CYCLIC VERTICAL DEVIATION*

BY Henry S. Metz, MD AND (BY INVITATION) Steven S. Searl, MD

INTRODUCTION THE WORD CIRCADIAN IS DERIVED FROM THE LATIN "CIRCA DIEM" OR "ABOUT A DAY" and refers to the mysterious 24-hour rhythms which control all brain outputs-behavioral, autonomic, or neuroendocrine-of all animals or humans who live on earth with its 24-hour alternation of light and dark- ness.1 Circadian strabismus was reported as early as 1958,2 and although unusual, is not rare.3-8 Almost all of these patients have cyclic esotropia, although two vertical deviations have been described. Costenbader and Mousel4 reported a right hypertropia along with a right esotropia with a cyclic pattern and Windsor and Berg5 reported an individual with an acquired incomitant, vertical, cyclic tropia with diplopia. This deviation was noted following superficial trauma to the skin ofthe lid over the trochlea region. A vertical component has been noted in cyclic third nerve palsy,9",0 but this condi- tion demonstrates involvement ofthe medial rectus, levator and pupillary sphincter and ciliary muscles as well. A case is presented with acquired cyclic hypertropia and exotropia following craniofacial surgery, along with the management of this prob- lem.

CASE REPORT A 34-year-old Caucasian woman was seen with a complaint of vertical double vision every other day. Her history included craniofacial surgery for fronto-orbital fibrous dysplasia of the left side 13 months previously. Following this procedure, she had constant diplopia with a left hypertropia and exotropia. This persisted for 10 months and disappeared with single vision and no deviation. One month later, a cyclic vertical strabismus began spontaneously with a 48-hour cycle, 24 hours of *From the Department of Ophthalmology, University of Rochester School of Medicine and Dentistry, Rochester, New York. Supported in part by a grant from Research to Prevent Blindness. TR. AM. OPHTH. Soc. vol. LXXXII, 1984 Cyclic Vertical Deviation 159

FIGURE 1 Eyes orthophoric on "straight" day. orthophoria alternating with 24 hours of left hypertropia and diplopia. At the time of the initial examination, the cyclic pattern had been present for 9 weeks. Uncorrected vision was 20/20-2 in each eye. External and pupillary findings were both normal. The slit lamp, ocular tension, and ophthalmoscopic examinations were normal bilaterally. Cover testing revealed orthophoria at both distance and near fixation (Fig 1) and ocular rotations were full in each eye. The Worth -4 dot flashlight test indicated a fusion response at distance and near. The Titmus stereo test at near revealed 40 seconds of arc stereopsis. The following day, cover test measurements at distance were 20 prism diopters (A) of left hypertropia with 10 A of left exotropia. At near, there was 15 A of left hypertropia and 10 A of left exotropia (Fig 2). Rotations remained full. Sensory testing revealed a diplopia response and stereopsis could not be demonstrated. Surgery was planned on a day when the patient would be expected to be straight and the deviation was rechecked 1 day prior to surgery, a strabismic day. The left superior rectus was recessed 3 mm on an adjustable suture, the left inferior rectus resected 4 mm, and the right lateral rectus recessed 6 mm on an adjustable suture. The day after surgery (normally a strabismic day), the left superior rectus suture was advanced about 1 mm resulting in orthophoria by cover test. Both adjustable sutures were tied. 160 Metz

FIGURE 2 Left hypertropia and exotropia on strabismic, alternate day.

The patient has remained essentially orthophoric and free of diplopia for 10 months following surgery (Fig 3). On one occasion, she reported about 30 minutes of vertical diplopia after awakening, but this has not recurred. A small lid fissure discrepancy due to the fibrous dysplasia and subsequent craniofacial surgery persists, but is deemed acceptable.

DISCUSSION It has been estimated that about 1 in 3500 strabismic patients manifests a cyclic pattern.4 Helveston3 believes that circadian esotropes develop a constant deviation iffollowed for a sufficient length oftime, and that these patients are basically strabismic with cycles of remission rather than straight with periods of esotropia. We did not follow our patient a suffi- cient length oftime to see whether this would also have been true for this vertical cyclic pattern. Circadian esotropia has been reported following strabismus surgery for intermittent exotropia,6"11 and retinal detachment surgery.7 Our patient developed a cyclic pattern 10 months after craniofacial surgery, not stra- bismus surgery. Cyclic Vertical Deviation 161

FIGURE 3 Eyes orthophoric daily, 7 months following surgery (on a day the patient would have otherwise been deviated). Two studies of saccadic velocity on both the tropic and straight days have shown normal saccadic velocity-amplitude relationships.7'8 This sug- gests that ocular motor nerve dysfunction does not play a part in the etiology of these cyclic deviations. Windsor and Berg5 reported a patient with an incomitant cyclic hyper- tropia and exotropia immediately after trauma in the region of the troch- lea. Our patient's cyclic deviation was comitant, followed craniofacial surgery not trochlear trauma, and was delayed 10 months following sur- gery. Although the cause ofcircadian esotropia is not understood, strabismus surgery, planned to correct the deviation on the tropic day, invariably results in a "cure. "3,6,7,12-15 Surgery does not produce an overcorrection on the nonstrabismic day. The cyclic hypertropia reported, although only followed for 10 months, had done equally well following surgery, with an absence of symptomatic diplopia. In 1979, Knapp'6 reported two adults with cyclic hypertropia. He felt they both had evidence of thyroid ophthalmopathy and neither was asso- ciated with trauma or surgery. Surgery to correct the vertical deviation resulted in a straight eye position daily with a follow-up of 3 to 4 years. 162 Metz

SUMMARY A 34-year-old Caucasian woman underwent craniofacial surgery for fron- to-orbital fibrous dysplasia. She developed vertical diplopia for 10 months after surgery, which then disappeared for 1 month. The deviation re- turned with a circadian pattern, 24 hours of hypertropia and exotropia with diplopia alternating with 24 hours of straight eyes and fusion. Three months after the onset of this pattern, surgery was performed, resulting in straight eye position and fusion daily. The similarities to cyclic esotropia are discussed. The etiology ofcircad- ian strabismus remains unknown.

REFERENCES 1. Michener JA: Space. New York, Random House, 1982, p 784. 2. Burian HM: Round table discussion, in Allen JH (ed): Strabismus Ophthalmic Sym- posium I. St Louis, CV Mosby Co, 1958, pp 462-502. 3. Helveston EM: Cyclic strabismus. Am OrthoptJ 1973; 23:48-51. 4. Costenbader FD, Mousel DK: Cyclic esotropia. Arch Ophthalmol 1964; 71:180-181. 5. Windsor CE, Berg EF: Circadian heterotropia. Am J Ophthalmol 1969; 67:565-571. 6. Muchnick RS, Sanfilippo S, Dunlap E: Cyclic esotropia developing after strabismus surgery. Arch Ophthalmol 1976; 94:459-460. 7. Metz HS, Jampolsky A: Alternate day esotropia. J Pediatr Ophthalmol Strabismus 1979; 16:40-42. 8. Troost BT, Abel L, Noreika J, et al: Acquired cyclic esotropia in an adult. Am J Ophthalmol 1981; 91:8-13. 9. Lowenfeld IE, Thompson HS: Oculomotor paresis with cyclic spasms: A critical review of the literature and a new case. Surv Ophthalmol 1975; 20:81-124. 10. Clarke WN, Scott WE: Cyclic third nerve palsy. J Pediatr Ophthalmol 1975; 12:94-99. 11. Uemura Y, Tomita M, Tanaka Y: Consecutive cyclic esotropia. J Pediatr Ophthalmol 1977; 14:278-280. 12. Helveston EM: Surgical treatment of cyclic esotropia. Am Orthop J 1976; 26:87-88. 13. Hess JE: Cyclic esotropia-a case history. Am Orthop J 1974; 24:83-85. 14. Hiles D: Cyclic "V" esotropia. J Pediatr Ophthalmol 1973; 10:147-151. 15. Scoccianti L: Su di un caso di strabismo circadiano. Ann Ocul 1976; 102:11-18. 16. Knapp P: Special types of muscle anomalies associated with Grave' disease. Ophthal- mology 1979; 86:2081-2084.

DISCUSSION DR ARTHUR JAMPOLSKY. Doctor Metz has called our attention to a group of patients exhibiting unexplained, rhythmic changes in the amount of strabismus deviation. The importance of trying to understand possible mechanisms, and possible rela- tionship of diverse factors, is much greater than the mere curiosity of an unusual case to be added to the nontrivial rhythmic strabismus patients. I would like to attempt to relate some apparently unrelated facts that may be relevant to our understanding of these rhythmic deviations. Cyclic Vertical Deviation 163

We might start with the lowly amoeba and the heliotropic movements ofsimilar lower forms toward, and away from, light sources. Light stimuli induce motor tonus changes. Higher up the evolutionary scale, we find skin pigment spots that are especially sensitive to light detection. Such pigment collections later become invaginated and incorporated into our eye-cup. The presence of choroidal pig- ment in our visual system, and the absence of it as in enucleation, have direct hypothalamic-pituitary effects relative to our pigment regulatory mechanism. Ophthalmologists are well familiar with the effects of sympathetic ophthalmia and Harada's disease, in causing poliosis, vitiligo, and other widespread pigmentary changes. Such eye-pigment correlations with skin-pigment effects are seen in the ability of some animals to match their perceived environmental texture and color, with complex changes in their own skin pigment, to precisely match their envi- ronmental surroundings. There is a complex relationship among the factors of eye pigment, skin pigment, light/dark stimuli and rhythms, and muscle tonus, in- cluding eye muscle tonus changes. One cannot discuss light (wakefulness) and dark (sleep) effects upon motor tonus without implicating the factor ofattention. The state of attention in regulat- ing our eye muscle tonus, and in initiating our eye motor systems, has been well known since the time of Helmholtz. Ophthalmologists are again quite aware ofthe inattention which precipitates intermittent exotropia into a tropia, and the inat- tention that exacerbates dissociated vertical deviations. In recent years much has been learned about the state of alertness (attention-inattention) in relation to the reticular formation, and the brain stem. Here are the generators of rhythmic patterns, such as occur during sleep (REM), eye movements mediated by nonvis- ual cortex pathways. Another nonvisual cortex mediated eye movement is the unilateral exotropia (divergence) that frequently occurs subsequent to acquired poor vision in an eye (cataract, vitreous haze, etc). This exodeviation is the direct consequence of unequal inputs into the visual system, with a probable nonvisual cortex pathway, directly affecting muscle tonus (in, Symposium in Strabismus, Transactions of the New Orleans Academy of Ophthalmology, St Louis, CV Mosby Co, 1978; pp 358-492). One of the best examples of vertical eye muscle tonus being directly and quantitatively affected by the amount of light entering the eyes is the Bielschow- sky phenomenon. That is, with the dominant eye fixing, and the nondominant eye occluded, the latter will be driven downward by a gradual increase in darkening filters before the fixing eye. In other words, quantitatively decreasing the amount of light into the fixing eye, causes a predictable and quantitative change in the tonus of the eye muscles, such as to produce a quantitatively correlated hypo- tropia ofthe covered, nondominant eye. This is an unusual, direct, and repeatable observation, with important implications relative to Doctor Metz' case. Are the quantitative light-tonus changes of the Bielschowsky phenomenon related to the light/dark circadian rhythm quantitative changes in vertical eye muscle tonus changes (strabismic deviation changes)? 164 Metz

Every fisherman and hunter knows that light to darkness changes, and darkness to light changes, maximize the motor activity of fish and animals-and perhaps in humans, some rhythmic changes in eye muscle tonus. So it is, that our eye pigment and our skin pigment are related to changes in eye muscle tonus, which is also affected by changes in light input, light/dark cycles, and light input differences between the two eyes, with involvement of nonvisual cortex pathways, and the reticular system. Doctor Metz has called our attention to, and alerted us to, a nontrivial vertical deviation, with important theoretic and practical implications to our under- standing of strabismus and eye muscle tonus. I congratulate him upon arresting this interesting case, and for the courtesy ofsending me his paper far in advance of this meeting, and I thank the committee for the privilege of discussing it. DR STEWART WOLFF. I enjoyed Doctor Metz' paper very much. It brings to our attention this curious phenomenon that we have all seen. However, I don't think we should let the occasion escape some mention of its founder's name, the remarkable and still active, at 90 years, Curt Richter, whose life interest has been the pathophysiology of circadian rhythms. He has observed rhythms that occur every other day and thinks he might have seen a circadian mechanism operating every third day, although it would be rare. Four or more days, which has been reported in the literature, is probably not to be believed. Doctor Richter's atten- tion was brought to this phenomenon initially by a psychiatric patient who was schizophrenic every other day and just as sound as she could be on the day in between. In trying to find the origin ofcircadian mechanisms, Doctor Richter has worked with rats an other animals. Despite loss of vision, hearing and even after decortication, the circadian mechanism still exists. He believes the locus of the circadian mechanism to be in the ventral hypothalamus. There is other evidence that the center for circadian activity resides in the suprachiasmatic nuclei. In this interesting paper, two cases are mentioned-one reported and one culled from the literature. Both followed trauma. One wonders what the difference is be- tween cases that follow trauma and those that are apparently spontaneous. Mean- while, we still look for the source of this very interesting clinical phenomenon and, thanks to Doctor Metz' interesting paper, may be a little closer. DR ROBERT C. DREWS. Doctor Wolff's discussion has been very interesting to me. In keepinig with the Latin derivation of the term "circadian," it seems to me that the rhythm described in these cyclic squints occurring in a 48- rather than 24-hour cycle should be properly termed "bi-circadian." DR HENRY METZ. The first comment is related to Doctor Jampolsky's remarks. We should recognize that there may be a central cause or mechanism. Studies done on patients with circadian strabismus comparing their electroencephalogram on the deviated and the straight day show no differences. Saccadic velocities have been measured on consecutive days and are unchanged. Treatment with barbitu- rates has not altered the pattern. Cyclic Vertical Deviation 165

Of interest is a recent article in Investigative Ophthalmology (1984; 25:539) reporting a circadian pattern of retinomotor movements (position changes in the photoreceptors and RPE) in the green sunfish. It was found that cones undergo retinomotor movements not regulated by light/dark or temperature cycles, but by its own innate rhythm. I agree with Doctor Drews that the patient presented has a bi-circadian pat- tern.