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 Table of Contents  
Year : 2020  |  Volume : 21  |  Issue : 1  |  Page : 14-18

Effect of cycloplegic eye drops on pain after photorefractive keratectomy and corneal collagen cross-linking

Department of Ophthalmology, Tanta University, Tanta, Egypt

Date of Submission11-Aug-2019
Date of Decision11-Aug-2019
Date of Acceptance13-Nov-2019
Date of Web Publication28-Feb-2020

Correspondence Address:
MD, FRCS Hazem A Elbedewy
Department of Ophthalmology, Tanta University, Tanta 31511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/DJO.DJO_40_19

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Purpose The aim of this study was to evaluate the effectiveness of topical cycloplegic eye drops (cyclopentolate) on relieving ocular pain and discomfort after photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL).
Patients and methods This is a randomized controlled double-blind study that included 30 patients eligible for bilateral PRK or CXL. After removal of the corneal epithelium and completion of the procedure, a plano bandage soft contact lens was placed. Postoperative medications were topical prednisolone, moxifloxacin, and tear substitute, each four times/day for both eyes. For each patient, one eye had the cycloplegic drops and the other eye had placebo drops. All the patients were asked to complete three types of pain rating questionnaires: visual analog scale (VAS), verbal rating scale (VRS), and Mac-Gill pain questionnaire (PRI) at each time of postoperative follow-up.
Results VAS, VRS, and PRI mean scores at the first postoperative hour did not show any significant difference between cycloplegic and control eyes (P>0.50). However, the cycloplegic eyes had significantly lower mean VAS and PRI scores at 24 and 48 h, postoperatively (P<0.001 and 0.01, respectively). In the first postoperative day, 13.3% of the control eyes had mild pain, 66.7% had moderate pain, and 20% had severe pain, whereas 30.0% of the cycloplegic eyes had mild pain and 70% had moderate pain (0% had severe pain) on the VRS. All cycloplegic eyes had photophobia and blurring of vision during the first three postoperative days, which rapidly improved after cessation of the cycloplegic drops.
Conclusion Cycloplegic eye drops (cyclopentolate) were safe and effective in reducing pain and ocular discomfort after removal of the corneal epithelium in PRK and CXL with tolerable side effects, which rapidly improved after cessation of the drops.

Keywords: corneal epithelium, cross-linking, cycloplegic drops, pain, photorefractive keratectomy

How to cite this article:
Elbedewy HA, Sabry MM. Effect of cycloplegic eye drops on pain after photorefractive keratectomy and corneal collagen cross-linking. Delta J Ophthalmol 2020;21:14-8

How to cite this URL:
Elbedewy HA, Sabry MM. Effect of cycloplegic eye drops on pain after photorefractive keratectomy and corneal collagen cross-linking. Delta J Ophthalmol [serial online] 2020 [cited 2022 Jan 28];21:14-8. Available from: http://www.djo.eg.net/text.asp?2020/21/1/14/279722

  Introduction Top

Many medications and techniques have been described to mitigate the ocular pain after painful corneal surgeries or procedures such as photorefractive keratectomy (PRK) or corneal collagen cross-linking (CXL) [1]. This postoperative pain remains one of the most annoying adverse effects of such procedures [2]. The ocular pain is usually severe because the human cornea is heavily innervated through mid-stromal plexus (a moderately dense plexus), which then branches to subepithelial nerve plexus (a dense one) [3]. Loss or removal of the superficial corneal epithelium in PRK and CXL results in exposure of the corneal nerve endings causing varying degrees of pain and discomfort [4].

PRK is still widely used as a safe and effective operation for correction of mild to moderate refractive errors [5], where laser ablation is applied to the corneal stroma after epithelial debridement. This ablation causes severe postoperative pain, which limits PRK acceptance by the patients [6]. Ocular pain starts from the first postoperative day and may persist for 3 days till complete re-epithelialization occurs [5].

Many treatment options are available for patients with keratoconus and other ectatic conditions. However, treatment with corneal collagen CXL with ultraviolet A and riboflavin is considered the main conservative line of treatment. It can slow down the progression of the corneal ectatic condition and delay or even avoid the need for more invasive therapies (such as keratoplasty). This technique also includes an initial step of epithelium removal with a significant postoperative pain as in PRK [7].

Different approaches have been tried to manage such postoperative pain including intraoperative application of chilled balanced salt solution with postoperative use of cool artificial tears, topical anesthetics, topical NSAIDs, topical corticosteroids, contact lens for 4–5 days, and systemic analgesics [8],[9],[10],[11],[12],[13],[14],[15],[16].

In ophthalmological practice, topical cycloplegic eye drops are mainly used as mydriatics and to relief pain by alleviating the ciliary muscle spasm. Cycloplegics are also commonly used to decrease ocular pain after corneal abrasions, ocular trauma, and different types of uveitis [17],[18].

This study was designed to evaluate the safety and effectiveness of topical cycloplegic eye drops as a way to relieve pain after PRK and CXL.

  Patients and methods Top

This is a double-blind randomized controlled study that included 30 patients (60 eyes) who were fit for bilateral PRK surgery or bilateral CXL surgery between July and December 2017. The study was carried out in accordance with the ethical standards of the Declaration of Helsinki (revised 2013) and was approved by Tanta University Ethics Committee. A written informed consent to participate in the trial and for publication of data was obtained from every patient before enrollment in the study. Block randomization (five eyes/block) was used to randomly assign each eye to a study group. All the patients and study-included staff dealing with data collection or analysis were blinded for the eye drops and drugs assigned for each group. Allocation concealment was done using sequentially numbered dark opaque sealed envelopes, which were opened after the patient signed the written consent, and then the patients were enrolled into the respective group.

All the patients had the same preoperative complete ocular examination including full anterior segment examination, posterior segment examination, distance visual acuity testing both uncorrected and corrected, manifest and cycloplegic refractions, intraocular pressure measurement, and corneal topography using Pentacam scans (Oculus Inc., Lynnwood, Washington, USA). The patient would be excluded from the study if he/she had history of ocular surgeries, history of neurosensory pain disorders, and history of topical or systemic analgesics or NSAIDs 2 weeks before surgery.

In all cases, the corneal epithelium was removed by a spatula after instilling topical anesthetic eye drops for four to five times. In PRK, stromal laser ablation was performed using excimer laser WaveLight EX500 (Alcon, Fort Worth, Texas, USA). In CXL, the procedure was done using VEGA X-Linker (CSO, Scandicci, Florence, Italy).

At the end of each procedure, a plano bandage soft contact lens was placed on the cornea, which was removed after complete re-epithelialization. Postoperative medications were topical prednisolone, topical moxifloxacin, and topical tear substitute, each four times/day for both eyes. For each patient, one eye had cyclopentolate eye drops as cycloplegic eye drops (Cyclopentolate HCL; Busch & Lomb, a division of Valeant Pharmaceuticals North America LLC Bridgewater, New Jersey, USA), whereas the other eye had placebo drops, each three times/day (the label was removed from both bottles and the cycloplegic eye drops bottle was marked by a sign). The patients were instructed to use each drops for the exact assigned eye, and those who reported mistakes were excluded from the study.

Before surgery, all patients were interviewed and taught the pain questionnaires. Each one of the used scales was explained to every patient and evaluated to confirm that they understood it the right way. Every patient was asked about his pain and discomfort in each eye at 1, 24, and 48 h after surgery using three different subjective pain-scoring scales: visual analog scale (VAS), verbal rating scale (VRS), and Mac-Gill pain questionnaire (PRI). For VAS, every patient was asked to point his/her pain sensation severity on a line, with faces showing different expressions of pain, which is marked from 0 for ‘no pain’ to 10 for ‘the most severe intolerable pain the patient has ever experienced’ at equal intervals. For VRS, each patient was asked to rate his/her experience of pain on the Keele̛s verbal pain chart, which allows the patient to score the pain in a semiquantitative way, where 0=no pain, 1=minimal pain, 2=moderate pain, 3=severe pain, and 4=agonizing pain. For PRI, the pain score was measured as the sum of both the sensory and effective pain rating indices (S-PRI and A-PRI). This scale consists of 15 descriptors where the intensity of each one is rated on a four-point-scale: none, mild, moderate, and severe.

Statistical analysis

The data were tested for normality using Shapiro–Wilk’s test and then presented as mean±SD, median, numbers, and percentages. The analysis was done using SPSS, version 23 (SPSS Inc. Released 2015. IBM SPSS statistics for windows; IBM Corp., Armonk, New York, USA). Student’s t −test was used for comparing normally distributed quantitative variables, and Mann–Whitney’s test was used for not normally distributed ones. χ2 was used to study the association between qualitative variables, and whenever any of the expected cells were less than five, Fisher’s exact test was used. Two-sided P value of less than 0.05 was considered statistically significant.

  Results Top

This study included 45 patients. However, 15 were excluded; seven of them because they missed one follow-up, five owing to usage of the cycloplegic drops in both eyes, and three gave invalid/incomplete questionnaires. The mean age of the participants was 28.93±7.90 years. Males represented 53.3% (16 cases).

From what the patients reported, VAS, VRS, and PRI mean scores at the first postoperative hour did not show any significant difference between the cycloplegic eyes and the control eyes. However, the cycloplegic eye drops had significantly decreased mean VAS, VRS, and PRI scores at 24 and 48 h after surgery in the cycloplegic eyes ([Table 1]).
Table 1 Comparison between the two groups of eyes regarding the different pain scores at different time measures

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Regarding the grades of the VRS, most of the eyes in both groups had mild degree of pain 1 h after surgery. However, on the first postoperative day, the cycloplegic eyes had mild pain in nine (30.0%) eyes, and moderate in the other 21 (70.0%) eyes (none reported severe pain), whereas in the control group of eyes, four (13.3%) eyes had mild pain, 20 (66.7%) had moderate pain, and six (20.0%) had severe pain. On the second postoperative day, 20.0% of the cycloplegic eyes (six eyes) had no pain, whereas only 6.7% (two eyes) of the control group had no pain. Mild pain was present in 70.0% (21 eyes) and moderate pain was present in 10.0% (three eyes) of the cycloplegic group, whereas mild pain was present in 33.3% (10 eyes) and moderate pain was present in 60.0% (18 eyes) in the control group of eyes ([Table 2]).
Table 2 Different grades of verbal rating scale in the two groups at different time measures

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All patients reported photophobia and blurring of vision in the cycloplegic eyes during the first three postoperative days, which rapidly improved (within 12 h) after the cessation of the drops at the third postoperative day when complete healing of the corneal epithelium had occurred.

  Discussion Top

Corneal epithelium removal for PRK or CXL procedure causes exposure of the corneal nerve endings, leading to severe ocular pain, hence the mandatory need to control the postoperative pain after such procedures. No single ideal measure is present to control that pain. The use of chilled balanced salt solution intraoperatively blocks the impulse conduction along the nerve fibers and reduces the pain [16]. The use of bandage soft contact lens protects the de-epithelialized corneal stroma but can cause corneal edema and delayed re-epithelialization process owing to low oxygen permeability [19]. Many types of analgesic eye drops have been approved by the FDA like topical NSAID (e.g. diclofenac and ketorolac) to be used with corneal surface ablation procedures [9].

Relieving the ciliary muscle spasm by cycloplegics has a well-known role in the treatment of corneal trauma [17] and iritis [18]. This action of cycloplegics can be used to reduce the ocular pain after PRK or corneal CXL.

In this study, the patients reported nearly similar pain in both eyes an hour after surgery, but after 24 h, the patients reported significantly less pain in the cycloplegic eyes than in the control eyes by all used scales (VAS, VRS, and PRI). This continued till 48 h after surgery. Approximately one-fifth (six eyes) of the control eyes experienced severe pain on the VRS, whereas no eyes in the cycloplegic group had this degree of pain. After 48 h of surgery, none of the eyes in both groups had severe pain. More than two-thirds of the eyes in the cycloplegic group had mild pain by this time compared with nearly two-thirds of the control group who had moderate pain.

This remarkable effect of pain relieving by the cycloplegic drops was reported also by Joshaghani et al. [20], in their pilot study about the effect of homatropine eye drops to control pain after PRK. They measured the pain by the standard VAS, VRS, and PRI scales. Their patients reported significantly less pain by all used scales at the first 24 and 48 h after surgery in the homatropine eyes compared with the fellow eyes, and they concluded that homatropine eye drops may be useful in controlling the pain after PRK. In the present study, we used cyclopentolate because of its rapid onset of action as a cycloplegic (within 25–75 min), and its shorter duration of action with complete recovery of accommodation after 6–24 h. Homatropine on the contrary is considered a moderately long-acting mydriatic-cycloplegic, and the patient may experience cycloplegia and mydriasis for 24–72 h [21].

Many ophthalmologist use topical NSAID to control ocular pain in their patients after painful corneal procedures. Many preparations are available for ocular use, but mostly diclofenac, ketorolac, and nepafenac are the most widely used. In a study by Abri Aghdam et al. [22], the effect of NSAID was compared with cycloplegics in reducing the ocular pain using the same pain measuring tools. They found that the cycloplegic effect was lower than the diclofenac (NSAID) effect in reducing pain after PRK at 24 and 48 h after surgery. However, topical NSAIDs have many ocular adverse effects. Common less serious adverse effects include transient burning sensation, stinging, and conjunctival hyperemia [23]. More serious adverse effects include superficial punctate keratitis/epithelial defects, delayed epithelial healing, corneal infiltrates, or even corneal melts in the severe cases [24]. Cycloplegics have less severe adverse effects on the patients’ eyes. In the current study, the major complaint of the patients in the cycloplegic eye was photophobia and transient blurring of vision, which was relieved by using dark sunglasses for the first three postoperative days.

  Conclusion Top

Cycloplegic eye drops (cyclopentolate) were safe and effective in reducing pain and discomfort after removal of the corneal epithelium in PRK and corneal CXL. Most of the cycloplegic adverse effects disappeared rapidly after cycloplegic cessation.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2]


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