Cycloplegic Refractions in Children* Richard M. Robb, M.D. Robert A. Petersen, M.D. Boston, Massachusetts Acrropine Has BEEN For many years a standard drug for the cycloplegic refraction of children.’ Its relatively pro- longed duration of action has been a drawback, but its cycloplegic effective- ness remains unchallenged and the clin- ical impression has often been voiced that a child’s full hyperopic error can not be uncovered unless atropine has been used.* Cyclopentolate, since the first re- port of its use as a cycloplegic agent in 1951,* has offered the advantages of rela- tive effectiveness, rapidity of onset, and short duration of action.** The usual method of judging the effectiveness of a cycloplegic agent has been to measure residual accommodation at the height of the drug’s effect.":’ It is, however, diffi- cult to measure residual accommodation in young patients, and in only one small series has a comparative study of cyclo- plegie agents been reported in children under six years of age. Since eycloplegic drugs are employed so commonly in pe- diatric ophthalmology, it seemed of inter- est to determine the relative effectiveness of atropine and cyclopentolate in children From. the Department of Ophthalmology, Chil- dren's Hospital Medical Center. “This investigation was supported in part by PHS Center Grant #NBO3691 from the National Institute of Neurological Diseases and Blindness, Public Health Service, using another available refractive tech- nique. Retinoscopy was chosen because it is the technique used by most ophthal- mologists for patients in the pediatric age group. A certain lack of precision in such a study was anticipated because of the variable cooperation of the children and the inexactness of retinoscopy itself; but these handicaps are very much a part of clinical ophthalmology and it was felt that to the extent that any resultant var- iability could be identified in the data these factors might add to the pertinence of the study, Method Cycloplegic refractions were performed in the eye clinic of a large pediatric hos- pital. The 143 children selected for the study were ones in whom measurement of the refractive error was an important factor in the management of their ocular problem. The composition of the group was as follows: approximately half of the children were between three and six years of age, the rest being evenly di- vided between those younger than three and those older than six; by refractive error the majority were hyperopic, re- flecting the prevalence of hyperopia in childhood and the frequency of partly and fully accommodative esotropia in the clinic population; about 30% were Ne- 110groes, and of the remaining light-skinned individuals half had blue irides and half brown irides. One per cent cyclopentolate hydrochlo- ride was the cycloplegic agent used at the time of the initial examination. Two drops were instilled in each eye with an interval of several minutes between instillations. Retinoscopy was performed thirty to ninety minutes later, the interval deter- mined by the demands of the clinic sched- ule and the length of time required for the pupils to become fixed and dilated. In some darkly pigmented patients the pupils failed to become fully dilated, but in most instances it was possible to per- form the refraction after ninety minutes despite the reactive pupils. The patients returned for atropine refractions an aver- age of five weeks later, the range being from one week to twelve weeks. If atro- pine solution was used, graded concentra- tions from ¥ to 4% concentrations were instilled at home tid. for three days before the examination, the concentration depending on age and pigmentation. If atropine ointment was used a 1% concen- tration was instilled in all patients bi.d. for three days prior to the examination. Both refractions on a given patient were performed by the same examiner. It was not possible to disguise which cy- cloplegic agent had been used, but the time interval between the two refractions insured that the measurements could not be compared by memory and a conscious effort was made not to compare values before both examinations had been per- formed. The figures used were those of net retinoscopy with the patient fixating the light of the retinoscope. Residual ac- commodation could not be measured con- sistently because of the age of the pa- tients and it was, therefore, not recorded for the study. In analyzing the data all refractive er- rors were expressed as spherical a, lents, Values for the cy refraction were subtracted from | eee. tained using atropine so that a positive number would be obtained when atropine uncovered more hyperopia than did cy- clopentolate. The differences for the two eyes were averaged and treated as one value for each patient. Results As indicated in Table I, a total of 286 refractions on 143 patients were per- formed. Seven patients were excluded from the analysis because of anisometro- pia, which made the averaging of results from the two eyes of questionable signifi- cance; three patients had to be excluded because of inadequate cycloplegia of such a degree that refraction could not be com- pleted. Two of these three were inade- quately dilated with atropine, probably because of improper instillation, although the parents denied this. The other was a 13 month old Negro patient with high myopia who had reactive pupils after cy- clopentolate and could not be retino- scoped. With atropine the pupils became dilated and fixed and the patient was found to have a myopic error of — 10.50 sphere O.U. There remained 133 patients on whom adequate data was available for TABLE | CHILDREN REFRACTED WITH CYCLOPENTOLATE SOLUTION AND ATROPINE SOLUTION OR (OINTMENT. cal analyses: Included in sta! hyperopic 125 myopic Excluded because of anisometropia : Unable to refract 2 Total 143 TABLE Il DIFFERENCE IN CYCLOPENTOLATE AND ATROPINE REFRACTIONS ACCORDING TO REFRACTIVE ERROR™ Refractive Error x noes oF a ae a) +34 31 B ObF +42 67 36 92 449 2 27 87 between atropine and cyclopen- fa. less than —1.50. b, —1.50to-+1.50 & +150 to -+4.00 d. greater then +-4.00 umber of pationts in group, tandard deviation of the mean difference. yolue of + distribution, indicating whether x dif. fers significantly from zero. 11TABLE III DIFFERENCE IN CYCLOPENTOLATE AND ATRO- PINE REFRACTIONS ACCORDING TO PIGMEN- TATION [EXCLUDING HIGH MYOPES)* b. Lightskin, brown eyes +47 4927 . Brown skin, brown eyes 43 31 3177 ean difference between atropine and cyclopen- folete refractions. = number of patients in rou ‘andard deviation of the mean difference. 10 of + distribution, indicating whether x dif. fers significantly from zero. som, tea a. Light stin, blue eyes te 4 39 «(58 TABLE IV DIFFERENCE IN CYCLOPENTOLATE AND ATRO- PINE REFRACTIONS IN LIGHT-SKINNED, BROWN. EYED, HYPEROPIC CHILDREN ACCORDING TO AGE x nod ft +57 12 «218s bi. 3 to 6 years +44 «183063 ¢ Over 6 years +47 18 25 BO x= mean difference between atropine and cyclopen: tolate refractions. umber of patients in group. tandard deviation of the mean difference. =volue cf + distribution, indicating whether x dif. fers significantly from zero. a, Under 3 years TABLE V DIFFERENCE IN CYCLOPENTOLATE AND ATRO- BINE REFRACTIONS IN CHILDREN WITH _REAC. TIVE PUPILS AFTER CYCLOPENTOLATE | WITHOUT REGARD TO AGE AND EXCLUDING HIGH MYOPES)* 19 (out of 31) with brown skin, brown eves 2 (out of 49) with light skin, brown eves 0 [out of 45) with light skin, blue eyes x ede ctive pupils +4 2 3853 ean difference between stropine and cyclopen- tolate refractions. . ~ umber of patients in group, tondard deviation of the mean difference. lue of + distribution, indicating whether x dif- fers significantly from zero, comparison of the effect of the two cyclo- plegic agents. When patients were grouped according to refractive error (Table II), there ap- peared to be a real difference between the results obtained in the myopic patients and those obtained for the hyperopic ones. Patients with myopia less than -1.50 diop- ters were included in the hyperopic group since the working distance for retinoscopy was 67 cm. and all patients with a far point beyond that distance could be ex- pected to a ite on the retino- scope if any residual accommodation were available. In the myopic group the mean e between cyclopentolate and atropine refractions did not signifi- cantly differ from zero, whereas in the hyperopie groups the mean difference indicated that atropine had uncovered from one-third to one-half diopter more hyperopia than cyclopentolate. In addi- tion there seemed to be a trend in the hyperopie groups suggesting a larger mean difference as the hyperopia in- creased. It should be noted that this trend was not statistically significant when subjected to an analysis of variance (F=1.30). Since the highly myopic group behaved so differently from the others, it was omitted from further analyses in which other variables were being exam- ined, The remaining patients were divided into three subdivisions according to pig- mentation (Table III) to determine whether skin or iris pigmentation would be a useful guide in the choice of cyclo- plegics. The surprising feature of this analysis was that the Negro patients were not remarkably different from light- skinned, brown-eyed patients, whereas during the study the irides of Negro pa- tients had been distinctly harder to dilate than those of the light-skinned patients (vide infra). Although by analysis of variance there was no difference between groups according to pigmentation, if all patients with brown irides were lumped together and compared with patients with blue irides there was a greater mean difference in the brown-eyed group, a finding that was statistically significant at the five per cent level (t=1.98). ‘The light-skinned, brown-eyed, hyper- opie group (the largest relatively homog- eneous group) was further broken down into age categories (Table IV), but no relationship of mean difference to age could be demonstrated (F=.79). All children with reactive pupils after cyclopentolate were grouped together 112(Table V) and found to be surprisingly similar to the other groups of hyperopic patients in which no distinction had been made regarding pupillary reactivity. As indicated above, most of the patients with reactive pupils were Negroes. There was no difference in any of the groups in the results of the two exam- iners, and no difference could be ascribed to the use of atropine solution as opposed to atropine ointment. Discussion It was apparent from the size of the standard deviations recorded with the data that the comparisons being made in this study were subject to a variability of significant proportions. Part of the var- iability certainly could be accounted for by the inexactness of the retinoscopic endpoint. Although skill in retinoscopy varies with the examiner, as does patient cooperation, it is probably fair to estimate that for most retinoscopists spherical dif- ferences of 0.50 diopter are much more reliably discerned than those of 0.25 diopter or less. If atropine uncovers from one-third to one-half diopter more hy- peropia than eyclopentolate in selected groups, it is apparent that the difference is of the same order of magnitude as the smallest increment of refractive error discernible in the method. On the other hand, in any normal dis- tribution of values 95% of all chance var- iations are expected to fall within the range of the mean + two standard devia- tions. If we take 0.33 diopters as an aver- age standard deviation for our groups and we are dealing with a mean difference of approximately 0.40 diopters, then statis- tically 95 of 100 children would have atro- pine refractions revealing from 1.06 D more to 0.26 D less hyperopia than the corresponding cyclopentolate refractions, Whether one wants to accept this kind of potential difference may depend on the circumstances surrounding a given re- fraction in a particular patient. One sug- gestion to be considered is that when cy cyclopentolate is used, a smaller amount or perhaps nothing at all be subtracted from the full retinoscopie error in pre- scribing glasses which are intended to fully neutralize a hyperopic error. Another observation arising from ex- perience beyond the data reported herein is that in some hyperopic patients refrac- tions performed several months to a year after the initial examination may reveal a greater hyperopic error than either atropine or cyclopentolate had originally uncovered. A frequent clue to this possi- bility is the recurrence of an esodeviation in a patient whose heterotropia had ini- tially been fully corrected with glasses. Whether this represents a real change in refractive error or an uncovering of pre- viously latent hyperopia is unclear. It would not necessarily indicate that a previously used short acting cycloplegic agent had provided inaccurate informa- tion. To the extent that the inconvenience of atropine’s long duration of action would discourage repeated refractions as they seemed indicated, it would be pref- erable to use the shorter acting agent. ‘The fact that patients with reactive pu- pils after eyclopentolate had about the same mean difference as did those with non-reactive pupils is surprising. The pa- tients with reactive pupils were nearly all Negroes, a matter of common observa- tion. One is led to the thought that there may be a differential of time or extent of action of cyclopentolate on iris as opposed to ciliary body in these heavily pigment- ed eyes. Such a differential action is sug- gested by a previous study of cycloplegic agents in adults of differing pigmentation in which cyclopentolate produced paraly- sis of accommodation much earlier and more effectively than it produced my- driasis.’ Lacking any other cogent explanation, ‘we presume that the myopic patients be- haved differently from the hyperopic ones in this study because there was no gain for the former to accommodate on the retinoscopic target during the examina- tion. 113Summary A group of 143 children were refracted by retinoscopy using, on separate occa- sions, cyclopentolate and atropine as cy- cloplegic agents. In hyperopic patients, atropine uncovered from one-third to one- half diopter more hyperopia than cyclo- pentolate. The standard deviation from this mean difference was of the same magnitude as the difference in the two refractions, indicating a significant varia- bility inherent in the method of measur- ing the refractive errors. The influences of age, pigmentation, reactivity of pupils, and amount of refractive error were ana- lyzed in the hyperopic group, each ac- counting for surprisingly little variation in the observed mean difference, There was no mean difference in the refractions obtained with atropine and cyclopentolate in a small group of myopic patients. 300 Longwood Avenue Boston, Mass. 02115 1, Gres, B. C.: Dibutoline Sulfate, Compara- tive Clinical Study of Cycloplegic Hffccts, Arch. Ophthal., 43:446-453, March 1950. 2 Stoans, AE: Manual of Refraction, Little, Brown, & Co., Boson, 1961. 3. Pamsriy, B. ‘S. and Mere, M, M: A New and Cycloplegic Drug; Am. J. ‘Ophth., 34:572-575, April 1951. 4, Gonpox, D. M. and Enrennerc, M. H.: Cyclo- pentolate HCl: A New Mydriatic and Cyclo~ plegic Agent, A Pharmacologic and Clinical Evaluation; Am, J. Ophth., 38:831-838, De- cember 1954, 5. Guries, B. S.: Choice of Mydriatics and Cy- cloplegics for Diagnostic Examinations in Children. Diagnostic Procedures in Pediatric Ophthalmology, Edited by L. Apt, Little Brown & Co., Boston, 1963. Gentes, B. C.: Three New Cycloplegic Drugs, Clinical Report; Arch. Ophth, 51:467-472, April 1954, Cnr, L: Experiences with Cyelogyl. Trans. Ophthal. Soc. UK., 79:665-670, 1959. }. Hantum, A. V.: Symposit The Nonsurgical Treatment of Strabismus. The Management of the Deviation, Am. Orthop. J., II:28-87, 1961 9. Bansex, R. F. and Smime, W. O.: A Compara- tive Study of Mydriatie and Cycloplegic Agents: In Human Subjects Without Eye Disease. Am. J. Ophthal. 44:617-622, November 1957. 114