Rosa, Nicola*; De Bernardo, Maddalena*; Borrelli, Maria*; Filosa, Maria Luisa*; Lanza, Michele*
Purpose. To investigate the effect of oxybuprocaine eye drops on corneal volume (CV) and corneal thickness measurements.
Methods. Central corneal thickness (CCT), corneal thinnest point (CTP), and CV of 78 eyes of 78 healthy volunteers were measured with Pentacam, before and 5 min after the administration of oxybuprocaine eye drops. The fellow non-anesthetized eyes were used as control.
Results. Before topical anesthesia, the mean CCT was 546.76 ± 35.3 μm, after anesthesia, it was 547.76 ± 36.56 μm (p = 0.86). In the fellow eyes, the first mean CCT was 548.82 ± 35.2 μm and the second was 547.55 ± 35.9 μm (p = 0.82). The mean CTP before anesthesia was 543.99 ± 35.23 μm, after it was 544.89 ± 36.3 μm (p = 0.88). In the fellow eyes, the first mean CTP was 544.15 ± 35.35 μm and the second was 542.81 ± 36 μm (p = 0.81). Before topical anesthesia, the mean CV was 60.55 ± 3.84 mm3, after it was 60.66 ± 3.97 mm3 (p = 0.86). In the fellow eyes, the first mean CV was 60.93 ± 3.87 mm3 and the second was 60.73 ± 4 mm3 (p = 0.75).
Conclusions. Oxybuprocaine eye drops do not appear to induce a significant corneal swelling and do not affect the measurements when comparing CCT measured with optical or ultrasound devices.
The measurement of corneal thickness (CT) is important to confirm the values of intraocular pressure with Goldmann applanation tonometry (GAT),1 to determine the function of the endothelial cells and to decide which patients may undergo corneal refractive surgery. Several methods have been developed to measure CT, such as ultrasonic pachymetry (US), scanning slit topography/pachymetry (Orbscan), and rotating Scheimpflug camera (Pentacam). Until now, US pachymetry has been considered to be the gold standard, and several authors have compared other devices to US pachymetry.
US pachymetry is a contact method, which requires topical anesthesia, whereas the other two are non-contact and do not require anesthetic eye drops. Corneal anesthesia with eye drops is routinely used to perform not only US pachymetry2,3 but also several different ophthalmic examinations such as GAT,4,5 ultrasound biometry,6 cataract surgery, and corneal refractive surgery. The most frequently used anesthetic eye drops are proparacaine and oxybuprocaine HCl [4-amino-3-butoxybenzoate-2- (diethylamino)-ethylester].
Herse and Siu7 observed a significant average increase of ∼15 μm in central CT values as a result of corneal edema, 2 to 4 min after instillation of 2 drops of 0.5% proparacaine. The effect of oxybuprocaine HCl eye drops on corneal thickness has been studied in two different articles with an Orbscan8 and with a non-contact specular microscope.9 The first author could not find any significant increase in corneal thickness, whereas the second author found an increase in CT that returned to baseline in 80 s. To the best of our knowledge, a rotating Scheimpflug camera has been used to study the effects of proparacaine10 but no studies have been performed with this device to check the effects of oxybuprocaine. Moreover, the Pentacam is able to measure not only the corneal thickness in a single point but also the corneal volume (CV). For this reason, we decided to use this device to check the effects of oxybuprocaine HCl eye drops on the cornea.
Seventy-eight eyes of 78 young volunteers (37 males and 41 females) (mean age = 30 ± 11 years) who came to our Outpatients Department (Second University of Naples, Naples, Italy) were included in this prospective study. Patients with systemic and ocular diseases, which could potentially interfere with the purpose of the study such as diabetes, ocular surface diseases, corneal epithelial abnormalities, dry eyes, keratoconus, uveitis, corneal and lens opacities, glaucoma, previous intraocular or corneal surgery, pregnancy and contact lens wearers, were excluded from the study. The volunteers were informed about the purpose of the study and gave informed consent. The study was performed in adherence to the tenets of the declaration of Helsinki and Institutional Review Board approval was obtained. The measurements of CT and CV, with the standard diameter of 10 mm around the central cornea, were made in both eyes by the same observer. The measurements were repeated 5 min after the instillation of two drops of oxybuprocaine (Benoxinato Cloridrato, Alfa Intes, Casoria, Italy) in the OD; the OS was the control. All the measurements were made with a Pentacam (Oculus, Wetzlar, Germany). This device uses a rotating Scheimpflug camera and a monochromatic slit light source (blue led at 475 nm) that rotate together around the optical axes of the eye to calculate a three-dimensional model of the anterior segment, including CT and CV measurements. Within 2 s, the system rotates 180° and acquires 25 or 50 images (depending on the user settings).11,12
For this study, the “25 images per scan” option was chosen. The software is almost fully automated, minimizing bias. The center of the cornea is measured in each of the single images of a scan. This allows precise values for the central CT. All measurements were performed between 11.00 a.m. and 12.00 p.m. CT, CV, and corneal thinnest point (CTP) were chosen for statistical evaluation. All data were entered into a Microsoft Excel spreadsheet. Paired differences were calculated and presented as maximum, minimum, mean, and standard deviation values. The level of statistical significance and the correlation between the two measurements were calculated by the Student paired t-test and Pearson correlation coefficients. Bland-Altman plots were used to find a potential dependency between differences and means of two measurements.13,14 p values of <0.05 were considered to be statistically significant. Statistical analysis was performed by Microsoft Excel.
The measurements before and after the administration of eye drops listed in Table 1 show that there is a non-significant increase in central corneal thickness (CCT) and CTP and CV after anesthesia with oxybuprocaine eye drops, with 90% of the differences in CCT ranging between +21 and −16 μm with only one patient who showed an increase of more than 20 μm. There was no significant thinning of the fellow non-anesthetized eyes (Figs. 1 and 2).
When we correlated the difference in thickness with the first measurement, we found a lack of correlation between these two values in the non-treated eyes and an extremely weak tendency of the differences to increase with increased thickness in the anesthetized eyes (Figs. 3 and 4).
DISCUSSION AND CONCLUSIONS
Corneal anesthesia is required to perform applanation tonometry, US pachymetry, cataract surgery, diagnostic ultrasound, corneal refractive surgery, contact lens fundus examination, and other ophthalmic procedures. One of the most frequently used anesthetic drops is oxybuprocaine HCl or benoxinate [4-amino-3- butoxybenzoate- 2-(diethylamino)-ethylester], an ester-linked agent used in 0.4% solution. Oxybuprocaine produces a rapid onset of corneoconjunctival anesthesia, 15 to 20 s, and lasts 15 to 20 min. The corneal thickness can be measured by US or by non-contact devices such as Pentacam, Orbscan, specular microscopy, etc. Orbscan and Pentacam systems have a high degree of comfort for the patient. They are non-contact methods with no need for anesthesia nor risk of corneal infection. In previous articles, Pentacam measurements were found to be thicker than those obtained with Orbscan II and the differences were not related to the measured corneal thickness, although the overestimation tended to decrease for corneal thickness measurements >560 μm.15,16 The reason for these differences is unclear, but distinct methodologies in each device and the use of a correction factor in Orbscan might induce this tendency. US pachymetry has been used worldwide to measure CCT, but it requires anesthesia, so it cannot be used to determine the changes induced by anesthetic eye drops. Recently, devices that do not require anesthesia have been introduced into the market, making these studies possible. Probably, for this reason, only a few authors to date have investigated the effect of anesthetic eye drops on the corneal thickness in a limited number of patients.
Hershe and Siu7, using an optical pachymeter, found the CCT to be 15 μm thicker after instillation of two drops of 0.5% proparacaine that lasted about 2 min, whereas the difference was not significant after the instillation of one drop. They attributed the increase in the corneal thickness to the appearance of a transitory edema of the corneal stroma. Lam and Chen10 measuring CT in 40 patients (20 patients measured with a specular microscope and 20 with a Pentacam) found no significant difference over 10 min after the instillation of one drop of 0.5% proparacaine eye drops.
Asensio et al.8 using an Orbscan II in 26 patients found no significant differences in the mean corneal thickness at each corneal location between the measurements obtained before and after the instillation of two oxybuprocaine eye drops. The non-significant change before and after instillation of anesthetic eye drops may be explained by the fact that the measurement of single corneal points could be inadequate to detect such a change, but our finding of a non-significant change in CV does support the previous findings.
Nam et al.9 measured the corneal thickness with a non-contact specular microscope in 18 healthy young subjects before and after the instillation of two different anesthetic eye drops, namely oxybuprocaine and proparacaine in both eyes. They found an average increase of 9 μm in the corneal thickness after both proparacaine and oxybuprocaine that returned to baseline within 80 s; after proparacaine instillation, they found a second transient increase about 5 min later that was not observed after oxybuprocaine instillation. They suggested that the different behavior could have been related to the different preservatives used; in fact, proparacaine eye drops were preserved with 0.01% benzalkonium chloride, whereas oxybuprocaine with thimerosal, edetate disodium, boric acid, sodium chloride, and purified water.
US pachymetric studies have detected significant differences between observers when corneal thickness measurements were performed by two different observers on the same sample. In our opinion, this is due mostly to a bias induced by the probe placement required by the ultrasound unit,17 and it is not related to the use of anesthetic drops, which we have shown to have no influence on corneal thickness.
In this study, Pentacam pachymetric measurements were performed by the same physician but this could not bias the measurements as they are fully automated. Although penetration of the anesthetics into the stroma may inhibit cellular metabolism of the keratocytes and of the endothelial cells and may lead to corneal edema,18 and Weekers19 reported that topical anesthetics caused an alteration of the Na+/K+ endothelium pump, resulting in increased osmotic pressure in the cornea of rabbits with subsequent increased hydration of the stroma, our study indicated that this would not produce significant clinical changes. We deduce that the cause of changes in corneal thickness, which are reported in other articles, is due to the preservatives present in the ophthalmic solutions which may, in turn, cause possible structural/functional damage to both the corneal epithelium and endothelium.20
Several authors claim that the effect of anesthetic eye drops on the values of corneal thickness is important in preoperative LASIK examinations to prevent leaving the corneal bed too thin after treatment. This is because the residual bed depth is dependent on the depth of laser ablation2 to avoid the potential risk of post surgical keratectasia.21,22 We partly disagree with this statement because in our study, we found that the difference in the values of CT in 90% of the patients ranged between +21 and −16 μm with only one patient who showed an increase of more than 20 μm. From a clinical point of view, these values have minimal impact on both refractive surgery and of GAT measurements.
One of the criticisms of our study might be that we evaluated only healthy corneas and we did not study subjects affected by glaucoma, diabetes, dry eye, or other diseases where precise measurement of CCT is very important. However, in our opinion, corneas with glaucoma and diabetes should not show significant differences, thus our findings may be relevant in these cases. On the contrary, further studies are required to clarify whether anesthetic drops make a difference in the case of dry eyes, where the altered epithelium might affect these measurements.
Second University of Naples
Via Pansini 5
80100 Naples, Italy
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