A C T A O P H T H A L M O L O G I C A VOL. 5 3 1 9 7 5
The Department of Ophthalmology (Heads: Aiiels Ehlers and Viggo A . lensen). drhus Kommunehos~ital,University of Aarhus, Denmark
CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, PIGMENTARY RETINOPATHY, AND HEART BLOCK (KEARNS-SAYRE SYNDROME) Report of a Case BY
MARTIN LOWES
Chronic progressive external ophthalmoplegia associated with a pigmentary retinopathy and heart block was described by Kearns & Sayre in 1958. They suggested that the triad represented a syndrome. The cases recorded since then are reviewed and summarised, and several common features are noted. Little attention has previously been paid to the retinopathy. A similar case is presented, and the pigment changes, retinal function, and fluorescein angiography are examined. There is no clinical evidence for the diagnosis of classical retinitis pigmentosa. The prognosis and aetiology of the condition are discussed.
Key words: chronic progressive external ophthalmoplegia - pigmentary retinopathy - heart block - retinal function - fluorescein angiography Kearns-Sayre syndrome.
Kearns & S a y r e (1958) presented two cases of chronic progressive external ophthalmoplegia associated w i t h a pigm e nta r y retinopathy and h e a r t block, and were of the opinion that the triad could be classed a s a syndrome. Received May 2, 1975.
610
Ophthalrnoplcgia, Retinopathy and Heart Block
The first patient was a 34-year-old male of slight build whose main complaint was shortness of breath on exertion. The patient exhibited a bilateral ptosis, external ophthalmoplegia, and a divergent strabismus. A n electrocardiogram revealed complete heart block. Ophthalmoscopic examination showed normal optic discs and retinal vessels. The pigment epithelium of the retina had a peculiar stippled appearance and a metallic sheen which was particularly marked around the optic discs where the choroidal vessels were prominent and clearly seen. The visual acuity was normal. Visual fields revealed a huge enlargement of the blind spots which seemed to match the areas of most markedly disturbed retina around the discs. The second patient was a 17-year-old male of small stature who presented with spells of unconsciousness. The patient experienced progressive deafness and had to repeat a school grade because of poor work. A n electrocardiogram showed complete heart block. Bilateral ptosis, external ophthalmoplegia, and a divergent strabismus were noted. Ophthalmoscopy revealed normal optic discs, but the retinal arterioles were attenuated. The pigment epithelium was mottled and had a fluorescent appearance, again most marked around the discs. Pigment clumping was observed peripherally. Visual acuity was 20/40 in the right eye and 20/60 in the left eye. Visual fields showed huge enlargement of the blind spot with breakthrough to the periphery on the right side, and a n atypical ring scotoma on the left side. The second patient died from a cardiac arrest. Histological studies of the retina revealed numerous atrophic areas. The pigment epithelium could be identified in only a few places, and for the most part was entirely absent. I n the areas of retinal disturbance only the outer layers of the retina were affected; the bipolar and ganglion-cell layer were normal, and there was no evidence of optic atrophy. Since the original description by Kearns PC Sayre, a number cases have been recorded in the literature and these are summarised in Table I. It can be seen from the Table that the cases are similar in many respects, and the recognition of this triad of symptoms as a syndrome seems justified until the pathomorphological basis has been elucidated. The patients can present at any age, though commonly in early adulthood (average age on presentation 25 years). The cases are evenly distributed as regards sex. A cardiac symptom is the main complaint. The patients are frequently of small stature and often of low average intelligence. Common to all cases were chronic progressive external ophthalmoplegia, cardiac conduction defects, and a pigmentary retinopathy. Ketinal function has been investigated in only a few cases. Associated findings are deafness, elevated cerebrospinal fluid protein. and abnormal electroencephalographic tracings. As far as prognosis is con61 1 40:'
s
Key:
present - absent 0 not determined
+
Enlarged blind spot Abnormal dark adaptation Abnormal ERG Fluorescein angiography Dead Cardiac pacemaker
Cardiac conduction defects Pigmentary retinopathy Deafness Elevated C.S.F. protein Abnormal EEG Asymptomatic diabetes
-
o + o o 0 +
0
+
+ + +
+
35 M
5
+
19 F
6
o
+
+
-
o
+
39 F
8
o
+
13 M
9
+
1
+
F
23
0
+
1
F
16
1
1
M
27
2
1
+ - 0 0 0 0 0 - - o - o + + o o + - + + o o o o o o o o o + o o o o o o o + + 0 0 0 0 0 0 0 0 0 0 + - - - - _ - - - - _ +
o
F
32
7
~~
17 F
3
1
+
0
+ o o o
Cases 1 b 2, Kearns & Sayre (1958). Case 3, Thorson 8c Bell (1959). Case 4, Jager et al. (1960). Case 5, Lind & Prame (1963). Cases 6, 7, 8 & 9, Kearns (1965). Case 10, Daroff et al. (1966). Cases 1 1 & 12, Drachmann (1968). Case 13, Shastri et al. (1971). Case 14, Mdttyus et al. (1973). Case 15, Pilling & Nanton (1974).
_
-
0
o 0 ~ o + o o
+ + +
0 - t
+
13 M
4
~~
14 M
4
23 F
24 F
Author’s case
,]
o o o o 0 + -
o + - + o + o + 0 + + +
+ + + + + + + + + o ++ - 0 + + O O + - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + o + o o o o + o + + + + ++ - + + o o o + + + + + + +o ~ + ~ + + ~ ~ + ++ ++ -
+
+
+
M
+
61
17
M
3
h.I
Age on presentation (years) Sex Cardiac complaints Small stature Low average intelligence Ptosis and ophthalmoplegia
2
34
1
Cases
~~
Table I. Reported cases of ophthalmoplegia, retinopathy and heart block.
+
Ophthalmoplegia, Retinopathy and Heart Block
cerned, four patients have died from cardiac causes, but the more recent cases have all been successfully treated with a cardiac pacemaker. A similar case is presented, and emphasis is laid on the pigmentary retinopathy. Case report
A 24-year-old woman, previously in good health, was admitted to the cardiological department, Arhus Kommunehospital, in March 1974 because of repeated syncopal attacks which had commenced 1 year earlier. A complete atrio-ventricular heart block was diagnosed, and a cardiac pacemaker inserted with good effect. Since that time the patient has remained well with no further fainting attacks. The patient was noticed to have a marked ptosis and was referred to the eye department. Ptosis of both eyes had begun to develop around the age of 10 years. Photographs confirmed that there had been no ptosis in early childhood. At the time of admission there was a n almost complete external ophthalmoplegia. There were no complaints of double vision or night blindness. The only other complaint was an incessant tinnitus. Examination revealed a thin woman of small stature (height 153 cm, weight 35.5 kg) and of low average intelligence. Her physical condition was rather poor which
Fig. I . Fundus photograph of the left eye showing marked thinning of the pigment epithelium in the peripapillary area. 613
Martin Lowes
Fig. 2. Visual fields showing enlargement of the blind spots.
hampered investigations. There was a marked bilateral ptosis, a n almost total external ophthalmoplegia - the patient being able to turn both eyes laterally 5' and less than 5' in all other gaze directions. A 5' divergent strabismus was observed. There was no convergence, but the pupils reacted normally to light.
Visual acuity of the right eye was 0.5-1.50 sph and of the left eye 0.5-1.00 sph. Colour vision using American Optical pseudoisochromatic plates revealed a mild red/green defect with a medium-strong bluclyellow defect. OphthaZmoscopy of both eyes revealed clear media. The optic discs appeared normal, and there was no attenuation of the retinal vcssels. There was a marked peripapillary thinning of the pigment epithelium extcnding about 1*/z disc diameters from the margin of the nerve heads. The choroidal vessel architecture in this area was also disturbed, only the larger choroidal vessels were apparent, the choroicapillaris appeared sclerosed (Fig. 1). The choroidal vessels in the remainder of the fundus were also clearly visible, but appeared normal. Diffuse, small, irregular pigment aggregations, exhibiting confluence, were seen, beginning discretely around the peripapillary atrophic area and extending with increasing density towards the periphery where they were particularly marked. The pigmentation in no way resembled the bone corpuscle aggregations seen in retinitis pigmentosa, nor was there any pigment sheathing of the retinal vessels. The macula areas were covered by pigment, and the normal reflexes were absent.
Visual jields plotted with both the Bjerrum screen and the Goldmann perimeter revealed marked enlargement of the blind spots, but otherwise the fields were normal. (Fig. 2). Dark adaptation was measured using the Goldmann-Weekers adaptometer and showed a normal cone component, but a slightly raised threshold of the rod component. Unfortunately, the examination could not be carried on for longer than 20 min because of patient tiredness. The curve was biphasic. (Fig. 3). 614
Ophthalmoplegia, Retinopathy and Heart Block ERG
light adapted
lo7,
0.5 ERG Calibration m" 0.2 sec.
106 ERG 7 10 mins
105 104-
l 102
5
o 10
3
15
20
25
30
2 35 min
Fig. 3. Dark adaptation and electroretinography.
Elcctroretinography exhibited a n abnormal response of the negative (-) type. There was an a-wave of 300 p V with a markedly reduced b-wave. The response in the photopic and scotopic state was unaltxed. (Fig. 3). Fluorescein angiography in colour revealed normal retinal vessels. There was an almost uninhibited view c l the choroidal vessel architecture which could be clearly seen at the time of the commencement of the venous filling of the retinal vessels. The increased choroidal fluorescence indicates atrophy of the retinal pigment epithelium, and on this background pigment accumulations could be seen. It was also observed that there was a reduced fluorescence of the peripapillary area suggestive of choroidal vessel atrophy around the optic discs. (Fig. 4 a). At a later stage the choroidal fluorescence almost obscured the details of the retinal vessels. (Fig. 4 b). Biopsy of rectus superior muscle revealed dense fibrous tissue to which a few muscle fibres were attached, and as Par as it could be observed, there were no degenerative changes of the fibre segments or inflammatory reaction. Blood vessels were normal; no inflammation was present. Biopsy of the pectoralis muscle was normal. Otological exnmination demonstrated a bilateral perceptive hearing loss of 30-35 db most marked for high tones. Neurological cxanzination was normal apart from the ophthalmoplegia and a somewhat bulbar type of speech. Tensilon test was negative. Electroencephalography was mildly abnormal with diffuse slow 5-7 cps activity more marked on the left side. Investigations. Normal laboratory results included: Sedimentation rate 8 mm/hi. Haemoglobin 14 go/,. MCV 89. MCHC 34. Leucocytes 5700. Blood urea 21 mgo/o. Serum creatinine 0.6 m@/o. SGOT 24. SGPT 18. Serum aldolase 4.3. Serum T3 4.9O/o. Serum T4 9.3 ugQ/o. PBI 5.7 ugo/o. Serum cholesterol 188 mgo/o. Serum triglyceride
615
Martin Lowes
Fig. 4a. Fig. 4b. Fluorescein angiography in colour of the right eye showing increased choroidal fluorescence and pigment accumulations. (a) 18 sec. (b) 23 sec.
103 mgO/o (no hypolipoproteinaemia). Serum potassium 3.9. Serum sodium 140. Serum protein 7.3 g "/o (electrophoretic pattern was normal apart from serum albumin 3.81). VDRL negative. GR negative. Abnormal findings included: Fasting blood glucose 104-196 mgO/o (normal 70-1 10 m@/o). L D H 496 (normal 100-400). Cerebrospinal fluid contained glucose 59 mgo/o (normal 40-70 m@/o), total protein 87 mgo/o (normal 20-40 mgo/o), white cells 0/3, red cells 0/3. CSF protein electro4.1 (
The Department of Ophthalmology (Heads: Aiiels Ehlers and Viggo A . lensen). drhus Kommunehos~ital,University of Aarhus, Denmark
CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, PIGMENTARY RETINOPATHY, AND HEART BLOCK (KEARNS-SAYRE SYNDROME) Report of a Case BY
MARTIN LOWES
Chronic progressive external ophthalmoplegia associated with a pigmentary retinopathy and heart block was described by Kearns & Sayre in 1958. They suggested that the triad represented a syndrome. The cases recorded since then are reviewed and summarised, and several common features are noted. Little attention has previously been paid to the retinopathy. A similar case is presented, and the pigment changes, retinal function, and fluorescein angiography are examined. There is no clinical evidence for the diagnosis of classical retinitis pigmentosa. The prognosis and aetiology of the condition are discussed.
Key words: chronic progressive external ophthalmoplegia - pigmentary retinopathy - heart block - retinal function - fluorescein angiography Kearns-Sayre syndrome.
Kearns & S a y r e (1958) presented two cases of chronic progressive external ophthalmoplegia associated w i t h a pigm e nta r y retinopathy and h e a r t block, and were of the opinion that the triad could be classed a s a syndrome. Received May 2, 1975.
610
Ophthalrnoplcgia, Retinopathy and Heart Block
The first patient was a 34-year-old male of slight build whose main complaint was shortness of breath on exertion. The patient exhibited a bilateral ptosis, external ophthalmoplegia, and a divergent strabismus. A n electrocardiogram revealed complete heart block. Ophthalmoscopic examination showed normal optic discs and retinal vessels. The pigment epithelium of the retina had a peculiar stippled appearance and a metallic sheen which was particularly marked around the optic discs where the choroidal vessels were prominent and clearly seen. The visual acuity was normal. Visual fields revealed a huge enlargement of the blind spots which seemed to match the areas of most markedly disturbed retina around the discs. The second patient was a 17-year-old male of small stature who presented with spells of unconsciousness. The patient experienced progressive deafness and had to repeat a school grade because of poor work. A n electrocardiogram showed complete heart block. Bilateral ptosis, external ophthalmoplegia, and a divergent strabismus were noted. Ophthalmoscopy revealed normal optic discs, but the retinal arterioles were attenuated. The pigment epithelium was mottled and had a fluorescent appearance, again most marked around the discs. Pigment clumping was observed peripherally. Visual acuity was 20/40 in the right eye and 20/60 in the left eye. Visual fields showed huge enlargement of the blind spot with breakthrough to the periphery on the right side, and a n atypical ring scotoma on the left side. The second patient died from a cardiac arrest. Histological studies of the retina revealed numerous atrophic areas. The pigment epithelium could be identified in only a few places, and for the most part was entirely absent. I n the areas of retinal disturbance only the outer layers of the retina were affected; the bipolar and ganglion-cell layer were normal, and there was no evidence of optic atrophy. Since the original description by Kearns PC Sayre, a number cases have been recorded in the literature and these are summarised in Table I. It can be seen from the Table that the cases are similar in many respects, and the recognition of this triad of symptoms as a syndrome seems justified until the pathomorphological basis has been elucidated. The patients can present at any age, though commonly in early adulthood (average age on presentation 25 years). The cases are evenly distributed as regards sex. A cardiac symptom is the main complaint. The patients are frequently of small stature and often of low average intelligence. Common to all cases were chronic progressive external ophthalmoplegia, cardiac conduction defects, and a pigmentary retinopathy. Ketinal function has been investigated in only a few cases. Associated findings are deafness, elevated cerebrospinal fluid protein. and abnormal electroencephalographic tracings. As far as prognosis is con61 1 40:'
s
Key:
present - absent 0 not determined
+
Enlarged blind spot Abnormal dark adaptation Abnormal ERG Fluorescein angiography Dead Cardiac pacemaker
Cardiac conduction defects Pigmentary retinopathy Deafness Elevated C.S.F. protein Abnormal EEG Asymptomatic diabetes
-
o + o o 0 +
0
+
+ + +
+
35 M
5
+
19 F
6
o
+
+
-
o
+
39 F
8
o
+
13 M
9
+
1
+
F
23
0
+
1
F
16
1
1
M
27
2
1
+ - 0 0 0 0 0 - - o - o + + o o + - + + o o o o o o o o o + o o o o o o o + + 0 0 0 0 0 0 0 0 0 0 + - - - - _ - - - - _ +
o
F
32
7
~~
17 F
3
1
+
0
+ o o o
Cases 1 b 2, Kearns & Sayre (1958). Case 3, Thorson 8c Bell (1959). Case 4, Jager et al. (1960). Case 5, Lind & Prame (1963). Cases 6, 7, 8 & 9, Kearns (1965). Case 10, Daroff et al. (1966). Cases 1 1 & 12, Drachmann (1968). Case 13, Shastri et al. (1971). Case 14, Mdttyus et al. (1973). Case 15, Pilling & Nanton (1974).
_
-
0
o 0 ~ o + o o
+ + +
0 - t
+
13 M
4
~~
14 M
4
23 F
24 F
Author’s case
,]
o o o o 0 + -
o + - + o + o + 0 + + +
+ + + + + + + + + o ++ - 0 + + O O + - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + o + o o o o + o + + + + ++ - + + o o o + + + + + + +o ~ + ~ + + ~ ~ + ++ ++ -
+
+
+
M
+
61
17
M
3
h.I
Age on presentation (years) Sex Cardiac complaints Small stature Low average intelligence Ptosis and ophthalmoplegia
2
34
1
Cases
~~
Table I. Reported cases of ophthalmoplegia, retinopathy and heart block.
+
Ophthalmoplegia, Retinopathy and Heart Block
cerned, four patients have died from cardiac causes, but the more recent cases have all been successfully treated with a cardiac pacemaker. A similar case is presented, and emphasis is laid on the pigmentary retinopathy. Case report
A 24-year-old woman, previously in good health, was admitted to the cardiological department, Arhus Kommunehospital, in March 1974 because of repeated syncopal attacks which had commenced 1 year earlier. A complete atrio-ventricular heart block was diagnosed, and a cardiac pacemaker inserted with good effect. Since that time the patient has remained well with no further fainting attacks. The patient was noticed to have a marked ptosis and was referred to the eye department. Ptosis of both eyes had begun to develop around the age of 10 years. Photographs confirmed that there had been no ptosis in early childhood. At the time of admission there was a n almost complete external ophthalmoplegia. There were no complaints of double vision or night blindness. The only other complaint was an incessant tinnitus. Examination revealed a thin woman of small stature (height 153 cm, weight 35.5 kg) and of low average intelligence. Her physical condition was rather poor which
Fig. I . Fundus photograph of the left eye showing marked thinning of the pigment epithelium in the peripapillary area. 613
Martin Lowes
Fig. 2. Visual fields showing enlargement of the blind spots.
hampered investigations. There was a marked bilateral ptosis, a n almost total external ophthalmoplegia - the patient being able to turn both eyes laterally 5' and less than 5' in all other gaze directions. A 5' divergent strabismus was observed. There was no convergence, but the pupils reacted normally to light.
Visual acuity of the right eye was 0.5-1.50 sph and of the left eye 0.5-1.00 sph. Colour vision using American Optical pseudoisochromatic plates revealed a mild red/green defect with a medium-strong bluclyellow defect. OphthaZmoscopy of both eyes revealed clear media. The optic discs appeared normal, and there was no attenuation of the retinal vcssels. There was a marked peripapillary thinning of the pigment epithelium extcnding about 1*/z disc diameters from the margin of the nerve heads. The choroidal vessel architecture in this area was also disturbed, only the larger choroidal vessels were apparent, the choroicapillaris appeared sclerosed (Fig. 1). The choroidal vessels in the remainder of the fundus were also clearly visible, but appeared normal. Diffuse, small, irregular pigment aggregations, exhibiting confluence, were seen, beginning discretely around the peripapillary atrophic area and extending with increasing density towards the periphery where they were particularly marked. The pigmentation in no way resembled the bone corpuscle aggregations seen in retinitis pigmentosa, nor was there any pigment sheathing of the retinal vessels. The macula areas were covered by pigment, and the normal reflexes were absent.
Visual jields plotted with both the Bjerrum screen and the Goldmann perimeter revealed marked enlargement of the blind spots, but otherwise the fields were normal. (Fig. 2). Dark adaptation was measured using the Goldmann-Weekers adaptometer and showed a normal cone component, but a slightly raised threshold of the rod component. Unfortunately, the examination could not be carried on for longer than 20 min because of patient tiredness. The curve was biphasic. (Fig. 3). 614
Ophthalmoplegia, Retinopathy and Heart Block ERG
light adapted
lo7,
0.5 ERG Calibration m" 0.2 sec.
106 ERG 7 10 mins
105 104-
l 102
5
o 10
3
15
20
25
30
2 35 min
Fig. 3. Dark adaptation and electroretinography.
Elcctroretinography exhibited a n abnormal response of the negative (-) type. There was an a-wave of 300 p V with a markedly reduced b-wave. The response in the photopic and scotopic state was unaltxed. (Fig. 3). Fluorescein angiography in colour revealed normal retinal vessels. There was an almost uninhibited view c l the choroidal vessel architecture which could be clearly seen at the time of the commencement of the venous filling of the retinal vessels. The increased choroidal fluorescence indicates atrophy of the retinal pigment epithelium, and on this background pigment accumulations could be seen. It was also observed that there was a reduced fluorescence of the peripapillary area suggestive of choroidal vessel atrophy around the optic discs. (Fig. 4 a). At a later stage the choroidal fluorescence almost obscured the details of the retinal vessels. (Fig. 4 b). Biopsy of rectus superior muscle revealed dense fibrous tissue to which a few muscle fibres were attached, and as Par as it could be observed, there were no degenerative changes of the fibre segments or inflammatory reaction. Blood vessels were normal; no inflammation was present. Biopsy of the pectoralis muscle was normal. Otological exnmination demonstrated a bilateral perceptive hearing loss of 30-35 db most marked for high tones. Neurological cxanzination was normal apart from the ophthalmoplegia and a somewhat bulbar type of speech. Tensilon test was negative. Electroencephalography was mildly abnormal with diffuse slow 5-7 cps activity more marked on the left side. Investigations. Normal laboratory results included: Sedimentation rate 8 mm/hi. Haemoglobin 14 go/,. MCV 89. MCHC 34. Leucocytes 5700. Blood urea 21 mgo/o. Serum creatinine 0.6 m@/o. SGOT 24. SGPT 18. Serum aldolase 4.3. Serum T3 4.9O/o. Serum T4 9.3 ugQ/o. PBI 5.7 ugo/o. Serum cholesterol 188 mgo/o. Serum triglyceride
615
Martin Lowes
Fig. 4a. Fig. 4b. Fluorescein angiography in colour of the right eye showing increased choroidal fluorescence and pigment accumulations. (a) 18 sec. (b) 23 sec.
103 mgO/o (no hypolipoproteinaemia). Serum potassium 3.9. Serum sodium 140. Serum protein 7.3 g "/o (electrophoretic pattern was normal apart from serum albumin 3.81). VDRL negative. GR negative. Abnormal findings included: Fasting blood glucose 104-196 mgO/o (normal 70-1 10 m@/o). L D H 496 (normal 100-400). Cerebrospinal fluid contained glucose 59 mgo/o (normal 40-70 m@/o), total protein 87 mgo/o (normal 20-40 mgo/o), white cells 0/3, red cells 0/3. CSF protein electro4.1 (
