IOL implantation or IOL removal in association with vitreoretinal surgery, bottle height during surgery, time interval between the start of surgery and the removal of corneal epithelium, total duration of surgery, postoperative intraocular pressure, or postoperative use of topical and general medications. In particular, no significant between-group difference was found in the number of postoperative topical medications and their frequency of application. In the HPMC 2% group, corneal reepithelialization was achieved at 1 week in 2 patients (10%), at 2 weeks after eye patching in 6 patients (30%), at 3 and 4 weeks after bandage contact lens application in 13 (65%) and 16 (80%) patients, respectively, and after 4 weeks in 20 patients (100%) (Table 1). Although reepithelialization was eventually achieved in every patient, in the HPMC 2% group, 3 patients experienced recurrent epithelial defects (15%) and 7 patients showed corneal haze (35%) (Fig. 1). In the sodium hyaluronate 1.2% group, corneal reepithelialization was achieved at 1 week in 13 patients (65%), at 2 weeks after eye patching 19 in patients (95%), and at 3 weeks after bandage contact lens application in 20 patients (100%) (Table 1). No patients in the sodium hyaluronate 1.2% group experienced recurrent epithelial defects and none showed corneal haze. The sodium hyaluronate 1.2% group showed a significantly better corneal status at 1 week (P = 0.0008), at 2 weeks (P , 0.0001), and at
TABLE 1. Postoperative Corneal Status in the HPMC 2% and Sodium Hyaluronate 1.2% Groups
HPMC 2% Number of patients (M/F) 20 (12/8) Age, mean 6 SD, yr 63.55 6 10 Endothelial cell count, 1792 6 273 mean 6 SD, cells/mm2 Lens status (phakic/pseudophakic) 10/10 Duration of surgery, 228 6 44 mean 6 SD, min Reepithelialization 1 week 2 (number of patients) Reepithelialization 2 weeks 6 (number of patients) Reepithelialization 3 weeks 13 (number of patients) Reepithelialization 4 weeks 16 (number of patients) Reepithelialization .4 weeks 20 (number of patients) Haze (number of patients) 7
Sodium Hyaluronate 1.2%
P
20 (13/7) 69.7 6 12 1703 6 280
1.0 0.07 0.33
8/12 235 6 42
0.75 0.56
13
0.0008*
19
,0.0001*
20
0.008*
20
0.10
20
—
0
0.008*
*Statistically significant.
www.corneajrnl.com |
943
Cornea Volume 33, Number 9, September 2014
Tosi et al
FIGURE 1. Corneal haze in a patient in the HPMC 2% group.
3 weeks (P = 0.008). No significant differences were found at 4 weeks (P = 0.1). Corneal haze was significantly more frequent in the HPMC 2% group than in the sodium hyaluronate 1.2% group (P = 0.008) (Table 1).
DISCUSSION The direct mechanical trauma caused by the hand-held contact lens panoramic viewing system that we routinely use and the increased surgical time needed for PVR cases make corneal scraping during vitrectomy necessary in most of these challenging cases in our practice. For this reason, we decided to investigate the postoperative corneal status in the worst case scenario (contact panoramic view lenses for PVR cases) to understand whether the use of different OVDs for corneal protection during surgery could impact postoperative reepithelialization time. Perry et al13 and Foulks et al14 found that the duration of retinal surgery was not correlated with the occurrence of postoperative corneal epithelial defects, whereas Brightbill et al3 and Virata et al1 showed an increased incidence of corneal epithelial defects when surgery lasted longer. Moreover, Virata et al1 and Friberg et al7 found an increased incidence of postoperative corneal epithelial defects and intentional intraoperative epithelial debridement, respectively, when hand-held (instead of sew-on or noncontact) lenses were used for posterior segment visualization during vitrectomy, thus hypothesizing a detrimental mechanical effect of hand-held lenses and suggesting a role for OVDs in corneal protection. Although Virata et al1 reported the postoperative reepithelialization time in their series, they did not mention any correlation between reepithelialization time and preoperative, intraoperative, or postoperative factors. The logical consequence of the abovementioned considerations is that the preservation of corneal integrity during vitreoretinal surgery demands greater attention. At the beginning of the vitrectomy era, Pruett et al6 suggested the use of HA for intraoperative corneal protection. However, mainly because of the excessive costs, which made the use
944
| www.corneajrnl.com
of HA for corneal protection impractical, the literature lacks comprehensive data on corneal outcomes after HA compared with other lubricants. More recently, Garcia-Valenzuela et al4 found increased intraoperative corneal clarity and a decreased need for epithelial debridement when 0.3% HPMC, carbopol 980, phosphonic acid, sorbitol, water, and 0.028% sodium perborate instead of 2.5% methylcellulose, boric acid, edetate disodium, sodium borate, potassium chloride, water and 0.01% benzalkonium chloride were used; and Prinz et al5 experimentally showed HA 1.5% as the preferred OVD for prolonged corneal hydration, suggesting its use in vitreoretinal surgery. However, Garcia-Valenzuela et al4 did not mention the behavior of the corneas analyzed in the postoperative period, or any differences in reepithelialization time. Attention should be focused on the postoperative corneal status and healing process in addition to the incidence of intraoperative clouding and immediate postoperative epithelial defects. The 2 populations analyzed herein are highly homogeneous because no significant between-group differences were present regarding the preoperative, intraoperative, and postoperative factors that might affect the corneal integrity. Significant difference was found between the postoperative corneal status in the HPMC 2% and sodium hyaluronate 1.2% groups: in fact, in the latter group, reepithelialization time was faster and the final postoperative corneal status was significantly better. Surprisingly, no significant difference was found between the 2 groups in terms of the time interval from the start of surgery to the time of corneal epithelium removal. This lack of intraoperative differences might be related to the mechanical corneal trauma (albeit minimal) caused by scleral buckle placement, performed in all patients at the beginning of the surgery. Since the 1980s and early 1990s, many authors have reported the beneficial effect of HA in protecting the corneal epithelial cells of dry eye patients10,15 and suggested the intraoperative use of topical sodium hyaluronate for corneal protection.4,6,16 Wysenbeek et al17 reported better corneal epithelium protection against dryness in experimental animals using sodium hyaluronate 1% rather than hydroxymethylcellulose or phosphate-buffered saline. In a cell culture, Nishida et al15 showed that HA not only stimulated corneal epithelial migration but also did so through a pathway that was not dependent on fibronectin and epidermal growth factor, the natural corneal epithelium migration stimulators. Although sodium hyaluronate has been found to heal skin wounds in both normal and diabetic rats,10 this effect was not confirmed by Arzeno and Miller’s study of corneal healing in albino rabbits.18 However, the results of Arzeno and Miller18 cannot be said to refute the previously mentioned studies because their experiment was very particular: it evaluated the resistance of a sutured intentional corneal wound also involving the endothelium, after having filled the anterior chamber with sodium hyaluronate or balanced salt solution. Although limited by the relatively low number of patients analyzed, because of the restrictive inclusion criteria, and the lack of preoperative measurement of corneal sensation with the use of an esthesiometer, our results support the intraoperative use of sodium hyaluronate for the postoperative restoration of corneal integrity. Although in vivo confocal microscopy might have helped clarify the differences in the Ó 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 9, September 2014
healing mechanisms,2 we hypothesize that the effect of sodium hyaluronate on the cornea might be related to both the stimulation of epithelial corneal migration14 and a nontoxic effect of sodium hyaluronate during the operation once the corneal epithelium has been removed.10,19 In fact, once debridement has been performed, sodium hyaluronate is nontoxic for the cornea devoid of its epithelium, being a natural biological molecule10; on the contrary, the nonnatural animal HPMC with its solid particles might cause prolonged toxicity after deep corneal penetration.10,19 We recommend the use of sodium hyaluronate as a corneal protective agent, at least in the more challenging vitreoretinal scenarios. The cost of postoperative corneal complications, resulting in additional medication and in the delay of patient rehabilitation, together with more follow-up visits, may outweigh any initial economic advantage in the use of less expensive products. REFERENCES 1. Virata SR, Kylstra JA, Singh HT. Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses. Retina. 1999;19:287–290. 2. Chen WL, Lin CT, Ko PS, et al. In vivo confocal microscopic findings of corneal wound healing after corneal epithelial debridement in diabetic vitrectomy. Ophthalmology. 2009;116:1038–1047. 3. Brightbill FS, Myers FL, Bresnick GH. Postvitrectomy keratopathy. Am J Ophthalmol. 1978;85:651–655. 4. Garcia-Valenzuela E, Abdelsalam A, Eliott D, et al. Reduced need for corneal epithelial debridement during vitreo-retinal surgery using two different viscous surface lubricants. Am J Ophthalmol. 2003;136:1062–1066. 5. Prinz A, Fennes C, Buehl W, et al. Efficacy of ophthalmic viscosurgical devices in maintaining corneal epithelial hydration and clarity: in vitro assessment. J Cataract Refract Surg. 2012;38:2154–2159.
Ó 2014 Lippincott Williams & Wilkins
Impact of Topical HPMC Versus Sodium Hyaluronate
6. Pruett RC, Schepens CL, Swann DA. Hyaluronic acid vitreous substitute. A six-year clinical evaluation. Arch Ophthalmol. 1979;97: 2325–2330. 7. Friberg TR, Ohji M, Scherer JJ, et al. Frequency of epithelial debridement during diabetic vitrectomy. Am J Ophthalmol. 2003;135:553–554. 8. Oskouee SJ, Amuzadeh J, Rajabi MT. Bandage contact lens and topical indomethacin for treating persistent corneal epithelial defects after vitreoretinal surgery. Cornea. 2007;26:1178–1181. 9. Machemer R, Aaberg TM, Freeman HM, et al. An updated classification of retinal detachment with proliferative vitreoretinopathy. Am J Ophthalmol. 1991;112:159–165. 10. Liesegang TJ. Viscoelastic substances in ophthalmology. Surv Ophthalmol. 1990;34:268–293. 11. Fruscella S, Billi B, Neuschüler R, et al. Anterior segment surgery with use of a new type of sodium hyaluronate preparation IAL. Ophthalmologica. 1987;194:181–184. 12. Virata SR, Kylstra JA. Postoperative complications following vitrectomy for proliferative diabetic retinopathy with sew-on and noncontact wideangle viewing lenses. Ophthalmic Surg Lasers. 2001;32:193–197. 13. Perry HD, Foulks GN, Thoft RA, et al. Corneal complications after closed vitrectomy through the pars plana. Arch Ophthalmol. 1978;96: 1401–1403. 14. Foulks GN, Thoft RA, Perry HD, et al. Factors related to corneal epithelial complications after closed vitrectomy in diabetics. Arch Ophthalmol. 1979;97:1076–1078. 15. Nishida T, Nakamura M, Mishima H, et al. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991;53:753–758. 16. Federman JL, Decker WL, Grabowski WM. Cover slip lens. Am J Ophthalmol. 1983;95:848–849. 17. Wysenbeek YS, Loya N, Ben Sira I, et al. The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. Invest Ophthalmol Vis Sci. 1988;29:194–199. 18. Arzeno G, Miller D. Effect of sodium hyaluronate on corneal wound healing. Arch Ophthalmol. 1982;100:152. 19. Rosen ES, Gregory RP, Barnett F. Is 2% hydroxypropylmethylcellulose a safe solution for intraoperative clinical applications? J Cataract Refract Surg. 1986;12:679–684.
www.corneajrnl.com |
945
Impact of Intraoperative Topical Hydroxypropyl Methylcellulose 2% Versus Sodium Hyaluronate 1.2% on Corneal Reepithelialization After Intentional Epithelial Debridement During Vitrectomy Gian Marco Tosi, MD, PhD, Davide Marigliani, MD, Tommaso Bacci, MD, Angelo Balestrazzi, MD, PhD, Gianluca Martone, MD, PhD, and Maria Sole Polito, MD
Purpose: The aim of this study was to assess the impact of the intraoperative use of topical hydroxypropyl methylcellulose (HPMC) 2% versus sodium hyaluronate 1.2% on corneal reepithelialization time and final corneal status after intentional epithelial debridement during vitrectomy for proliferative vitreoretinopathy.
Methods: Forty eyes of 40 patients were included in the study, divided into 2 groups of 20 eyes. HPMC 2% and sodium hyaluronate 1.2% were used as corneal protectors in the first and second group, respectively. Patients’ charts were reviewed to determine any differences between the HPMC 2% and sodium hyaluronate 1.2% groups in relation to the preoperative, intraoperative, and postoperative factors that could impact postoperative corneal reepithelialization. Postoperative reepithelialization time and final corneal status were recorded. Results: No significant between-group differences in preoperative, intraoperative, and postoperative factors were found. Reepithelialization time was significantly shorter in the sodium hyaluronate 1.2% group than in the HPMC 2% group, although reepithelialization was eventually achieved in every patient in both groups. Corneal sequelae were significantly more frequent in the HPMC 2% group than in the sodium hyaluronate 1.2% group.
Conclusions: The choice of the ophthalmic viscosurgical device for intraoperative corneal protection may significantly influence the postoperative corneal status after complicated retinal detachment. Key Words: proliferative vitreoretinopathy, vitrectomy, postoperative complications, persistent corneal epithelial defect, viscosurgical devices (Cornea 2014;33:942–945)
Received for publication March 26, 2014; revision received June 9, 2014; accepted June 10, 2014. Published online ahead of print July 22, 2014. From the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. The authors have no funding or conflicts of interest to disclose. Reprints: Gian M. Tosi, MD, PhD, Department of Medicine, Surgery and Neuroscience (Ophthalmology Section), University of Siena, Siena, Italy (e-mail: [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins
942
| www.corneajrnl.com
I
ntraoperative corneal clarity is critical for successful vitreoretinal surgery, especially in complicated cases that require extensive membrane peeling. Reduced corneal clarity makes intentional intraoperative epithelial debridement necessary. This is always followed by postoperative corneal epithelial defects that take time to repair, causing patient discomfort, requiring intensive care from physicians, and increasing the risk of infection and permanent corneal sequelae.1 Intraoperative corneal epithelial edema and clouding might be related to preoperative systemic disease (eg, diabetes) or ocular conditions (eg, ocular surface disease, previous vitreoretinal surgery, ocular trauma), or intraoperative factors (eg, duration of procedure, increased intraocular pressure).1–3 Concerning the intraoperative factors, the use of viscous surface lubricants for corneal protection4–6 and viewing systems1,7 during vitrectomy have been debated in the literature. Since the beginning of the vitrectomy era, the use of preservative-free ophthalmic viscosurgical devices (OVD) such as hyaluronic acid (HA) has been suggested to ensure intraoperative protection of the cornea.6 More recently, topical compounds containing 2.5% methylcellulose and 0.3% hydroxypropyl methylcellulose (HPMC),4 or HA 1.5%,5 together with noncontact and contact viewing systems for vitrectomy1,7 have been evaluated from the point of view of corneal clarity maintainance4,5 and the incidence of immediate postoperative corneal epithelial defects.1,7 The healing of postoperative corneal epithelial defects may require eye patching and bandage contact lens application; although in some cases, the defect still persists for several weeks, eventually developing into stromal opacity or infectious keratitis.1,8 In the present series, we assessed the impact of intraoperative topical HPMC 2% versus sodium hyaluronate 1.2% on postoperative corneal reepithelialization time and the final corneal status after intentional epithelial debridement during contact panoramic viewing system–assisted vitrectomy for proliferative vitreoretinopathy (PVR).
MATERIALS AND METHODS We reviewed the clinical records of consecutive patients affected by retinal detachment with PVR who underwent scleral buckling and vitrectomy at the Cornea Volume 33, Number 9, September 2014
Cornea Volume 33, Number 9, September 2014
Ophthalmology Section of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy, between January 2009 and August 2013. The research conformed to the provisions of the 1995 Declaration of Helsinki (as revised in Edinburgh in 2000), and the institutional review board approved the study. The inclusion criteria were: a PVR grade greater than CP-3 and CA-3 (updated PVR classification)9; the intraoperative use as a corneal lubricant of either HPMC 2% (Gel 4000, Bruschettini, Genoa, Italy)10 or sodium hyaluronate 1.2% (IAL; Bausch & Lomb Inc, Rochester, NY)10,11; use of the same contact panoramic viewing system during surgery (AVI lenses)12; and having undergone intentional corneal epithelial debridement during surgery. The exclusion criteria were: a history of diabetes mellitus; previous intraocular surgery, except cataract surgery; glaucoma; ocular traumas; anterior segment disease, including corneal dystrophies; and ocular surface disease. All patients were operated on under general or local anesthesia and subjected to scleral buckling and vitrectomy. Intraocular tamponade with silicone oil was applied in all patients. Cataract surgery through phacoemulsification and intraocular lens (IOL) implantation was performed in phakic patients, and IOL removal was performed when deemed necessary to achieve adequate posterior segment visualization. All patients, including those who were pseudophakic and those who were scheduled to have cataract surgery, were subjected to corneal endothelial cell count. Postoperatively the duration of the corneal epithelial defect was defined as the time to the first follow-up visit with no fluorescent staining. After intraoperative corneal epithelial debridement, patients were subjected to postoperative eye patching if no closure of the epithelial defect was obtained at 1-week follow-up; a bandage contact lens was applied if no closure was obtained at 2-week follow-up; and topical steroids and nonsteroidal antiinflammatory drugs were discontinued, whereas the bandage contact lens was maintained, if no closure had been obtained at 3-week follow-up. Patients’ charts were reviewed to determine any differences between the HPMC 2% and sodium hyaluronate 1.2% groups in relation to the preoperative, intraoperative, and postoperative factors that could impact postoperative corneal reepithelialization. Between-group difference in the number of topical postoperative medications and their frequency of application was evaluated. Follow-up visit charts at 1, 2, 3, 4, 6, 8, 10, 12, 14, and 16 weeks were reviewed in all patients. The main outcome measures were: postoperative reepithelialization time, including the need for eye patching, bandage contact lens application, or discontinuation of topical steroids and nonsteroidal antiinflammatory drugs; reopening of the corneal epithelial defect; and the final corneal status. Corneal haze was graded on a scale based on the visibility of iris details. Before performing any statistical comparisons, we verified that the quantitative variables studied followed a normal distribution for any follow-up period, using the Kolmogorov– Smirnov test. Quantitative variables were compared between groups using a 2-tailed Mann–Whitney test (95% confidence interval). Qualitative variables were compared between groups using Fisher exact test (95% confidence interval). A P value ,0.05 was considered significant. Ó 2014 Lippincott Williams & Wilkins
Impact of Topical HPMC Versus Sodium Hyaluronate
RESULTS Forty eyes of 40 patients were included in the study, divided into 2 groups of 20 eyes. No significant betweengroup differences were found regarding: age, sex, type of dilating drops, the use of betadine for surgical field preparation, preoperative intraocular pressure, preoperative endothelial cell count, performance of anterior segment procedures such as cataract surgery with IOL implantation or IOL removal in association with vitreoretinal surgery, bottle height during surgery, time interval between the start of surgery and the removal of corneal epithelium, total duration of surgery, postoperative intraocular pressure, or postoperative use of topical and general medications. In particular, no significant between-group difference was found in the number of postoperative topical medications and their frequency of application. In the HPMC 2% group, corneal reepithelialization was achieved at 1 week in 2 patients (10%), at 2 weeks after eye patching in 6 patients (30%), at 3 and 4 weeks after bandage contact lens application in 13 (65%) and 16 (80%) patients, respectively, and after 4 weeks in 20 patients (100%) (Table 1). Although reepithelialization was eventually achieved in every patient, in the HPMC 2% group, 3 patients experienced recurrent epithelial defects (15%) and 7 patients showed corneal haze (35%) (Fig. 1). In the sodium hyaluronate 1.2% group, corneal reepithelialization was achieved at 1 week in 13 patients (65%), at 2 weeks after eye patching 19 in patients (95%), and at 3 weeks after bandage contact lens application in 20 patients (100%) (Table 1). No patients in the sodium hyaluronate 1.2% group experienced recurrent epithelial defects and none showed corneal haze. The sodium hyaluronate 1.2% group showed a significantly better corneal status at 1 week (P = 0.0008), at 2 weeks (P , 0.0001), and at
TABLE 1. Postoperative Corneal Status in the HPMC 2% and Sodium Hyaluronate 1.2% Groups
HPMC 2% Number of patients (M/F) 20 (12/8) Age, mean 6 SD, yr 63.55 6 10 Endothelial cell count, 1792 6 273 mean 6 SD, cells/mm2 Lens status (phakic/pseudophakic) 10/10 Duration of surgery, 228 6 44 mean 6 SD, min Reepithelialization 1 week 2 (number of patients) Reepithelialization 2 weeks 6 (number of patients) Reepithelialization 3 weeks 13 (number of patients) Reepithelialization 4 weeks 16 (number of patients) Reepithelialization .4 weeks 20 (number of patients) Haze (number of patients) 7
Sodium Hyaluronate 1.2%
P
20 (13/7) 69.7 6 12 1703 6 280
1.0 0.07 0.33
8/12 235 6 42
0.75 0.56
13
0.0008*
19
,0.0001*
20
0.008*
20
0.10
20
—
0
0.008*
*Statistically significant.
www.corneajrnl.com |
943
Cornea Volume 33, Number 9, September 2014
Tosi et al
FIGURE 1. Corneal haze in a patient in the HPMC 2% group.
3 weeks (P = 0.008). No significant differences were found at 4 weeks (P = 0.1). Corneal haze was significantly more frequent in the HPMC 2% group than in the sodium hyaluronate 1.2% group (P = 0.008) (Table 1).
DISCUSSION The direct mechanical trauma caused by the hand-held contact lens panoramic viewing system that we routinely use and the increased surgical time needed for PVR cases make corneal scraping during vitrectomy necessary in most of these challenging cases in our practice. For this reason, we decided to investigate the postoperative corneal status in the worst case scenario (contact panoramic view lenses for PVR cases) to understand whether the use of different OVDs for corneal protection during surgery could impact postoperative reepithelialization time. Perry et al13 and Foulks et al14 found that the duration of retinal surgery was not correlated with the occurrence of postoperative corneal epithelial defects, whereas Brightbill et al3 and Virata et al1 showed an increased incidence of corneal epithelial defects when surgery lasted longer. Moreover, Virata et al1 and Friberg et al7 found an increased incidence of postoperative corneal epithelial defects and intentional intraoperative epithelial debridement, respectively, when hand-held (instead of sew-on or noncontact) lenses were used for posterior segment visualization during vitrectomy, thus hypothesizing a detrimental mechanical effect of hand-held lenses and suggesting a role for OVDs in corneal protection. Although Virata et al1 reported the postoperative reepithelialization time in their series, they did not mention any correlation between reepithelialization time and preoperative, intraoperative, or postoperative factors. The logical consequence of the abovementioned considerations is that the preservation of corneal integrity during vitreoretinal surgery demands greater attention. At the beginning of the vitrectomy era, Pruett et al6 suggested the use of HA for intraoperative corneal protection. However, mainly because of the excessive costs, which made the use
944
| www.corneajrnl.com
of HA for corneal protection impractical, the literature lacks comprehensive data on corneal outcomes after HA compared with other lubricants. More recently, Garcia-Valenzuela et al4 found increased intraoperative corneal clarity and a decreased need for epithelial debridement when 0.3% HPMC, carbopol 980, phosphonic acid, sorbitol, water, and 0.028% sodium perborate instead of 2.5% methylcellulose, boric acid, edetate disodium, sodium borate, potassium chloride, water and 0.01% benzalkonium chloride were used; and Prinz et al5 experimentally showed HA 1.5% as the preferred OVD for prolonged corneal hydration, suggesting its use in vitreoretinal surgery. However, Garcia-Valenzuela et al4 did not mention the behavior of the corneas analyzed in the postoperative period, or any differences in reepithelialization time. Attention should be focused on the postoperative corneal status and healing process in addition to the incidence of intraoperative clouding and immediate postoperative epithelial defects. The 2 populations analyzed herein are highly homogeneous because no significant between-group differences were present regarding the preoperative, intraoperative, and postoperative factors that might affect the corneal integrity. Significant difference was found between the postoperative corneal status in the HPMC 2% and sodium hyaluronate 1.2% groups: in fact, in the latter group, reepithelialization time was faster and the final postoperative corneal status was significantly better. Surprisingly, no significant difference was found between the 2 groups in terms of the time interval from the start of surgery to the time of corneal epithelium removal. This lack of intraoperative differences might be related to the mechanical corneal trauma (albeit minimal) caused by scleral buckle placement, performed in all patients at the beginning of the surgery. Since the 1980s and early 1990s, many authors have reported the beneficial effect of HA in protecting the corneal epithelial cells of dry eye patients10,15 and suggested the intraoperative use of topical sodium hyaluronate for corneal protection.4,6,16 Wysenbeek et al17 reported better corneal epithelium protection against dryness in experimental animals using sodium hyaluronate 1% rather than hydroxymethylcellulose or phosphate-buffered saline. In a cell culture, Nishida et al15 showed that HA not only stimulated corneal epithelial migration but also did so through a pathway that was not dependent on fibronectin and epidermal growth factor, the natural corneal epithelium migration stimulators. Although sodium hyaluronate has been found to heal skin wounds in both normal and diabetic rats,10 this effect was not confirmed by Arzeno and Miller’s study of corneal healing in albino rabbits.18 However, the results of Arzeno and Miller18 cannot be said to refute the previously mentioned studies because their experiment was very particular: it evaluated the resistance of a sutured intentional corneal wound also involving the endothelium, after having filled the anterior chamber with sodium hyaluronate or balanced salt solution. Although limited by the relatively low number of patients analyzed, because of the restrictive inclusion criteria, and the lack of preoperative measurement of corneal sensation with the use of an esthesiometer, our results support the intraoperative use of sodium hyaluronate for the postoperative restoration of corneal integrity. Although in vivo confocal microscopy might have helped clarify the differences in the Ó 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 9, September 2014
healing mechanisms,2 we hypothesize that the effect of sodium hyaluronate on the cornea might be related to both the stimulation of epithelial corneal migration14 and a nontoxic effect of sodium hyaluronate during the operation once the corneal epithelium has been removed.10,19 In fact, once debridement has been performed, sodium hyaluronate is nontoxic for the cornea devoid of its epithelium, being a natural biological molecule10; on the contrary, the nonnatural animal HPMC with its solid particles might cause prolonged toxicity after deep corneal penetration.10,19 We recommend the use of sodium hyaluronate as a corneal protective agent, at least in the more challenging vitreoretinal scenarios. The cost of postoperative corneal complications, resulting in additional medication and in the delay of patient rehabilitation, together with more follow-up visits, may outweigh any initial economic advantage in the use of less expensive products. REFERENCES 1. Virata SR, Kylstra JA, Singh HT. Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses. Retina. 1999;19:287–290. 2. Chen WL, Lin CT, Ko PS, et al. In vivo confocal microscopic findings of corneal wound healing after corneal epithelial debridement in diabetic vitrectomy. Ophthalmology. 2009;116:1038–1047. 3. Brightbill FS, Myers FL, Bresnick GH. Postvitrectomy keratopathy. Am J Ophthalmol. 1978;85:651–655. 4. Garcia-Valenzuela E, Abdelsalam A, Eliott D, et al. Reduced need for corneal epithelial debridement during vitreo-retinal surgery using two different viscous surface lubricants. Am J Ophthalmol. 2003;136:1062–1066. 5. Prinz A, Fennes C, Buehl W, et al. Efficacy of ophthalmic viscosurgical devices in maintaining corneal epithelial hydration and clarity: in vitro assessment. J Cataract Refract Surg. 2012;38:2154–2159.
Ó 2014 Lippincott Williams & Wilkins
Impact of Topical HPMC Versus Sodium Hyaluronate
6. Pruett RC, Schepens CL, Swann DA. Hyaluronic acid vitreous substitute. A six-year clinical evaluation. Arch Ophthalmol. 1979;97: 2325–2330. 7. Friberg TR, Ohji M, Scherer JJ, et al. Frequency of epithelial debridement during diabetic vitrectomy. Am J Ophthalmol. 2003;135:553–554. 8. Oskouee SJ, Amuzadeh J, Rajabi MT. Bandage contact lens and topical indomethacin for treating persistent corneal epithelial defects after vitreoretinal surgery. Cornea. 2007;26:1178–1181. 9. Machemer R, Aaberg TM, Freeman HM, et al. An updated classification of retinal detachment with proliferative vitreoretinopathy. Am J Ophthalmol. 1991;112:159–165. 10. Liesegang TJ. Viscoelastic substances in ophthalmology. Surv Ophthalmol. 1990;34:268–293. 11. Fruscella S, Billi B, Neuschüler R, et al. Anterior segment surgery with use of a new type of sodium hyaluronate preparation IAL. Ophthalmologica. 1987;194:181–184. 12. Virata SR, Kylstra JA. Postoperative complications following vitrectomy for proliferative diabetic retinopathy with sew-on and noncontact wideangle viewing lenses. Ophthalmic Surg Lasers. 2001;32:193–197. 13. Perry HD, Foulks GN, Thoft RA, et al. Corneal complications after closed vitrectomy through the pars plana. Arch Ophthalmol. 1978;96: 1401–1403. 14. Foulks GN, Thoft RA, Perry HD, et al. Factors related to corneal epithelial complications after closed vitrectomy in diabetics. Arch Ophthalmol. 1979;97:1076–1078. 15. Nishida T, Nakamura M, Mishima H, et al. Hyaluronan stimulates corneal epithelial migration. Exp Eye Res. 1991;53:753–758. 16. Federman JL, Decker WL, Grabowski WM. Cover slip lens. Am J Ophthalmol. 1983;95:848–849. 17. Wysenbeek YS, Loya N, Ben Sira I, et al. The effect of sodium hyaluronate on the corneal epithelium. An ultrastructural study. Invest Ophthalmol Vis Sci. 1988;29:194–199. 18. Arzeno G, Miller D. Effect of sodium hyaluronate on corneal wound healing. Arch Ophthalmol. 1982;100:152. 19. Rosen ES, Gregory RP, Barnett F. Is 2% hydroxypropylmethylcellulose a safe solution for intraoperative clinical applications? J Cataract Refract Surg. 1986;12:679–684.
www.corneajrnl.com |
945
