Thursday, July 27, 2006

The Effects of Eye Drops on Corneal Thickness in Adult Myopia.

Abstract

Purpose:
To study the effects of Complex Tropicamide (0.5% Tropicamide and 0.5% phenylephrine HCI) and Saline solution on corneal thickness in adult myopic patients with the Orbscan II system.


Design:
Prospective, nonrandomized, clinical trial.


Methods:
The thinnest pachymetry of the cornea was obtained before and 1.5 hours after administration of three drops of Complex Tropicamide to the left eyes of 58 patients (58 eyes) and Saline solution to their 31 right eyes, respectively. The corneal thickness of the other 27 right eyes before and 1.5 hours after eyelid closure without exposure to eye drops was used as the control group.


Results:
The thinnest pachymetry of the cornea was significantly higher after exposure to eye drops in the Tropicamide group (23.36 ± 15.01 µm; t = -11.855). Similar findings were also noted in the Saline group (7.13 ± 8.11 µm, t = -4.894). The difference between the two groups was also significant (t = 6.737). There were no statistically changes in corneal thickness in control group. The drops tested have no effect on the location of the thinnest corneal site and its distance form the visual axis.


Conclusion:
Eye drops including Saline solutions may have significant effects on the corneal thickness in myopia, and this may have implications for corneal refractive surgery.



Discussion

Central corneal thickness (CCT) has become an area of research interest due to the advancement of excimer laser corneal refractive surgery, particularly in laser in situ keratomileusis (LASIK). It was considered to be one of the most important factor for stability of refractive surgeries and correlated to the occurrence of corneal ectasia and keratoconus. However, corneal shape or thickness can be affected by various factors such as mechanical forces, atropine sulphate ointment 1%, topical anesthetic, and long-term contact lens wear. In addition, human corneal thickness also displays diurnal variation. Accurate assessment of the corneal thickness is, therefore, important to allow safe surgery.



LASIK is the most popular refractive procedure in China. It involves the creation of anterior corneal flap and removal of midstromal tissue by excimer laser photoablation. As residual bed thickness is an independent significant determinant for posterior corneal ectasia, CCT had to be sufficient to ensure at least 250 µm in the posterior stroma after keratorefractive surgery.

Corneal thickness has been evaluated by various methods. Ultrasound pachymetry has been used to measure corneal thickness worldwide. It is also the reference against which the more sophisticated devices are currently tested and was regarded as "gold standard" in this field. However, recent studies demonstrated the Orbscan II pachymetry measurements correlated well with the ultrasound measurements in eyes with clear corneas, and it is the most repeatable technique for measuring corneal thickness as well.



We previously demonstrated that the corneal refractive power in myopic children measured with topography was significantly decreased after 5 days of ointment atropine 1%. Complex Tropicamide is widely used for clinical examination, and the active ingredients are tropicamide and epinephrine. The former has cycloplegic effect and the latter has mydriatic effect. We have shown that the corneal thickness increased after administration of Complex Tropicamide, and the causes could be many. It is possible that this increase is due to the disruption of corneal physiological metabolism or epithelial barrier function from the active or inactive ingredient such as [epsilon]-aminocaproic acid and benzalkonium chloride within the Complex Tropicamide. This may also be confirmed by the difference in corneal alteration between Tropicamide and saline solution groups. However, we cannot explain the increase in thickness in patients receiving saline solution alone as saline does not contain any preservatives and is similar to the tear film in pH and osmotic pressure. The 1.5-hour closed eyelid may have similar "diurnal effects" on the corneal thickness as studies indicate that the corneal thickness was slightly increased overnight and gradually return to baseline measurements after eye opening. However, the results from our control group deny the above-mentioned "hypothesis" as no significant changes were noted in the control group. One possible explanation is that the Saline solution is not human tears after all. The microenvironmental differences in every aspect between Saline solution and nature tear film could be the explanation for the changeable measurements of corneal thickness. Furthermore, no visual blur or corneal edema was noted in the subject analyzed following the instillation.



Further analysis from total 58 left eyes before eye drops instillation (mean age, 23.9 ± 4.9 years) revealed that the mean corneal thinnest value was 525.96 ± 42.93 µm (normal range from 441.82 to 610.10 µm). Considering the mean increase of 22.48 µm for Tropicamide group, we can conclude that approximately 3.68% to 5.09% of the total corneal thickness increased 1.5 hours after administrating complex Tropicamide solution.



Corneal thickness can be evaluated by a number of methods including ultrasonic pachymetry, optical slit lamp pachymetry, confocal microscopy, and optical coherence tomography. Ultrasonic pachymetry is believed to be the most reliable and was considered as "Gold Standard" in determining the CCT. Although it is a widely used, accurate assessment of the corneal thickness cannot be made without disturbing the anterior cornea. The tip of the probe may disturb the precorneal tear film and even disrupt the epithelium. It is also difficult to control patient's gaze during repeated measurements, and the placement of the probe is difficult to reproduce. Furthermore, it can only be carried out in anesthetized eyes. Topical anesthesia seems to have more effects on cornea than saline solution. Asensio et al have found that some individuals can present important increases and decreases in corneal thickness values only 3 minutes after administration of two drops of oxybuprocaine 0.4% to 26 patients (26 eyes), although the changes were no significant differences. The dramatic changes on corneal topography 20 minutes after 4 drops of Benoxil (Oxybuprocaine) 0.4% solution were also detected by Do et al.16 In our recent study with Orbscan II, both THN and CCT of 2 mm in diameter were dramatically increased 5 minutes later after the instillation of one drop of the topical anesthetic Benoxil (Oxybuprocaine) 0.4% solution.



It is known that corneal thickness increases peripherally. For the maximal safety of LASIK, the purpose of corneal thickness measurement is to find the exact values at the thinnest point for the whole cornea. However, ultrasonic probe is unable to locate and kept accurately at the thinnest point in serial examinations, and this may result in large variation in corneal thickness measurement. Some investigators did not measure in the exact center of the cornea. The probe tip was placed 1.5 mm temporal to the cornea light reflex. In fact, the thinnest site on the entire cornea was located at an average of 0.90 (0.51) mm from the visual axis. This site was most commonly located in the inferotemporal quadrant (69.57%), followed by the superotemporal, inferonasal, and superonasal quadrants.



None of these problems exists with the described Orbscan technique. The instrument's software analyses up to 240 data points per slit and calculates the elevation of the anterior and posterior surface of the cornea as well as the entire corneal thickness. The system can also identifies the thinnest point location and display its actual values (THN) simultaneously even if the examined eye happened to move slightly but within the permit range of the system. It is a noninvasive, noncontact, well-controlled method of excellent reproducibility both in clinical and in research studies.



In summary, our study demonstrated thickening of cornea after instillation of Saline solution as well as Complex Tropicamide in the adult myopia. Furthermore, it is possible that other eye drops commonly used in our clinical would have similar effects based on the finding with Saline solution. To our understanding, it could be advisable to calculate a greater preoperative residual bed depth than usual if preoperative corneal thickness is measured using corneal anesthetic eye drops or any other eye drops, and this, in return, may also have implications for the outcome of corneal refractive surgery and even for the accuracy of applanation tonometry, considering that more than 60% of the eyes in Tropicamide group would suffer 20-µm increase in corneal thickness. The values of corneal thinnest, rather than that of mean CCT, should be taken into account by refractive surgeons for the maximum safety of performance. As Orbscan allows an exact measurement of corneal thickness without the multiple sources of bias known from ultrasonic pachymetry and it is the only available device which can identify the thinnest point location and display its actual values, its role in corneal refraction surgery should be reassessed and be emphasized.

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