No. 4 Reports 467

Pupillary Light in Amblyopia

Monobu Ko.se, Renpei Nago.ro., Arsushi Yoshido, and Issei Honodo

The pupillary light reflex of 15 strabismic and anisometropic 0.8 or better. Their ages ranged from 8 to 12 years, amblyopes, and eight subjects who had recovered from func- and the visual acuity of the amblyopic before the tional amblyopia was studied by using an infrared electro- treatments ranged from 0.03 to 0.6. The duration of pupillogram. Ten of the fifteen amblyopes had significantly treatments was from 9 months to 3 years. Six of the longer latencies of contraction when the amblyopic eyes were subjects had anisometropic amblyopia and two had stimulated than when the normal eyes were stimulated. How- strabismic amblyopia. ever, there was no relationship between the delay in pupillary All of the subjects were dark-adapted for 10 min, light and reduced visual acuity of amblyopic eyes. The amplitudes and maximum velocities of the contraction and the pupillary light reflex was recorded by an in- were not altered significantly in amblyopic and normal eyes. frared electropupillogram ( corder, Hamamatsu TV All of the subjects who had recovered showed no significant Co.) that measures the pupillary area continuously. difference of the latencies of the pupillary responses to stim- The sampling rate is 16.7 msec and variation of am- ulation between normal and amblyopic eyes. These findings plitude is below ±1%.3 The stimulus was diffuse light indicate that a retinal mechanism in amblyopic eyes may be of 500 msec duration. The intensity of the light stimulus responsible for the abnormally long pupillary light reflex was fixed at one lux. Subjects were instructed to fixate latency. Invest Ophthalmol Vis Sci 25:467-471, 1984 a red spot that was placed 1 m in front of them. The direct of both eyes and the consensual Electrophysiological and psychophysical studies have reflex of amblyopic were recorded for each subject, shown that functional amblyopia is associated with while in four cases the consensual reflex of normal eye abnormal visual processing at various levels of visual was also measured. Light stimulation was performed system. It has also been shown that amblyopic carefully so that light entered the eye along the visual show static and dynamic anomalies to light. Harms1 axis, especially when the consensual reflex for strabis- made pupilloscopic studies with perimetric stimulation mic amblyopia was recorded. Individual pupillary re- of light and found that the pupillomotor sensitivity sponses were measured three times at an interval of 5 was greater with peripheral than central stimulation min because the sampling time of 16.7 msec is relatively in the amblyopic eyes. Dolenek2 also reported that the large for the latency of pupillary reflexes. Signals of pupillary light reflex had longer latencies of contraction pupillary area and light stimulus were stored on mag- and dilation on stimulation of amblyopic eyes than of netic tape. A signal processor (San Ei Sokki Co.) was normal eyes. It, however, remains unclear wherein the used to digitalize the data with a time bin of 1 msec. pupillomotor system the pupillary abnormalities lie, The latency of the light reflex was determined as the and whether they are correlated with depth of ambly- time between the onset of stimulus and the point that opia. Therefore, it was felt that a quantitative analysis declined below the baseline and followed by continuous of pupillary responses to light may be important to decrease in pupillary area. The amplitude was defined understand the mechanism for amblyopia. as the largest values of the contractions and the max- In the present study, an infrared electropupillograph imum velocity was calculated as the largest values of was used to measure pupillary area precisely. The pur- the derivative from contractions. The mean values of pose was to examine the pupillary light reflex of stra- these parameters of contractions were measured from bismic and anisometropic amblyopia and to clarify the three trials. the relationship between parameters of pupillary re- Results. Patients with amblyopia: In 10 of the 15 sponses and depth of amblyopia. patients with unilateral functional amblyopia, the la- Materials and Methods. The pupillary light reflex tencies of the direct pupillary reflexes were longer when was measured from 15 unilateral functional amblyopic the amblyopic eyes were stimulated. In the remaining patients and 8 subjects who had recovered from am- five patients, the difference of latencies between am- blyopia by appropriate treatment. Eight out of the fif- blyopic and normal eyes was less than 16.7 msec. Six teen patients were strabismic and seven were aniso- of the ten patients had strabismic amblyopia, and four metropic amblyopes. The visual acuity of the normal had anisometropic amblyopia (Table 1A). The visual eyes was 0.9 or better, with or without correction, acuity of the amblyopic eyes in the patients who had whereas that of the amblyopic eyes was 0.5 or less. increased latencies ranged from 0.06 to 0.5. The - Their ages ranged from 8 to 51 years with no history lographic patterns of the light reflex in two cases are of treatment for amblyopia. All of the subjects who shown in Figure 1. Two responses of each reflex were had recovered from amblyopia had visual acuity of superimposed with the onset of stimulus aligned. These

Downloaded from iovs.arvojournals.org on 10/01/2021 468 INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / April 1984 Vol. 25

Table 1. Clinical data of the 10 patients having longer latencies to stimulation of amblyopic eyes (A) and of the eight subjects who had recovered from amblyopia (B)

A Case Sex Age Phoria or tropia Visual acuity

1 F 10 ortho R.E. 0.1 (0.5X + 3.5Dcyl + 1.0D900) L.E. 1.5 (n.c.) 2 M 12 +20* R.E. 0.1 (0.2X -0.5D) L.E. 1.5 (n.c.) 3 F 24 ortho R.E. 0.8 (1.0X - 1.5D) L.E. 0.01 (n.c.) 4 M 25 +40* R/L 16* R.E. 0.06 (n.c.) L.E. 1.5 (n.c.) 5 M 16 -12* R.E. 0.7 (0.9X cyl - 0.5D 180°) L.E. 0.05 (0.1X - 5.0D) 6 M 9 +20* R.E. 1.2 (n.c.) L.E. 0.3 (n.c.) 7 M 51 ortho R.E. 0.02(0. IX - 5.5D) L.E. 0.8 (1.2X - 1.0D) 8 M 8 + 14* R.E. 1.0 (n.c.) L.E. 0.2 (0.4X + 1.5D) 9 M 30 ortho R.E. 0.9 (n.c.) L.E. 0.2(0.3X + 1.0D) 10 F 25 -30*L/R20* R.E. 0.01 (n.c.) L.E. 1.2 (n.c.)

Visual acuity B Case Age Sex Before After Duration

1 11 M R.E. 1.0 1.0 2 yrs L.E. 0.06 1.0 2 9 M R.E. 0.6 2.0 1 yr L.E. 0.08 1.0 3 9 M R.E. 1.2 1.5 1 yr L.E. 0.5 0.9 4 8 F R.E. 1.5 1.5 9 mon L.E. 0.03 0.9 5 12 F R.E. 0.4 0.8 3 yrs L.E. 0.9 1.2 6 12 M R.E. 0.03 1.2 1 yr L.E. 0.6 1.5 7 11 M R.E. 0.04 0.8 2 yrs L.E. 1.0 1.2 8 12 F R.E. 0.1 0.9 1 yr L.E. 1.2 1.2

responses demonstrate the trajectories and latencies of 284 msec with mean of 267 ± 12.3 msec. The direct the contractions for each trial condition. The latencies reflex and consensual reflex of amblyopic eye had a of direct reflex of normal eye (1), direct reflex of am- mean latency of 295 ± 14.5 msec and 275 ± 10.9 blyopic eye (2), and consensual reflex of amblyopic msec, respectively. The direct reflex of amblyopic eye eye (3) in Figure 1A were 263 msec, 300 msec, and was significantly longer than the direct reflex of normal 267 msec, respectively. In Figure IB, consensual reflex eye and the consensual reflex of amblyopic eye (t of normal eye had approximately the same increased = 4.67, P < 0.0001 and t = 3.34, P < 0.001). There latency as the direct reflex of amblyopic eye; the direct was, however, no significant difference of pupillary reflex of normal eye (1) had latency of 271 msec, direct reflex latencies between normal and amblyopic eyes reflex of amblyopic eye (2) 292 msec, consensual reflex when the normal eyes were stimulated (t = 1.54, P of amblyopic eye when the normal eye was stimulated < 0.05). (3) 275 msec, and consensual reflex of normal eye In order to determine whether the prolongation of when the amblyopic eye was stimulated (4) 300 msec. latency was correlated with the depth of amblyopia, The mean latencies of the 10 patients calculated from relationship between the difference of latency and yisual three trials are shown in Table 2 A. The latency of the acuity of amblyopic eye was studied. The difference direct reflex of normal eye ranged from 243 msec to of latency of direct reflex between normal and amr

Downloaded from iovs.arvojournals.org on 10/01/2021 No. 4 Reports 469

blyopic eyes ranged from 17 msec to 50 msec with Table 2. Mean latencies of pupillary light reflexes in average of 28.1 msec. A calculation of the correlation amblyopes (A) and in the subjects who had between difference of latency and visual acuity indi- recovered from amblyopia (B) cated that there was no significant correlation (coef- Amblyopic eye ficient of correlation: -0.216) (Fig. 2). Normal eye The amplitude and maximum velocity of contrac- A direct reflex Direct reflex Consensual reflex tion in 7 of the 10 patients were measured. The mean Case (msec) (msec) (msec) amplitudes for direct reflex of normal eye, the direct, 1 263 300 267 and consensual reflexes of amblyopic eye were 12.6 2 270 300 285 ± 1.4 mm2, 11.0 ± 3.0 mm2, and 11.5 ± 1.3 mm2, 3 256 283 252 4 267 299 273 respectively. The maximum velocity was 35.0 ± 4.6 5 271 292 275 mm2/sec for direct reflex of normal eye, 33.3 ± 7.7 6 280 300 281 mm2/sec for direct reflex of amblyopic eye, and 35.7 7 260 310 275 8 243 260 9 278 302 285 10 284 307 285

Treated eye Normal eye B direct reflex Direct reflex Consensual reflex Case (msec) (msec) (msec)

1 290 286 300 2 286 287 285 3 266 268 268 4 268 268 269 5 270 262 265 6 281 282 272 7 256 270 261 8 295 298 288

The latencies were calculated from three trials. In total mean of the 10 amblyopes, direct reflex of normal eye, direct, and consensual reflexes of am- blyopic eye were 267 ± 12.3 msec, 295 ± 14.5 msec, and 275 ± 10.9 msec, respectively. The latencies for direct reflex of normal eye, direct, and consensual reflexes of treated eye were 277 ± 12.4 msec, 277 ± 13.5 msec, and 276 ± 13.5 msec, respectively. B ±5.1 mm2/sec for consensual reflex of amblyopic eye. There was no significant difference in the amplitude and maximum velocity among the reflexes (P > 0.05). Subjects recovered from amblyopia: Eight subjects who had recovered from unilateral amblyopia were measured for direct reflex of both eyes and consensual reflex of treated eyes (Table 1B). The mean latency of direct reflex of normal eyes was 277 ± 12.4 msec. The values of latency averaged 277 ± 13.5 msec for direct reflex of the treated eyes and 276 ± 13.4 msec for consensual reflex of the treated eyes (Table 2B). There were no significant differences (t = 0.17, P > 0.05 and t = 0.07, P > 0.05, respectively). Discussion. The present pupillographic study has shown that in 10 of 15 amblyopic patients, the pupillary Fig. 1. Pupillographic patterns of light reflexes in two patients. A reflexes had significantly longer latencies when the am- was a 24-year-old anisometropic and B was a 25-year-old strabismic amblyope. Two responses of each reflex were superimposed with blyopic eyes were stimulated. The increased latency onset of stimulus aligned. (1) Direct reflex of normal eye. (2) Direct was observed in both strabismic and anisometropic reflex of amblyopic eye. (3) Consensual reflex of the pupil of the amblyopes. The amplitudes and maximum velocities amblyopic eye when the normal eye was stimulated. (4) Consensual of the contractions, however, did not differ significantly reflex of the normal eye when the amblyopic eye was stimulated. Dotted line in A and B indicate the onset of contraction in each when either eye was stimulated. reflex. Upward step in C denotes stimulation of light. Calibration The findings that both direct and consensual reflexes represents 250 msec and 10 mm2. to stimulation of amblyopic eyes had longer latencies

Downloaded from iovs.arvojournals.org on 10/01/2021 470 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / April 1984 Vol. 25

50"

u I/) w 40H

u z LLJ Fig. 2. Relationship between < 30 delay of latencies and reduced visual acuity of amblyopic eyes. Ordinate shows difference of la- tency that is the difference of di- (J rect reflex latencies between nor- z mal and amblyopic eyes. Ab- 2 0 scissa represents visual acuity of amblyopic eyes. There was no significant relationship.

10"

0.1 0.2 0.3 0.4 0.5 VISUAL ACUITY of AMBLYOPIC EYE

suggest that the pupillary afferent from amblyopic eyes motor outflow to stimulation by light.6 In optic neuritis was responsible for the prolongation of latency whereas with central scotoma, for instance, severely decreased the pupillomotor efferent was normal. Furthermore, amplitude and increased latency of pupillary light reflex the absence of a difference in the amplitudes and max- to stimulation have been reported.7 Ikeda and Wright8 imum velocities of pupillary responses would indicate could show that the ganglion cells of the area centralis a slowing in the pathways of processing of visual in- of the cat are affected critically by defocusing the stim- formation since abnormal integration of pupillomotor ulus, whereas peripheral ganglion cells respond to such signals may result in an alteration of dynamic param- stimuli, indicating that the neural transformation at eters in responses.4 The increase in pupillary light reflex the macular region may be subjected to alteration by latency, and the difference of the direct reflex latency abnormal visual experience. Thus, the functional rear- between the normal and amblyopic eyes, are similar rangements of macular region attribute to squint or to the increase in visually evoked response latency of anisometropia, producing delay in information pro- 10 to 25 msec.5 No delay of the reflexes was, however, cessing that may result in abnormally long pupillary observed in any of the subjects who had recovered light reflex latencies. from functional amblyopia. The increased latency in In the present study, it was found that the degree the reflex for amblyopia, therefore, seems to be a re- of delay was not correlated significantly with the degree versible phenomenon that disappears following ap- of reduced visual acuity, even though the long pupillary propriate treatments, suggesting that the site for the light reflex latencies represented a loss of functional delay probably would be in an intraretinal mechanism advantages of macular region. No correlation between rather than changes of fibers. them is in good agreement with the finding that the Pupillary responses represent mainly activity of the decreased amplitude of visually evoked responses was 910 macular region that responds with vigorous pupillo- not correlated with the depth of amblyopia. These

Downloaded from iovs.arvojournals.org on 10/01/2021 No. 4 Reporrs 471

observations suggest that the site or mechanism for 2. Dolenek A: Beitrag zur Pupillographie. Ophthalmologica 139:77, the increased latency of pupillary light reflex and re- 1960. 3. Ishikawa S, Naito M, and Inaba K: A new videopupillography. duced visual acuity may be different. In addition, the Ophthalmologica (Basel) 160:248, 1970. delay of reaction times by psychophysical experi- 4. Kase M, Shintomi Y, and Hanada I: Studies of frequency response ments1 u2 was greater than that of the reflexes of pupil. characteristics on pupillary light reflex. Acta Soc Ophthalmol Thus, the in amblyopia has abnormal Jpn 84:1612, 1980. processings of higher integration centers as well as ret- 5. Yinon U, Jakoboritz L, and Auerbach E: The visual evoked response to stationary checkerboard patterns in children with inal macular region. strabismus amblyopia. Invest Ophthalmol 13:293, 1974. Key words: pupillary light reflex, functional amblyopia, 6. Schweitzer NMJ: Threshold measurements on the light reflex of the pupil in the dark adapted eye. Doc Ophthalmol 10:1, strabismic amblyopia, anisometropic amblyopia, infrared 1956. electropupillogram, long latency 7. Thompson HS: Afferent pupillary defects: pupillary findings as- Acknowledgments. The authors wish to thank Dr. H. Mat- sociated with defects of the afferent arm of the pupillary light suda of the Department of Ophthalmology, Hokkaido Uni- reflex arc. Am J Ophthalmol 62:860, 1966. versity, School of Medicine, and Dr. D. I. Hamasaki of Bas- 8. Ikeda H and Wright MJ: Is amblyopia due to inappropriate stimulation of "sustained" visual pathways during development? com Palmer Eye Institute, University of Miami for their Br J Ophthalmol 58:165, 1974. critical reading of the manuscript. 9. Levi DM: Patterned and unpatterned visual evoked responses From the Department of Ophthalmology, Hokkaido University in strabismus and anisometropic amblyopia. Am J Optom Phy- School of Medicine, Sapporo, 060, Japan. Submitted for publication: siolOpt 52:455, 1975. April 6, 1983. Reprint requests: Manabu Kase, Department of Oph- 10. Sokol S and Bloom B: Visually evoked cortical responses of thalmology, Hokkaido University, School of Medicine, Sapporo, amblyopes to a spatially alternating stimulus. Invest Ophthalmol 060, Japan. 12:936, 1973. 11. Ciuffreda KJ, Kenyon RV, and Stark L: Increased saccadic la- References tencies in amblyopic eyes. Invest Ophthalmol Vis Sci 17:697, 1978 1. Harms H: Ort und Wesen der Bildhemmung bei Schielenden. 12. Hamasaki DI and Flynn JT: Amblyopic eyes have longer reaction Albrecht von Graefes Arch Klin Ophthalmol 138:149, 1938. times. Invest Ophthalmol Vis Sci 21:846, 1981.

Palisade Endings in Human Extraocular Musdes

F. J. R. Richmond,* W. 5. W. Johnston,* R. S. Doker,t and M. J. SreinbochJ

The presence of nerve terminals in the tendinous insertions Much emphasis has been placed in the past 100 of human eye muscles was investigated histologically in adult years on a preeminent role for corollary discharge in human eye muscles obtained from donor eyes and in muscle the perception of eye position.1 However, some ex- pieces resected from juvenile patients undergoing surgical perimental findings do not support the view that cor- correction for strabismus. Lateral and medial recti, superior ollary discharge is the only element essential for eye and inferior oblique muscles from adults, were stained "en position sense.2"4 Recently, Steinbach and Smith5 have bloc" using a silver impregnation method. Numbers of nerve shown that patients who have undergone repeated ex- terminals were isolated that resembled "palisade endings" traocular muscle surgery have an altered ability to rec- previously described in other species. A single palisade ending ognize their eye position. Since the surgery removed usually appeared as an interwoven network of fine neural only small amounts of tissue near the global insertions filaments that cupped the inserting tip of a single extrafusal of eye muscles, the suggestion was made that sensory fiber. A collection of palisade endings on several neighboring muscle fibers were supplied by a single myelinated that receptors in the tendon might play a previously un- branched from a nerve bundle in the muscle mass. The pres- suspected role in proprioceptive processes. ence of nerve terminals at the distal musculotendinous in- Little is known about the sensory innervation at the terface of juvenile muscle also was observed when some re- musculotendinous interface of human eye muscles. In sected specimens of lateral and medial recti were sectioned many mammals, a rich supply of specialized terminals and stained using Holmes' silver method with a picrofuschin called "palisade endings" or "musculotendinous cyl- counterstain. No conventional Golgi tendon organs were seen. inders" is present at tendinous attachments of extra- Invest Ophthalmol Vis Sci 25:471-476, 1984 ocular muscles.6"8 The anatomic studies of Dogiel6

Downloaded from iovs.arvojournals.org on 10/01/2021