Effects of benoxinate hydrochloride 0.4% on the morphological appearance of the cornea using confocal microscopy

doi:10.1016/j.clae.2003.11.001

Contact Lens and Anterior Eye

Volume 27, Issue 1, March 2004, Pages 45-48

https://doi.org/10.1016/j.clae.2003.11.001 Get rights and content

Abstract

Purpose: To investigate whether benoxinate hydrochloride 0.4% used to make confocal microscopy more comfortable alters the morphology of the cornea as viewed with the confocal microscope. Methods: Confocal microscopy was performed on both eyes of 10 subjects prior to instillation of either topical anaesthetic or non-preserved sterile saline, on two randomly ordered occasions. Images of all corneal layers were analysed quantitatively and qualitatively in a masked fashion. Results: The images were similar in appearance in 5/10 subjects, there was greater clarity when anaesthetic was instilled in 4/10 subjects, and in the remaining subject there was greater clarity when saline was used. Anaesthetic had no influence on anterior keratocyte density (AKD), posterior keratocyte density (PKD) or endothelial cell density (ECD). Conclusions: Local anaesthetic does not affect corneal morphology as imaged using the confocal microscope. However, failure to use anaesthetic may lead to a degradation of image quality due to patient discomfort and excessive eye movements.

Introduction

Topical anaesthesia is used prior to undertaking a wide variety of ophthalmic procedures such as contact tonometry, removal of foreign bodies, ultrasound pachymetry, gonioscopy and more recently confocal microscopy. It provides an adequate length of time of nerve inhibition for the majority of ophthalmic procedures and does not subject the patient to the risk of general anaesthesia.

Benoxinate hydrochloride 0.4% is the local anaesthetic used in our laboratory prior to the confocal microscopy examination. No major side effects have been reported to be associated with this drug. It produces a temporary sensation of stinging or burning and in rare cases can cause epithelial desquamation. Local allergic reactions are rare [1]. One drop produces anaesthesia in about 20 s. The duration of anaesthesia (10–20 min) [2] is adequate for confocal microscopy. There do not appear to have been any studies examining the effects of topical anaesthesia on corneal features when examining the cornea with an in vivo slit scanning confocal microscope.

Previous research into the effect of topical anaesthesia has concentrated on the corneal epithelium and has utilised conventional microscopy techniques such as scanning electron microscopy [3], [4], [5]. Topical anaesthesia would not be expected to have an effect on the quantitative assessment of keratocyte density (KD) and endothelial cell density (ECD). However, it was considered prudent to fully investigate this prior to conducting larger studies using the confocal microscope.

Section snippets

Confocal microscopy

The subjects underwent examination with a Tomey ConfoScan confocal microscope Model P4 (Erlangen, Germany). This instrument provides en face two-dimensional images of the cornea with a lateral resolution of approximately 1–2 μm, and high contrast. The field of view examined by the confocal microscope is an area (x- and y-axes) of $315 μm ×236$ μm (i.e.7.4×10⁴ μm²) and the depth of field (z-axis) thickness is approximately 10 μm. The components of the ConfoScan system are as follows: ConfoScope

Results

Intra-examiner variation was assessed using paired sample t-tests. No statistically significant difference was demonstrated, indicating that repeated measurements from individual examiners were consistent. Inter-examiner variation was assessed using analysis of variance tests. No statistically significant difference was demonstrated between examiners for anterior KD (P=0.53), posterior KD (P=0.26) or ECD (P=0.48).

Quantitative analysis of the epithelial basal cell layer was not possible due to

Discussion

The main effect of ocular anaesthetics is the prevention of pain. There have not been any published studies documenting the effects of topical anaesthetics on corneal morphology in the in vivo human eye. One study looking at the effects of 0.5% amethocaine on the human cornea using electron microscopy demonstrated toxic effects to the superficial epithelial cells. These toxic changes were attributed to change in pH caused when instilling 0.5% amethocaine [6]. Amethocaine has a pH of 3.7–6.0

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Given the numerous clinical uses of LSCM as outlined in Section 1, the potential application of NC-LSCM in offering a more comfortable option to apprehensive patients who cannot tolerate corneal contact or eye drops should not be underestimated. Although this paper compares images obtained from anaesthetised corneas (C-LSCM) and non-anaesthetised corneas (NC-LSCM), it is unlikely that any differences observed can be attributed to the effects of anaesthetic on corneal morphology in view of the demonstration of Perez-Gomez et al. [12] that the use of corneal anaesthetics does not affect the appearance of corneal substructures as imaged with the corneal confocal microscope. It is noteworthy that the lenses in the Rostock Corneal Module of the contact and non-contact instruments have different numerical apertures (0.95 and 0.45, respectively).
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Whilst these changes are unlikely to be significant for regular IVCM examinations (average duration 2–5 min), they may become important in more prolonged examinations in which multiple scans are completed, such as mapping corneal architecture or measuring repeatability indices (Patel and McGhee, 2005, 2006). Use of corneal anaesthetic is known to be associated with accelerated desquamation of the superficial epithelium as well as loss of epithelial microvilli and damage to the cell membrane, (Hopkins and Pearson, 1998) however, no alteration in basal epithelium, sub-basal nerve plexus, corneal stroma or endothelium has been observed with IVCM following a single application of local anaesthetic (Auran et al., 1995; Perez-Gomez et al., 2004). As discussed previously, the instillation of topical fluorescein increases the visibility of the epithelium and the percentage of hyper-reflective cells, although this has not been substantiated by subsequent studies (Mocan and Irkec, 2007).
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Effects of benoxinate hydrochloride 0.4% on the morphological appearance of the cornea using confocal microscopy

Abstract

Introduction

Section snippets

Confocal microscopy

Results

Discussion

Am. J. Ophthalmol.

Exp. Eye Res.

Adverse reactions to topical ocular anaesthetics

J. Am. Optom. Assoc.