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Comparison of tropicamide and cyclopentolate for cycloplegic refractions in myopic adult refractive surgery patients
Comparison of tropicamide and cyclopentolate for cycloplegic refractions in myopic adult refractive surgery patients Elizabeth M. Hofmeister, MD, Sandor E. Kaupp, MS, Steven C. Schallhorn, MD Purpose: To compare tropicamide 1%, a shorter-acting cycloplegic agent, with cyclopentolate 1% for cycloplegic refractions in adult refractive surgery patients. Setting: Navy Refractive Surgery Center, Ophthalmology, Naval Medical Center, San Diego, California. Methods: The study was prospective, single center, with randomized sequencing of cycloplegic agent; each patient received both agents. Thirty consecutive myopic adult refractive surgery patients (mean age 35.4 years) participated. A complete preoperative examination, including cycloplegic refraction, was obtained twice, 1 week apart. The patient and the examiner were masked to the medication. Main outcome measures included cycloplegic and manifest refractions, best corrected distance acuity, near-point accommodation, pupil diameters, and subjective appraisal of experience with cycloplegic agents. Results: Twenty-eight of 30 patients completed both examinations. Both eyes were measured, but comparisons were limited to right and left eyes, independently. No statistically significant difference was found between the tropicamide and cyclopentolate cycloplegic refractions (mean difference in MSE 6 SD, OD Z 0.054 6 0.214 diopters (D), t Z 1.33, P Z .10; OS Z 0.054 6 0.253 D, t Z 1.12, P Z .14). Five eyes of 3 patients had a difference of 0.50 D or greater between the 2 agents; less myopia with cyclopentolate. Near-point testing revealed less residual accommodation with cyclopentolate (difference in MSE, OD Z ÿ0.27 6 0.51 D, t Z 2.68, P Z .006; OS Z ÿ0.32 6 0.49 D, t Z 3.46, P Z .001). Subjectively, 24 of 28 (86%) patients preferred tropicamide, 1 (4%) preferred cyclopentolate, and 3 (10%) had no preference. Conclusions: There was no statistically significant difference in mean cycloplegic refractions. Cyclopentolate was more effective than tropicamide in reducing accommodative amplitude in adult myopes (near-point testing). Patients strongly preferred tropicamide. J Cataract Refract Surg 2005; 31:694–700 ª 2005 ASCRS and ESCRS
T
opically applied drugs to paralyze the ciliary muscles in the eye are generally used to help estimate the refractive error of an eye for treatment in refractive surgery. They are also used to dilate the pupil to examine the retina and optic nerve for pathology prior to surgery. Longer acting agents are thought to provide more effective cycloplegia. Cyclopentolate provides cycloplegia for 12 to 24 hours, while tropicamide is expected to provide 4 to 10 hours of cycloplegia. Studies in children have suggested that cyclopentolate and tropicamide might be equally efficacious for cycloplegic 2005 ASCRS and ESCRS Published by Elsevier Inc.
refractions.1–6 There have been only 2 studies comparing cyclopentolate and tropicamide in adult populations. The first, published in 1961, showed that both medications decreased accommodation to a similar degree but that accommodation returned much more quickly with tropicamide.7 A more recent study of adult patients compared subjective manifest refraction with wavefront aberrometry measurements with cyclopentolate to tropicamide and phenylephrine.8 Tropicamide and cyclopentolate yielded similar degrees of myopia. Our premise in the study detailed in this report was that 0886-3350/05/$-see front matter doi:10.1016/j.jcrs.2004.10.068
TROPICAMIDE VS CYCLOPENTOLATE FOR ADULT MYOPIC CYCLOPLEGIC REFRACTIONS
no difference in cycloplegic refractions in adult patients would be found between cyclopentolate and tropicamide with mild to moderate myopia.
Patients and Methods A complete refractive surgery preoperative examination was obtained twice on each patient: once using tropicamide and once using cyclopentolate as cycloplegic agents. The sequence of drug application was chosen at random by the study coordinator. The ophthalmic technicians had no knowledge of which cycloplegic agent was applied. The 2 examinations were separated by at least 1 week, and data were collected on both eyes. The primary outcome measure was cycloplegic refraction with each of the 2 mydriatic agents. Careful manifest and cycloplegic subjective refractions were performed using the Nidek automated phoropter (model RT-1200 or 2100). Secondary outcome measures included near point of accommodation, precycloplegia and postcycloplegia as measured on a Prince rule, pupil size precycloplegia and postcycloplegia (using a Keeler PupilScan II), acuity on back illuminated ETDRS (Early Treatment of Diabetic Retinopathy Study) chart at 4 m (Lighthouse 25 in 25 in box with a Precision Vision Logarithmic Visual Acuity 2000 chart for 4 m), keratometry, corneal topography, and a patient satisfaction survey. Near points of accommodation were obtained at the phoropter (with the patient’s distance correction in place) using a Prince rule. Each eye was tested individually by moving an accommodative target closer to the patient until the patient could no longer keep the target in focus. The satisfaction survey asked patients how long their pupils remained dilated and how long their reading vision remained impaired. Additionally, after the second examination, the survey asked patients whether they preferred either of these medications.
Accepted for publication October 8, 2004. From the Navy Refractive Surgery Center, Department of Ophthalmology, Naval Medical Center, San Diego, California. Presented as a poster at the annual meeting of the American Academy of Ophthalmology, October 2000. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. No author has a proprietary or financial interest in any product described in this article. Reprint requests to Dr. Elizabeth M. Hofmeister, c/o Clinical Investigation Department, Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, California 92134-1005, USA.
The ophthalmic technicians measured the same set of patients on consecutive weeks using the same eye lane in our clinic. This ensured the use of the same instrumentation and charts and conditions of illumination. Pupil diameters under cycloplegia were measured both weeks by a single technician (who did not determine any of the refractive errors) using the same pupillometer just before the subject was seen for determination of manifest or cycloplegic refraction. The number of patients in the study was calculated to detect a mean difference of 0.25 D, at a minimum, between cycloplegic refractions with the 2 agents. This was based on the premise that subjective refractions are only accurate and reproducible to 0.25 D in sphere or cylinder. The standard deviation of difference in cycloplegic refractions is 0.313 D. This calculation of variance was from determinations of repetitive cycloplegic refractions made at the Navy Refractive Surgery Center, Ophthalmology, Naval Medical Center San Diego. The power calculation was performed for an a of 0.05 and a b of 0.20, yielding a sample size of 25; that is, 25 eyes of 25 patients. To allow for study attrition, a sample size of 30 eyes was used. A difference of 0.50 D or greater would normally change surgical planning for refractive surgery. Differences in refractive errors, extent of near point accommodation, acuity, and pupil diameters under cycloplegia were compared using matched pair analysis of variance (ie, t test, 1- or 2-sided, where a Z 0.05). Results and statistical analysis were done on right and left eyes separately, maintaining a datum per patient per examination for each statistic. In a single patient, the eyes would respond similarly to cycloplegics. Therefore, the denominator for the calculations was the number of patients and never the number of eyes. Approval for the study was obtained from the Institutional Review Board, and the study consent was approved by the Committee for the Protection of Human Subjects of the Clinical Investigation Department, Naval Medical Center, San Diego (CIP #S-00-027). Patients were solicited consecutively from a waiting list of patients previously screened and found eligible for refractive surgery. Those included were male and female military health care beneficiaries of all races who were from 21 to 50 years old to be treated for low to moderate myopia or myopic astigmatism. Patient characteristics are summarized in Table 1. Patients were excluded if they had any condition that might affect repeatability of refractions or would make them a poor candidate for refractive surgery. These conditions included collagen–vascular diseases, autoimmune diseases, immunodeficiency diseases, ocular herpes (zoster or simplex), diabetes, female subjects who were pregnant or breastfeeding, and subjects who were using certain medications including steroids, antimetabolites, isotretinoin, amiodorone, and sumatriptin. Patients with prior intraocular surgery (including cataract surgery), prior corneal surgery, active
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Table 1.
Patient demographics and refractive treatments in this
study. No. of Patients
28
Mean age (range) (y)
35.4 (21–50)
Men
24 (86%)
Women
4 (14%)
Ethnicity White
14 (50%)
Asian
6 (22%)
Hispanic
4 (14%)
African American
4 (14%)
Mean refractive error (spherical equivalent) OD (range) (D)
ÿ3.02 (ÿ1.0 to ÿ5.12)
OS (range) (D)
ÿ3.14 (ÿ1.0 to ÿ5.25)
recurrent corneal erosions, dry eye syndrome, clinically significant lens opacity, or clinical evidence of trauma (including scarring) were also excluded. Patients were randomly assigned to receive 1 of the cycloplegic drugs first and the other second using a random number table. The randomization table was available only to 1 of the investigators (E.M.H.) and a technician who coordinated patient flow and administered agents. Examiners and patients were blinded to randomization. The coordinating technician administered medications in the following manner: each patient received a drop of topical anesthetic, proparacaine 1%, followed by 2 drops of the cycloplegic medication, either cyclopentolate 1% (Cyclogyl) or tropicamide 1% (Mydriacyl).1 Each drop was separated by 5 minutes. The coordinating technician arranged for cycloplegic refractions to be obtained 30 minutes after instillation of tropicamide and 60 minutes after instillation of cyclopentolate. The randomization code was to be revealed only in the event of an adverse reaction to the medication, and there were none.
Results Two complete examinations were obtained in both eyes of 28 of the 30 patients who enrolled. One in 7 of the patients was female (4 of 28); half were white (14) and the other half were approximately an equal proportion of Asian (6), Hispanic (4), and African American (4). The mean age was 35 years (range 21 to 50 years). Two patients were lost to follow-up after their first examination and were not included in the data analysis. The same ophthalmic technician performed both cycloplegic examinations in each patient in the same clinic eye lane using the same charts, instruments, 696
and levels of illumination. The technician had no documentation of the previous week’s examination on which to base his/her determination of refractive error. This ophthalmic technician measured manifest and cycloplegic refractions, along with uncorrected and best corrected acuities and near-point accommodation in both eyes at each visit. Refractions No statistically significant difference was found in cycloplegic refractions induced by either cycloplegic agent (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14; Figures 1 and 2). The group mean spherical equivalent refraction during tropicamide cycloplegia was, in right eyes, ÿ2.635 D (n Z 28; range ÿ0.88 to ÿ5.00 D) and during cyclopentolate, the mean was ÿ2.708 D (n Z 28; range ÿ1.00 to ÿ5.13 D). In left eyes, the mean spherical equivalent refraction during tropicamide cycloplegia was ÿ2.908 D (n Z 28; range ÿ1.00 to ÿ5.38 D); during cyclopentolate, the mean was ÿ2.978 D (n Z 28; range ÿ1.00 to ÿ5.25 D). The mean difference in individual eye refractive errors, tropicamide spherical equivalent minus cyclopentolate spherical equivalent, was 0.054 D in both right and left eyes (n Z 28; right eye SD Z 6 0.214 D, and left eye SD Z 6 0.253 D). The cyclopentolate cycloplegic refractions were 0.054 D less myopic than the tropicamide refractions. These were not statistically significant differences. Five eyes of 3 patients had a difference of 0.50 D or greater between the 2 cycloplegic refractive errors (Table 2, Figure 2), with the trend toward less myopia with cyclopentolate (3 had a difference of 0.50 D; 2 eyes had a difference of 0.625 D spherical equivalent). Two of the 3 patients were 36 years old, and the other was 39. Two were Hispanic men, and the third, a white woman. The largest measured difference, in sphere and cylinder terms, was 60.50 D, and it was measured in 3 individuals. This led to a spherical equivalent change of 0.50 or 0.625 D in 5 eyes of 3 people. In these 3 individuals, less refractive myopia was measured under the influence of cyclopentolate. Pupil Size After Administration of Cycloplegic Agent The pupil diameter of each patient’s eyes was measured by 1 technician just before the patient had the
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Figure 1. Frequency of differences in cycloplegic refractive error determined with the use of cyclopentolate and tropicamide as cycloplegic agents (cyclopentolate refraction–tropicamide refraction). The differences for each of the 56 eyes of 28 patients were calculated using spherical equivalent refractions and are graphed in 0.125 D increments. No difference was found between the mean spherical equivalent cycloplegic refractions (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14).
cycloplegic refractive error and near-point accommodation determined. In each patient’s eye, the difference in pupil diameter (cyclopentolate-induced pupil size minus tropicamide induced pupil size) was calculated. No statistically significant difference was found for the group in pupil diameters between the use of cycloplegic agents for the right or left eyes (diameter difference for OD Z ÿ0.157 6 0.61 mm, t Z 1.35, P Z .19; OS Z 0.014 6 0.80, t Z 0.09, P Z .92). Near-Point Accommodation Significantly less residual accommodation was found with use of cyclopentolate. On average, a difference of O0.25 D of accommodation was found between the 2 agents, with the tropicamide eyes able to accommodate more than the cyclopentolate eye (OD Z ÿ0.27 6 0.51 D, t Z 2.68, P Z .006; OS Z ÿ0.32 6 0.49 D, t Z 3.46, P Z .001) (Figure 3). Figure 2. The refractive error determined with the use of cyclopentolate (ordinate) versus that determined using tropicamide (abscissa) for the 28 patients (right and left eyes) in this study. All refractions are given in diopters of spherical equivalent. The 5 eyes of 3 individuals who were found to be R0.50 D less myopic with the use of tropicamide are circled. The other 51 eyes were within 0.375 D or less of the line of equality (dark line). No difference was found between the mean spherical equivalent cycloplegic refractions (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14).
Reliability of Refractive Error Measurements Reliability of refractions was assessed by comparing reproducibility of subjective dry refractive errors (manifest refraction) between the 2 visits for each subject. Subjective dry refractions averaged a difference of 0.03 6 0.15 D for right and left eyes (t Z 1.44, P Z .08) between the first and second examination.
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Table 2. Demographic and refractive characteristics of 3 patients (5 eyes) with measured difference in cycloplegic refractive errors of 0.50 D or greater. Data for both eyes of each subject from both visits are given.
Sex
Manifest Tropicamide Manifest Cyclopentolate Difference (C–T) Age Refraction Refraction Refraction Refraction in Spherical Ethnicity (Y) Eye (Sphere Cylinder) (Sphere Cylinder) (Sphere Cylinder) (Sphere Cylinder) Equivalent
Female White
36
OD
ÿ1.25 ÿ0.50 D
ÿ1.50 ÿ0.50 D
ÿ1.25 ÿ0.50 D
ÿ1.00 ÿ0.50 D
OS
ÿ1.25 ÿ2.50 D
ÿ1.50 ÿ2.50 D
ÿ1.00 ÿ2.50 D
ÿ1.00 ÿ2.50 D
C0.50 D
Male
36
OD
ÿ2.75 ÿ0.75 D
ÿ2.75 ÿ0.75 D
ÿ2.75 ÿ0.50 D
ÿ2.50 ÿ0.50 D
C0.375 D
OS
ÿ3.00 ÿ0.50 D
ÿ3.00 ÿ0.25 D
ÿ2.75 ÿ0.25 D
ÿ2.50 ÿ0.00 D
C0.63 D
OD
ÿ4.50 ÿ0.75 D
ÿ4.50 ÿ0.75 D
ÿ4.25 ÿ1.00 D
ÿ4.00 ÿ0.75 D
C0.50 D
OS
ÿ4.75 ÿ0.50 D
ÿ5.00 ÿ0.50 D
ÿ4.50 ÿ0.25 D
ÿ4.50 ÿ0.25 D
C0.63 D
Male
Hispanic
Hispanic
39
C0.50 D
tropicamide rated an average of about 1.0, very low on the 7-point discomfort scale (SD Z 0.82 and 0.83, respectively; 0 through 6 scale; t Z 0.42, PO.6) (Figure 4). The patients faithfully reported the difference in duration of dilation between the drugs; average duration reported as 3.7 hours for tropicamide and 21 hours for cyclopentolate (t Z 7.46, P!!.01). Twenty-four of 28 (86%) patients preferred tropicamide, citing a more rapid return of near vision, 1 individual (4%) preferred cyclopentolate, and 3 individuals (10%) reported no preference. Figure 3. Frequency of differences in near point of accommodation (D) for the 56 eyes of the 28 patients found between the use of cyclopentolate and tropicamide for cycloplegia. On average, R0.25 D more accommodation was uncovered with the use of cyclopentolate relative to the use of tropicamide (OD Z ÿ0.27 6 0.51 D, t Z 2.67, P Z .006; OS Z ÿ0.34 6 0.50, t Z 3.46, P Z .001).
Two of the 56 determinations of manifest refraction resulted in a spherical equivalent refractive error of 6 0.375 D; all others were within 0.25 D of the previous weeks determination, and 45% (25:56) of the manifest refractions (spherical equivalent) were the same. This resulted in a mean difference in best corrected visual acuity (BCVA) of C0.03 6 0.05 logMAR for right and left eyes. This small improvement in BCVA (t Z 5.01, P!.001) for all eyes tested represents a 1.5 letter improvement on the 5-letter line of the ETDRS charts utilized in this study. Five of the 56 eyes (9%) improved by 1 line or more (0.10 to 0.14 logMAR). This improvement in BCVA is not the result of changes in manifest refraction (R Z ÿ0.149, P Z .274). Subjective Survey The patients did not find either mydriatic agent imparted any greater discomfort. Cyclopentolate and 698
Discussion Successful refractive surgery requires an accurate assessment of the refractive state of the eye. This typically is composed of a dry or manifest refraction as well as a cycloplegic refraction. The purpose of the cycloplegic examination is to ensure that accommodation is suspended. With significant residual accommodation not detected in a preoperative workup, overcorrection and subsequent hyperopia may result in a myopic treatment. Similarly, a hyperopic treatment may result in undercorrection and residual hyperopia. Cycloplegic agents available for use in the United States are summarized in Table 3. Atropine is the most potent cycloplegic agent and the longest acting. It is not routinely used as a diagnostic agent in adults because of its extremely long duration of action, but is often used for cycloplegic retinoscopy and amblyopia therapy in children because children are capable of much greater accommodation. Weaker, shorter-acting agents are generally not thought to be as effective at paralyzing the ciliary muscle as the longer duration agents. However, several studies in children have suggested
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Figure 4.
The 7-point discomfort scale. A score of zero was given if no discomfort was marked and 6 for severe discomfort.
Table 3. Cycloplegic agents available in the United States listed in order of longest onset of effect to shortest, which, with 1 exception, mimics duration of influence. Name Atropine Homatropine
Onset of Action
Duration of Cycloplegia
6–24 hours
10–15 days
1 hour
1–2 days
Scopolamine
30–60 minutes
3–4 days
Cyclopentolate
30–60 minutes
12–24 hours
Tropicamide
20–30 minutes
4–10 hours
that the weaker agents, such as cyclopentolate and tropicamide, may indeed provide adequate cycloplegia for cycloplegic retinoscopy. Cyclopentolate has been compared to atropine in several pediatric studies. Results in older studies caution that cyclopentolate might not be as effective as atropine for cycloplegic refractions in children.9–11 More recent studies comparing cyclopentolate and atropine in children have shown no significant difference between cycloplegic refractions achieved with the 2 agents.12,13 Several studies have compared cyclopentolate to tropicamide in children.1–6 These studies found cyclopentolate to be slightly more efficacious than tropicamide but noted that the differences between the 2 were small and would not significantly influence a prescription for treatment of the refractive error. In adults, there have been few studies comparing various cycloplegic agents. The results of 1 study, conducted in 1957 prior to the introduction of tropicamide, actually suggested that cyclopentolate was more effective than atropine at reducing accommodation.14 One published study compared tropicamide, cyclopentolate, and homatropine in adults.7 It showed that tropicamide and cyclopentolate were equal in their effectiveness at reducing accommodation, and both were superior to homatropine for examinations performed within 1 hour of drop instillation. A recent study looked at the effects of mydriasis on wavefront aberrometry measurements with phenylephrine, tropicamide, and cyclopentolate.8 The cycloplegic wavefront autorefraction was compared with subjective manifest refraction.
Tropicamide induced 0.35 D less myopia than the subject refraction, and cyclopentolate induced 0.42 D less myopia. We found no statistically significant difference between tropicamide and cyclopentolate for cycloplegic refractions (mean difference 0.05 6 0.25 D) in a group of 28 prospective myopic refractive surgery patients. Five eyes of 3 patients showed a difference in spherical equivalent cycloplegic refraction of 0.5 D or more. This would make a difference in the prescribed treatment for refractive surgery in these cases. Data from these 3 patients are summarized in Table 2. Among these 3 patients, 2 eyes had a difference of 0.625 D spherical equivalent; 3 eyes varied by 0.50 D manifest spherical equivalent when measured from week to week. Five others varied by 0.375 D, and 46 of 56 varied by 0.25 D or less. We think this is excellent evidence that the manner of determining refractive error was not a large factor in investigating the differences in cycloplegic refractions. It is possible that the 3 individuals found to be less myopic by 0.50 or 0.63 D with the use of cyclopentolate were not truly less myopic but the result of random variation in measurement of refractive errors. With a sample size of only 3 in 28 patients, a convincing statistical treatment of this question is not possible. It is important to realize that there may be a difference between the manifest and cycloplegic refractions that is not due to accommodation. Cycloplegia not only suspends accommodation but also causes mydriasis. In an eye with significant aberrations, pupil dilation may affect the refraction as the patient attempts to place the circle of least confusion on the macula. In this study, there was no difference in the extent of pupillary dilation with either drug at the time the refractive error was determined. For the 3 patients in whom the cycloplegic refractions were different by R0.5 D, pupil measurements did not vary by greater than 0.6 mm, within 1 standard deviation of repetitive measurement (SD Z 0.79 mm). Consequently, we have no evidence that the refractive differences were due to
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anything more than residual loss of accommodation with cyclopentolate. An important question to ask is whether cycloplegic refractions are even necessary. In this study, 8 of 56 (14%) cycloplegic refractions, using tropicamide or cyclopentolate, were 0.50 D of spherical equivalent less myopic than the manifest refraction determined prior to cycloplegia. These 8 eyes may have been offered a different refractive treatment based on the cycloplegic refractions. Using all this study’s measurements of manifest and cycloplegic refraction determined with both cyclopentolate and tropicamide (56 comparisons with both agents or 112 cases), the mean refractive error was less under cycloplegia by 0.17 D spherical equivalent. The mean difference, cycloplegia minus manifest refraction, for the 28 patients with use of either drug was significantly decreased (1 sample test where the null hypothesis was that the difference was zero, t Z 6.00 and 5.00, for OD and OS with cyclopentolate, respectively; t Z 3.48 and 3.35, for OD and OS with tropicamide, respectively; P!.001). The need to measure cycloplegic refraction is militated by our results, even for low to moderate myopic refractive errors, when considering refractive surgical treatments. With the recent advent of wavefront-guided refractive surgery, cycloplegic refractions should continue to play an important role in the preoperative evaluation of a prospective refractive surgery candidate. Excessive accommodation during the wavefront capture can lead to inaccurate treatment plans.
References 1. Proskurina OV. [Cycloplegic efficiency of the drugs cyclopentolate and tropicamide vs atropinization.] (Russian) Vestn Oftalmol 2002; 118(6):42–45
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2. Manny RE, Hussein M, Scheiman M, et al. Tropicamide (1%): an effective cycloplegic agent for myopic children. Invest Ophthalmol Vis Sci 2001; 42:1728–1735 3. Owens H, Garner LF, Yap MKH, et al. Age dependence of ocular biometric measurements under cycloplegia with tropicamide and cyclopentolate. Clin Exp Optom 1998; 81:159–162 4. Lin LL-K, Shih Y-F, Hsiao C-H, et al. The cycloplegic effects of cyclopentolate and tropicamide on myopic children. J Ocul Pharmacol Ther 1998; 14:331–335 5. Mutti DO, Zadnik K, Egashira S, et al. The effect of cycloplegia on measurement of the ocular components. Invest Ophthalmol Vis Sci 1994; 35:515–527 6. Egashira SM, Kish LL, Twelker JD, et al. Comparison of cyclopentolate versus tropicamide cycloplegia in children. Optom Vis Sci 1993; 70:1019–1026 7. Gettes BC, Belmont O. Tropicamide: comparative cycloplegic effects. Arch Ophthalmol 1961; 66:336–340 8. Giessler S, Hammer T, Duncker GIW. Aberrometrie in Mydriasis – welch Art der Mydriasis ist zu bevorzungen? Klin Monatsbl Augenheilkd 2002; 219:655–659 9. Rosenbaum AL, Bateman JB, Bremer DL, Liu PY. Cycloplegic refraction in esotropic children; cyclopentolate versus atropine. Ophthalmology 1981; 88:1031–1034 10. Ingram RM, Barr A. Refraction of 1-year-old children after cycloplegia with 1% cyclopentolate: comparison with findings after atropinisation. Br J Ophthalmol 1979; 63:348–352 11. Robb RM, Petersen RA. Cycloplegic refractions in children. Pediatr Ophthalmol 1968; 5:110–114 12. Kawamoto K, Hayasaka S. Cycloplegic refractions in Japanese children: a comparison of atropine and cyclopentolate. Ophthalmologica 1997; 211:57–60 13. C ¸ elebi S, Aykan U. The comparison of cyclopentolate and atropine in patients with refractive accommodative esotropia by means of retinoscopy, autorefractometry and biometric lens thickness. Acta Ophthalmol Scand 1999; 77:426–429 14. Barbee RF, Smith WO Jr. A comparative study of mydriatic and cycloplegic agents in human subjects without eye disease. Am J Ophthalmol 1957; 44:617–622
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opically applied drugs to paralyze the ciliary muscles in the eye are generally used to help estimate the refractive error of an eye for treatment in refractive surgery. They are also used to dilate the pupil to examine the retina and optic nerve for pathology prior to surgery. Longer acting agents are thought to provide more effective cycloplegia. Cyclopentolate provides cycloplegia for 12 to 24 hours, while tropicamide is expected to provide 4 to 10 hours of cycloplegia. Studies in children have suggested that cyclopentolate and tropicamide might be equally efficacious for cycloplegic 2005 ASCRS and ESCRS Published by Elsevier Inc.
refractions.1–6 There have been only 2 studies comparing cyclopentolate and tropicamide in adult populations. The first, published in 1961, showed that both medications decreased accommodation to a similar degree but that accommodation returned much more quickly with tropicamide.7 A more recent study of adult patients compared subjective manifest refraction with wavefront aberrometry measurements with cyclopentolate to tropicamide and phenylephrine.8 Tropicamide and cyclopentolate yielded similar degrees of myopia. Our premise in the study detailed in this report was that 0886-3350/05/$-see front matter doi:10.1016/j.jcrs.2004.10.068
TROPICAMIDE VS CYCLOPENTOLATE FOR ADULT MYOPIC CYCLOPLEGIC REFRACTIONS
no difference in cycloplegic refractions in adult patients would be found between cyclopentolate and tropicamide with mild to moderate myopia.
Patients and Methods A complete refractive surgery preoperative examination was obtained twice on each patient: once using tropicamide and once using cyclopentolate as cycloplegic agents. The sequence of drug application was chosen at random by the study coordinator. The ophthalmic technicians had no knowledge of which cycloplegic agent was applied. The 2 examinations were separated by at least 1 week, and data were collected on both eyes. The primary outcome measure was cycloplegic refraction with each of the 2 mydriatic agents. Careful manifest and cycloplegic subjective refractions were performed using the Nidek automated phoropter (model RT-1200 or 2100). Secondary outcome measures included near point of accommodation, precycloplegia and postcycloplegia as measured on a Prince rule, pupil size precycloplegia and postcycloplegia (using a Keeler PupilScan II), acuity on back illuminated ETDRS (Early Treatment of Diabetic Retinopathy Study) chart at 4 m (Lighthouse 25 in 25 in box with a Precision Vision Logarithmic Visual Acuity 2000 chart for 4 m), keratometry, corneal topography, and a patient satisfaction survey. Near points of accommodation were obtained at the phoropter (with the patient’s distance correction in place) using a Prince rule. Each eye was tested individually by moving an accommodative target closer to the patient until the patient could no longer keep the target in focus. The satisfaction survey asked patients how long their pupils remained dilated and how long their reading vision remained impaired. Additionally, after the second examination, the survey asked patients whether they preferred either of these medications.
Accepted for publication October 8, 2004. From the Navy Refractive Surgery Center, Department of Ophthalmology, Naval Medical Center, San Diego, California. Presented as a poster at the annual meeting of the American Academy of Ophthalmology, October 2000. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. No author has a proprietary or financial interest in any product described in this article. Reprint requests to Dr. Elizabeth M. Hofmeister, c/o Clinical Investigation Department, Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, California 92134-1005, USA.
The ophthalmic technicians measured the same set of patients on consecutive weeks using the same eye lane in our clinic. This ensured the use of the same instrumentation and charts and conditions of illumination. Pupil diameters under cycloplegia were measured both weeks by a single technician (who did not determine any of the refractive errors) using the same pupillometer just before the subject was seen for determination of manifest or cycloplegic refraction. The number of patients in the study was calculated to detect a mean difference of 0.25 D, at a minimum, between cycloplegic refractions with the 2 agents. This was based on the premise that subjective refractions are only accurate and reproducible to 0.25 D in sphere or cylinder. The standard deviation of difference in cycloplegic refractions is 0.313 D. This calculation of variance was from determinations of repetitive cycloplegic refractions made at the Navy Refractive Surgery Center, Ophthalmology, Naval Medical Center San Diego. The power calculation was performed for an a of 0.05 and a b of 0.20, yielding a sample size of 25; that is, 25 eyes of 25 patients. To allow for study attrition, a sample size of 30 eyes was used. A difference of 0.50 D or greater would normally change surgical planning for refractive surgery. Differences in refractive errors, extent of near point accommodation, acuity, and pupil diameters under cycloplegia were compared using matched pair analysis of variance (ie, t test, 1- or 2-sided, where a Z 0.05). Results and statistical analysis were done on right and left eyes separately, maintaining a datum per patient per examination for each statistic. In a single patient, the eyes would respond similarly to cycloplegics. Therefore, the denominator for the calculations was the number of patients and never the number of eyes. Approval for the study was obtained from the Institutional Review Board, and the study consent was approved by the Committee for the Protection of Human Subjects of the Clinical Investigation Department, Naval Medical Center, San Diego (CIP #S-00-027). Patients were solicited consecutively from a waiting list of patients previously screened and found eligible for refractive surgery. Those included were male and female military health care beneficiaries of all races who were from 21 to 50 years old to be treated for low to moderate myopia or myopic astigmatism. Patient characteristics are summarized in Table 1. Patients were excluded if they had any condition that might affect repeatability of refractions or would make them a poor candidate for refractive surgery. These conditions included collagen–vascular diseases, autoimmune diseases, immunodeficiency diseases, ocular herpes (zoster or simplex), diabetes, female subjects who were pregnant or breastfeeding, and subjects who were using certain medications including steroids, antimetabolites, isotretinoin, amiodorone, and sumatriptin. Patients with prior intraocular surgery (including cataract surgery), prior corneal surgery, active
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Table 1.
Patient demographics and refractive treatments in this
study. No. of Patients
28
Mean age (range) (y)
35.4 (21–50)
Men
24 (86%)
Women
4 (14%)
Ethnicity White
14 (50%)
Asian
6 (22%)
Hispanic
4 (14%)
African American
4 (14%)
Mean refractive error (spherical equivalent) OD (range) (D)
ÿ3.02 (ÿ1.0 to ÿ5.12)
OS (range) (D)
ÿ3.14 (ÿ1.0 to ÿ5.25)
recurrent corneal erosions, dry eye syndrome, clinically significant lens opacity, or clinical evidence of trauma (including scarring) were also excluded. Patients were randomly assigned to receive 1 of the cycloplegic drugs first and the other second using a random number table. The randomization table was available only to 1 of the investigators (E.M.H.) and a technician who coordinated patient flow and administered agents. Examiners and patients were blinded to randomization. The coordinating technician administered medications in the following manner: each patient received a drop of topical anesthetic, proparacaine 1%, followed by 2 drops of the cycloplegic medication, either cyclopentolate 1% (Cyclogyl) or tropicamide 1% (Mydriacyl).1 Each drop was separated by 5 minutes. The coordinating technician arranged for cycloplegic refractions to be obtained 30 minutes after instillation of tropicamide and 60 minutes after instillation of cyclopentolate. The randomization code was to be revealed only in the event of an adverse reaction to the medication, and there were none.
Results Two complete examinations were obtained in both eyes of 28 of the 30 patients who enrolled. One in 7 of the patients was female (4 of 28); half were white (14) and the other half were approximately an equal proportion of Asian (6), Hispanic (4), and African American (4). The mean age was 35 years (range 21 to 50 years). Two patients were lost to follow-up after their first examination and were not included in the data analysis. The same ophthalmic technician performed both cycloplegic examinations in each patient in the same clinic eye lane using the same charts, instruments, 696
and levels of illumination. The technician had no documentation of the previous week’s examination on which to base his/her determination of refractive error. This ophthalmic technician measured manifest and cycloplegic refractions, along with uncorrected and best corrected acuities and near-point accommodation in both eyes at each visit. Refractions No statistically significant difference was found in cycloplegic refractions induced by either cycloplegic agent (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14; Figures 1 and 2). The group mean spherical equivalent refraction during tropicamide cycloplegia was, in right eyes, ÿ2.635 D (n Z 28; range ÿ0.88 to ÿ5.00 D) and during cyclopentolate, the mean was ÿ2.708 D (n Z 28; range ÿ1.00 to ÿ5.13 D). In left eyes, the mean spherical equivalent refraction during tropicamide cycloplegia was ÿ2.908 D (n Z 28; range ÿ1.00 to ÿ5.38 D); during cyclopentolate, the mean was ÿ2.978 D (n Z 28; range ÿ1.00 to ÿ5.25 D). The mean difference in individual eye refractive errors, tropicamide spherical equivalent minus cyclopentolate spherical equivalent, was 0.054 D in both right and left eyes (n Z 28; right eye SD Z 6 0.214 D, and left eye SD Z 6 0.253 D). The cyclopentolate cycloplegic refractions were 0.054 D less myopic than the tropicamide refractions. These were not statistically significant differences. Five eyes of 3 patients had a difference of 0.50 D or greater between the 2 cycloplegic refractive errors (Table 2, Figure 2), with the trend toward less myopia with cyclopentolate (3 had a difference of 0.50 D; 2 eyes had a difference of 0.625 D spherical equivalent). Two of the 3 patients were 36 years old, and the other was 39. Two were Hispanic men, and the third, a white woman. The largest measured difference, in sphere and cylinder terms, was 60.50 D, and it was measured in 3 individuals. This led to a spherical equivalent change of 0.50 or 0.625 D in 5 eyes of 3 people. In these 3 individuals, less refractive myopia was measured under the influence of cyclopentolate. Pupil Size After Administration of Cycloplegic Agent The pupil diameter of each patient’s eyes was measured by 1 technician just before the patient had the
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Figure 1. Frequency of differences in cycloplegic refractive error determined with the use of cyclopentolate and tropicamide as cycloplegic agents (cyclopentolate refraction–tropicamide refraction). The differences for each of the 56 eyes of 28 patients were calculated using spherical equivalent refractions and are graphed in 0.125 D increments. No difference was found between the mean spherical equivalent cycloplegic refractions (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14).
cycloplegic refractive error and near-point accommodation determined. In each patient’s eye, the difference in pupil diameter (cyclopentolate-induced pupil size minus tropicamide induced pupil size) was calculated. No statistically significant difference was found for the group in pupil diameters between the use of cycloplegic agents for the right or left eyes (diameter difference for OD Z ÿ0.157 6 0.61 mm, t Z 1.35, P Z .19; OS Z 0.014 6 0.80, t Z 0.09, P Z .92). Near-Point Accommodation Significantly less residual accommodation was found with use of cyclopentolate. On average, a difference of O0.25 D of accommodation was found between the 2 agents, with the tropicamide eyes able to accommodate more than the cyclopentolate eye (OD Z ÿ0.27 6 0.51 D, t Z 2.68, P Z .006; OS Z ÿ0.32 6 0.49 D, t Z 3.46, P Z .001) (Figure 3). Figure 2. The refractive error determined with the use of cyclopentolate (ordinate) versus that determined using tropicamide (abscissa) for the 28 patients (right and left eyes) in this study. All refractions are given in diopters of spherical equivalent. The 5 eyes of 3 individuals who were found to be R0.50 D less myopic with the use of tropicamide are circled. The other 51 eyes were within 0.375 D or less of the line of equality (dark line). No difference was found between the mean spherical equivalent cycloplegic refractions (mean difference 6 SD; OD Z 0.05 6 0.21 D, t Z 1.33, P Z .10; OS Z 0.05 6 0.25 D, t Z 1.12, P Z .14).
Reliability of Refractive Error Measurements Reliability of refractions was assessed by comparing reproducibility of subjective dry refractive errors (manifest refraction) between the 2 visits for each subject. Subjective dry refractions averaged a difference of 0.03 6 0.15 D for right and left eyes (t Z 1.44, P Z .08) between the first and second examination.
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Table 2. Demographic and refractive characteristics of 3 patients (5 eyes) with measured difference in cycloplegic refractive errors of 0.50 D or greater. Data for both eyes of each subject from both visits are given.
Sex
Manifest Tropicamide Manifest Cyclopentolate Difference (C–T) Age Refraction Refraction Refraction Refraction in Spherical Ethnicity (Y) Eye (Sphere Cylinder) (Sphere Cylinder) (Sphere Cylinder) (Sphere Cylinder) Equivalent
Female White
36
OD
ÿ1.25 ÿ0.50 D
ÿ1.50 ÿ0.50 D
ÿ1.25 ÿ0.50 D
ÿ1.00 ÿ0.50 D
OS
ÿ1.25 ÿ2.50 D
ÿ1.50 ÿ2.50 D
ÿ1.00 ÿ2.50 D
ÿ1.00 ÿ2.50 D
C0.50 D
Male
36
OD
ÿ2.75 ÿ0.75 D
ÿ2.75 ÿ0.75 D
ÿ2.75 ÿ0.50 D
ÿ2.50 ÿ0.50 D
C0.375 D
OS
ÿ3.00 ÿ0.50 D
ÿ3.00 ÿ0.25 D
ÿ2.75 ÿ0.25 D
ÿ2.50 ÿ0.00 D
C0.63 D
OD
ÿ4.50 ÿ0.75 D
ÿ4.50 ÿ0.75 D
ÿ4.25 ÿ1.00 D
ÿ4.00 ÿ0.75 D
C0.50 D
OS
ÿ4.75 ÿ0.50 D
ÿ5.00 ÿ0.50 D
ÿ4.50 ÿ0.25 D
ÿ4.50 ÿ0.25 D
C0.63 D
Male
Hispanic
Hispanic
39
C0.50 D
tropicamide rated an average of about 1.0, very low on the 7-point discomfort scale (SD Z 0.82 and 0.83, respectively; 0 through 6 scale; t Z 0.42, PO.6) (Figure 4). The patients faithfully reported the difference in duration of dilation between the drugs; average duration reported as 3.7 hours for tropicamide and 21 hours for cyclopentolate (t Z 7.46, P!!.01). Twenty-four of 28 (86%) patients preferred tropicamide, citing a more rapid return of near vision, 1 individual (4%) preferred cyclopentolate, and 3 individuals (10%) reported no preference. Figure 3. Frequency of differences in near point of accommodation (D) for the 56 eyes of the 28 patients found between the use of cyclopentolate and tropicamide for cycloplegia. On average, R0.25 D more accommodation was uncovered with the use of cyclopentolate relative to the use of tropicamide (OD Z ÿ0.27 6 0.51 D, t Z 2.67, P Z .006; OS Z ÿ0.34 6 0.50, t Z 3.46, P Z .001).
Two of the 56 determinations of manifest refraction resulted in a spherical equivalent refractive error of 6 0.375 D; all others were within 0.25 D of the previous weeks determination, and 45% (25:56) of the manifest refractions (spherical equivalent) were the same. This resulted in a mean difference in best corrected visual acuity (BCVA) of C0.03 6 0.05 logMAR for right and left eyes. This small improvement in BCVA (t Z 5.01, P!.001) for all eyes tested represents a 1.5 letter improvement on the 5-letter line of the ETDRS charts utilized in this study. Five of the 56 eyes (9%) improved by 1 line or more (0.10 to 0.14 logMAR). This improvement in BCVA is not the result of changes in manifest refraction (R Z ÿ0.149, P Z .274). Subjective Survey The patients did not find either mydriatic agent imparted any greater discomfort. Cyclopentolate and 698
Discussion Successful refractive surgery requires an accurate assessment of the refractive state of the eye. This typically is composed of a dry or manifest refraction as well as a cycloplegic refraction. The purpose of the cycloplegic examination is to ensure that accommodation is suspended. With significant residual accommodation not detected in a preoperative workup, overcorrection and subsequent hyperopia may result in a myopic treatment. Similarly, a hyperopic treatment may result in undercorrection and residual hyperopia. Cycloplegic agents available for use in the United States are summarized in Table 3. Atropine is the most potent cycloplegic agent and the longest acting. It is not routinely used as a diagnostic agent in adults because of its extremely long duration of action, but is often used for cycloplegic retinoscopy and amblyopia therapy in children because children are capable of much greater accommodation. Weaker, shorter-acting agents are generally not thought to be as effective at paralyzing the ciliary muscle as the longer duration agents. However, several studies in children have suggested
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Figure 4.
The 7-point discomfort scale. A score of zero was given if no discomfort was marked and 6 for severe discomfort.
Table 3. Cycloplegic agents available in the United States listed in order of longest onset of effect to shortest, which, with 1 exception, mimics duration of influence. Name Atropine Homatropine
Onset of Action
Duration of Cycloplegia
6–24 hours
10–15 days
1 hour
1–2 days
Scopolamine
30–60 minutes
3–4 days
Cyclopentolate
30–60 minutes
12–24 hours
Tropicamide
20–30 minutes
4–10 hours
that the weaker agents, such as cyclopentolate and tropicamide, may indeed provide adequate cycloplegia for cycloplegic retinoscopy. Cyclopentolate has been compared to atropine in several pediatric studies. Results in older studies caution that cyclopentolate might not be as effective as atropine for cycloplegic refractions in children.9–11 More recent studies comparing cyclopentolate and atropine in children have shown no significant difference between cycloplegic refractions achieved with the 2 agents.12,13 Several studies have compared cyclopentolate to tropicamide in children.1–6 These studies found cyclopentolate to be slightly more efficacious than tropicamide but noted that the differences between the 2 were small and would not significantly influence a prescription for treatment of the refractive error. In adults, there have been few studies comparing various cycloplegic agents. The results of 1 study, conducted in 1957 prior to the introduction of tropicamide, actually suggested that cyclopentolate was more effective than atropine at reducing accommodation.14 One published study compared tropicamide, cyclopentolate, and homatropine in adults.7 It showed that tropicamide and cyclopentolate were equal in their effectiveness at reducing accommodation, and both were superior to homatropine for examinations performed within 1 hour of drop instillation. A recent study looked at the effects of mydriasis on wavefront aberrometry measurements with phenylephrine, tropicamide, and cyclopentolate.8 The cycloplegic wavefront autorefraction was compared with subjective manifest refraction.
Tropicamide induced 0.35 D less myopia than the subject refraction, and cyclopentolate induced 0.42 D less myopia. We found no statistically significant difference between tropicamide and cyclopentolate for cycloplegic refractions (mean difference 0.05 6 0.25 D) in a group of 28 prospective myopic refractive surgery patients. Five eyes of 3 patients showed a difference in spherical equivalent cycloplegic refraction of 0.5 D or more. This would make a difference in the prescribed treatment for refractive surgery in these cases. Data from these 3 patients are summarized in Table 2. Among these 3 patients, 2 eyes had a difference of 0.625 D spherical equivalent; 3 eyes varied by 0.50 D manifest spherical equivalent when measured from week to week. Five others varied by 0.375 D, and 46 of 56 varied by 0.25 D or less. We think this is excellent evidence that the manner of determining refractive error was not a large factor in investigating the differences in cycloplegic refractions. It is possible that the 3 individuals found to be less myopic by 0.50 or 0.63 D with the use of cyclopentolate were not truly less myopic but the result of random variation in measurement of refractive errors. With a sample size of only 3 in 28 patients, a convincing statistical treatment of this question is not possible. It is important to realize that there may be a difference between the manifest and cycloplegic refractions that is not due to accommodation. Cycloplegia not only suspends accommodation but also causes mydriasis. In an eye with significant aberrations, pupil dilation may affect the refraction as the patient attempts to place the circle of least confusion on the macula. In this study, there was no difference in the extent of pupillary dilation with either drug at the time the refractive error was determined. For the 3 patients in whom the cycloplegic refractions were different by R0.5 D, pupil measurements did not vary by greater than 0.6 mm, within 1 standard deviation of repetitive measurement (SD Z 0.79 mm). Consequently, we have no evidence that the refractive differences were due to
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anything more than residual loss of accommodation with cyclopentolate. An important question to ask is whether cycloplegic refractions are even necessary. In this study, 8 of 56 (14%) cycloplegic refractions, using tropicamide or cyclopentolate, were 0.50 D of spherical equivalent less myopic than the manifest refraction determined prior to cycloplegia. These 8 eyes may have been offered a different refractive treatment based on the cycloplegic refractions. Using all this study’s measurements of manifest and cycloplegic refraction determined with both cyclopentolate and tropicamide (56 comparisons with both agents or 112 cases), the mean refractive error was less under cycloplegia by 0.17 D spherical equivalent. The mean difference, cycloplegia minus manifest refraction, for the 28 patients with use of either drug was significantly decreased (1 sample test where the null hypothesis was that the difference was zero, t Z 6.00 and 5.00, for OD and OS with cyclopentolate, respectively; t Z 3.48 and 3.35, for OD and OS with tropicamide, respectively; P!.001). The need to measure cycloplegic refraction is militated by our results, even for low to moderate myopic refractive errors, when considering refractive surgical treatments. With the recent advent of wavefront-guided refractive surgery, cycloplegic refractions should continue to play an important role in the preoperative evaluation of a prospective refractive surgery candidate. Excessive accommodation during the wavefront capture can lead to inaccurate treatment plans.
References 1. Proskurina OV. [Cycloplegic efficiency of the drugs cyclopentolate and tropicamide vs atropinization.] (Russian) Vestn Oftalmol 2002; 118(6):42–45
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2. Manny RE, Hussein M, Scheiman M, et al. Tropicamide (1%): an effective cycloplegic agent for myopic children. Invest Ophthalmol Vis Sci 2001; 42:1728–1735 3. Owens H, Garner LF, Yap MKH, et al. Age dependence of ocular biometric measurements under cycloplegia with tropicamide and cyclopentolate. Clin Exp Optom 1998; 81:159–162 4. Lin LL-K, Shih Y-F, Hsiao C-H, et al. The cycloplegic effects of cyclopentolate and tropicamide on myopic children. J Ocul Pharmacol Ther 1998; 14:331–335 5. Mutti DO, Zadnik K, Egashira S, et al. The effect of cycloplegia on measurement of the ocular components. Invest Ophthalmol Vis Sci 1994; 35:515–527 6. Egashira SM, Kish LL, Twelker JD, et al. Comparison of cyclopentolate versus tropicamide cycloplegia in children. Optom Vis Sci 1993; 70:1019–1026 7. Gettes BC, Belmont O. Tropicamide: comparative cycloplegic effects. Arch Ophthalmol 1961; 66:336–340 8. Giessler S, Hammer T, Duncker GIW. Aberrometrie in Mydriasis – welch Art der Mydriasis ist zu bevorzungen? Klin Monatsbl Augenheilkd 2002; 219:655–659 9. Rosenbaum AL, Bateman JB, Bremer DL, Liu PY. Cycloplegic refraction in esotropic children; cyclopentolate versus atropine. Ophthalmology 1981; 88:1031–1034 10. Ingram RM, Barr A. Refraction of 1-year-old children after cycloplegia with 1% cyclopentolate: comparison with findings after atropinisation. Br J Ophthalmol 1979; 63:348–352 11. Robb RM, Petersen RA. Cycloplegic refractions in children. Pediatr Ophthalmol 1968; 5:110–114 12. Kawamoto K, Hayasaka S. Cycloplegic refractions in Japanese children: a comparison of atropine and cyclopentolate. Ophthalmologica 1997; 211:57–60 13. C ¸ elebi S, Aykan U. The comparison of cyclopentolate and atropine in patients with refractive accommodative esotropia by means of retinoscopy, autorefractometry and biometric lens thickness. Acta Ophthalmol Scand 1999; 77:426–429 14. Barbee RF, Smith WO Jr. A comparative study of mydriatic and cycloplegic agents in human subjects without eye disease. Am J Ophthalmol 1957; 44:617–622
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