- Email: [email protected]
Optic neuropathy associated with sleep apnea syndrome
Optic Neuropathy Apnea Syndrome Daniel S. Mojon,
MD,’ Johannes Mathis, W. Hess, MD2
Christian
Associated with Sleep MD,2 Mario Zulauf, MD,3
Fritz Koerner, MD,’
Objective: The study aimed to determine ocular abnormalities in sleep apnea syndrome @AS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. Design: The study design was a case series. Participants: Nine patients referred for evaluation of suspected SAS participated. Intervention: Complete ophthalmologic examination, including computerized perimetry, was performed. Main Outcome Measures: Correlations between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and to grade SAS, and visual field indices using the Spearman rank correlation coefficient (rs) were measured. Results: One patient was excluded from the statistical analysis because of optic nerve drusen with constricted visual fields, another because of tilted discs with corresponding temporal visual field defects. All three patients with severe SAS and one patient with moderate SAS had relative nasal arcuate visual field defects; two patients with severe SAS also had paracentral relative defects. One patient with normal polysomnographic result and two patients with mild or moderate SAS had normal visual fields. The RDI correlated positively with the mean visual field defect (r, = 0.81, P < 0.05) and with the visual field loss variance (rs = 0.78, P < 0.05). The clinical ophthalmologic examination results were normal in all seven patients. In two of the three patients with severe SAS treated with continuous positive airway pressure (CPAP), visual field defects remained stable over 18 months. The patient with optic nerve drusen also had severe SAS and was, therefore, treated with CPAP. His constricted visual fields improved dramatically after treatment. Conclusions: Visual fields of patients with SAS showed defects consistent with an optic neuropathy. The CPAP therapy seems to stabilize or even reverse visual field defects. Ophthalmology 7998; 1052374477
Sleep apnea syndrome (SAS) is a disease characterized by recurrent complete or partial upper airway obstructions during sleep.1,2 These obstructive respiratory disturbances may last from 10 seconds up to 2 minutes, leading to severe hypoxia and hypercapnia. Obstructions are terminated only after arousal from sleep, when upper airway muscle tone increases. Several hundreds of respiratory disturbances may occur during one night and cause severe sleep disruption with consequential daytime sleepiness. Typically, middle-aged and older, obese men with a longlasting history of loud snoring are affected.3 The repetitive sympathetic activation during arousal from sleep may cause serious cardiac arrhythmias and
Originally Revision
received: May 2, 1997. accepted: October 17, 1997.
’ Department
of Ophthalmology,
* Department
of Neurology,
3 Department land.
of Ophthalmology,
University University
of Bern, Bern, Switzerland.
of Bern,
University
Bern,
Switzerland.
of Basel,
Presented in part at the Annual Meeting of the American Ophthalmology, Chicago, October, 1996. Reprint requests to Daniel S. Mojon, ogy, University of Bern, Inselspital,
874
Base],
Switzer-
Academy
MD, Department of OphthalmolCH-3010 Bern, Switzerland.
of
systemic hypertension. Such patients often show pulmonary-arterial hypertension, car pulmonale, and, in severe forms, polycythemia. Sleep apnea syndrome now is recognized as an important risk factor for cardiovascular and neurovascular diseases.’ Sleep apnea syndrome usually is diagnosed by overnight polysomnography (PSG), including simultaneous recording of electroencephalography, electromyogram, electro-oculogram, electrocardiogram, oxymetry, chest excursions, and air flow through the mouth and nose. From the polysomnographic data, the respiratory disturbance index (RDI) is calculated, a value often used to diagnose and grade SAS. The treatment of first choice to prevent upper airway obstructions is the application of nasal continuous positive airway pressure (CPAP) with a mask during sleep.’ Ophthalmologic findings in patients with SAS include floppy eyelid syndrome4 and keratoconus.5 In a case report, optic disc edema has been associated with SAS.6 Recently, Hayreh’ described patients with anterior ischemit optic neuropathy with a high prevalence of SAS. In the current study, we performed ophthalmologic examinations (including computerized perimetry) in patients referred for suspected SAS and correlated the visual field defects with the RDIs determined during all night sleep.
Mojon et al * Optic Neuropathy
Methods Subjects We included nine patients consecutively admitted for SAS evaluation at the University Hospital of Bern after informed consent was obtained. The protocol and informed consent were approved by the Ethical Committee of the Medical Faculty of the University of Bern, Bern, Switzerland. We excluded from statistical analysis all patients with conditions causing visual field defects.
Ophthalmologic
Examination
Visual Field Data Analysis For each patient, the mean defect (MD) and loss variance (LV) were calculated by averaging values from both eyes. A visual field test was considered reliable if false-positive and falsenegative answers were less than 15%.”
Neurologic,
and Laboratory
Examination
In addition to a general physical examination, including blood pressure measurement, complete blood count, chemical profile, and fasting blood glucose, a neurologic examination was performed.
Sleep Studies Overnight PSG was recorded during at least 6 hours, beginning at 10:00 PM, in a quiet, custom-built sleep laboratory. Recordings were done with a Neurofax encephalograph (Nihon Khoden, Tokyo, Japan), including electroencephalography (C4Al and Ol-A2 according to the lo-20 electroencephalogram system), electro-oculography (horizontal and vertical), electromyography (submental and anterior tibia1 muscle right and left), and nasal and oral airflow by thermistors. Simultaneously, inductive plethysmography (chest, abdomen, and sum) was measured by using a Respitrace Model 150 (Ambulatory Monitoring, Inc., Ardsley, NY), and oxygen saturation was measured with an Ohmeda Biox 3700 pulse oxymeter (Ohmeda, Inc., Louisville, CO).
Polysomnographic
ments, Madison, WI). The automatic analysis was observed on the computer screen and corrected when necessary. Sleep apnea syndrome was diagnosed and graded according to the RDI: normal RDI, less than 10; mild SAS, 10 greater than RDI less than 20; moderate SAS, 20 greater than RDI less than 40; and severe SAS, RDI greater than 40.’
Statistical
Analysis
Correlation between RDI and MD or LV was calculated using the Spearman rank correlation coefficient (0”
Results
All patients were seen by the same ophthalmologist (DM). At the time of the ophthalmologic examination, the result of the work-up for SAS by oxymetry and PSG was unknown. A complete medical history was taken. Clinical ophthalmologic examinations included best visual acuity, applanation tonometry, slitlamp visualization of the anterior eye segment, including gonioscopy, fundus examination in mydriasis with three-mirror gonioscope, and stereophotography of optic nerve head. Octopus computerized perimetry was performed using the Glaucoma Program Gl by two experienced perimetrists. Patient alertness was checked on a video screen during the whole examination. Patients with abnormal visual fields had diurnal eye pressure curve and blood-cell velocity measurements in the nailfold capillaries after cold provocation.8
General,
with SAS
Data Analysis
The raw data were stored on a personal computer and analyzed offline with sleep analysis software (UltraSom, Nicolet Instru-
The clinical and polysomnographic data of the seven patients included in the statistical analysis are summarized in Table 1. According to the RDI, one patient had mild SAS, two patients had moderate SAS, and three patients had severe SAS. One patient referred for suspected SAS had a normal PSG. His final diagnosis was chronic fatigue syndrome. One patient with severe SAS was excluded from our statistical analysis because of optic nerve drusen. Another patient with normal PSG was excluded because of tilted disks associated with high cornea1 astigmatism and bitemporal visual field defects. All three patients with severe SAS and one patient with moderate SAS (patient 5) had relative nasal arcuate defects. The two most severe cases (patients 1 and 2) also had paracentral relative defects. One patient with normal PSG and two patients with mild or moderate SAS had normal visual fields. The number of RDIs during night sleep correlated positively with the mean visual field defect (Fig 1, r, = 0.8 1, P < 0.05) and with the visual field LV (Fig 2, rr = 0.78, P < 0.05). The diurnal curve and the measurement of blood-cell velocity in the nailfold capillaries after cold provocation were normal in all patients, and false-positive and false-negative answers during perimetry were less than 15%. In two patients with severe SAS, visual field defects remained unchanged over 18 months. The 50-year-old man excluded from statistical analysis because of optic nerve drusen had constricted visual fields and markedly narrowed retinal arteries in each eye. He reported having lost his side vision over the past year. A magnetic resonance image brain scan was normal. He was treated with CPAP because of severe SAS. His visual fields improved subjectively and objectively dramatically after CPAP treatment (MD before treatment in the right eye was 19.8 and in the left eye was 18.9; MD after treatment in the right eye was 6.7 and in the left eye was 6.4). In conclusion, SAS is a frequent breathing disorder caused by intermittent upper airway obstruction during sleep and concurrent hypoxia, negative intrathoracic pressure, and sympathetic activation. Because airway obstructions are terminated by an arousal reaction, normal sleep is disrupted. Long-term cardiovascular sequelae and complications include pulmonary and systemic arterial hypertension, cardiac arrhythmias, myocardial infarction, and stroke.’ Recently, Hayreh7 reported several patients with anterior ischemic optic neuropathy having a history of SAS. In the current study, visual fields of patients with SAS showed relative arcuate nasal and paracentral defects consistent with an optic neuropathy. Generalized visual field depressions, frequently observed with inattentiveness, were not observed. The MD and LV correlated positively with the RDI (Figs 1,2). The reliability parameters, false-positive and false-negative answers, and the comments of the perimetrists on patient performance indicate
87.5
Ophthalmology Table 1. Clinical
Volume
and Polysomnographic
10.5, Number 5, May 1998 Data of Sleep Apnea Syndrome Suspects Polysomnographic Data
Case No.
Age (yrs)
Sex
History of Other Diseases Hypertension, chronic ohstrucnve pulmonary &ease BronchIal asthma, ulcer None Coronary heart disease, hypercholestermem~a None BronchIal asthma, hypcrcholesterinemla, hypertension Dlahetes mellitus, tinmtus
1
61
M
2 3 4
55 42 58
M M M
5 6
50 53
M M
7
54
M
Desaturation Index (N/hr)
Mean O1 Value (%)
SAS Cfmficatlon
73
100
71
23
SWSre
70 70 31
91 56 18
78 85 94
30 57 89
Sevcrr Severe Moderate
24 12
25 3
85 93
41 81
M&rate Mtld
2
0
94
86
Normal
RDI = respiratory dlsturhance index; N/hr = number of events per hour.
that visual field defects were not caused by decreased attention. This is essential in patients with SAS because of possible daytime sleepiness and impaired attention. Two patients with severe SAS treated with CPAP were observed over 18 months. Visual field defects remained unchanged, indicating a permanent lesion. It might be that further visual field deterioration was prevented by CPAP therapy. Because of the observational character of our study, we can only conclude that an association between SAS and visual field defects exists. Our data do not allow any conclusion about a direct causal relationship between SAS and visual field defects. In particular, we cannot exclude a third factor influencing both SAS and visual fields.‘” The cardiovascular responses to hypoxemia are complex and differ depending on whether hypoxemia develops during apnea with hypercapnia or during hyperventilation with hypocapnia. In the latter situation (e.g., at high altitudes), the systemic circulation responds to hypoxemia with vasodilation and with increased heart rate and cardiac output to maintain blood pressure and oxygen delivery to the peripheral tissues. In contrast, voluntary breath holding or apnea results in peripheral vasoconstriction, bradycardia, and decreased cardiac output with regional vasodilation of the cerebral and myocardial circulations to preserve oxygen delivery to these critical organs.” This difference
might explain the lack of funduscopic findings associated with other hypoxic conditions, such as altitude illnessI and respiratory insufficiency.‘j If we hypothesize that SAS causes the optic neuropathy, the damage may result from impaired optic nerve head blood flow autoregulation,14 secondary to repetitive prolonged apneas. Alternatively, optic nerve vascular dysregulation might be secondary to SAS-induced arterial hypertension and arteriosclerosis7.‘5 or imbalance between nitric oxide (a vasodilator) and endothelin (a vasoconstrictor).‘5 Repetitive prolonged hypoxia also might directly damage the optic nerve. Because of the large stores of carbon dioxide and excellent buffering capacity of our body, changes in PaC02 and pH during apneas remain modest in contrast to changes in PaO, and seem, therefore, not to be harmful.” Episodic increased intracranial pressure has been reported in patients with SAS’” and is thought to be responsible in one patient with SAS for bilateral optic disc edema resolving after permanent tracheotomy.6 Recently, in patients with SAS, platelet activation normalizing after CPAP treatment was found.” Therefore, optic neuropathy also might be secondary microinfarcts in the optic nerve. Interestingly, the visual field defects of one patient with optic nerve drusen improved dramatically subjectively and objectively after CPAP therapy. In a number of anecdotal oral case reports, pseudotumor
1
2 .
35 -
.
1 .
30 25 -
2MD
3 .
5 .
7
20 LW 15 :
0-O 4 .
6 -2 -4 -c 0
3 .
l
IO
20
30
40
50
60
70
80
RDI Figure 1. Respiratory disturbance Index versus visual held mean defect.
876
2 .
0
10
20
30
40
50
60
70
80
RDI Figure 2. Respmtory disturbance index vcrbus visual field loss varlancc.
Mojon et al * Optic Neuropathy cerebri has been found in association with SAS. In this case, papilledema has improved with CPAP treatment. Some of our patients also might have suffered from papilledema, which had resolved at the time of our examination. Because of the small sample size of our study, larger series are needed to confirm our findings and to better understand the association between SAS and visual field defects.
8. 9. 10.
References 1. Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndromes. In: Guilleminault C, Dement WC, eds. Sleep Apnea Syndromes. New York: A. R. Liss, 1978; 1- 12. (Kroc Foundation series; v. II.) 2. Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine, 2nd ed. Philadelphia: Saunders, 1994;667-77. 3. Douglass AB, Bornstein R, Nino-Murcia G, et al. The Sleep Disorders Questionnaire I: creation and multivariate structure of SDQ. Sleep 1994; 17:160-7. 4. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am J Ophthalmol 1981;92:568-75. 5. Culbertson WW, Tseng SC. Cornea1 disorders in floppy eyelid syndrome. Cornea 1994; 13:33 -42. 6. Bucci FA Jr, Krohel GB. Optic nerve swelling secondary to the obstructive sleep apnea syndrome. Am J Ophthalmol 1988; 105:428-30. 7. Hayreh SS. Acute ischemic disorders of the optic nerve.
11. 12. 13. 14. 15. 16.
17.
with
SAS
Pathogenesis, clinical manifestations, and management. Ophthalmol Clin North Am 1996; 9:407-42. Gasser P, Flammer J. Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma. Am J Ophthalmol 1991; 111:585-8. Zulauf M, Caprioli J, Boeglin RJ, Lee M. Number of stimuli as a reliability parameter in perimetry. Ger J Ophthalmol 1992; 1:86-90. Glantz SA. Primer of biostatistics, 3rd ed. New York: McGraw Hill, 1992;242-3, 262-3. Parish JM, Shepard JW Jr. Cardiovascular effects of sleep disorders. Chest 1990; 97: 1220-6. Wiedman M. High altitude retinal hemorrhage. Arch Ophthalmol 1975;93:401-3. Spalter HF. Bruce GM. Ocular changes in pulmonary insufficiency. Trans Am Acad Ophthalmol Otolaryngol 1964;68: 661-76. Hayreh SS. The 1994 Von Sallman Lecture. The optic nerve head circulation in health and disease. Exp Eye Res 1995;61:259-72. Luscher TF. The endothelium and cardiovascular diseasea complex relation [editorial]. N Engl J Med 1994;330: 1081-3. Sugita Y, Iijima S, Teshima Y, et al. Marked episodic elevation of cerebrospinal fluid pressure during nocturnal sleep in patients with sleep apnea hypersomnia syndrome. Electroencephalogr Clin Neurophysiol 1985;60:214-9. Bokinsky G, Miller M, Ault K, et al. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation. Chest 1995; 108:625-30.
877
MD,’ Johannes Mathis, W. Hess, MD2
Christian
Associated with Sleep MD,2 Mario Zulauf, MD,3
Fritz Koerner, MD,’
Objective: The study aimed to determine ocular abnormalities in sleep apnea syndrome @AS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. Design: The study design was a case series. Participants: Nine patients referred for evaluation of suspected SAS participated. Intervention: Complete ophthalmologic examination, including computerized perimetry, was performed. Main Outcome Measures: Correlations between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and to grade SAS, and visual field indices using the Spearman rank correlation coefficient (rs) were measured. Results: One patient was excluded from the statistical analysis because of optic nerve drusen with constricted visual fields, another because of tilted discs with corresponding temporal visual field defects. All three patients with severe SAS and one patient with moderate SAS had relative nasal arcuate visual field defects; two patients with severe SAS also had paracentral relative defects. One patient with normal polysomnographic result and two patients with mild or moderate SAS had normal visual fields. The RDI correlated positively with the mean visual field defect (r, = 0.81, P < 0.05) and with the visual field loss variance (rs = 0.78, P < 0.05). The clinical ophthalmologic examination results were normal in all seven patients. In two of the three patients with severe SAS treated with continuous positive airway pressure (CPAP), visual field defects remained stable over 18 months. The patient with optic nerve drusen also had severe SAS and was, therefore, treated with CPAP. His constricted visual fields improved dramatically after treatment. Conclusions: Visual fields of patients with SAS showed defects consistent with an optic neuropathy. The CPAP therapy seems to stabilize or even reverse visual field defects. Ophthalmology 7998; 1052374477
Sleep apnea syndrome (SAS) is a disease characterized by recurrent complete or partial upper airway obstructions during sleep.1,2 These obstructive respiratory disturbances may last from 10 seconds up to 2 minutes, leading to severe hypoxia and hypercapnia. Obstructions are terminated only after arousal from sleep, when upper airway muscle tone increases. Several hundreds of respiratory disturbances may occur during one night and cause severe sleep disruption with consequential daytime sleepiness. Typically, middle-aged and older, obese men with a longlasting history of loud snoring are affected.3 The repetitive sympathetic activation during arousal from sleep may cause serious cardiac arrhythmias and
Originally Revision
received: May 2, 1997. accepted: October 17, 1997.
’ Department
of Ophthalmology,
* Department
of Neurology,
3 Department land.
of Ophthalmology,
University University
of Bern, Bern, Switzerland.
of Bern,
University
Bern,
Switzerland.
of Basel,
Presented in part at the Annual Meeting of the American Ophthalmology, Chicago, October, 1996. Reprint requests to Daniel S. Mojon, ogy, University of Bern, Inselspital,
874
Base],
Switzer-
Academy
MD, Department of OphthalmolCH-3010 Bern, Switzerland.
of
systemic hypertension. Such patients often show pulmonary-arterial hypertension, car pulmonale, and, in severe forms, polycythemia. Sleep apnea syndrome now is recognized as an important risk factor for cardiovascular and neurovascular diseases.’ Sleep apnea syndrome usually is diagnosed by overnight polysomnography (PSG), including simultaneous recording of electroencephalography, electromyogram, electro-oculogram, electrocardiogram, oxymetry, chest excursions, and air flow through the mouth and nose. From the polysomnographic data, the respiratory disturbance index (RDI) is calculated, a value often used to diagnose and grade SAS. The treatment of first choice to prevent upper airway obstructions is the application of nasal continuous positive airway pressure (CPAP) with a mask during sleep.’ Ophthalmologic findings in patients with SAS include floppy eyelid syndrome4 and keratoconus.5 In a case report, optic disc edema has been associated with SAS.6 Recently, Hayreh’ described patients with anterior ischemit optic neuropathy with a high prevalence of SAS. In the current study, we performed ophthalmologic examinations (including computerized perimetry) in patients referred for suspected SAS and correlated the visual field defects with the RDIs determined during all night sleep.
Mojon et al * Optic Neuropathy
Methods Subjects We included nine patients consecutively admitted for SAS evaluation at the University Hospital of Bern after informed consent was obtained. The protocol and informed consent were approved by the Ethical Committee of the Medical Faculty of the University of Bern, Bern, Switzerland. We excluded from statistical analysis all patients with conditions causing visual field defects.
Ophthalmologic
Examination
Visual Field Data Analysis For each patient, the mean defect (MD) and loss variance (LV) were calculated by averaging values from both eyes. A visual field test was considered reliable if false-positive and falsenegative answers were less than 15%.”
Neurologic,
and Laboratory
Examination
In addition to a general physical examination, including blood pressure measurement, complete blood count, chemical profile, and fasting blood glucose, a neurologic examination was performed.
Sleep Studies Overnight PSG was recorded during at least 6 hours, beginning at 10:00 PM, in a quiet, custom-built sleep laboratory. Recordings were done with a Neurofax encephalograph (Nihon Khoden, Tokyo, Japan), including electroencephalography (C4Al and Ol-A2 according to the lo-20 electroencephalogram system), electro-oculography (horizontal and vertical), electromyography (submental and anterior tibia1 muscle right and left), and nasal and oral airflow by thermistors. Simultaneously, inductive plethysmography (chest, abdomen, and sum) was measured by using a Respitrace Model 150 (Ambulatory Monitoring, Inc., Ardsley, NY), and oxygen saturation was measured with an Ohmeda Biox 3700 pulse oxymeter (Ohmeda, Inc., Louisville, CO).
Polysomnographic
ments, Madison, WI). The automatic analysis was observed on the computer screen and corrected when necessary. Sleep apnea syndrome was diagnosed and graded according to the RDI: normal RDI, less than 10; mild SAS, 10 greater than RDI less than 20; moderate SAS, 20 greater than RDI less than 40; and severe SAS, RDI greater than 40.’
Statistical
Analysis
Correlation between RDI and MD or LV was calculated using the Spearman rank correlation coefficient (0”
Results
All patients were seen by the same ophthalmologist (DM). At the time of the ophthalmologic examination, the result of the work-up for SAS by oxymetry and PSG was unknown. A complete medical history was taken. Clinical ophthalmologic examinations included best visual acuity, applanation tonometry, slitlamp visualization of the anterior eye segment, including gonioscopy, fundus examination in mydriasis with three-mirror gonioscope, and stereophotography of optic nerve head. Octopus computerized perimetry was performed using the Glaucoma Program Gl by two experienced perimetrists. Patient alertness was checked on a video screen during the whole examination. Patients with abnormal visual fields had diurnal eye pressure curve and blood-cell velocity measurements in the nailfold capillaries after cold provocation.8
General,
with SAS
Data Analysis
The raw data were stored on a personal computer and analyzed offline with sleep analysis software (UltraSom, Nicolet Instru-
The clinical and polysomnographic data of the seven patients included in the statistical analysis are summarized in Table 1. According to the RDI, one patient had mild SAS, two patients had moderate SAS, and three patients had severe SAS. One patient referred for suspected SAS had a normal PSG. His final diagnosis was chronic fatigue syndrome. One patient with severe SAS was excluded from our statistical analysis because of optic nerve drusen. Another patient with normal PSG was excluded because of tilted disks associated with high cornea1 astigmatism and bitemporal visual field defects. All three patients with severe SAS and one patient with moderate SAS (patient 5) had relative nasal arcuate defects. The two most severe cases (patients 1 and 2) also had paracentral relative defects. One patient with normal PSG and two patients with mild or moderate SAS had normal visual fields. The number of RDIs during night sleep correlated positively with the mean visual field defect (Fig 1, r, = 0.8 1, P < 0.05) and with the visual field LV (Fig 2, rr = 0.78, P < 0.05). The diurnal curve and the measurement of blood-cell velocity in the nailfold capillaries after cold provocation were normal in all patients, and false-positive and false-negative answers during perimetry were less than 15%. In two patients with severe SAS, visual field defects remained unchanged over 18 months. The 50-year-old man excluded from statistical analysis because of optic nerve drusen had constricted visual fields and markedly narrowed retinal arteries in each eye. He reported having lost his side vision over the past year. A magnetic resonance image brain scan was normal. He was treated with CPAP because of severe SAS. His visual fields improved subjectively and objectively dramatically after CPAP treatment (MD before treatment in the right eye was 19.8 and in the left eye was 18.9; MD after treatment in the right eye was 6.7 and in the left eye was 6.4). In conclusion, SAS is a frequent breathing disorder caused by intermittent upper airway obstruction during sleep and concurrent hypoxia, negative intrathoracic pressure, and sympathetic activation. Because airway obstructions are terminated by an arousal reaction, normal sleep is disrupted. Long-term cardiovascular sequelae and complications include pulmonary and systemic arterial hypertension, cardiac arrhythmias, myocardial infarction, and stroke.’ Recently, Hayreh7 reported several patients with anterior ischemic optic neuropathy having a history of SAS. In the current study, visual fields of patients with SAS showed relative arcuate nasal and paracentral defects consistent with an optic neuropathy. Generalized visual field depressions, frequently observed with inattentiveness, were not observed. The MD and LV correlated positively with the RDI (Figs 1,2). The reliability parameters, false-positive and false-negative answers, and the comments of the perimetrists on patient performance indicate
87.5
Ophthalmology Table 1. Clinical
Volume
and Polysomnographic
10.5, Number 5, May 1998 Data of Sleep Apnea Syndrome Suspects Polysomnographic Data
Case No.
Age (yrs)
Sex
History of Other Diseases Hypertension, chronic ohstrucnve pulmonary &ease BronchIal asthma, ulcer None Coronary heart disease, hypercholestermem~a None BronchIal asthma, hypcrcholesterinemla, hypertension Dlahetes mellitus, tinmtus
1
61
M
2 3 4
55 42 58
M M M
5 6
50 53
M M
7
54
M
Desaturation Index (N/hr)
Mean O1 Value (%)
SAS Cfmficatlon
73
100
71
23
SWSre
70 70 31
91 56 18
78 85 94
30 57 89
Sevcrr Severe Moderate
24 12
25 3
85 93
41 81
M&rate Mtld
2
0
94
86
Normal
RDI = respiratory dlsturhance index; N/hr = number of events per hour.
that visual field defects were not caused by decreased attention. This is essential in patients with SAS because of possible daytime sleepiness and impaired attention. Two patients with severe SAS treated with CPAP were observed over 18 months. Visual field defects remained unchanged, indicating a permanent lesion. It might be that further visual field deterioration was prevented by CPAP therapy. Because of the observational character of our study, we can only conclude that an association between SAS and visual field defects exists. Our data do not allow any conclusion about a direct causal relationship between SAS and visual field defects. In particular, we cannot exclude a third factor influencing both SAS and visual fields.‘” The cardiovascular responses to hypoxemia are complex and differ depending on whether hypoxemia develops during apnea with hypercapnia or during hyperventilation with hypocapnia. In the latter situation (e.g., at high altitudes), the systemic circulation responds to hypoxemia with vasodilation and with increased heart rate and cardiac output to maintain blood pressure and oxygen delivery to the peripheral tissues. In contrast, voluntary breath holding or apnea results in peripheral vasoconstriction, bradycardia, and decreased cardiac output with regional vasodilation of the cerebral and myocardial circulations to preserve oxygen delivery to these critical organs.” This difference
might explain the lack of funduscopic findings associated with other hypoxic conditions, such as altitude illnessI and respiratory insufficiency.‘j If we hypothesize that SAS causes the optic neuropathy, the damage may result from impaired optic nerve head blood flow autoregulation,14 secondary to repetitive prolonged apneas. Alternatively, optic nerve vascular dysregulation might be secondary to SAS-induced arterial hypertension and arteriosclerosis7.‘5 or imbalance between nitric oxide (a vasodilator) and endothelin (a vasoconstrictor).‘5 Repetitive prolonged hypoxia also might directly damage the optic nerve. Because of the large stores of carbon dioxide and excellent buffering capacity of our body, changes in PaC02 and pH during apneas remain modest in contrast to changes in PaO, and seem, therefore, not to be harmful.” Episodic increased intracranial pressure has been reported in patients with SAS’” and is thought to be responsible in one patient with SAS for bilateral optic disc edema resolving after permanent tracheotomy.6 Recently, in patients with SAS, platelet activation normalizing after CPAP treatment was found.” Therefore, optic neuropathy also might be secondary microinfarcts in the optic nerve. Interestingly, the visual field defects of one patient with optic nerve drusen improved dramatically subjectively and objectively after CPAP therapy. In a number of anecdotal oral case reports, pseudotumor
1
2 .
35 -
.
1 .
30 25 -
2MD
3 .
5 .
7
20 LW 15 :
0-O 4 .
6 -2 -4 -c 0
3 .
l
IO
20
30
40
50
60
70
80
RDI Figure 1. Respiratory disturbance Index versus visual held mean defect.
876
2 .
0
10
20
30
40
50
60
70
80
RDI Figure 2. Respmtory disturbance index vcrbus visual field loss varlancc.
Mojon et al * Optic Neuropathy cerebri has been found in association with SAS. In this case, papilledema has improved with CPAP treatment. Some of our patients also might have suffered from papilledema, which had resolved at the time of our examination. Because of the small sample size of our study, larger series are needed to confirm our findings and to better understand the association between SAS and visual field defects.
8. 9. 10.
References 1. Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndromes. In: Guilleminault C, Dement WC, eds. Sleep Apnea Syndromes. New York: A. R. Liss, 1978; 1- 12. (Kroc Foundation series; v. II.) 2. Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine, 2nd ed. Philadelphia: Saunders, 1994;667-77. 3. Douglass AB, Bornstein R, Nino-Murcia G, et al. The Sleep Disorders Questionnaire I: creation and multivariate structure of SDQ. Sleep 1994; 17:160-7. 4. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am J Ophthalmol 1981;92:568-75. 5. Culbertson WW, Tseng SC. Cornea1 disorders in floppy eyelid syndrome. Cornea 1994; 13:33 -42. 6. Bucci FA Jr, Krohel GB. Optic nerve swelling secondary to the obstructive sleep apnea syndrome. Am J Ophthalmol 1988; 105:428-30. 7. Hayreh SS. Acute ischemic disorders of the optic nerve.
11. 12. 13. 14. 15. 16.
17.
with
SAS
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