Sleep disorders in children with congenital anophthalmia and microphthalmia

Sleep Disorders in Children with Congenital Anophthalmia and Microphthalmia B r a d l e y V. Davitt, M D , a C h a r l e s M o r g a n , M D , b a n d O s c a r A. C r u z , M D a

Purpose: The increased incidence of sleep disorders among blind patients has been documented in the sleep medicine literature. Blind patients lack the normal regulatory control of retinal input over their circadian rhythms, which can lead to abnormalities in their sleep-wake cycles. Our study was conducted to determine the incidence of sleep disorders in children with anophthalmia or microphthalmia and to offer therapeutic alternatives. Methotls:A 13-question survey was distributed to families of children with anophthalmia, microphthalmia, or both identified through the Anophthalmia/Microphthalmia Registry in Philadelphia, Pennsylvania. The survey included questions regarding the children's medical and ocular histories and any sleep disorders they may have experienced. Questions regarding daily schedules, family history, and social history were also included. Results:Surveyswere returned from 13 children with bilateral anophthalmia or microphthalmia. Ten of 13 (77%) anophthalmic/microphthalmic children were reported to have frequent early-morning waking and extensive daytime sleeping. Specific medical and social problems did not appear to be associated with the development ofthese sleep disorders. Strict daily schedules were often helpful in entraining the children's sleep-wake cycles. (',onclusion:Withoutthe contribution of retinal inputto help regulate circadian rhythms, most children with bilateral anophthalmia or microphthalmia will experience sleep disorders. These children may benefit from the introduction of strict daily schedules, medical therapy (melatonin), or both. An attempt should also be made to preserve any existing light perception. (J AAPOS 1997;2:151-3)

tudies in sleep medicine have described a high incidence of sleep disorders among blind patients. 1-5 In the endocrinology literature, blind patients have also been shown to have circadian rhythm abnormalities. 6 Although circadian rhythms can be entrained by nonphotic signals, such as activity cycles, feeding schedules, and social interactions, retinal input may be the most important variable in the synchronization of the circadian rhythm with light-dark cycles. Without such cues, the sleep cycles of some patients shift approximately 1 hour per day, periodically causing them to be awake at night and sleep during the day. This free-running sleep-wake cycle occurs because the endogenous circadian rhythm of humans approaches 25 hours. Patients who are blind from anophthalmia and microphthalmia might therefore be expected to have sleep disorders. T o date, however, no such relationship between bilateral congenital blindness and

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From the Departments of Ophthalmology and Pediatrics, St. Louis University School of Medicine, St. Louis, Missouri, ~and the Deparement of Ophthahnology, Manhattan Eye, Ear, and Throat Hospital, New York, New York. b Presented as a poster at the 23rd Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus, Charleston, South Carolina, April 2-6, 1997. Reprint requests: Bradley V. Davitt, MD, Cardinal Glennon Children's Hospital, 1465 S. Grand Blvd., St. Lozds, MO 63104. Copyright © 1997 by the Arlzev'loanAssodationj~r Pediatric Ophthalmology and Strabismus. 1091-8531/97/$5.00 + 0 75/1/83847

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sleep disorders has been reported in the ophthalmologic literature. We report a series that is the first to address sleep disorders exclusively in those patients with anophthalmia or microphthalmia. METHODS Patients with bilateral congenital anophthalmia, microphthalmia, or both were located through the Anophthalmia/Microphthalmia Registry in Philadelphia, Pennsylvania. T o ens.ure patient-parent confidentiality, a 13question survey was sent to and distributed to these patients' families by the Registry. Although these families were asked to complete the survey and to contact the authors with follow-up if desired, at no time did the authors directly contact the families. The survey inquired about specific ocular diagnosis, age, and visual acuity. Several questions were designed not only to identify a sleep disorder but also to highlight those factors that may have influenced the problem, such as the child's ease of settling, general health status, family problems, and the child's inherent fears. The respondents were also asked for a description of a daily schedule, if one was implemented. In addition, if other children were in the family, the respondents were asked to report any of their developmental or medical problems and any sleeping pattern problems. The surveys were returned, carefully and consistently reviewed by one examiner (C. M.), and recorded. September 1997 I ~ I

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Table 1. Summaryof surveyresults Patient No. Vision Age 1 2 3 4 5 6 7 8 9 10 11 12 13

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NLP OU LP OD, NLP OS NLP OU NLP OU NLP OU NLP OU NLP OU NLP OU NLP OU NLP OU NLP 0U NLP 0D, LP OS NLP 0U

6 yr 3 yr 1 yr 4 yr 14 mo 8 yr 4.5 yr 4 yr 8 mo 8 yr 4.5 yr 3 yr 11 yr

Diagnosis

Sleep problem

Change with regimen

Medical diagnosis

Sibling/ sleep problem

Yes Yes Yes Yes Yes No Yes Yes No Yes Yes Yes No

Yes Yes Yes Yes Yes NA Yes Yes NA Yes Yes Yes NA

Apnea None None None None None None None None None None None None

Yes/no Yes/no Yes/no NA Yes/no Yes/no Yes/no NA NA Yes/no Yes/no Yes/no NA

A,A M,A M,A A,A A,A A,A A,A M,M M,A M,M M,A M,A A,A

A, Anophthalmos;M, microphthalmos.

RESULTS Of the 18 surveys distributed by the Anophthalmia/ Microphthalmia Registry, 14 were returned. One patient was excluded from the study because she had unilateral microphthalmia with normal vision in the fellow eye. The survey results are summarized in Table 1. Forty-six percent of the respondents carried the diagnosis of bilateral anophthalmia, and 15 % had bilateral microphthalmia. The remaining 39% were microphthalmic in one eye and anophthalmic in the other. The average age of the patients at the time of the survey response was 4.5 years, with 62 % being male. Seventy-seven percent reported that their anophthalmic/ microphthalmic children suffered from a sleep disturbance. Health status, inherent fears, family crisis, and parental presence at bedtime did not appear to significantly influence these sleep disorders. A free-nmning sleep-wake cycle sleep disorder had already been diagnosed in one patient. All these families indicated frequent or prolonged early-morning waking, or both, and extensive daytime sleeping. Only one patient had an additional medical diagnosis. Sleep apnea had been diagnosed in this patient, but it was reportedly not an active problem. No other families reported additional medical or behavioral problems, such as autism, attention deficit disorder with hyperactivity, oppositional defiant disorder, or regulatory disorders. All the families who reported sleep problems instituted a strict daily schedule with their children. All reported significant improvement in their children's sleep-wake cycle but acknowledged relapses if the new regimen was abandoned. The sleeping problems were observed by the families immediately after birth in those children affected. The average age at the time that schedules were implemented was 1 year. DISCUSSION The entity of sleep is not completely understood. It is a delicately balanced process controlled through coordination of several neuronal systems. The eye, and specifically the

retina, is known to play a role in the regulation of sleep. Projections from the retina have been demonstrated to extend to the hypothalamus, where the circadian pacemaker is located in the suprachiasmatic nucleus.6,7 Therefore, in addition to providing visual imaging, the photosensory system also provides photic input to the suprachiasmatic nucleus to synchronize (entrain) circadian rhythms to a precise 24-hour period coordinated with the solar light-dark cycle? Although there are contributions from nonphotic signals, such as social cues, clocks, regular mealtimes, activity cycles, and work obligations, retinal interaction with the hypothalamus may be the most important variable in the synchronization of the circadian rhythm with lightdark cycles. Congenitally blind patients have been shown to have abnormalities in the circadian rhythm regulation of sleep, body temperature, alertness, performance, cortisol secretion, and urinary electrolyte excretion. 9,1°Insufficient or ill-timed exposure to light has been implicated in a number of clinical syndromes, including winter depression, shift work maladaptation syndrome, and jet lag. H Although some blind individuals appear to be entrained by nonvisual cues, others exhibit circadian rhythm abnormalities. Many patients appear to be continually free-running, so that sometimes their sleep-wake activity cycles will be in accord with their environment, but at other times they are out of phase. 11This was found in one of our patients. Miles et al. '° reported such a patient who, blind from birth as a result of retrolental fibroplasia, was found to have circadian rhythms that were desynchronized to a 24.9-hour period. At least one third of blind people with free-nmning circadian rhythms are believed to have a sleep disorder that is actually caused by their underlying rhythm abnormality? Forty percent to 76% of blind people have a high incidence of sleep complaints, with some having intractable sleep disorders, suggesting that circadian disruption may be at fault. 2-s'1°Their complaints include an inability to fall asleep at the desired clock time, frequent nighttime

aTou,xal ofAAPOS Volume 1 Number 3 September 1997 awakenings, excessive daytime sleepiness, and multiple naps. Sasaki et al. s surveyed 74 subjects at a boarding school for the blind with ages ranging from 13 to 18 years; 59.7% of the subjects with no light perception vision had sleepwaking disorders in contrast to 32.5% of the subjects who were characterized as having low vision. Possible therapeutic approaches to treating sleep disorders in children with anophthalmia or microphthalmia include developing social cues for entrainment, chemotherapeutic agents (such as melatonin), and promoting or restoring even trace amounts of vision. Further therapeutic research should include developing nonphotic social methods for entrainment of underlying circadian rhythms. 6 As has been observed elsewhere, our study confirms that strict daily schedules are helpful in the entrainment of blind children who exhibit sleep disorders more frequently than partially sighted or fully sighted children. 12,I3 Admittedly, families may have difficulty enforcing these schedules over prolonged periods, and some blind children may be unresponsive to them. Patients who are both blind and mentally retarded may have particular difficulty perceMng social cues related to normal sleep-wake rhythms. 2 For some blind patients with sleep disorders, medical therapy may prove helpful. Melatonin has been given on an experimental basis to blind people with sleep difficulties related to delayed ffee-nmning sleep-wake cycles.14asMelatonin is secreted by the pineal gland when it is stimulated by retinohypothalamic projections. It fimctions as a hormonal signal regarding the length of the night or darkness. It has been helpful in some patients to stabilize the timing of sleep onset and to entrain the sleep-wake cycle to a normal 24-hour period. 1>~8Espezel et al. 19specifically used melatonin in the treatment of visually impaired children with sleep disorders. In addition to experiencing relief from sleep disorders, children who received melatonin were often more alert and sociable and showed developmental gains. Substantial social, psychologic, and economic benefits to the children's families were also noted. Light perception is very important and possibly essential for the normal regulation of the human circadian pacemaker, but the quantity of light needed may be very small. Sack et al. 6 reported a subject who was subjectively blind but had reactive pupils and who had entrainment of his sleep pattern. Patients like this provide evidence that the retinohypothalamic system may remain functional in some cases of "total blindness." It also suggests that the level of light needed for entrainment may be quite low. T h e question has been raised as to whether the low functional visual outcome attained by surgery in some cases of stage V retinopathy of prematurity contributes sufficiently to the patient's overall quality of life to justify the cost of an extensive surgical procedure, z° Often these patients achieve "anatomic success" but have no better than light perception vision. Sadun et al. 7 have suggested that restoring any

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visual input may have significant impact on the overall well-being of the child in a manner unrelated to the meager improvement i~L visual function. Indeed, a well-adjusted sleep-wake schedule may be critically important to maximizing the potential for attention, learning, and performance of a child blinded from anophthalmia or microphthalmia.

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2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13. 14. 15. 16. 17. 18. 19. 20.

References KleinT, Martens H, Dijk DJ, et al. Circadiansleepregulationin the absence of fight perception: chronic non-24-hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule. Sleep 1993;16:333-43. OkawaM, NanamiT, Wada S, et al. Four congenitallyblind children with circadiansleep-wakerhythm disorder. Sleep 1987;10:101-10. MilesLE, Wilson MA. High incidenceof cyclicsleep/wakedisorders in the blind [abstract].SleepRes 1977;6:192. Martens H, Endlieh H, Hildebrandt G, Moog R. Sleep/wake distribution in blind subjects with and without sleep comt~laints [abstract]. SleepRes 1990;19:398. Sasaki H, Nakata H, Murakami S, et al. Circadian sleep-waking rhythm disturbance in blind adolescence. Jpn J Psych Neurol 1992;46:209. Sack RL, LewyAJ, BloodML, Keith LD, Nakagawa H. Circadian rhythm abnormalities in totally blind people: incidenceand clinical significance.J Clin EndocrinolMetab 1992;75:127-34. SadunAA,Johnson BM, SchaechterJ.Neuroanatomyof the human visual system,Part 1II: three retinal projectionsto the hypothalamus. Neuro-Ophthalmol 1986;6:371-9. Moore RY, Lenn NJ. A retinohypothalamicprojection in the rat. J Comp Neurol 1972;146:1-14. Sack RL, Lewy AJ. Abstract. Trans Soc Res Biol Rhythms 1988;1:94a. Miles LE, Raynal DM, Wilson MA. Blind man living in normal societyhas circadianrhythms of 24.9 hours. Science1977;198:421-3. Moore RY. Disorders of circadian function and human circadian timing system. In: Klein DC, Moore RY, Reppert SM, eds. Snprachiasmatic nucleus: the minds' clock. New York: Oxford UniversityPress; 1991. p. 429-41. Tr6ster H, BrambringM, van der BurgJ. Sleepdisordersin visually handicapped children. Prax Kinderpsychol Kinderpsychiat 1995;44:36-44. MindellJA, Goldberg R, Fry JM. Treatment of a circadianrhythm disturbancein a 2-year-oldblindchild.J Vis ImpairBlind 1996;2:162-6. LapierreO, DumontM. Melatonintreatmentofa non-24-hoursleepwake cyclein a bfindretarded child. BiolPsychol1995;38:119-22. Sack RL, LewyAJ, Blood ML, et al. Melatonin administration to blind people: phase advances and entrainment. J Biol Rhythms 1991;6:249-61. FolkardS,ArendtJ, AldhousM, et al. Melatoninstabifizessleeponset time in a blind man without entrainment of cortisolor temperature rhythms. Neurosci Lett 1990;113:193-8. SarrafzadehA, Wirz-JustieeA, ArendtJ, et al. Melatonin stabilizes sleep onset in a blind man. Sleep 1990;13:51-4. Palm L, Blennow G, Wetterberg L. Correction of non 24-hour sleep/wake cycleby melatonin in a blind retarded boy. Ann Nenrol 1991;29:336-9. BrodskyMC. The apparentlyblind infant. In: BrodskyMC, Baker RS, Hamed LM, eds. Pediatric neuro-ophthalmology.New York: Springer-Verlag; 1996. p. 1-41. EspezelH, JanJE, O'DormellME, Milner R. The use ofmelatonin to treat sleep-wake-rhythmdisorders in children who are visually impaired.J Vis Impair Blind 1996;1:43-50.