ORIGINAL STUDY Alcohol cotton bud technique for removal of corneal epithelium at the slit lamp in corneal crosslinking

Alcohol cotton bud technique for removal of corneal epithelium at the slit lamp in corneal crosslinking

S Ballim MBChB, FC Ophth(SA), MMed Ophth(UKZN); Honorary lecturer, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa ORCID: https://orcid.org/ 0000-0001-5088-0606

S Mahomed MBChB, MMed(PHM), PhD(PHM); Senior lecturer, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa ORCID: https://orcid.org/0000-0001-7095-9186

Corresponding author: Dr Shaheer Ballim, Postnet Suite 247, Private Bag X10, Musgrave Road, Durban, 4062, South Africa; tel: +27 31 2075450; email: shaheerballim@gmail.com

Abstract

Aim: To describe the procedure and patient outcomes of a novel technique for the removal of corneal epithelium during corneal crosslinking.

Methods: This is a retrospective case series of patients who underwent epithelium-off corneal crosslinking for keratoconus using a new technique to remove the corneal epithelium at a private ophthalmology clinic. Demographic and clinical data, keratometry, rate of epithelial healing, degree of corneal haze and incidence of any complications were recorded over a median follow-up period of 36 weeks. The corneal epithelium was removed at the slit lamp under topical anaesthesia. A cotton bud dampened in 70% alcohol facilitated easy and non-traumatic removal of the epithelium in an 8–9 mm diameter for subsequent corneal crosslinking.

Results: Thirty-six eyes of 23 patients had crosslinking using this technique. The median number of days to epithelial closure was three (range two to six). Of the 27 eyes not lost to follow-up, 23 eyes (85.19%) showed decrease or stability (within 1 dioptre) of Kmax. The procedure did not inhibit the effect of corneal crosslinking for keratoconus. Fifteen eyes (55.55%) showed improvement in visual acuity, 11 eyes (40.70%) showed stability of visual acuity, and one eye (3.70%) showed deterioration in visual acuity by one line or more. There was one case of sterile corneal infiltrates (2.78%); no other complications were noted. All patients found the procedure acceptable in terms of patient experience and comfort. The technique used minimal resources and time.

Conclusion: The findings of this study suggest that this novel technique may be provide a safe and effective method for removing corneal epithelium before corneal crosslinking.

Keywords: corneal epithelium removal, keratoconus, crosslinking, resource-constrained

Funding: No financial support was received by any of the authors for performing this research.

Conflict of interest: The authors have no conflicts of interest to declare.

Introduction

Corneal crosslinking is an important aspect in the management of patients with keratoconus. The procedure has been shown to prevent progression of the disease, and in some cases improve vision, by strengthening and stiffening the cornea.1 The most effective technique includes removal of the corneal epithelium as part of the procedure.2 The standard Dresden protocol involves epithelial removal of the central 7 mm.3 The corneal epithelium has shown to be a significant barrier to the corneal absorption of hydrophilic molecules such as riboflavin.4 Removal of the epithelium therefore markedly improves uptake of riboflavin into the corneal stroma in preparation for ultraviolet radiation in corneal crosslinking.

Various techniques and instruments have been reported for removal of the corneal epithelium. These instruments include a blunt spatula,1,5 a blunt knife,6 and an ophthalmic scalpel.7,8 The use of specialised instruments has also been reported such as an Amoils epithelial scrubber/brush, and an Epi Clear device (Orca Surgical).9-11 The choice of instrument is often based on the surgeon’s preference. Corneal epithelium can also be removed with ablative laser as in transepithelial photorefractive keratectomy.12-14 Some of these instruments, and the chemical solutions used, are not easily available in resource-constrained settings.

In South Africa, there are no standard guidelines to indicate how the corneal epithelium should be removed. Anecdotal reports include manual removal with a blunt instrument, spatula or blade; and use of 20% ethyl alcohol solution in a ring or well to soak the epithelium before removal with a cotton bud or microsponge. The technique described in this research was originally necessitated in the context of a public health sector eye clinic in South Africa due to a lack of easily available equipment and consumables, together with the challenge of a high disease burden of keratoconus. The technique was found to be safe, cost-effective and timeefficient (author’s anecdotal experience). The technique was then successfully implemented in private practice.

The aims of the study are to describe a novel technique for the removal of corneal epithelium at the slit lamp during corneal crosslinking, to audit the safety and efficacy of the technique and to describe patient outcomes.

Materials and methods

This retrospective observational descriptive case series comprised 36 eyes of 23 patients with keratoconus who underwent epithelial removal for corneal crosslinking treatment at a private corneal practice in Durban, South Africa.

Ethics approval was obtained from the University of KwaZulu-Natal Bioethical Research Committee (BE567/18). Informed consent was obtained from all patients prior to treatment. The study adhered to the tenets of the Declaration of Helsinki.

The inclusion criteria were all patients who underwent the specified technique of epithelial removal before corneal crosslinking and who were assessed clinically and with Scheimpflug tomography preoperatively at the study site from January 2017 to August 2018. Clinical diagnosis of keratoconus was confirmed by Scheimpflug tomography. Progression of keratoconus was established by deteriorating visual acuity and refractive error or deteriorating serial topography or corneal thickness. All eyes were assessed to have a residual stromal thickness of at least 400 microns obtainable at the commencement of ultraviolet radiation and maintainable throughout ultraviolet radiation with isotonic or hypotonic riboflavin as guided by intraoperative pachymetry. The thinnest preoperative pachymetry was 396 microns. Comorbidities other than atopic conjunctivitis were noted. Patients with active ocular inflammation or infections, corneal scar, corneas deemed too thin to achieve a stromal bed of 400 microns at the time of ultraviolet radiation, or patients requiring general anaesthetic were excluded.

All patients underwent ophthalmic examination including distance visual acuity testing with best available correction, slit-lamp biomicroscopy and Scheimpflug-based corneal topography/ tomography (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany) preoperatively.

All procedures were performed by a single surgeon. Topical anaesthesia with two drops of tetracaine hydrochloride 1% spaced two minutes apart was followed by two drops of povidone iodine 5% into the conjunctival sac, two minutes apart. Eyelids were cleaned with povidone iodine and a sterile wire speculum was inserted to keep the eye open for the removal of the epithelium. The patient’s head was positioned at the slit lamp and a beam of height 8–9 mm was used for illumination, to aid with measurement of the intended epithelial defect. A sterile cotton bud (from a sterile pack or a dry pus swab) was dampened by contact with a 70% isopropyl alcohol-saturated pad (commonly used for skin disinfection) (Figure 1).

Figure 1. Alcohol cotton bud removal of corneal epithelium

This ensured that the cotton bud was not soaked as would have been the case if it was dipped into a 70% alcohol solution. The alcoholdampened cotton bud was then used to contact the corneal epithelium in an 8–9 mm circular area in a repeated ‘dabbing’ fashion for 10–15 seconds. This resulted in a loosening of the epithelial sheet of the cornea in the central 8–9 mm zone. The epithelium was then wiped off in a circular shearing manoeuvre to the desired size of epithelial removal. The speculum was then removed and the crosslinking procedure was commenced (Table I).

Table I: Corneal crosslinking methods

Parameter: Treatment target Variable: Ectasia

Parameter: Fluence (total) (J/cm2) Variable: 5.31 to 5.4

Parameter: Soak time and interval (minutes) Variable: 30(q2)

Parameter: Intensity (mW) Variable: 5.9 to 9

Parameter: Treatment time (minutes) Variable: 10 to 15

Parameter: Epithelium status Variable: Off

Parameter: Chromophore Variable: Riboflavin (various)

Parameter: Chromophore carrier Variable: Hydroxypropyl methylcellulose USP 10 mg

Parameter: Chromophore osmolarity Variable: Iso-osmolar/ hypo-osmolar

Parameter: Chromophore concentration Variable: 0.1%

Parameter: Light source Variable: Lightmed

Parameter: Irradiation mode Variable: Continuous (interval)

Parameter: Protocol modifications Variable: Not applicable

Parameter: Protocol abbreviation in manuscript Variable: Not applicable

Riboflavin-phosphate 0.1% was instilled every 1–2 minutes for 30 minutes. Hypotonic 0.5% riboflavin solution was used in cases where the stromal bed was less than 400 microns in thickness. Topical tetracaine hydrochloride 1% was instilled every 10 minutes. Pachymetry was performed before ultraviolet light radiation. Continuous ultraviolet A light was then radiated on the central 8–9 mm of the cornea for 10 to 15 minutes to achieve a fluence of 5.31 J/cm2 to 5.4 J/cm2 (Lightlink CXL, Lightmed Corporation, CA). A bandage contact lens or 72-hour collagen corneal shield and topical preservative-free chloramphenicol 0.5% was applied at the end of the procedure. Dexamethasone 0.1% with tobramycin 0.3% was prescribed for two weeks after surgery. The bandage contact lens was removed 2–3 days postoperatively.

Subjective reports of any pain during the epithelial removal were recorded. Slit-lamp biomicroscopy was performed 2–7 days postoperatively to assess for corneal haze and number of days to epithelial closure. Patients were required to have repeated visits for examination and Scheimpflug scans (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany). Not all patients had follow-up of a year or more at the time of data collection. Those patients that were not lost to followup were recorded with postoperative topographic and tomographic parameters: maximum simulated keratometry values representing anterior corneal steepness (Kmax), and pachymetry at the thinnest point of the cornea as measured by the Scheimpflug scan. Evidence of corneal haze, distance visual acuity testing with best available correction and evidence of any complications were noted.

The data was analysed using SPSS version 25. Quantitative data was summarised using the mean and standard deviation. The Shapiro-Wilk test was used to test for normal distribution. The paired samples t-test was used to compare preoperative and postoperative Kmax and corneal thickness. A p-value of less than 0.05 was considered significant.

Results

Thirty-six eyes of 23 patients underwent epithelial removal with the described technique for corneal crosslinking during the study period. The median age of the patients was 23 years (range 12–34). Twenty-eight of the eyes were from male patients and eight eyes were from female patients. There was one eye with co-existent quiescent herpes zoster ophthalmicus uveitis and two eyes of one patient with bilateral preoperative dry eye. No other comorbidities were noted.

The mean preoperative Kmax was 59.34 D±7.48 (range: 45.8–83.3). The mean preoperative pachymetry at the thinnest point was 450.67 µm±33.30 (range: 396–537) before epithelial removal and application of hypotonic riboflavin if necessary. No eyes had preoperative haze. All patients found the epithelial removal to be acceptably comfortable without reports of pain at the time of epithelial removal. All eyes had greater than 400 µm of residual stromal thickness measured by ultrasound pachymetry (Ocuscan RxP, Alcon, Texas, USA) immediately before commencement of ultraviolet light radiation.

At the first postoperative review (2–7 days post-surgery), 22 (61.11%) eyes had haze associated with the crosslinking. The median number of days to epithelial closure was three (range two to six). There was one case of sterile corneal infiltrates (2.78%). No other complications were noted.

Nine of 36 eyes were lost to follow-up. Of the remaining 27 eyes, the median followup postoperatively with repeat Scheimpflug scan was 36 weeks (range: 3–83). There was no significant change in the mean Kmax from 60.19 preoperatively to 59.49 postoperatively (Table II).

Table II: Changes in Scheimpflug tomography (n=27)

Mean Kmax (range) Preoperative: 60.19±7.75 (45.8–83.3) Postoperative: 59.49±8.18 (45.3–81.7) p: 0.055

Mean pachymetry (range) Preoperative: 453.74±32.67 (397–537) Postoperative: 431.37±39.58 (369–520) p: 0.000

Objective haze was observed in 13 eyes (48.15%). Twentythree eyes (85.19%) showed decrease or stability (within 1 dioptre) of Kmax. One eye (3.70%) showed deterioration in visual acuity by one line or more, 11 eyes (40.7%) showed stability of visual acuity and 15 eyes (55.55%) showed improvement in visual acuity by one line or more (Figure 2).

Figure 2. Visual acuity at follow-up

Discussion

This is the first published report of the use of a 70% alcohol-dampened cotton bud for removal of the corneal epithelium in a South African setting. The use of alcohol assists in the removal of corneal epithelium by breaking the hemidesmosome anchors to the basement membrane, thus mobilising the stratified squamous epithelium as a sheet from the basement membrane at the level of the lamina lucida, without damaging the basement membrane.15,16 This process facilitates quick and non-traumatic removal of the corneal epithelium. There are numerous reports of alcohol-assisted manual techniques, all of which use a 20% alcohol solution. These reports include using an alcohol well for 20 seconds, alcohol-soaked filter paper (20% alcohol) for 60 seconds and 20% ethyl alcohol in a 9 mm ring for 40 seconds, followed by manual epithelial debridement with cellulose sponge, rotating brush or blunt spatula.17-20

Corneal haze is the most common reported complication of corneal crosslinking. The incidence of corneal haze differs greatly among study populations ranging from 10–90%.21 Our corneal haze

incidence of 61% on first postoperative visit and 41% at the time of postoperative scans is in keeping with other studies. It is likely that this incidence will decrease further with longer postoperative follow-up of our cohort of patients. Our only other reported complication was sterile infiltrates in one eye. We had no cases of microbial keratitis, permanent scars or golden striae. In our study, all epithelial defects were healed at one week. This is a favourable outcome compared to other reports where up to 25% of patients had a persistent epithelial defect even after one week and 20% of patients had punctate epitheliopathy in the first three months.22

Most eyes (96%) showed stabilisation or improvement of visual acuity. Deterioration in visual acuity was only found in one eye (3.70%), which is much lower than that reported in a review of 45 studies of corneal crosslinking with epithelial removal.22 The mean steepness of the cornea as reflected by Kmax was stable postoperatively suggestive of halted progression of the keratoconus. There was a significant decrease in the mean corneal thickness postoperatively. Twenty-three of 27 (85.19%) showed flattening or stability of maximum curvature (within 1 dioptre). The positive postoperative findings demonstrate the effectiveness of this novel technique of epithelial removal.

The limitations of this study include the short follow-up period and loss to follow-up. The factors that may have contributed to loss to follow-up include financial resources, and some patients did not think that followup was necessary despite being contacted by the practice. The lack of a standardised scale to assess pain is not ideal for the assessment of surgical outcomes and complications. The biochemical effect of isopropyl alcohol (as opposed to ethanol) on the cornea requires histological investigation to determine its mechanism of action and potential toxicity. The use of isopropyl alcohol as opposed to ethanol, and the 70% concentration used, was based on the type of alcohol swabs available in our setting, where ethanol-soaked swabs are not commercially available.

Conclusion

The technique described uses minimal time and resources, and may provide a safe and effective option for removal of the corneal epithelium. The technique has a low complication rate without hindering the effect of the subsequent crosslinking and is found to be acceptable to patients with regard to comfort. Further research is required to assess the long-term effects of 70% isopropyl alcohol on the cornea. Case-controlled and histological studies are indicated to confirm these outcomes before planned training and implementation of this technique in resource-constrained settings where safe and cheap methods for the removal of corneal epithelium are needed.

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