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Clinical and Experimental Ophthalmology 2014; 42: 810–814 doi: 10.1111/ceo.12343
Original Article Effect of topical diclofenac on postoperative photorefractive keratectomy pain: a randomized, controlled trial Alireza Eslampoor MD,1 Asieh Ehsaei PhD2,3 and Mojtaba Abrishami MD4,5 1
Cornea Research Center, Faculty of Medicine, 2Refractive Errors Research Center, School of Paramedical Sciences, Department of Optometry, School of Paramedical Sciences, 4Eye Research Center, Faculty of Medicine, Mashhad University of Medical Sciences and 5Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran 3
ABSTRACT Background: A major disadvantage of photorefractive keratectomy is postoperative pain and discomfort. This study aims to evaluate whether topical diclofenac 0.1% therapy adds any extra benefit to systemic diclofenac in controlling pain after photorefractive keratectomy. Design: Prospective randomized, double-masked clinical trial applied in the Khatam-al-Anbia Eye Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Participants: Sixty-eight individuals (age range, 18–35 years) having bilateral photorefractive keratectomy for myopic correction with or without astigmatism. Methods: All patients received 100 mg of extendedrelease oral diclofenac two times (12-h interval) before photorefractive keratectomy surgery. Postoperatively, patients were randomized into the case and control groups. Case group was administered the diclofenac 0.1% drop, one drop 2 h preoperatively and four times daily postoperatively for 3 days, whereas the control group was given artificial tears instead. Main Outcome Measures: Pain level, photophobia and functional activity were evaluated by the patient after operation.
Results: Two days after surgery, no statistically significant difference in pain level was noted between both groups. In addition, photophobia and functional activity was not different between the case and control groups. Eyelid oedema and conjunctival injection levels were significantly higher in the control group (P < 0.001). Conclusions: Administration of topical diclofenac to a standardized postoperative pain regime did not alleviate post-photorefractive keratectomy pain, although it is effective in local signs like eyelid oedema and conjunctival injection. It can be concluded that oral diclofenac is sufficient in the management of post-photorefractive keratectomy pain and addition of the topical diclofenac is unnecessary. Key words: cornea, diclofenac, pain, photorefractive keratectomy.
INTRODUCTION Excimer laser photorefractive keratectomy (PRK) has been widely used for the correction of refractive errors.1,2 A major disadvantage of this surgical procedure is pain and discomfort after the surgery, which may be due to severe damage to sensitive corneal sensory nerve fibres or locally released inflammatory substances, as corneal debridement
■ Correspondence: Dr Mojtaba Abrishami, Farabi Eye Hospital, Qazvin Square, Tehran 1336616351, Iran. Email: [email protected] Received 20 August 2013; accepted 27 March 2014. Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources. © 2014 Royal Australian and New Zealand College of Ophthalmologists
Postoperative photorefractive keratectomy pain induces severe inflammation.3,4 Pain usually starts within 1 h after PRK, increases during the next 3–4 h and disappears once corneal re-epithelialization is complete.5,6 The inadequate pain management after PRK procedure remains an important issue for both clinicians and patients.3–5,7–10 Topical anaesthetics, topical nonsteroidal anti-inflammatory agents (NSAIDs) and bandage soft contact lenses are all part of the recommended therapeutic regime to manage pain after PRK. However, the use of topical NSAIDs after PRK surgery has been viewed with some skepticism. Topical NSAIDs such as diclofenac can cause corneal complications when used excessively and for prolonged periods.11,12 This drug also slows epithelial closure; therefore, when combined with a contact lens, requires regular follow-up check-ups until epithelial closure because the risk of infection appears to be greater.13 The aim of the present study was to determine the role of topical diclofenac administration after surgery in management of postPRK pain.
811
Surgical procedure Each patient was given 100 mg of extended-release oral diclofenac (Modafenac, Modava Pharmaceutical, Tehran, Iran) at 9 pm on the night before the operation and at 9 am on the day of the operation. In addition, just before the surgery, the eye was anaesthetized with two drops (with 10-min interval) of tetracaine 0.5% (Anestocaine, Sina darou, Tehran, Iran). Standardized epithelial debridement was performed with an 8.5-mm well, into which 20% alcohol was instilled and left for 20 s over the cornea. The alcohol was removed from the eye with a sponge, and the ocular surface was washed with 20 cc of a balanced salt solution. Epithelial layer debridement was performed by using two dry sponges. The same surgeon (AE) performed all PRK procedures using the Technolas 217z excimer laser (Technolas, Munich, Germany), with the advanced personalized, aspheric and tissue saving profiles according to the conditions of the patient. After surgery, a plano bandage soft contact lens was placed to both eyes. All procedures were performed at Khatam-al-Anbia Eye Hospital, Mashhad, Iran.
METHODS Study population
Postoperative protocol
Sixty-eight adult subjects having bilateral PRK for myopia with or without astigmatism participated in this prospective randomized, double-masked, clinical trial. At enrolment visit, a detailed review of medical and ophthalmic histories and current medications were recorded, and full examination was performed. The examination included cycloplegic refraction, visual acuity measurements, slit-lamp biomicroscopy, corneal topography and corneal thickness measurement. All qualified patients included those whose spherical equivalent refraction was less than or equal to −7.00 D and had stable refractions for at least 6 months. In addition, all patients had central corneal thickness between 480 and 600 μm. The following exclusion criteria were adopted: any previous ocular disease or surgery; history of allergic reaction to NSAIDs; any bleeding disorder; and a history of peptic ulcer, glaucoma, collagen vascular disease, hypertension, diabetes mellitus or heart disease (including congenital, ischaemic or chest pain).
Following ablation, patients were randomly assigned into two groups. Both patients and an ophthalmologist were masked with regard to the post-PRK applied treatment. Case group was administered the diclofenac 0.1% drop (Dicloptin 0.1%, Sina darou) one drop 2 h preoperatively and one drop four times daily postoperatively for 3 days. However, patients in the control group were given artificial tears. In addition, both groups of patients received chloramphenicol 0.5% (chlobiotic 0.5%, Sina Darou) and betamethasone 0.1% (betasonate 0.1%, Sina Darou) drops four times per day (10-min interval). Chloramphenicol was continued for a week or until corneal re-epithelialization was completed. Betamethasone was continued for 2 weeks and was tapered slowly in 6 weeks. In addition, in both groups, the bandage soft contact lens was not removed until complete corneal re-epithelialization was confirmed (usually between third and fifth postoperative day). Two days after surgery, post-PRK examination included slitlamp biomicroscopy to determine whether conjunctival injection, chemosis or lid swelling was present and to evaluate corneal clarity, anterior chamber inflammation and corneal epithelial defect. Patients were also asked to assess their level of pain, photophobia and functional activity. In addition, eyelid oedema and conjunctival injection of each patient were assessed and scored by an ophthalmologist after surgery. All these aforementioned variables
Ethical consideration Informed consent was obtained from each participant after the nature of the experimental procedures had been explained. The research followed the tenets of the Declaration of Helsinki and was approved by the Mashhad University of Medical Sciences Research Ethics Committee.
© 2014 Royal Australian and New Zealand College of Ophthalmologists
812
Eslampoor et al.
Table 1. Variables and scales adopted in the present study to assess the photorefractive keratectomy outcome Variable Pain Score Photophobia
Functional activity Eyelid oedema
Conjunctival injection
Table 2. Descriptive comparison of pain score and other scaled variables in case (n = 38) and control (n = 30) groups
Scale 0–10: (0 illustrates no pain and 10 represents the worst possible pain) 0: no photophobia 1: photophobia in light without glass 2: photophobia in darkness without glass 3: photophobia in light with glass 4: photophobia in darkness with glass 1: no limitation (the patient’s activity is unrestricted by pain) 2: as mild limitation 3: severe limitation 0: no oedema and erythema 1: mild oedema 2: moderate oedema and erythema 3: severe oedema and ptosis 0: no conjunctival injection 1: very mild conjunctival injection (only in temporal and nasal, near the limbus) 2: mild conjunctival injection in two quadrants 3: moderate conjunctival injection in four quadrants 4: severe conjunctival injection with engorged vessels and chemosis
were scaled according to the Table 1 and compared between the case and control groups.
Data analysis All statistical analyses were performed using SPSS version 18 (SPSS, Inc., Chicago, IL, USA). Student’s t-tests were used to compare the differences in pain score and other variables between the case and control groups. The level of significance was set at P values less than 0.05.
RESULTS Of the 68 patients included in this study, 38 patients (case group) were randomized to receive topical diclofenac as part of the post-PRK medications. For the rest of the study population (control group, n = 30), this topical NSAID was eliminated from their therapeutic regime. The case group consisted of 14 men and 24 women, with the mean ± standard deviation age of 29.16 ± 4.43 years (range 20–35 years). In addition, the control group included 16 men and 14 women, with the mean ± standard deviation age of 26.90 ± 5.02 years (range 19–35 years). There was no significant difference in the age distribution of the two groups (P = 0.26). Table 2 illustrates the mean pain scores and the outcome levels of other investigated variables. There
Pain score Photophobia Functional activity Eyelid oedema Conjunctival injection
Case group
Control group
P value
4.32 ± 2.72 1.24 ± 0.71 1.61 ± 0.49 0.74 ± 0.50 0.74 ± 0.45
3.97 ± 2.67 1.30 ± 0.65 1.50 ± 0.51 1.00 ± 0.00 1.00 ± 0.26
0.850 0.700 0.249
Clinical and Experimental Ophthalmology 2014; 42: 810–814 doi: 10.1111/ceo.12343
Original Article Effect of topical diclofenac on postoperative photorefractive keratectomy pain: a randomized, controlled trial Alireza Eslampoor MD,1 Asieh Ehsaei PhD2,3 and Mojtaba Abrishami MD4,5 1
Cornea Research Center, Faculty of Medicine, 2Refractive Errors Research Center, School of Paramedical Sciences, Department of Optometry, School of Paramedical Sciences, 4Eye Research Center, Faculty of Medicine, Mashhad University of Medical Sciences and 5Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran 3
ABSTRACT Background: A major disadvantage of photorefractive keratectomy is postoperative pain and discomfort. This study aims to evaluate whether topical diclofenac 0.1% therapy adds any extra benefit to systemic diclofenac in controlling pain after photorefractive keratectomy. Design: Prospective randomized, double-masked clinical trial applied in the Khatam-al-Anbia Eye Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Participants: Sixty-eight individuals (age range, 18–35 years) having bilateral photorefractive keratectomy for myopic correction with or without astigmatism. Methods: All patients received 100 mg of extendedrelease oral diclofenac two times (12-h interval) before photorefractive keratectomy surgery. Postoperatively, patients were randomized into the case and control groups. Case group was administered the diclofenac 0.1% drop, one drop 2 h preoperatively and four times daily postoperatively for 3 days, whereas the control group was given artificial tears instead. Main Outcome Measures: Pain level, photophobia and functional activity were evaluated by the patient after operation.
Results: Two days after surgery, no statistically significant difference in pain level was noted between both groups. In addition, photophobia and functional activity was not different between the case and control groups. Eyelid oedema and conjunctival injection levels were significantly higher in the control group (P < 0.001). Conclusions: Administration of topical diclofenac to a standardized postoperative pain regime did not alleviate post-photorefractive keratectomy pain, although it is effective in local signs like eyelid oedema and conjunctival injection. It can be concluded that oral diclofenac is sufficient in the management of post-photorefractive keratectomy pain and addition of the topical diclofenac is unnecessary. Key words: cornea, diclofenac, pain, photorefractive keratectomy.
INTRODUCTION Excimer laser photorefractive keratectomy (PRK) has been widely used for the correction of refractive errors.1,2 A major disadvantage of this surgical procedure is pain and discomfort after the surgery, which may be due to severe damage to sensitive corneal sensory nerve fibres or locally released inflammatory substances, as corneal debridement
■ Correspondence: Dr Mojtaba Abrishami, Farabi Eye Hospital, Qazvin Square, Tehran 1336616351, Iran. Email: [email protected] Received 20 August 2013; accepted 27 March 2014. Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources. © 2014 Royal Australian and New Zealand College of Ophthalmologists
Postoperative photorefractive keratectomy pain induces severe inflammation.3,4 Pain usually starts within 1 h after PRK, increases during the next 3–4 h and disappears once corneal re-epithelialization is complete.5,6 The inadequate pain management after PRK procedure remains an important issue for both clinicians and patients.3–5,7–10 Topical anaesthetics, topical nonsteroidal anti-inflammatory agents (NSAIDs) and bandage soft contact lenses are all part of the recommended therapeutic regime to manage pain after PRK. However, the use of topical NSAIDs after PRK surgery has been viewed with some skepticism. Topical NSAIDs such as diclofenac can cause corneal complications when used excessively and for prolonged periods.11,12 This drug also slows epithelial closure; therefore, when combined with a contact lens, requires regular follow-up check-ups until epithelial closure because the risk of infection appears to be greater.13 The aim of the present study was to determine the role of topical diclofenac administration after surgery in management of postPRK pain.
811
Surgical procedure Each patient was given 100 mg of extended-release oral diclofenac (Modafenac, Modava Pharmaceutical, Tehran, Iran) at 9 pm on the night before the operation and at 9 am on the day of the operation. In addition, just before the surgery, the eye was anaesthetized with two drops (with 10-min interval) of tetracaine 0.5% (Anestocaine, Sina darou, Tehran, Iran). Standardized epithelial debridement was performed with an 8.5-mm well, into which 20% alcohol was instilled and left for 20 s over the cornea. The alcohol was removed from the eye with a sponge, and the ocular surface was washed with 20 cc of a balanced salt solution. Epithelial layer debridement was performed by using two dry sponges. The same surgeon (AE) performed all PRK procedures using the Technolas 217z excimer laser (Technolas, Munich, Germany), with the advanced personalized, aspheric and tissue saving profiles according to the conditions of the patient. After surgery, a plano bandage soft contact lens was placed to both eyes. All procedures were performed at Khatam-al-Anbia Eye Hospital, Mashhad, Iran.
METHODS Study population
Postoperative protocol
Sixty-eight adult subjects having bilateral PRK for myopia with or without astigmatism participated in this prospective randomized, double-masked, clinical trial. At enrolment visit, a detailed review of medical and ophthalmic histories and current medications were recorded, and full examination was performed. The examination included cycloplegic refraction, visual acuity measurements, slit-lamp biomicroscopy, corneal topography and corneal thickness measurement. All qualified patients included those whose spherical equivalent refraction was less than or equal to −7.00 D and had stable refractions for at least 6 months. In addition, all patients had central corneal thickness between 480 and 600 μm. The following exclusion criteria were adopted: any previous ocular disease or surgery; history of allergic reaction to NSAIDs; any bleeding disorder; and a history of peptic ulcer, glaucoma, collagen vascular disease, hypertension, diabetes mellitus or heart disease (including congenital, ischaemic or chest pain).
Following ablation, patients were randomly assigned into two groups. Both patients and an ophthalmologist were masked with regard to the post-PRK applied treatment. Case group was administered the diclofenac 0.1% drop (Dicloptin 0.1%, Sina darou) one drop 2 h preoperatively and one drop four times daily postoperatively for 3 days. However, patients in the control group were given artificial tears. In addition, both groups of patients received chloramphenicol 0.5% (chlobiotic 0.5%, Sina Darou) and betamethasone 0.1% (betasonate 0.1%, Sina Darou) drops four times per day (10-min interval). Chloramphenicol was continued for a week or until corneal re-epithelialization was completed. Betamethasone was continued for 2 weeks and was tapered slowly in 6 weeks. In addition, in both groups, the bandage soft contact lens was not removed until complete corneal re-epithelialization was confirmed (usually between third and fifth postoperative day). Two days after surgery, post-PRK examination included slitlamp biomicroscopy to determine whether conjunctival injection, chemosis or lid swelling was present and to evaluate corneal clarity, anterior chamber inflammation and corneal epithelial defect. Patients were also asked to assess their level of pain, photophobia and functional activity. In addition, eyelid oedema and conjunctival injection of each patient were assessed and scored by an ophthalmologist after surgery. All these aforementioned variables
Ethical consideration Informed consent was obtained from each participant after the nature of the experimental procedures had been explained. The research followed the tenets of the Declaration of Helsinki and was approved by the Mashhad University of Medical Sciences Research Ethics Committee.
© 2014 Royal Australian and New Zealand College of Ophthalmologists
812
Eslampoor et al.
Table 1. Variables and scales adopted in the present study to assess the photorefractive keratectomy outcome Variable Pain Score Photophobia
Functional activity Eyelid oedema
Conjunctival injection
Table 2. Descriptive comparison of pain score and other scaled variables in case (n = 38) and control (n = 30) groups
Scale 0–10: (0 illustrates no pain and 10 represents the worst possible pain) 0: no photophobia 1: photophobia in light without glass 2: photophobia in darkness without glass 3: photophobia in light with glass 4: photophobia in darkness with glass 1: no limitation (the patient’s activity is unrestricted by pain) 2: as mild limitation 3: severe limitation 0: no oedema and erythema 1: mild oedema 2: moderate oedema and erythema 3: severe oedema and ptosis 0: no conjunctival injection 1: very mild conjunctival injection (only in temporal and nasal, near the limbus) 2: mild conjunctival injection in two quadrants 3: moderate conjunctival injection in four quadrants 4: severe conjunctival injection with engorged vessels and chemosis
were scaled according to the Table 1 and compared between the case and control groups.
Data analysis All statistical analyses were performed using SPSS version 18 (SPSS, Inc., Chicago, IL, USA). Student’s t-tests were used to compare the differences in pain score and other variables between the case and control groups. The level of significance was set at P values less than 0.05.
RESULTS Of the 68 patients included in this study, 38 patients (case group) were randomized to receive topical diclofenac as part of the post-PRK medications. For the rest of the study population (control group, n = 30), this topical NSAID was eliminated from their therapeutic regime. The case group consisted of 14 men and 24 women, with the mean ± standard deviation age of 29.16 ± 4.43 years (range 20–35 years). In addition, the control group included 16 men and 14 women, with the mean ± standard deviation age of 26.90 ± 5.02 years (range 19–35 years). There was no significant difference in the age distribution of the two groups (P = 0.26). Table 2 illustrates the mean pain scores and the outcome levels of other investigated variables. There
Pain score Photophobia Functional activity Eyelid oedema Conjunctival injection
Case group
Control group
P value
4.32 ± 2.72 1.24 ± 0.71 1.61 ± 0.49 0.74 ± 0.50 0.74 ± 0.45
3.97 ± 2.67 1.30 ± 0.65 1.50 ± 0.51 1.00 ± 0.00 1.00 ± 0.26
0.850 0.700 0.249
