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The Erg in Hereditary Central Retinal Degeneration or Heredomacular Disease⋆
T H E ERG IN H E R E D I T A R Y C E N T R A L R E T I N A L D E G E N E R A T I O N OR H E R E D O M A C U L A R DISEASE* ( C E N T R A L TAFETORETINAL
DEGENERATION)
A. D. RUEDEMANN, JR., M.D. Detroit, Michigan The purpose of this paper is to describe the electroretinographic changes in heredi tary central retinal degeneration. I n this study, the various entities are grouped to gether under the following classification: A degenerative process primarily involving the central retina of both eyes, present in more than one member of a family. T h e vision may or may not be severely affected. Central fields may indicate a central scotoma. Ophthalmoscopic examination of several mem bers of a family reveal polymorphous changes predominantly involving the central retinal area. These usually cannot be related to acuity or fields.
e. Slow rounded b-wave with rela tively normal amplitude. f. Reduced, slowed, flattened flicker, "single hump flicker." 3. T h e E R G changes are notable. This indicates more pathologic alterations in the still-functioning retinal elements. Changes in the E R G indicate that a larger area of the retina is affected than just the macular area. T h e more retina involved, the greater the E R G changes. 4. T h e right and left eyes are not neces sarily similar.
T h e characteristic polymorphism of fa milial central retinal degeneration presents an intriguing problem in E R G evaluation. Several points may be made at the outset: 1. In our laboratory, involved members of a family invariably have an abnormal E R G . The E R G changes indicate similar abnormalities varying only in severity in the involved members. 2. The characteristic E R G changes are: a. Increased latency of the a-wave. b. Loss of a-wave amplitude particu larly of early components (n 1 ; p i ) . c. Notable convexity of the a-wave re lated to loss of amplitude. d. Reduction of a-wave amplitude, xcomponent of b-wave of red re sponse.
T h e electroretinographic techniques uti lized are essentially as previously de scribed. 1-3 In addition practically all of the patients have been tested in the lightadapted state, utilizing computer technique. A standard Mnemetron computer ( N o . 400B) is connected in series with a Tektronix dual beam oscilloscope ( N o . 5 0 2 ) . A second dual beam oscilloscope is used to dis play the added responses. A Mnemetron counter ( N o . 562) is utilized to predeter mine the number of stimuli to be counted
* From the Kresge Eye Institute, Wayne State University, and the Department of Ophthalmology, Detroit Receiving Hospital. This study was sup ported in part by the Detroit General Hospital Re search Corporation. Presented in part at the meet ing of the Wilmer Residents Association, The Johns Hopkins University and Hospital, Baltimore, Mary land, May, 1964, and at the Kresge Eye Institute 10th annual alumni reunion, Detroit, Michigan, September, 1964.
METHOD
(fig.i). T w o responses are utilized with the com puter, L 0 1 6 (approximately 50 flashes) and L 0 4 20/sec (approximately 500 flashes). The results are evaluated in the usual fash ion and compared to the normal range. RESULTS A.
C E N T R A L PIGMENTARY
Family
290
DEGENERATION
1 (tables 1 and 2 )
Mr. J. T., KISS, a 60-year-old white man, was first tested by ERG on October 10, 19S8. The pa tient stated that he had lost central vision in both eyes in his midforties. Vision in 1964 was reduced
THE ERG IN RETINAL DEGENERATION
291
HEADBAND LEFT GROUND CONTACT LENS INDIFFERENT CONTACT LENS RIGHT GROUND
Fig. 1. (Ruedemann). Sche matic drawing of equipment orienta tion. Contact lenses and headband are standard. Ruedemann-Noell ERG lenses, Jardon Laboratories, Detroit, Michigan. The square marked amplifier actually represents two Telecardio amplifiers and their power supply (a 45-volt battery for each amplifier). The filter box is preset at 0.1 cycles/second and 0.25 kilocycles/second.
COMPUTER DUAL-BEAM OSCILLOSCOPE
to less than 20/200, right eye; less than 20/200, left eye. Vision in the right eye was 20/50— in 1959. The right eye became intermittently dark. The patient had difficulty in bright light, sunlight diminished his vision. There was no history of retinal hemorrhage. Fundus examination showed large areas of central pigmentary degeneration (figs. 2-a and b). Visual fields reveal large cen tral scotomas (fig 3).
DUAL- BEAM OSCILLOSCOPE DISPLAY
The ERG, evaluated on three occasions, has remained essentially the same (figs. 4a, 4b and 4c), being typical for central retinal degeneration. This patient has been previously reported.4 The patient has a 58-year-old sister, K207, who has been evaluated by ERG on one occasion. Vision is reduced to 20/200. Ophthalmoscopic, visual fields, and ERG are essentially the same as those of her brother.
Fig. 2 (Ruedemann). KI55. (a) Central retinal area, left eye. The entire posterior central fundus is involved, (b) Central retinal area, right eye.
A. D. RUEDEMANN, JR.
292
TABLE 1 AMPLITUDE IN MICROVOLTS
K155 J. T. Brother (66 yr)
K207 C. S. Sister (58 yr)
K240 J. F. Sister (54 yr)
R L
46 50
89 122
T.D. 97
87-149
K L
77 85
211 216
T.D. 184
164-284
R L
25 25
44 55
T.D. 49
39- 77
R L
53 40
67 89
T.D. 42
55-117
R L
80 80
433 499
T.D. 316
302-514
R L
T.D. 10
22 11
T.D. 22
14- 38
x-wave
R L
20 20
33 33
T.D. 54
5 1 - 97
b-smooth
R L
36 55
144 194
T.D. 162
103-267
T.D. T.D.
N.I. N.I.
T.D. 137
141-251
FAMILY: Al
L016 a-wave b-vvave
L 0 4 20/sec. D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) n, R L
Normal Range
Pi
R L
T.D. T.D.
N.I. N.I.
T.D. 137
131-241
no
R L
53 70
N.I. N.I.
T.D. 179
172-276
P2
R L
42 40
N.I. N.I.
T.D. 105
119-283
P3
R L
105 100
N.I. N.I.
T.D. 242
265-425
R L
25 25
N.I. N.I.
N.I. N.I.
3 9 - 77
Averaged L 0 4 20/sec.
T.D.—technical difficulties; N.I.—not included in protocol. There is a 56-year-old sister, K240, who has 20/30 vision in both eyes and an essentially nor mal ERG. The only finding on this patient is angioid streaks in both eyes. There has been no evi dence of retinal hemorrhage in any of the three patients to date. No other family history has been recorded.
Family 2 (tables 3 and 4) Mrs. D. M., K55, a 45-year-old white woman,
noted acute loss of vision in the third grade asso ciated with a severe exanthematous process and high fever. A younger sister, Mrs. V. N., K59, aged 41 years had notable loss of vision at the same time with the same symptoms. The two sis ters had corrected vision of 20/200, O.U. No other family history could be elicited. Ophthalmoscopic examination was essentially the same in both sisters (fig. 5a and b). Visual fields were difficult to obtain but indicated definite central scotomas (fig. 6).
THE ERG IN RETINAL DEGENERATION
293
TABLE 2
LATENCIES AND PEAK TIMES IN MILLISECONDS K155 T.T. Brother (66 yr)
K207 C. S. Sister (58 yr)
K240 J. F . Sister (54 yr)
R L
28 30
25 25
T.D. 25
20- 24
R L
54 54
45 45
TD. 47
3 9 - 45
R L
36 36
33 33
T.D. 35
2 9 - 33
R L
80 80
57 57
T.D. 66
5 7 - 77
R L
T.D. 38
29 29
T.D. 29
2 1 - 25
x-wave
R L
20 20
41 41
T.D. 49
4 5 - 55
b-smooth
R L
128 140
119 119
T.D. 156
90-138
10 10
N.I. N.I.
T.D. 4
FAMILY: A l
L016 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) a-wave R L
Normal Range
4-
5
ni
R L
T.D. T.D.
N.I. N.I.
T.D. 18
15- 19
Pi
R L
T.D. T.D.
N.I. N.I.
T.D. 21
20- 24
n2
R L
32 31
N.I. N.I.
T.D. 27
24- 28
P2
R L
36 34
N.I. N.I.
T.D. 31
2 9 - 35
P3
R L
42 41
N.I. N.I.
T.D. 37
3 4 - 40
T.D.—technical difficulties; N.I.—not included in protocol. The ERG was essentially the same in both cases ; that of the older sister, K55, is shown in Figures 7a, 7b and 7c. Both sisters have been evaluated on three occasions and the ERGs have remained essentially the same (April 1958, 1960 and 1964). B. STARGARDT'S DISEASE
Family 1 (tables 5 and 6) S. D., K982, an 18-year-old white girl and R. D., K983, a 14-year-old white boy, had loss of visual acuity one year apart. K982 began to lose vision in 1955, K983 in 1956. Both children had
noted a progressive loss of vision since those dates. Present visual acuity was less than 20/200 in both eyes. The eye findings were negative ex cept for the ophthalmoscopic examination which revealed a definite stippling and a beaten-bronze appearance of the central retinal zones in both eyes. There was, however, involvement of the midperipheral retina as well. Color vision could not be evaluated in either child and visual fields were not too reliable because of poor acuity. There was no other family history. The ERGs were adequately recorded and markedly reduced to all intensity of stimuli. The latencies and peak times were increased (figs. 8a, 8b and 8c).
A. D. R U E D E M A N N , JR.
Left
CENTRAL FIELD Right
K.I55 J.T 4-30-64 18/1000 WHITE NORMAL LIMITS VISION TOO POOR TO EVALUATE FOR COLOR Fig. 3 (Ruedemann). KI55. Central fields, 18/1000 white, O.U.
LO 16
L 0 4 20/sec.
VH/X/V NORMAL
NORMAL
K. 155 J.T.
K. 155 J.T.
Fig. 4a (Ruedemann). Lightadapted ERG. The upper and lower pictures on the left are the response to a maximum intensity stimulus in the light, no filter ( L 0 1 6 ) . The upper left picture is recorded from a normal. Both eyes are recorded. The broad vertical bar is a 200 mV calibration sweep. The lower left picture is the response of K1S5 to the same stimulus. There is obvious slowing with reduction in both a- and b-wave amplitude. The pictures on the right are the responses to a 20/second flicker ( L 0 4 20/sec). In the upper pic ture, the response from the right and left eyes of a normal indi vidual is illustrated. In the lower picture the response from the right and left eyes of KISS may be noted. There is a marked reduction in amplitudes.
THE ERG IN RETINAL DEGENERATION
DO 4 Fig. 4b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal, response to moderate intensity stimulus with no filter. (Lower) Response of right and left eyes of K155. Left eye, broad tracing; right eye, nar row tracing. Note the slowing of the response with reduction in amplitudes. Right side: D016 10 and 5 msec/cm. (Upper) Response of normal right and left eyes to maximum intensity stimulus with fast oscilloscope sweep speeds. (Lower) K155, response is slowed and reduced.
DR 16
295
DO 16 10 8 5 msec/cm.
NORMAL
NORMAL
K.I55 J.T.
K.I55 J.T.
L04 20/sec. AVERAGED
Fig. 4c (Ruedemann). Left side: Dark-adapted red response (DR16). (Upper) Normal (Lower) K155, markedly reduced responses of both eyes. Right side: Light-adapt ed 20/second flicker averaged (L04 20/sec averaged). (Upper) Normal response. (Lower) K155, response is slowed and reduced in amplitude, "single hump" flicker.
NORMAL
NORMAL
K. 155 J.T.
K. 155 J.T.
C. VlTELLINE DEGENERATION OF THE MACULA
Family 1 (pedigree, fig. 9, tables 7 and 8 ) M. H., K764, a 28-year-old Negress, had 20/30 vision uncorrected, O.U. Exudative lesions involved the entire macular areas in both eyes. Visual fields were full, O.U. There were no cen tral scotomas. The ERG was reduced, particular
ly the a-wave. The latencies were increased but, actually, her ERG was not as well recorded as were those of her daughters. The eldest daughter, M. H., aged 13-years, K760, had noted some loss of central vision, espe cially in the left eye. Ophthalmoscopic examina tion revealed a lesion similar to those seen in cen tral serous retinopathy, most notable in the right eye (fig. 10a and b). Vision was 20/40 in the right eye and 20/25 in the left. Visual fields r<--
A. D. R U E D E M A N N . JR.
296 TABLE 3
at low-normal limits in both eyes, with increased latencies.
AMPLITUDES IN MICROVOLTS
KS5 D. M. Sister (38 yr)
FAMILY: Α2
L016 a-wave b-wave
b-smooth
Normal Range
15 34
56 39
87-149
R L
46 64
148 132
164-284
5 20
T.D. T.D.
39- 77
20 29
70 86
55-117
R L
150 200
240 191
302-514
25 20
T.D. T.D.
14- 38
R L
0 0
26 25
51- 97
«R L
107 132
N.Sm. N.Sm.
103-267
60 67
141-251
D016 (Fast sweep speed) R T.D. m L T.D.
The main feature of this family was that two of three members had no visual com plaints ; one had obvious central lesions, while all three had abnormal ERGs. D.
HEREDOMACULAR DEGENERATION
Family 1 (tables 9 and 10) O. S., K157, a 33-year-old white woman, had had notable loss of visual acuity most of her life. TABLE 4
R L
DR16 a-wave
b-smooth
y. N.
Sister (35 yr)
R L
L 0 4 20/sec. D04 a-wave
K59
LATENCIES AND PEAK TIMES IN MILLISECONDS
K55 D. M. Sister (38 yr)
K59 V. N. Sister (35 yr)
Normal Range
R L
28 26
26 26
2 0 - 24
R L
46 46
48 50
3 9 - 45
R L
40 40
38 38
2 9 - 33
R L
76 76
78 78
5 7 - 77
FAMILY A2
LOI 6 a-wave b-wave D04 a-wave b-smooth
R L
T.D. T.D.
60 67
131-241
50 67
100 96
172-276
R L
48 50
T.D. T.D.
2 1 - 25
R L R L
30 57.
30 T.D.
119-283
R L
0 0
54 48
4 5 - 55
P2
R L
60 96
100 96
265-425
R L
96 96
N.Sm. N.Sm.
90-138
P3
R L
5 13
T.D. 33
39- 77
Pi
Averaged L04 20/sec.
DR16 a-wave
b-smooth
T.D.—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolts. vealed a central scotoma of less than five degrees in both eyes (fig. 11). The E R G responses were re duced in amplitudes on the a-wave side. The la tencies and peak times were increased (figs. 12a, 12b and 12c). T. H., K765, a nine-year-old girl, was seen on two occasions. Actually, she had no visual difficulties and her eye examination was within normal limits. Vision was 20/30, O.U. The fundus findings were negative. Visual fields showed a small central scotoma, left eye. The E R G was
D016 (Fast sweep speed) R 10 L 10
10 10
4-
5
ni
R L
T.D. T.D.
22 21
15- 19
Pi
R L
T.D. T.D.
25 25
20- 24
n2
R L
32 31
31 31
24- 28
P2
R L
40 42
34 T.D.
2 9 - 35
Ps
R L
44 46
41 40
34- 40
T.D.—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolt.s
THE ERG IN RETINAL DEGENERATION
297
Fig. S (Ruedemann). K55. (a) Fundus, left eye. The changes in the fundus are essentially limited to the posterior central area (b) Fundus, right eye.
CENTRAL FIELD
Left
Right
K. 55
D.M. 5/1000 WHITE
4-24-64
VISION TOO POOR TO EVALUATE FOR COLOR Fig. 6 (Ruedemann). Central fields, KSS.
A. D. R U E D E M A N N , JR.
298
L0I6
LO 4 20/sec.
Λ/ΗΛ\Λ\Λ
NORMAL
K. 55 D.M.
NORMAL
K. 55 D.M. DO 16 10 8 5 msec/cm.
DO 4
Fig. 7b (Ruedemann). Darkadapted ERG. Left side: D 0 4 . (Upper) Normal response. (Lower) K5S, response is slowed and re duced, O.U. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) KSS, response is slowed and reduced, O.U.
Fig. 7a (Ruedemann). Lightadapted ERG. Left side: L 0 1 6 . (Upper) Normal response. (Lower) KS5, response is slowed and re duced, O.U. Right side: L 0 4 20/ sec. (Upper) Normal response. (Lower) K5S, response is practi cally flat, O.U.
NORMAL
NORMAL
K. 55 D.M.
K.55 D.M.
The patient has a sister with a similar disease. Visual acuity was reduced to less than 20/200 and the patient had poor fixation. Ophthalmoscopic examination revealed central lesions in both eyes ; the greatest changes seemed to be in the central pigment epithelium (fig. 13a and b ) . Visual fields were not reliable (fig. 14). The E R G showed marked loss of E R G components, particularly on the a-wave side (figs. 15a, 15b and ISc).
L. P., K1174, a 20-year-old white woman, showed findings similar in all respect to those of her sister. Family
2 ( p e d i g r e e , fig. 16, t a b l e s 11 a n d 1 2 )
T o date the father, mother and three sons have been evaluated by ERG. The mother had an es sentially normal E R G while the father and three
THE ERG IN RETINAL DEGENERATION
DR 16
Fig. 7c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K5S, response is slowed and reduced, O.U. Right side: L04 20/sec, averaged. (Upper) Normal response. (Lower) KS5, response is markedly reduced, "single hump flicker," O.U.
NORMAL
K.55 D.M. sons had abnormal ERGs. The mother had nor mal visual acuity. The father, B. D., K784, a 39-year-old white man, had macular lesions, O.U., (fig. 17-a and b) and a central scotoma (fig. 18), with reduced visual acuity and poor color vision in both eyes. The ERG was at the lower limits of normal and latencies were not increased (figs. 19a, 19b and 19c). The paternal mother had a similar disease. M. D., K782, a 14-year-old boy, had visual acu ity of 20/100 with granularity of both fundi and reduced and abnormal ERGs. This patient has been tested on two occasions. W. D., K780, a 16-year-old boy, had visual acuity of 20/100 in both eyes with a salt and pepper or gold-dust granularity of both maculas. B. D., K781, an 11-year-old boy, had visual acuity of 20/100, central scotomas, slightly defec tive color vision and essentially the same macular lesions. The ERGs in the three sons were essentially the same, reduced and abnormal. Latencies were not increased.
Family 3 (pedigree, fig. 20, tables 13 and 14) To date six members of this family, the moth er and five children, have been evaluated by ERG. The mother had a normal eye examination, except for nuclear cataracts, and a normal ERG. E. G., K1021, a nine-year-old Negress, had visual acuity correctable to 20/20, O.U. There was notable granularity of the macular area in both eyes and a central scotoma. The ERG was definitely abnormal to all intensity of stimuli. M. L. G., K94S, the four-year-old sister was evaluated by ERG. Visual fields, color test and
299
LO 4 20/sec. AVERAGED
NORMAL
K. 55 D.M.
visual acuity were essentially normal, as was the ERG. R. G., K1022, the six-year-old sister, was also evaluated by ERG. The ERG seemed to be below normal limits. H. G, K934, the 11-year-old brother, had cor rected visual acuity of 20/50 in both eyes ; dis crete central lesions were seen in both eyes (fig. 21) Color vision was normal. There were central scotomas. The ERG was generally reduced to all intensity of stimuli and components of response (figs. 22a, 22b and 22c). M. G, K944, the 10-year-old brother, had visual acuity of 20/200 in the amblyopic right eye. The vision in the left eye was 20/20. There was marked esotropia, a definite central scotoma by central fields, and a questionable macular le sion by ophthalmoscopy. The ERG was definitely reduced in both eyes, more so in the right eye. There was a marked difference between the ERGs of the right and left eyes. This was par ticularly shown in the computer ERG which showed a marked loss in the flicker, particularly in the right eye (fig. 23). DISCUSSION OF RESULTS
Twenty-one patients in seven families having various types of central retinal de generation have been evaluated in this labo ratory. A number of other cases of macular lesions and no family history have also been evaluated by routine ERG. The results are similar in most cases. In the introduction certain points relating to the ERG changes in heredomacular de-
A. D. R U E D E M A N N , JR.
300 TABLE 5
AMPLITUDES IN MICROVOLTS
K982 S. D. Sister (18 yr)
K983 R. D. Brother (13 yr)
R L
31 39
T.D. 34
87-149
b-wave
R L
36 49
T.D. 39
164-284
L 0 4 20/sec.
R L
10 15
T.D. T.D.
Ά9- 77
FAMILY: Bl
L016 a-wave
Ü04 a-wave b-smooth DR16 a-wave
b-smooth
Normal Range
TABLE 6
R L
10 19
40 29
55-117
R L
110 172
170 172
302-514
R L
5 5
14- 38
R L
15 15
51- 97
R L
N.Sm. N.Sm.
D016 (Fast sweep speed) T.D. R L T.D.
wave. Eight of the 10 cases had increased time measurements for other a-wave re sponses, LOI6, D04, DR 16. The peak time for a-wave was increased in 12 of 21 cases for L 0 1 6 ; nine of 20 cases for D 0 4 ; 12 of 18 cases for DR16. The negative humps of the a-wave for DO 16, ni and n2 were increased in eight of 17 cases and nine of 20 cases, respectively. The positive hump of the a-wave pi had an
103-267
50 57
141-251
LATENCIES AND PEAK TIMES IN MILLISECONDS
FAMILY:
K982 S. D. Sister (18 yr)
K893 R. D. Brother (13 yr)
Normal Range
R L
24 28
T.D. 28
20- 24
R L
52 54
T.D. 38
3 9 - 45
R L
36 36
34 34
2 9 - 33
R L
72 76
76 76
57- 77
Bl
L016 a-wave b-wave D04 a-wave b-smooth
Pi
R L
T.D. T.D.
50 57
131-241
R L
60 57
70 76
172-276
R L
40 40
0 0
2 1 - 25
n2
R L
10 19
T.D. 19
119-283
R L
60 60
0 0
4 5 - 55
P!
R L
80 67
T.D. 76
265-425
R L
N.Sm. N.Sm.
0 0
90-138
Ps
R L
10 15
T.D. 13
39- 77
Averaged L 0 4 20/sec.
DR16 a-wave
b-smooth
D016 (Fast sweep speed) 12 R 12 L
generation were made : 1. Involved members of a family have an abnormal ERG. These changes vary only in severity in the involved members. 2. The characteristic ERG changes are: a. Increased latency of the a-wave. Of 20 cases, 10 had increased latency of the a-
5
R L
T.D. T.D.
20 19
15- 19
Pi
R L
T.D. T.D.
23 23
2 0 - 24
n2
R L
30 30
30 29
24- 28
R L
34 34
T.D. 32
29- 35
R L
42 42
T.D. 40
34- 40
111
T.D.—technical difficulties; N.Sm—no smooth measurable; O—flat or less than 5 microvolts.
4-
Pa
T.D.-—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolts.
THE ERG IN RETINAL DEGENERATION
L016
301
L 0 4 20/sec.
VS/S/ΝΛ Fig. 8a (Ruedemann). Lightadapted ERG. Left side: L016 (Upper) Normal response. (Lower) K982, note reduced and slowed re sponse, O.U. Right side: L04 20/ sec. (Upper) Normal response. (Lower) K982, the flicker response is practically flat, O.U.
NORMAL
K.982 increased latency in only one of 17 cases measured. b. Loss of a-wave amplitude. Of 21 cases, 13 had reduced a-wave amplitude for L 0 1 6 ; 14 of 20 cases had reduced a-wave amplitude for D 0 4 ; and eight of 18 cases had reduced a-wave amplitude for DR16. For the early components of DO 16— ni, pi, n2, the amplitudes were reduced be low the normal range in 12 of 17 cases for
D04
K.982
S.D.
iii; 11 of 17 cases for pi; 11 of 20 cases for p 2 . c. Notable convexity of the a-wave re lated to loss of amplitude is best noted in the response to D04. A convex a-wave was seen in 16 of 21 cases. d. Reduction of a-wave amplitude and x-component of b-wave, red response. The a-wave portion of the red response is difficult to measure. The x-component of the
D016 10 a 5 msec/cm.
NORMAL
K.982
S.D.
NORMAL
Fig. 8b (Ruedemann). Darkadapted ERG. Left side: D04 (Up per) Normal response. (Lower) K982, slowed and reduced response. Upsweep at the end of the response is due to lid activity. Right side: D016, fast sweep speed. (Upper) Normal response. (Lower) K982, response is markedly slowed and re duced.
NORMAL
S.O.
K.982
S.D.
A. D. RUEDEMANN, JR.
302
DR 16
L04 20/sec. AVERAGED
NORMAL
K.982
NORMAL
S.D.
K.982
b-wave is usually clearly recognized. In this series, 18 of 20 cases had an x-wave below normal range. e. Slow rounded b-wave with relatively normal amplitudes. This statement encom passes three distinct factors: the observed round, smoothed wave form, the slowed re sponse and the diminished amplitudes. In 21 cases, 15 had a rounded b-wave; nine cases had increased b-wave peak time; 16 cases had reduced b-wave amplitude. f. Reduced, slowed, flattened flicker, "single hump flicker." Again, observation is important. It is likely that the slowed re sponse tends to fuse the two humps of the flicker response. The amplitude measure ment is a separate function. In this series,
B I
m
Fig. 8c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K982, practically flat re sponse, O.U. Right side: L04 20/ sec, averaged. (Upper) Normal response. (Lower) K982, "single hump" flicker response.
EH8>*
Fig. 9 (Ruedemann). Pedigree of Family Cl (tables 7 and 8).
15 of 20 cases had a "single hump flicker" while 13 of 18 cases had a reduced ampli tude. (These values are obtained from rou tine and computer records.) 3. The results are straightforward. In disease of the central retina it would appear that the ERG changes are similar. The ERG changes would indicate a larger area of retina is involved than that limited to the area of the macula. 4. The right and left eyes are not neces sarily similar. This is shown very nicely in K944, M. G., who had 20/20 vision in one eye and 20/200 in the other eye. The ERG was reduced in the amblyopic eye. This difference is striking when one compares the computer 20/sec. flicker. Several important differentials must be made: The difference between peripheral retinal disease and central retinal disease. By com paring a young woman with night blindness and normal central visual acuity with one of the patients in this series some standard of comparison is provided: K. H., K984, a 17-year-old white girl, had corrected visual acuity of 20/20—, O.U.. She had a history of night blindness. Her sister had night blindness. K984 had congenital deafness. Visual fields revealed partial midring scotomas with (Text continued on page 308)
T H E ERG IN RETINAL DEGENERATION
303
TABLE 7 AMPLITUDES IN MICROVOLTS
K764 M. H. Mother (28 yr)
K760 M. H. Daughter (13 yr)
K765 T. H. Daughter (9yr)
Normal Range
R L
33 51
74 65
56 56
87-149
b-wave
R L
130 176
125 116
130 140
164-284
L 0 4 20/sec.
R L
T.D. T.D.
23 33
33 33
3 9 - 77
R L
T.D. T.D.
96 76
38 38
55-117
R L
T.D. T.D.
277 248
258 258
302-514
R L
T.D. T.D.
5 5
T.D. T.D.
14- 38
x-wave
R L
T.D. T.D.
33 14
28 19
5 1 - 97
b-smooth
R L
T.D. T.D.
N.Sm. N.Sm.
N.Sm. N.Sm.
103-267
FAMILY: C l
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
D 0 1 6 (Fast sweep speed) L
R
96 86
115 115
143 124
141-251
Pi
R L
86 86
105 105
143 124
131-241
Π2
R L
162 162
201 182
201 182
172-276
P2
R L
57 96
86 86
105 86
119-283
P3
R L
162 220
162 162
201 182
265-425
R L
T.D. T.D.
T.D. T.D.
T.D. T.D.
ni
Averaged L 0 4 20/sec.
T.D.—technical difficulties; N.Sm.—no smooth measurable.
3 9 - 77
A. D. RUEDEMANN, JR.
304
TABLE 8 LATENCIES AND PEAK TIMES IN MILLISECONDS K764 M. H. Mother (28 yr)
K760 M. H. Daughter (13 yr)
K76S T. H . Daughter (9yr)
R L
26 24
22 24
20 20
20- 24
R L
42 42
40 40
38 38
3 9 - 45
R L
T.D. T.D.
32 30
30 30
29- 33
R L
T'D. T.D.
68 66
64 64
57- 77
R L
T.D. T.D.
22 20
T.D. T.D.
2 1 - 25
x-wave
R L
T.D. T.D.
40 40
T.D. T.D.
4 5 - 55
b-smooth
R L
T.D. T.D.
N.Sm. N.Sm.
T.D. T.D.
90-138
FAMILY: C l
LOI 6 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) R a-wave L
4 6
4 4
5 5
Normal Range
4-
5
m
R L
20 18
16 16
20 17
15- 19
Pi
R L
22 20
22 22
21 22
20- 24
n2
R L
30 29
28 28
27 26
24- 28
P2
R L
34 33
31 32
30 30
29- 35
Pa
R L
40 39
38 38
36 35
34- 40
T.D.·—technical difficulties; N.Sm.—no smooth measurable.
THE ERG IN RETINAL DEGENERATION
30S
Fig. 10. (Ruedemann). K760. (a) Central lesion, left eye. (b) Central lesion, right eye. Note the difference in the photos of the two eyes.
CENTRAL FIELD
Left
Right
K.760
M.H. 7-31-64 1/1000 WHITE NORMAL COLOR PERCEPTION
Fig. 11 (Ruedemann). K760. Central fields.
A. D. RUEDEMANN, JR.
306
L04
20/sec.
Fig. 12a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K760, slowed and reduced re sponse. Right side: L04 20/sec. (Upper) Normal response. (Low er) K760, reduced response, O.U.
K.760
M. H.
K.760
M.H. D016 10 8k 5 msec/cm.
D04
Fig. 12b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K760. The response is slowed and amplitudes are reduced, O.U. Right side: DO 16, fast sweep speed. (Upper) Normal response. (Lower) K760. The response is slowed and reduced, O.U.
K.760 DR 16
M.H.
K.760
M.H.
L04 20/sec. AVERAGED
Fig. 12c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K760, response is slowed and reduced. Right side: L04 20/ sec, averaged. (Upper) Normal response. (Lower) K760, responses are reduced, O.U.
K.760
M.H.
K.760
M.H.
THE ERG IN RETINAL DEGENERATION
307
Fig. 13 (Ruedemann). K1S7. (a) Central fundus, left eye. (b) Central fundus, right eye.
Left
CENTRAL FIELD Right
K. 157 O.S. 3/IOOO WHITE NORMAL LIMITS
2-4-64
ABNORMAL COLOR PERCEPTION Fig. 14 (Ruedemann). K157. Central fields.
A. D. RUEDEMANN, JR.
308 TABLE 9
The differences between peripheral retinal disease (characterized by night blindness,
AMPLITUDES IN MICROVOLTS
K157 O.S. Sister (33 yr)
K1174 L. P. Sister (20 yr)
R L
56 74
78 88
87-149
b-wave
R L
117 132
230 260
164-284
L 0 4 20/sec.
R L
15 20
34 42
3 9 - 77
R L
32 67
48 67
55-117
R L
347 353
FAMILY: D l
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
392 430
Normal Range
302-514
R L
5 5
0 0
14- 38
x-wave
R L
10 20
15 14
5 1 - 97
b-smooth
R L
87 132
93 98
103-267
DO 16 (Fast sweepispeed) 63 R m 67 L
143 124
141-251
Pi
R L
63 67
134 124
131-241
Π2
R L
158 162
191 191
172-276
P2
R L
74 105
105 96
119-283
P»
R L
168 201
287 287
265-425
R L
7 10
9 13
3 9 - 77
Averaged L 0 4 20/sec.
O—flat or 1less than 5 microvolts. marked loss of field peripherally. Ophthalmoscopic examination revealed some waxy pallor of the disc with attenuation of the vessels and granular pig mentation of the retina, O.U.,, more marked in the right eye. The E R G was markedly reduced to all intensity of stimulii, limiting the ιcomparison of ERGs to the computer or light-adapted E R G . The cornputer flicker of K984 and K982 showed that the amplitudes were essentially the same while the character of the flicker was markedly different (fig. 24).
loss of peripheral field, peripheral retinal change by ophthalmoscopy and normal or nearly normal visual acui ty) and central retinal disease by ERG are: 1. In peripheral deg eneration there is marked loss of amplitudes throughout the ERG, more notable in the b-wave amplitudes. The a-wave is the last to disappear. The time of onset of various components is
T A B L E 10 LATENCIES AND PEAK TIMES IN MILLISECONDS
K157 O.S. Sister (33 yr)
K1174 L. P. Sister (20 yr)
Normal Range
R L
28 28
28 26
2 0 - 24
R L
42 42
42 42
3 9 - 45
R L
38 36
38 36
2 9 - 33
R L
80 78
68 66
5 7 - 77
R L
40 36
32 32
2 1 - 25
x-wave
R L
58 54
50 54
4 5 - 55
b-smooth
R L
146 140
132 130
90-138
DO 16 (Fast sweep speed) R a-wave 5 L 5
5 6
FAMILY: D l
L016 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
4-
5
ni
R L
20 19
20 21
15- 19
Pi
R L
22 21
23 23
2 0 - 24
n2
R L
30 29
29 29
2 4 - 28
P2
R L
34 34
33 33
2 9 - 35
Pa
R L
39 39
40 40
3 4 - 40
THE ERG IN RETINAL DEGENERATION
LOI6
309
L04 20/sec.
VSNV Fig. 15a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K157, slightly slowed and re duced response, O.U. Right side: L04 20/sec. (Upper) Normal re sponse. (Lower) K1S7, markedly reduced response.
NORMAL
K. 157 O.S. D04
K. 157 O.S.
DO 16 10 a 5 msec/cm.
NORMAL
O.S.
Fig. 15b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K1S7, markedly reduced re sponse. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) K157, the most notable changes are in the a-wave which is slowed and convex and reduced in amplitude.
NORMAL
-
K. 157
NORMAL
^
K. 157
normal until late in the disease when the, ERG is practically nonrecordable. The pho topic flicker, though reduced, has normal configuration. 2. In central retinal disease, there is some loss of a-wave amplitude. There is definite showing in onset of the ERG. All of the
O.S. photopic components are reduced and slowed, as evidenced by the flicker which is reduced to a single wave that lacks all com ponents. 3. The origin of the disease cannot be de termined by ERG. A disease originating in the choroid or pigment epithelium will not
A. D. RUEDEMANN, JR.
310
L04 20/sec AVERAGED
OR 16
Fig. 15c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K157, markedly reduced response. Right side: L04 20/sec, averaged. (Upper) Normal re sponse. (Lower) K1S7, markedly reduced response.
NORMAL
NORMAL
K. 157 O.S.
K. 157 O.S.
affect the ERG until enough visual cells are nonfunctional to cause a change in the ERG. Some cases have been studied, for exam ple, B. D., K784, in which there may be visual loss with central scotomas but there are obvious central fundus changes. The ERG is low normal in amplitude with nor mal latencies and peak times. These cases can be compared to those with marked cen tral involvement, poor visual acuity and gross central defects by central field. In experimental animals with hereditary visual cell degeneration, Noell5 has demon-
strated viable visual cells with a nonrecordable ERG. When one considers the anatomy of the posterior central retina, several features be come evident. The area of maximum cone concentration, called the macula lutea, is limited to an area about two mm in diameter. Cone concentration diminishes progressive ly, radially from the center of the macula, the fovea centralis. The area of field loss when the entire macula is destroyed is ap proximately 7.6 degrees. In terms of the total area of visual field, this does not repre(Text continued on page 316)
AI
π
f ? Φ? «fo
in QiiifrQ
άώ
m Fig. 16 (Ruedemann). Pedigree of Family D2 (tables 11 and 12).
T H E ERG IN RETINAL DEGENERATION
311
TABLE 11 AMPLITUDES IN MICROVOLTS K784 B. D . Father (39 yr)
K780 W. D. Son (16 yr)
K781 B. D . Son (11 yr)
K782 M. D. Son (14 yr)
R L
116 88
80 98
65 74
88 70
87-149
b-wave
R L
200 186
144 172
140 158
228 186
164-284
L 0 4 20/sec.
R L
46 51
33 42
33 33
42 42
3 9 - 77
R L
67 76
48 48
48 67
67 76
55-117
R L
353 373
258 306
277 315
449 325
302-514
R L
23 28
14 14
14 T.D.
19 19
14- 38
x-wave
R L
61 33
19 23
23 19
23 19
5 1 - 97
b-smooth
R L
T.D. 153
N.Sm. N.Sm.
N.Sm. N.Sm.
N.Sm. N.Sm.
103-267
172 134
115 124
T.D. 124
105 96
141-251
FAMILY: D2
L016 a-wave
D04 a-wave b-wave DR16 a-wave
D 0 1 6 (Fast ί»weep speed) R ni L
Normal Range
Pi
R L
172 134
115 124
T.D. 124
96 96
131-241
ns
R L
220 201
143 162
153 191
182 153
172-276
P2
R L
124 T.D.
115 124
67 96
153 124
119-283
P3
R L
239 229
153 172
153 191
277 229
265-425
Average L 0 4 R 20/sec. L
N.I. N.I.
N.I. N.I.
N.I. N.I.
N.I. N.I.
3 9 - 77
T.D.—technical difficulties; N.Sm.—no smooth measurable; N.I.—not included in protocol.
A. D. RUEDEMANN, JR.
312
TABLE 12 LATENCIES AND PEAK TIMES IN MILLISECONDS K784 B . D . Father (39 yr)
K780 W. D. Son (16 yr)
K781 B. D . Son (11 yr)
K782 M . D. Son (14 yr)
R L
20 22
26 26
26 24
22 22
20- 24
R L
40 42
38 38
40 40
38 38
39- 45
R L
30 30
32 32
36 34
32 32
29- 33
R L
64 64
68 68
74 70
68 68
57- 77
R L
30 28
32 30
28 T.D.
24 24
2 1 - 25
x-wave
R L
46 44
40 40
46 44
40 40
4 5 - 55
b-smooth
R L
T.D. 120
N.Sm. N.Sm.
N.Sm. N.Sm.
N.Sm. N.Sm.
90-138
FAMILY: D2
L016 a-wave b-wave D04 a-wave b-wave DR16 a-wave
D016 (Fast sweep speed) a-wave R L
4 5
4 4
4 4
4 4
Normal Range
4-
5
ni
R L
IS 18
18 19
T.D. 19
18 18
15- 19
Pi
R L
17 20
22 22
T.D. 21
21 20
20- 24
n2
R L
24 24
28 28
27 26
26 26
24- 28
P2
R L
28 T.D.
33 32
31 30
31 31
29- 35
P3
R L
33 34
37 37
37 36
36 36
34- 40
T.D.—technical difficulties; N.Sm.—no smooth measurable.
THE ERG IN RETINAL DEGENERATION
313
Fig. 17 (Ruedemann). K784. (a) Central fundus, left eye. (b) Central fundus, right eye.
CENTRAL FIELD Left
Right
K. 784
B.D. 1/1000 WHITE
4-I0-63
NORMAL LIMITS ABNORMAL COLOR PERCEPTION Fig. 18 (Ruedemann). K784. Central fields reveal small central scotomas, O.U.
314
LO 16
A. D. RUEDEMANN, JR.
LO 4 20/sec.
Λ/ΧΛΝ/V NORMAL
NORMAL
Fig. 19a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K874, response is at the lower normal limits. Right side: L04 20/ sec. (Upper) Normal response. (Lower) K784, response is at the lower normal limits.
K. 7 8 4 B.D.
D04
Fig. 19b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K784, response is at lower normal limits. Right side: D016, fast sweep speed. (Upper) Nor mal response. (Lower) K784, re sponse is at lower normal limits.
0016 10 ft 5 msec/cm.
NORMAL
NORMAL
K.784 B.D.
K.784 B.D.
THE ERG IN RETINAL DEGENERATION
DR 16
315
C I II
m
# i | h ■ ; #4 Q.
Fig. 20 (Ruedemann). Pedigree of Family D3 (tables 13 and 14).
NORMAL
K.784 B.D. Fig. 19c (Ruedemann). DR16. (Upper) Normal response. (Lower) K784, response is at low nor mal limits.
Fig. 21 (Ruedemann). K934. Discrete central lesion, O.S.
L0I6
LO 4
NORMAL
K.934
20/sec.
NORMAL
H.G.
K.934
H.G.
Fig. 22a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K934. The response from the right and left eyes is slowed and reduced. Right side: L 0 4 20/sec. (Upper) Normal response. (Low er) K934. Reduced amplitudes.
A. D. RUEDEMANN, JR.
316
D04
DO 16 10 8 5 msec./cm.
NORMAL
Fig. 22b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K934, response from the right and left eyes is slowed and re duced. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) K934, response from the right and left eyes is slowed and reduced.
NORMAL
K.934 H.G. L04 20/sec. AVERAGED
Fig. 22c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K934, reduced and ab normal response. Right side: L04 20/sec, averaged. (Upper) Nor mal response. (Lower) K934, re duced amplitudes, O.U. Right eye has a "single hump" flicker re sponse.
NORMAL
K.934 sent a major proportion of the field. The clinical ERG represents a response to a diffuse stimulus. The entire retina is stimulated. A separation of photopic or cone function from scotopic or rod function must necessarily relate to minor, rather than major, changes in the ERG. Hereditary central retinal degeneration is characteristically polymorphic. Visual acui ty, visual fields and other psycho-physical
H.G.
NORMAL
K.934
H.G.
tests do not necessarily relate to the ophthalmoscopic picture. The disease may be pro gressive in certain families. In many cases the central lesion ophthalmoscopically does not correspond exactly to the visual fields or visual acuity. In many families the central lesion ap pears to be deep to the visual cells, involving pigment epithelium, Bruch's membrane or choroid.
THE ERG IN RETINAL DEGENERATION
317
TABLE 13 AMPLITUDES IN MICROVOLTS
K934 H. G. Brother (10 yr)
K944 M. G. Brother (11 yr)
K1021 E.G. Sister (12 yr)
K1022 R. L. G. Sister (6yr)
R L
46 96
77 100
66 44
107 64
T.D. 114
87-149
b-wave sharp
R L
168 162
189 243
168 172
219 172
T.D. 243
164-284
L 0 4 20/sec.
R L
26 20
20 26
26 20
26 25
T.D. 62
3 9 - 77
R L
32 40
53 57
53 29
10 T.D.
74 48
55-117
R L
221 250
326 401
358 306
316 201
305 334
302-514
R L
15 15
20 29
10 10
10 10
20 14
14- 38
x-wave
R L
26 39
31 29
15 10
31 39
46 48
5 1 - 97
b-smooth
R L
T.D. T.D.
97 95
112 59
T.D. T.D.
71 76
103-267
R
74 70
137 143
105 96
105 67
168 153
141-251
L
Pi
R L
74 70
137 143
105 96
105 67
179 162
131-241
ns
R L
95 110
179 182
136 124
137 105
211 191
172-276
P2
R L
53 80
96 115
105 67
84 86
126 105
119-283
Pu
R L
137 170
221 267
200 191
221 210
253 239
265-425
Averaged L 0 4 20/sec. R L
26 28
T.D. 24
44 44
31 30
42 T.D.
39- 77
FAMILY:
D3
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
D 0 1 6 (Fast sweep speed) II!
T.D.—technical difficulties.
K945 M. L. G. Sister (4yr)
Normal Range
A. D. R U E D E M A N N , JR.
318
TABLE 14 LATENCIES AND PEAK TIMES IN MILLISECONDS
K934 H. G. Brother (10 yr)
K944 M.G. Brother (11 yr)
K1021 E.G. Sister (12 yr)
K1022 R. L. G. Sister (6yr)
R L
24 20
20 20
22 22
20 20
T.D. 18
20- 24
R L
42 42
42 44
42 42
40 40
T.D. 40
39- 45
R L
32 28
32 32
32 32
32 34
28 28
2 9 - 33
R L
68 66
68 72
68 68
70 70
58 68
57- 77
R L
22 22
20 20
26 26
24 22
20 24
2 1 - 25
x-wave
R L
54 54
42 40
34 34
40 40
40 40
4 5 - 55
b-smooth
R L
T.D. T.D.
124 124
112 110
T.D. T.D.
120 120
90-138
4 4
4 4
4 4
7 8
4 4
FAMILY:
D3
L016 a-wave b-wave sharp D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast :sweep speed) a-wave R L
K945 M. L. G. Sister (4yr)
Normal Range
4-
5
111
R L
20 19
18 18
20 20
21 21
18 17
15- 19
Pi
R L
22 21
22 21
25 23
23 23
20 19
20- 24
Π2
R L
26 26
25 26
29 29
27 27
23 23
24- 28
P2
R L
30 31
29 30
34 33
31 31
27 27
2 9 - 35
Pa
R L
35 36
37 37
40 40
37 37
33 33
3 4 - 40
T.D.—technical difficulties.
THE ERG IN RETINAL DEGENERATION Fig. 23 (Ruedemann). L04 20/sec, averaged. (Upper) Normal response. (Lower) K944, both flicker responses are below normal amplitudes, but the averaged flicker response from the right, amblyopic, eye is much lower in amplitudes.
319
L04 20/sec. AVERAGED
NORMAL
The minimal visual changes associated with visible fundus changes would indicate that the primary lesion is not in the retina. T h e characteristic, though minimal, changes in the E R G evident in family grcups would also suggest that the primary lesion is not in the retina. T h e E R G changes may not occur until the outer cellular changes are so severe that rather marked involvement of the pos terior central visual cells (cones) has oc curred. In those cases with marked visual loss, mild fundus changes and well-circum scribed field loss, minimal E R G changes may also occur.
K.944
COMPUTERIZED LO 4 20/sec.
NORMAL
LO 4 20/sec.
Fig. 24 (Ruedemann). L04 20/ sec, averaged (Computerized). (Upper) Normal response. (Low er) Comparison of computer flicker of K984, peripheral retinal disease, and K982, central retinal disease, showing equal amplitudes but dif ference in character.
NORMAL
VW K. 984
K.H.
K.982
S.D.
A. D. RUEDEMANN, JR.
320
Comparing the E R G s of the first two families with obvious massive posterior in volvement and those with significantly less posterior involvement emphasizes the nota bly greater E R G diminution where more retinal involvement is present. W h e n large numbers of cone cells are de stroyed, as in cases of massive posterior central disease, the E R G is more severely affected. The changes involve the whole E R G but more prominently the photopic re sponses. In those cases of lesser central involve ment, though visual acuity is similarly re duced, the E R G changes are not as marked. Even so, the most prominent changes are on the photopic side. The fact that E R G changes are present when such a small amount of total retina is apparently affected indicates that the visual cells are diseased over a larger area than that surmised from routine tests—visual acuity, visual fields, ophthalmoscopy. The E R G changes would appear to relate quantitatively to the amount of central ret ina involved. CONCLUSIONS
1. Other laboratories have noted little or no change in the E R G in familial central retinal degeneration. W e feel that there are several reasons for this: ( a ) inadequate in strumentation, ( b ) measurement of the bwave only, (c) inaccurate interpretation of dark- and light-adapted E R G s and ( d ) in adequate preadaptation period. 2. It is necessary to have a reliable, re producible technique based on many nor mals. 3. It is necessary to accept the normal day-to-day variation in physiologic function and obtain a real knowledge of variability.
4. Considering the polymorphism noted in familial central tapetoretinal degenera tion, the E R G most reliably identifies the disease. 5. The E R G cannot locate the origin of the disease. 6. The primary E R G changes are photo pic. 7. In central retinal disease, as in periph eral retinal disease, the more visual cells in volved, the greater the changes in the E R G . 690 Mullett Street (26).
APPENDIX
In this report five stimuli from the standard procedure are included for comparison. The stimuli L016, D04, D016, DR16, L04 20/ second are obtained utilizing a Grass PS2 photic stimulator. The intensities refer to the dial set tings of the machine. The red filter is of plastic (Grass) and its transmission is restricted to wavelengths above 590 millimicrons. L016 is the maximum stimulus given in a light adapted state with no filter. L04 20/second is a subfusion flicker at inten sity 4, no filter. D04 and DO 16 are given after five minutes dark adaptation ; 4 and 16 refer to the dial set tings. DR (red) 16 is a red light given during dark adaptation at intensity 16. The L016 and L04 20/second stimuli are srbjected to computer analysis. REFERENCES
1. Ruedemann, A. D., Jr., and Noell, W. K. : A contribution to the electroretinogram of retinitis pigmentosa. Am. J. Ophth., 47:564 (Jan. Pt. II) 1959. 2. Ruedemann, A. D., Jr. : The electroretino gram in hereditary visual cell degeneration. Tr. Am. Acad. Ophth. Otolaryng., 63:142, 1959. 3. ■ : The electroretinogram in chronic methyl alcohol poisoning in human beings. Tr. Am. Ophth. Soc, 59:480, 1961. 4. Ruedemann, A. D., Jr., and Noell, W. K. : The electroretinogram in central retinal dgeneration. Tr. Am. Acad. Ophth. Otolaryng., 65:576, 1961. 5. Noell, W. K. : Personal communication.
DEGENERATION)
A. D. RUEDEMANN, JR., M.D. Detroit, Michigan The purpose of this paper is to describe the electroretinographic changes in heredi tary central retinal degeneration. I n this study, the various entities are grouped to gether under the following classification: A degenerative process primarily involving the central retina of both eyes, present in more than one member of a family. T h e vision may or may not be severely affected. Central fields may indicate a central scotoma. Ophthalmoscopic examination of several mem bers of a family reveal polymorphous changes predominantly involving the central retinal area. These usually cannot be related to acuity or fields.
e. Slow rounded b-wave with rela tively normal amplitude. f. Reduced, slowed, flattened flicker, "single hump flicker." 3. T h e E R G changes are notable. This indicates more pathologic alterations in the still-functioning retinal elements. Changes in the E R G indicate that a larger area of the retina is affected than just the macular area. T h e more retina involved, the greater the E R G changes. 4. T h e right and left eyes are not neces sarily similar.
T h e characteristic polymorphism of fa milial central retinal degeneration presents an intriguing problem in E R G evaluation. Several points may be made at the outset: 1. In our laboratory, involved members of a family invariably have an abnormal E R G . The E R G changes indicate similar abnormalities varying only in severity in the involved members. 2. The characteristic E R G changes are: a. Increased latency of the a-wave. b. Loss of a-wave amplitude particu larly of early components (n 1 ; p i ) . c. Notable convexity of the a-wave re lated to loss of amplitude. d. Reduction of a-wave amplitude, xcomponent of b-wave of red re sponse.
T h e electroretinographic techniques uti lized are essentially as previously de scribed. 1-3 In addition practically all of the patients have been tested in the lightadapted state, utilizing computer technique. A standard Mnemetron computer ( N o . 400B) is connected in series with a Tektronix dual beam oscilloscope ( N o . 5 0 2 ) . A second dual beam oscilloscope is used to dis play the added responses. A Mnemetron counter ( N o . 562) is utilized to predeter mine the number of stimuli to be counted
* From the Kresge Eye Institute, Wayne State University, and the Department of Ophthalmology, Detroit Receiving Hospital. This study was sup ported in part by the Detroit General Hospital Re search Corporation. Presented in part at the meet ing of the Wilmer Residents Association, The Johns Hopkins University and Hospital, Baltimore, Mary land, May, 1964, and at the Kresge Eye Institute 10th annual alumni reunion, Detroit, Michigan, September, 1964.
METHOD
(fig.i). T w o responses are utilized with the com puter, L 0 1 6 (approximately 50 flashes) and L 0 4 20/sec (approximately 500 flashes). The results are evaluated in the usual fash ion and compared to the normal range. RESULTS A.
C E N T R A L PIGMENTARY
Family
290
DEGENERATION
1 (tables 1 and 2 )
Mr. J. T., KISS, a 60-year-old white man, was first tested by ERG on October 10, 19S8. The pa tient stated that he had lost central vision in both eyes in his midforties. Vision in 1964 was reduced
THE ERG IN RETINAL DEGENERATION
291
HEADBAND LEFT GROUND CONTACT LENS INDIFFERENT CONTACT LENS RIGHT GROUND
Fig. 1. (Ruedemann). Sche matic drawing of equipment orienta tion. Contact lenses and headband are standard. Ruedemann-Noell ERG lenses, Jardon Laboratories, Detroit, Michigan. The square marked amplifier actually represents two Telecardio amplifiers and their power supply (a 45-volt battery for each amplifier). The filter box is preset at 0.1 cycles/second and 0.25 kilocycles/second.
COMPUTER DUAL-BEAM OSCILLOSCOPE
to less than 20/200, right eye; less than 20/200, left eye. Vision in the right eye was 20/50— in 1959. The right eye became intermittently dark. The patient had difficulty in bright light, sunlight diminished his vision. There was no history of retinal hemorrhage. Fundus examination showed large areas of central pigmentary degeneration (figs. 2-a and b). Visual fields reveal large cen tral scotomas (fig 3).
DUAL- BEAM OSCILLOSCOPE DISPLAY
The ERG, evaluated on three occasions, has remained essentially the same (figs. 4a, 4b and 4c), being typical for central retinal degeneration. This patient has been previously reported.4 The patient has a 58-year-old sister, K207, who has been evaluated by ERG on one occasion. Vision is reduced to 20/200. Ophthalmoscopic, visual fields, and ERG are essentially the same as those of her brother.
Fig. 2 (Ruedemann). KI55. (a) Central retinal area, left eye. The entire posterior central fundus is involved, (b) Central retinal area, right eye.
A. D. RUEDEMANN, JR.
292
TABLE 1 AMPLITUDE IN MICROVOLTS
K155 J. T. Brother (66 yr)
K207 C. S. Sister (58 yr)
K240 J. F. Sister (54 yr)
R L
46 50
89 122
T.D. 97
87-149
K L
77 85
211 216
T.D. 184
164-284
R L
25 25
44 55
T.D. 49
39- 77
R L
53 40
67 89
T.D. 42
55-117
R L
80 80
433 499
T.D. 316
302-514
R L
T.D. 10
22 11
T.D. 22
14- 38
x-wave
R L
20 20
33 33
T.D. 54
5 1 - 97
b-smooth
R L
36 55
144 194
T.D. 162
103-267
T.D. T.D.
N.I. N.I.
T.D. 137
141-251
FAMILY: Al
L016 a-wave b-vvave
L 0 4 20/sec. D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) n, R L
Normal Range
Pi
R L
T.D. T.D.
N.I. N.I.
T.D. 137
131-241
no
R L
53 70
N.I. N.I.
T.D. 179
172-276
P2
R L
42 40
N.I. N.I.
T.D. 105
119-283
P3
R L
105 100
N.I. N.I.
T.D. 242
265-425
R L
25 25
N.I. N.I.
N.I. N.I.
3 9 - 77
Averaged L 0 4 20/sec.
T.D.—technical difficulties; N.I.—not included in protocol. There is a 56-year-old sister, K240, who has 20/30 vision in both eyes and an essentially nor mal ERG. The only finding on this patient is angioid streaks in both eyes. There has been no evi dence of retinal hemorrhage in any of the three patients to date. No other family history has been recorded.
Family 2 (tables 3 and 4) Mrs. D. M., K55, a 45-year-old white woman,
noted acute loss of vision in the third grade asso ciated with a severe exanthematous process and high fever. A younger sister, Mrs. V. N., K59, aged 41 years had notable loss of vision at the same time with the same symptoms. The two sis ters had corrected vision of 20/200, O.U. No other family history could be elicited. Ophthalmoscopic examination was essentially the same in both sisters (fig. 5a and b). Visual fields were difficult to obtain but indicated definite central scotomas (fig. 6).
THE ERG IN RETINAL DEGENERATION
293
TABLE 2
LATENCIES AND PEAK TIMES IN MILLISECONDS K155 T.T. Brother (66 yr)
K207 C. S. Sister (58 yr)
K240 J. F . Sister (54 yr)
R L
28 30
25 25
T.D. 25
20- 24
R L
54 54
45 45
TD. 47
3 9 - 45
R L
36 36
33 33
T.D. 35
2 9 - 33
R L
80 80
57 57
T.D. 66
5 7 - 77
R L
T.D. 38
29 29
T.D. 29
2 1 - 25
x-wave
R L
20 20
41 41
T.D. 49
4 5 - 55
b-smooth
R L
128 140
119 119
T.D. 156
90-138
10 10
N.I. N.I.
T.D. 4
FAMILY: A l
L016 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) a-wave R L
Normal Range
4-
5
ni
R L
T.D. T.D.
N.I. N.I.
T.D. 18
15- 19
Pi
R L
T.D. T.D.
N.I. N.I.
T.D. 21
20- 24
n2
R L
32 31
N.I. N.I.
T.D. 27
24- 28
P2
R L
36 34
N.I. N.I.
T.D. 31
2 9 - 35
P3
R L
42 41
N.I. N.I.
T.D. 37
3 4 - 40
T.D.—technical difficulties; N.I.—not included in protocol. The ERG was essentially the same in both cases ; that of the older sister, K55, is shown in Figures 7a, 7b and 7c. Both sisters have been evaluated on three occasions and the ERGs have remained essentially the same (April 1958, 1960 and 1964). B. STARGARDT'S DISEASE
Family 1 (tables 5 and 6) S. D., K982, an 18-year-old white girl and R. D., K983, a 14-year-old white boy, had loss of visual acuity one year apart. K982 began to lose vision in 1955, K983 in 1956. Both children had
noted a progressive loss of vision since those dates. Present visual acuity was less than 20/200 in both eyes. The eye findings were negative ex cept for the ophthalmoscopic examination which revealed a definite stippling and a beaten-bronze appearance of the central retinal zones in both eyes. There was, however, involvement of the midperipheral retina as well. Color vision could not be evaluated in either child and visual fields were not too reliable because of poor acuity. There was no other family history. The ERGs were adequately recorded and markedly reduced to all intensity of stimuli. The latencies and peak times were increased (figs. 8a, 8b and 8c).
A. D. R U E D E M A N N , JR.
Left
CENTRAL FIELD Right
K.I55 J.T 4-30-64 18/1000 WHITE NORMAL LIMITS VISION TOO POOR TO EVALUATE FOR COLOR Fig. 3 (Ruedemann). KI55. Central fields, 18/1000 white, O.U.
LO 16
L 0 4 20/sec.
VH/X/V NORMAL
NORMAL
K. 155 J.T.
K. 155 J.T.
Fig. 4a (Ruedemann). Lightadapted ERG. The upper and lower pictures on the left are the response to a maximum intensity stimulus in the light, no filter ( L 0 1 6 ) . The upper left picture is recorded from a normal. Both eyes are recorded. The broad vertical bar is a 200 mV calibration sweep. The lower left picture is the response of K1S5 to the same stimulus. There is obvious slowing with reduction in both a- and b-wave amplitude. The pictures on the right are the responses to a 20/second flicker ( L 0 4 20/sec). In the upper pic ture, the response from the right and left eyes of a normal indi vidual is illustrated. In the lower picture the response from the right and left eyes of KISS may be noted. There is a marked reduction in amplitudes.
THE ERG IN RETINAL DEGENERATION
DO 4 Fig. 4b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal, response to moderate intensity stimulus with no filter. (Lower) Response of right and left eyes of K155. Left eye, broad tracing; right eye, nar row tracing. Note the slowing of the response with reduction in amplitudes. Right side: D016 10 and 5 msec/cm. (Upper) Response of normal right and left eyes to maximum intensity stimulus with fast oscilloscope sweep speeds. (Lower) K155, response is slowed and reduced.
DR 16
295
DO 16 10 8 5 msec/cm.
NORMAL
NORMAL
K.I55 J.T.
K.I55 J.T.
L04 20/sec. AVERAGED
Fig. 4c (Ruedemann). Left side: Dark-adapted red response (DR16). (Upper) Normal (Lower) K155, markedly reduced responses of both eyes. Right side: Light-adapt ed 20/second flicker averaged (L04 20/sec averaged). (Upper) Normal response. (Lower) K155, response is slowed and reduced in amplitude, "single hump" flicker.
NORMAL
NORMAL
K. 155 J.T.
K. 155 J.T.
C. VlTELLINE DEGENERATION OF THE MACULA
Family 1 (pedigree, fig. 9, tables 7 and 8 ) M. H., K764, a 28-year-old Negress, had 20/30 vision uncorrected, O.U. Exudative lesions involved the entire macular areas in both eyes. Visual fields were full, O.U. There were no cen tral scotomas. The ERG was reduced, particular
ly the a-wave. The latencies were increased but, actually, her ERG was not as well recorded as were those of her daughters. The eldest daughter, M. H., aged 13-years, K760, had noted some loss of central vision, espe cially in the left eye. Ophthalmoscopic examina tion revealed a lesion similar to those seen in cen tral serous retinopathy, most notable in the right eye (fig. 10a and b). Vision was 20/40 in the right eye and 20/25 in the left. Visual fields r<--
A. D. R U E D E M A N N . JR.
296 TABLE 3
at low-normal limits in both eyes, with increased latencies.
AMPLITUDES IN MICROVOLTS
KS5 D. M. Sister (38 yr)
FAMILY: Α2
L016 a-wave b-wave
b-smooth
Normal Range
15 34
56 39
87-149
R L
46 64
148 132
164-284
5 20
T.D. T.D.
39- 77
20 29
70 86
55-117
R L
150 200
240 191
302-514
25 20
T.D. T.D.
14- 38
R L
0 0
26 25
51- 97
«R L
107 132
N.Sm. N.Sm.
103-267
60 67
141-251
D016 (Fast sweep speed) R T.D. m L T.D.
The main feature of this family was that two of three members had no visual com plaints ; one had obvious central lesions, while all three had abnormal ERGs. D.
HEREDOMACULAR DEGENERATION
Family 1 (tables 9 and 10) O. S., K157, a 33-year-old white woman, had had notable loss of visual acuity most of her life. TABLE 4
R L
DR16 a-wave
b-smooth
y. N.
Sister (35 yr)
R L
L 0 4 20/sec. D04 a-wave
K59
LATENCIES AND PEAK TIMES IN MILLISECONDS
K55 D. M. Sister (38 yr)
K59 V. N. Sister (35 yr)
Normal Range
R L
28 26
26 26
2 0 - 24
R L
46 46
48 50
3 9 - 45
R L
40 40
38 38
2 9 - 33
R L
76 76
78 78
5 7 - 77
FAMILY A2
LOI 6 a-wave b-wave D04 a-wave b-smooth
R L
T.D. T.D.
60 67
131-241
50 67
100 96
172-276
R L
48 50
T.D. T.D.
2 1 - 25
R L R L
30 57.
30 T.D.
119-283
R L
0 0
54 48
4 5 - 55
P2
R L
60 96
100 96
265-425
R L
96 96
N.Sm. N.Sm.
90-138
P3
R L
5 13
T.D. 33
39- 77
Pi
Averaged L04 20/sec.
DR16 a-wave
b-smooth
T.D.—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolts. vealed a central scotoma of less than five degrees in both eyes (fig. 11). The E R G responses were re duced in amplitudes on the a-wave side. The la tencies and peak times were increased (figs. 12a, 12b and 12c). T. H., K765, a nine-year-old girl, was seen on two occasions. Actually, she had no visual difficulties and her eye examination was within normal limits. Vision was 20/30, O.U. The fundus findings were negative. Visual fields showed a small central scotoma, left eye. The E R G was
D016 (Fast sweep speed) R 10 L 10
10 10
4-
5
ni
R L
T.D. T.D.
22 21
15- 19
Pi
R L
T.D. T.D.
25 25
20- 24
n2
R L
32 31
31 31
24- 28
P2
R L
40 42
34 T.D.
2 9 - 35
Ps
R L
44 46
41 40
34- 40
T.D.—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolt.s
THE ERG IN RETINAL DEGENERATION
297
Fig. S (Ruedemann). K55. (a) Fundus, left eye. The changes in the fundus are essentially limited to the posterior central area (b) Fundus, right eye.
CENTRAL FIELD
Left
Right
K. 55
D.M. 5/1000 WHITE
4-24-64
VISION TOO POOR TO EVALUATE FOR COLOR Fig. 6 (Ruedemann). Central fields, KSS.
A. D. R U E D E M A N N , JR.
298
L0I6
LO 4 20/sec.
Λ/ΗΛ\Λ\Λ
NORMAL
K. 55 D.M.
NORMAL
K. 55 D.M. DO 16 10 8 5 msec/cm.
DO 4
Fig. 7b (Ruedemann). Darkadapted ERG. Left side: D 0 4 . (Upper) Normal response. (Lower) K5S, response is slowed and re duced, O.U. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) KSS, response is slowed and reduced, O.U.
Fig. 7a (Ruedemann). Lightadapted ERG. Left side: L 0 1 6 . (Upper) Normal response. (Lower) KS5, response is slowed and re duced, O.U. Right side: L 0 4 20/ sec. (Upper) Normal response. (Lower) K5S, response is practi cally flat, O.U.
NORMAL
NORMAL
K. 55 D.M.
K.55 D.M.
The patient has a sister with a similar disease. Visual acuity was reduced to less than 20/200 and the patient had poor fixation. Ophthalmoscopic examination revealed central lesions in both eyes ; the greatest changes seemed to be in the central pigment epithelium (fig. 13a and b ) . Visual fields were not reliable (fig. 14). The E R G showed marked loss of E R G components, particularly on the a-wave side (figs. 15a, 15b and ISc).
L. P., K1174, a 20-year-old white woman, showed findings similar in all respect to those of her sister. Family
2 ( p e d i g r e e , fig. 16, t a b l e s 11 a n d 1 2 )
T o date the father, mother and three sons have been evaluated by ERG. The mother had an es sentially normal E R G while the father and three
THE ERG IN RETINAL DEGENERATION
DR 16
Fig. 7c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K5S, response is slowed and reduced, O.U. Right side: L04 20/sec, averaged. (Upper) Normal response. (Lower) KS5, response is markedly reduced, "single hump flicker," O.U.
NORMAL
K.55 D.M. sons had abnormal ERGs. The mother had nor mal visual acuity. The father, B. D., K784, a 39-year-old white man, had macular lesions, O.U., (fig. 17-a and b) and a central scotoma (fig. 18), with reduced visual acuity and poor color vision in both eyes. The ERG was at the lower limits of normal and latencies were not increased (figs. 19a, 19b and 19c). The paternal mother had a similar disease. M. D., K782, a 14-year-old boy, had visual acu ity of 20/100 with granularity of both fundi and reduced and abnormal ERGs. This patient has been tested on two occasions. W. D., K780, a 16-year-old boy, had visual acuity of 20/100 in both eyes with a salt and pepper or gold-dust granularity of both maculas. B. D., K781, an 11-year-old boy, had visual acuity of 20/100, central scotomas, slightly defec tive color vision and essentially the same macular lesions. The ERGs in the three sons were essentially the same, reduced and abnormal. Latencies were not increased.
Family 3 (pedigree, fig. 20, tables 13 and 14) To date six members of this family, the moth er and five children, have been evaluated by ERG. The mother had a normal eye examination, except for nuclear cataracts, and a normal ERG. E. G., K1021, a nine-year-old Negress, had visual acuity correctable to 20/20, O.U. There was notable granularity of the macular area in both eyes and a central scotoma. The ERG was definitely abnormal to all intensity of stimuli. M. L. G., K94S, the four-year-old sister was evaluated by ERG. Visual fields, color test and
299
LO 4 20/sec. AVERAGED
NORMAL
K. 55 D.M.
visual acuity were essentially normal, as was the ERG. R. G., K1022, the six-year-old sister, was also evaluated by ERG. The ERG seemed to be below normal limits. H. G, K934, the 11-year-old brother, had cor rected visual acuity of 20/50 in both eyes ; dis crete central lesions were seen in both eyes (fig. 21) Color vision was normal. There were central scotomas. The ERG was generally reduced to all intensity of stimuli and components of response (figs. 22a, 22b and 22c). M. G, K944, the 10-year-old brother, had visual acuity of 20/200 in the amblyopic right eye. The vision in the left eye was 20/20. There was marked esotropia, a definite central scotoma by central fields, and a questionable macular le sion by ophthalmoscopy. The ERG was definitely reduced in both eyes, more so in the right eye. There was a marked difference between the ERGs of the right and left eyes. This was par ticularly shown in the computer ERG which showed a marked loss in the flicker, particularly in the right eye (fig. 23). DISCUSSION OF RESULTS
Twenty-one patients in seven families having various types of central retinal de generation have been evaluated in this labo ratory. A number of other cases of macular lesions and no family history have also been evaluated by routine ERG. The results are similar in most cases. In the introduction certain points relating to the ERG changes in heredomacular de-
A. D. R U E D E M A N N , JR.
300 TABLE 5
AMPLITUDES IN MICROVOLTS
K982 S. D. Sister (18 yr)
K983 R. D. Brother (13 yr)
R L
31 39
T.D. 34
87-149
b-wave
R L
36 49
T.D. 39
164-284
L 0 4 20/sec.
R L
10 15
T.D. T.D.
Ά9- 77
FAMILY: Bl
L016 a-wave
Ü04 a-wave b-smooth DR16 a-wave
b-smooth
Normal Range
TABLE 6
R L
10 19
40 29
55-117
R L
110 172
170 172
302-514
R L
5 5
14- 38
R L
15 15
51- 97
R L
N.Sm. N.Sm.
D016 (Fast sweep speed) T.D. R L T.D.
wave. Eight of the 10 cases had increased time measurements for other a-wave re sponses, LOI6, D04, DR 16. The peak time for a-wave was increased in 12 of 21 cases for L 0 1 6 ; nine of 20 cases for D 0 4 ; 12 of 18 cases for DR16. The negative humps of the a-wave for DO 16, ni and n2 were increased in eight of 17 cases and nine of 20 cases, respectively. The positive hump of the a-wave pi had an
103-267
50 57
141-251
LATENCIES AND PEAK TIMES IN MILLISECONDS
FAMILY:
K982 S. D. Sister (18 yr)
K893 R. D. Brother (13 yr)
Normal Range
R L
24 28
T.D. 28
20- 24
R L
52 54
T.D. 38
3 9 - 45
R L
36 36
34 34
2 9 - 33
R L
72 76
76 76
57- 77
Bl
L016 a-wave b-wave D04 a-wave b-smooth
Pi
R L
T.D. T.D.
50 57
131-241
R L
60 57
70 76
172-276
R L
40 40
0 0
2 1 - 25
n2
R L
10 19
T.D. 19
119-283
R L
60 60
0 0
4 5 - 55
P!
R L
80 67
T.D. 76
265-425
R L
N.Sm. N.Sm.
0 0
90-138
Ps
R L
10 15
T.D. 13
39- 77
Averaged L 0 4 20/sec.
DR16 a-wave
b-smooth
D016 (Fast sweep speed) 12 R 12 L
generation were made : 1. Involved members of a family have an abnormal ERG. These changes vary only in severity in the involved members. 2. The characteristic ERG changes are: a. Increased latency of the a-wave. Of 20 cases, 10 had increased latency of the a-
5
R L
T.D. T.D.
20 19
15- 19
Pi
R L
T.D. T.D.
23 23
2 0 - 24
n2
R L
30 30
30 29
24- 28
R L
34 34
T.D. 32
29- 35
R L
42 42
T.D. 40
34- 40
111
T.D.—technical difficulties; N.Sm—no smooth measurable; O—flat or less than 5 microvolts.
4-
Pa
T.D.-—technical difficulties; N.Sm.—no smooth measurable; O—flat or less than 5 microvolts.
THE ERG IN RETINAL DEGENERATION
L016
301
L 0 4 20/sec.
VS/S/ΝΛ Fig. 8a (Ruedemann). Lightadapted ERG. Left side: L016 (Upper) Normal response. (Lower) K982, note reduced and slowed re sponse, O.U. Right side: L04 20/ sec. (Upper) Normal response. (Lower) K982, the flicker response is practically flat, O.U.
NORMAL
K.982 increased latency in only one of 17 cases measured. b. Loss of a-wave amplitude. Of 21 cases, 13 had reduced a-wave amplitude for L 0 1 6 ; 14 of 20 cases had reduced a-wave amplitude for D 0 4 ; and eight of 18 cases had reduced a-wave amplitude for DR16. For the early components of DO 16— ni, pi, n2, the amplitudes were reduced be low the normal range in 12 of 17 cases for
D04
K.982
S.D.
iii; 11 of 17 cases for pi; 11 of 20 cases for p 2 . c. Notable convexity of the a-wave re lated to loss of amplitude is best noted in the response to D04. A convex a-wave was seen in 16 of 21 cases. d. Reduction of a-wave amplitude and x-component of b-wave, red response. The a-wave portion of the red response is difficult to measure. The x-component of the
D016 10 a 5 msec/cm.
NORMAL
K.982
S.D.
NORMAL
Fig. 8b (Ruedemann). Darkadapted ERG. Left side: D04 (Up per) Normal response. (Lower) K982, slowed and reduced response. Upsweep at the end of the response is due to lid activity. Right side: D016, fast sweep speed. (Upper) Normal response. (Lower) K982, response is markedly slowed and re duced.
NORMAL
S.O.
K.982
S.D.
A. D. RUEDEMANN, JR.
302
DR 16
L04 20/sec. AVERAGED
NORMAL
K.982
NORMAL
S.D.
K.982
b-wave is usually clearly recognized. In this series, 18 of 20 cases had an x-wave below normal range. e. Slow rounded b-wave with relatively normal amplitudes. This statement encom passes three distinct factors: the observed round, smoothed wave form, the slowed re sponse and the diminished amplitudes. In 21 cases, 15 had a rounded b-wave; nine cases had increased b-wave peak time; 16 cases had reduced b-wave amplitude. f. Reduced, slowed, flattened flicker, "single hump flicker." Again, observation is important. It is likely that the slowed re sponse tends to fuse the two humps of the flicker response. The amplitude measure ment is a separate function. In this series,
B I
m
Fig. 8c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K982, practically flat re sponse, O.U. Right side: L04 20/ sec, averaged. (Upper) Normal response. (Lower) K982, "single hump" flicker response.
EH8>*
Fig. 9 (Ruedemann). Pedigree of Family Cl (tables 7 and 8).
15 of 20 cases had a "single hump flicker" while 13 of 18 cases had a reduced ampli tude. (These values are obtained from rou tine and computer records.) 3. The results are straightforward. In disease of the central retina it would appear that the ERG changes are similar. The ERG changes would indicate a larger area of retina is involved than that limited to the area of the macula. 4. The right and left eyes are not neces sarily similar. This is shown very nicely in K944, M. G., who had 20/20 vision in one eye and 20/200 in the other eye. The ERG was reduced in the amblyopic eye. This difference is striking when one compares the computer 20/sec. flicker. Several important differentials must be made: The difference between peripheral retinal disease and central retinal disease. By com paring a young woman with night blindness and normal central visual acuity with one of the patients in this series some standard of comparison is provided: K. H., K984, a 17-year-old white girl, had corrected visual acuity of 20/20—, O.U.. She had a history of night blindness. Her sister had night blindness. K984 had congenital deafness. Visual fields revealed partial midring scotomas with (Text continued on page 308)
T H E ERG IN RETINAL DEGENERATION
303
TABLE 7 AMPLITUDES IN MICROVOLTS
K764 M. H. Mother (28 yr)
K760 M. H. Daughter (13 yr)
K765 T. H. Daughter (9yr)
Normal Range
R L
33 51
74 65
56 56
87-149
b-wave
R L
130 176
125 116
130 140
164-284
L 0 4 20/sec.
R L
T.D. T.D.
23 33
33 33
3 9 - 77
R L
T.D. T.D.
96 76
38 38
55-117
R L
T.D. T.D.
277 248
258 258
302-514
R L
T.D. T.D.
5 5
T.D. T.D.
14- 38
x-wave
R L
T.D. T.D.
33 14
28 19
5 1 - 97
b-smooth
R L
T.D. T.D.
N.Sm. N.Sm.
N.Sm. N.Sm.
103-267
FAMILY: C l
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
D 0 1 6 (Fast sweep speed) L
R
96 86
115 115
143 124
141-251
Pi
R L
86 86
105 105
143 124
131-241
Π2
R L
162 162
201 182
201 182
172-276
P2
R L
57 96
86 86
105 86
119-283
P3
R L
162 220
162 162
201 182
265-425
R L
T.D. T.D.
T.D. T.D.
T.D. T.D.
ni
Averaged L 0 4 20/sec.
T.D.—technical difficulties; N.Sm.—no smooth measurable.
3 9 - 77
A. D. RUEDEMANN, JR.
304
TABLE 8 LATENCIES AND PEAK TIMES IN MILLISECONDS K764 M. H. Mother (28 yr)
K760 M. H. Daughter (13 yr)
K76S T. H . Daughter (9yr)
R L
26 24
22 24
20 20
20- 24
R L
42 42
40 40
38 38
3 9 - 45
R L
T.D. T.D.
32 30
30 30
29- 33
R L
T'D. T.D.
68 66
64 64
57- 77
R L
T.D. T.D.
22 20
T.D. T.D.
2 1 - 25
x-wave
R L
T.D. T.D.
40 40
T.D. T.D.
4 5 - 55
b-smooth
R L
T.D. T.D.
N.Sm. N.Sm.
T.D. T.D.
90-138
FAMILY: C l
LOI 6 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast sweep speed) R a-wave L
4 6
4 4
5 5
Normal Range
4-
5
m
R L
20 18
16 16
20 17
15- 19
Pi
R L
22 20
22 22
21 22
20- 24
n2
R L
30 29
28 28
27 26
24- 28
P2
R L
34 33
31 32
30 30
29- 35
Pa
R L
40 39
38 38
36 35
34- 40
T.D.·—technical difficulties; N.Sm.—no smooth measurable.
THE ERG IN RETINAL DEGENERATION
30S
Fig. 10. (Ruedemann). K760. (a) Central lesion, left eye. (b) Central lesion, right eye. Note the difference in the photos of the two eyes.
CENTRAL FIELD
Left
Right
K.760
M.H. 7-31-64 1/1000 WHITE NORMAL COLOR PERCEPTION
Fig. 11 (Ruedemann). K760. Central fields.
A. D. RUEDEMANN, JR.
306
L04
20/sec.
Fig. 12a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K760, slowed and reduced re sponse. Right side: L04 20/sec. (Upper) Normal response. (Low er) K760, reduced response, O.U.
K.760
M. H.
K.760
M.H. D016 10 8k 5 msec/cm.
D04
Fig. 12b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K760. The response is slowed and amplitudes are reduced, O.U. Right side: DO 16, fast sweep speed. (Upper) Normal response. (Lower) K760. The response is slowed and reduced, O.U.
K.760 DR 16
M.H.
K.760
M.H.
L04 20/sec. AVERAGED
Fig. 12c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K760, response is slowed and reduced. Right side: L04 20/ sec, averaged. (Upper) Normal response. (Lower) K760, responses are reduced, O.U.
K.760
M.H.
K.760
M.H.
THE ERG IN RETINAL DEGENERATION
307
Fig. 13 (Ruedemann). K1S7. (a) Central fundus, left eye. (b) Central fundus, right eye.
Left
CENTRAL FIELD Right
K. 157 O.S. 3/IOOO WHITE NORMAL LIMITS
2-4-64
ABNORMAL COLOR PERCEPTION Fig. 14 (Ruedemann). K157. Central fields.
A. D. RUEDEMANN, JR.
308 TABLE 9
The differences between peripheral retinal disease (characterized by night blindness,
AMPLITUDES IN MICROVOLTS
K157 O.S. Sister (33 yr)
K1174 L. P. Sister (20 yr)
R L
56 74
78 88
87-149
b-wave
R L
117 132
230 260
164-284
L 0 4 20/sec.
R L
15 20
34 42
3 9 - 77
R L
32 67
48 67
55-117
R L
347 353
FAMILY: D l
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
392 430
Normal Range
302-514
R L
5 5
0 0
14- 38
x-wave
R L
10 20
15 14
5 1 - 97
b-smooth
R L
87 132
93 98
103-267
DO 16 (Fast sweepispeed) 63 R m 67 L
143 124
141-251
Pi
R L
63 67
134 124
131-241
Π2
R L
158 162
191 191
172-276
P2
R L
74 105
105 96
119-283
P»
R L
168 201
287 287
265-425
R L
7 10
9 13
3 9 - 77
Averaged L 0 4 20/sec.
O—flat or 1less than 5 microvolts. marked loss of field peripherally. Ophthalmoscopic examination revealed some waxy pallor of the disc with attenuation of the vessels and granular pig mentation of the retina, O.U.,, more marked in the right eye. The E R G was markedly reduced to all intensity of stimulii, limiting the ιcomparison of ERGs to the computer or light-adapted E R G . The cornputer flicker of K984 and K982 showed that the amplitudes were essentially the same while the character of the flicker was markedly different (fig. 24).
loss of peripheral field, peripheral retinal change by ophthalmoscopy and normal or nearly normal visual acui ty) and central retinal disease by ERG are: 1. In peripheral deg eneration there is marked loss of amplitudes throughout the ERG, more notable in the b-wave amplitudes. The a-wave is the last to disappear. The time of onset of various components is
T A B L E 10 LATENCIES AND PEAK TIMES IN MILLISECONDS
K157 O.S. Sister (33 yr)
K1174 L. P. Sister (20 yr)
Normal Range
R L
28 28
28 26
2 0 - 24
R L
42 42
42 42
3 9 - 45
R L
38 36
38 36
2 9 - 33
R L
80 78
68 66
5 7 - 77
R L
40 36
32 32
2 1 - 25
x-wave
R L
58 54
50 54
4 5 - 55
b-smooth
R L
146 140
132 130
90-138
DO 16 (Fast sweep speed) R a-wave 5 L 5
5 6
FAMILY: D l
L016 a-wave b-wave D04 a-wave b-smooth DR16 a-wave
4-
5
ni
R L
20 19
20 21
15- 19
Pi
R L
22 21
23 23
2 0 - 24
n2
R L
30 29
29 29
2 4 - 28
P2
R L
34 34
33 33
2 9 - 35
Pa
R L
39 39
40 40
3 4 - 40
THE ERG IN RETINAL DEGENERATION
LOI6
309
L04 20/sec.
VSNV Fig. 15a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K157, slightly slowed and re duced response, O.U. Right side: L04 20/sec. (Upper) Normal re sponse. (Lower) K1S7, markedly reduced response.
NORMAL
K. 157 O.S. D04
K. 157 O.S.
DO 16 10 a 5 msec/cm.
NORMAL
O.S.
Fig. 15b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K1S7, markedly reduced re sponse. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) K157, the most notable changes are in the a-wave which is slowed and convex and reduced in amplitude.
NORMAL
-
K. 157
NORMAL
^
K. 157
normal until late in the disease when the, ERG is practically nonrecordable. The pho topic flicker, though reduced, has normal configuration. 2. In central retinal disease, there is some loss of a-wave amplitude. There is definite showing in onset of the ERG. All of the
O.S. photopic components are reduced and slowed, as evidenced by the flicker which is reduced to a single wave that lacks all com ponents. 3. The origin of the disease cannot be de termined by ERG. A disease originating in the choroid or pigment epithelium will not
A. D. RUEDEMANN, JR.
310
L04 20/sec AVERAGED
OR 16
Fig. 15c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K157, markedly reduced response. Right side: L04 20/sec, averaged. (Upper) Normal re sponse. (Lower) K1S7, markedly reduced response.
NORMAL
NORMAL
K. 157 O.S.
K. 157 O.S.
affect the ERG until enough visual cells are nonfunctional to cause a change in the ERG. Some cases have been studied, for exam ple, B. D., K784, in which there may be visual loss with central scotomas but there are obvious central fundus changes. The ERG is low normal in amplitude with nor mal latencies and peak times. These cases can be compared to those with marked cen tral involvement, poor visual acuity and gross central defects by central field. In experimental animals with hereditary visual cell degeneration, Noell5 has demon-
strated viable visual cells with a nonrecordable ERG. When one considers the anatomy of the posterior central retina, several features be come evident. The area of maximum cone concentration, called the macula lutea, is limited to an area about two mm in diameter. Cone concentration diminishes progressive ly, radially from the center of the macula, the fovea centralis. The area of field loss when the entire macula is destroyed is ap proximately 7.6 degrees. In terms of the total area of visual field, this does not repre(Text continued on page 316)
AI
π
f ? Φ? «fo
in QiiifrQ
άώ
m Fig. 16 (Ruedemann). Pedigree of Family D2 (tables 11 and 12).
T H E ERG IN RETINAL DEGENERATION
311
TABLE 11 AMPLITUDES IN MICROVOLTS K784 B. D . Father (39 yr)
K780 W. D. Son (16 yr)
K781 B. D . Son (11 yr)
K782 M. D. Son (14 yr)
R L
116 88
80 98
65 74
88 70
87-149
b-wave
R L
200 186
144 172
140 158
228 186
164-284
L 0 4 20/sec.
R L
46 51
33 42
33 33
42 42
3 9 - 77
R L
67 76
48 48
48 67
67 76
55-117
R L
353 373
258 306
277 315
449 325
302-514
R L
23 28
14 14
14 T.D.
19 19
14- 38
x-wave
R L
61 33
19 23
23 19
23 19
5 1 - 97
b-smooth
R L
T.D. 153
N.Sm. N.Sm.
N.Sm. N.Sm.
N.Sm. N.Sm.
103-267
172 134
115 124
T.D. 124
105 96
141-251
FAMILY: D2
L016 a-wave
D04 a-wave b-wave DR16 a-wave
D 0 1 6 (Fast ί»weep speed) R ni L
Normal Range
Pi
R L
172 134
115 124
T.D. 124
96 96
131-241
ns
R L
220 201
143 162
153 191
182 153
172-276
P2
R L
124 T.D.
115 124
67 96
153 124
119-283
P3
R L
239 229
153 172
153 191
277 229
265-425
Average L 0 4 R 20/sec. L
N.I. N.I.
N.I. N.I.
N.I. N.I.
N.I. N.I.
3 9 - 77
T.D.—technical difficulties; N.Sm.—no smooth measurable; N.I.—not included in protocol.
A. D. RUEDEMANN, JR.
312
TABLE 12 LATENCIES AND PEAK TIMES IN MILLISECONDS K784 B . D . Father (39 yr)
K780 W. D. Son (16 yr)
K781 B. D . Son (11 yr)
K782 M . D. Son (14 yr)
R L
20 22
26 26
26 24
22 22
20- 24
R L
40 42
38 38
40 40
38 38
39- 45
R L
30 30
32 32
36 34
32 32
29- 33
R L
64 64
68 68
74 70
68 68
57- 77
R L
30 28
32 30
28 T.D.
24 24
2 1 - 25
x-wave
R L
46 44
40 40
46 44
40 40
4 5 - 55
b-smooth
R L
T.D. 120
N.Sm. N.Sm.
N.Sm. N.Sm.
N.Sm. N.Sm.
90-138
FAMILY: D2
L016 a-wave b-wave D04 a-wave b-wave DR16 a-wave
D016 (Fast sweep speed) a-wave R L
4 5
4 4
4 4
4 4
Normal Range
4-
5
ni
R L
IS 18
18 19
T.D. 19
18 18
15- 19
Pi
R L
17 20
22 22
T.D. 21
21 20
20- 24
n2
R L
24 24
28 28
27 26
26 26
24- 28
P2
R L
28 T.D.
33 32
31 30
31 31
29- 35
P3
R L
33 34
37 37
37 36
36 36
34- 40
T.D.—technical difficulties; N.Sm.—no smooth measurable.
THE ERG IN RETINAL DEGENERATION
313
Fig. 17 (Ruedemann). K784. (a) Central fundus, left eye. (b) Central fundus, right eye.
CENTRAL FIELD Left
Right
K. 784
B.D. 1/1000 WHITE
4-I0-63
NORMAL LIMITS ABNORMAL COLOR PERCEPTION Fig. 18 (Ruedemann). K784. Central fields reveal small central scotomas, O.U.
314
LO 16
A. D. RUEDEMANN, JR.
LO 4 20/sec.
Λ/ΧΛΝ/V NORMAL
NORMAL
Fig. 19a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K874, response is at the lower normal limits. Right side: L04 20/ sec. (Upper) Normal response. (Lower) K784, response is at the lower normal limits.
K. 7 8 4 B.D.
D04
Fig. 19b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K784, response is at lower normal limits. Right side: D016, fast sweep speed. (Upper) Nor mal response. (Lower) K784, re sponse is at lower normal limits.
0016 10 ft 5 msec/cm.
NORMAL
NORMAL
K.784 B.D.
K.784 B.D.
THE ERG IN RETINAL DEGENERATION
DR 16
315
C I II
m
# i | h ■ ; #4 Q.
Fig. 20 (Ruedemann). Pedigree of Family D3 (tables 13 and 14).
NORMAL
K.784 B.D. Fig. 19c (Ruedemann). DR16. (Upper) Normal response. (Lower) K784, response is at low nor mal limits.
Fig. 21 (Ruedemann). K934. Discrete central lesion, O.S.
L0I6
LO 4
NORMAL
K.934
20/sec.
NORMAL
H.G.
K.934
H.G.
Fig. 22a (Ruedemann). Lightadapted ERG. Left side: L016. (Upper) Normal response. (Low er) K934. The response from the right and left eyes is slowed and reduced. Right side: L 0 4 20/sec. (Upper) Normal response. (Low er) K934. Reduced amplitudes.
A. D. RUEDEMANN, JR.
316
D04
DO 16 10 8 5 msec./cm.
NORMAL
Fig. 22b (Ruedemann). Darkadapted ERG. Left side: D04. (Upper) Normal response. (Low er) K934, response from the right and left eyes is slowed and re duced. Right side: D016, fast sweep speed. (Upper) Normal re sponse. (Lower) K934, response from the right and left eyes is slowed and reduced.
NORMAL
K.934 H.G. L04 20/sec. AVERAGED
Fig. 22c (Ruedemann). Left side: DR16. (Upper) Normal response. (Lower) K934, reduced and ab normal response. Right side: L04 20/sec, averaged. (Upper) Nor mal response. (Lower) K934, re duced amplitudes, O.U. Right eye has a "single hump" flicker re sponse.
NORMAL
K.934 sent a major proportion of the field. The clinical ERG represents a response to a diffuse stimulus. The entire retina is stimulated. A separation of photopic or cone function from scotopic or rod function must necessarily relate to minor, rather than major, changes in the ERG. Hereditary central retinal degeneration is characteristically polymorphic. Visual acui ty, visual fields and other psycho-physical
H.G.
NORMAL
K.934
H.G.
tests do not necessarily relate to the ophthalmoscopic picture. The disease may be pro gressive in certain families. In many cases the central lesion ophthalmoscopically does not correspond exactly to the visual fields or visual acuity. In many families the central lesion ap pears to be deep to the visual cells, involving pigment epithelium, Bruch's membrane or choroid.
THE ERG IN RETINAL DEGENERATION
317
TABLE 13 AMPLITUDES IN MICROVOLTS
K934 H. G. Brother (10 yr)
K944 M. G. Brother (11 yr)
K1021 E.G. Sister (12 yr)
K1022 R. L. G. Sister (6yr)
R L
46 96
77 100
66 44
107 64
T.D. 114
87-149
b-wave sharp
R L
168 162
189 243
168 172
219 172
T.D. 243
164-284
L 0 4 20/sec.
R L
26 20
20 26
26 20
26 25
T.D. 62
3 9 - 77
R L
32 40
53 57
53 29
10 T.D.
74 48
55-117
R L
221 250
326 401
358 306
316 201
305 334
302-514
R L
15 15
20 29
10 10
10 10
20 14
14- 38
x-wave
R L
26 39
31 29
15 10
31 39
46 48
5 1 - 97
b-smooth
R L
T.D. T.D.
97 95
112 59
T.D. T.D.
71 76
103-267
R
74 70
137 143
105 96
105 67
168 153
141-251
L
Pi
R L
74 70
137 143
105 96
105 67
179 162
131-241
ns
R L
95 110
179 182
136 124
137 105
211 191
172-276
P2
R L
53 80
96 115
105 67
84 86
126 105
119-283
Pu
R L
137 170
221 267
200 191
221 210
253 239
265-425
Averaged L 0 4 20/sec. R L
26 28
T.D. 24
44 44
31 30
42 T.D.
39- 77
FAMILY:
D3
L016 a-wave
D04 a-wave b-smooth DR16 a-wave
D 0 1 6 (Fast sweep speed) II!
T.D.—technical difficulties.
K945 M. L. G. Sister (4yr)
Normal Range
A. D. R U E D E M A N N , JR.
318
TABLE 14 LATENCIES AND PEAK TIMES IN MILLISECONDS
K934 H. G. Brother (10 yr)
K944 M.G. Brother (11 yr)
K1021 E.G. Sister (12 yr)
K1022 R. L. G. Sister (6yr)
R L
24 20
20 20
22 22
20 20
T.D. 18
20- 24
R L
42 42
42 44
42 42
40 40
T.D. 40
39- 45
R L
32 28
32 32
32 32
32 34
28 28
2 9 - 33
R L
68 66
68 72
68 68
70 70
58 68
57- 77
R L
22 22
20 20
26 26
24 22
20 24
2 1 - 25
x-wave
R L
54 54
42 40
34 34
40 40
40 40
4 5 - 55
b-smooth
R L
T.D. T.D.
124 124
112 110
T.D. T.D.
120 120
90-138
4 4
4 4
4 4
7 8
4 4
FAMILY:
D3
L016 a-wave b-wave sharp D04 a-wave b-smooth DR16 a-wave
DO 16 (Fast :sweep speed) a-wave R L
K945 M. L. G. Sister (4yr)
Normal Range
4-
5
111
R L
20 19
18 18
20 20
21 21
18 17
15- 19
Pi
R L
22 21
22 21
25 23
23 23
20 19
20- 24
Π2
R L
26 26
25 26
29 29
27 27
23 23
24- 28
P2
R L
30 31
29 30
34 33
31 31
27 27
2 9 - 35
Pa
R L
35 36
37 37
40 40
37 37
33 33
3 4 - 40
T.D.—technical difficulties.
THE ERG IN RETINAL DEGENERATION Fig. 23 (Ruedemann). L04 20/sec, averaged. (Upper) Normal response. (Lower) K944, both flicker responses are below normal amplitudes, but the averaged flicker response from the right, amblyopic, eye is much lower in amplitudes.
319
L04 20/sec. AVERAGED
NORMAL
The minimal visual changes associated with visible fundus changes would indicate that the primary lesion is not in the retina. T h e characteristic, though minimal, changes in the E R G evident in family grcups would also suggest that the primary lesion is not in the retina. T h e E R G changes may not occur until the outer cellular changes are so severe that rather marked involvement of the pos terior central visual cells (cones) has oc curred. In those cases with marked visual loss, mild fundus changes and well-circum scribed field loss, minimal E R G changes may also occur.
K.944
COMPUTERIZED LO 4 20/sec.
NORMAL
LO 4 20/sec.
Fig. 24 (Ruedemann). L04 20/ sec, averaged (Computerized). (Upper) Normal response. (Low er) Comparison of computer flicker of K984, peripheral retinal disease, and K982, central retinal disease, showing equal amplitudes but dif ference in character.
NORMAL
VW K. 984
K.H.
K.982
S.D.
A. D. RUEDEMANN, JR.
320
Comparing the E R G s of the first two families with obvious massive posterior in volvement and those with significantly less posterior involvement emphasizes the nota bly greater E R G diminution where more retinal involvement is present. W h e n large numbers of cone cells are de stroyed, as in cases of massive posterior central disease, the E R G is more severely affected. The changes involve the whole E R G but more prominently the photopic re sponses. In those cases of lesser central involve ment, though visual acuity is similarly re duced, the E R G changes are not as marked. Even so, the most prominent changes are on the photopic side. The fact that E R G changes are present when such a small amount of total retina is apparently affected indicates that the visual cells are diseased over a larger area than that surmised from routine tests—visual acuity, visual fields, ophthalmoscopy. The E R G changes would appear to relate quantitatively to the amount of central ret ina involved. CONCLUSIONS
1. Other laboratories have noted little or no change in the E R G in familial central retinal degeneration. W e feel that there are several reasons for this: ( a ) inadequate in strumentation, ( b ) measurement of the bwave only, (c) inaccurate interpretation of dark- and light-adapted E R G s and ( d ) in adequate preadaptation period. 2. It is necessary to have a reliable, re producible technique based on many nor mals. 3. It is necessary to accept the normal day-to-day variation in physiologic function and obtain a real knowledge of variability.
4. Considering the polymorphism noted in familial central tapetoretinal degenera tion, the E R G most reliably identifies the disease. 5. The E R G cannot locate the origin of the disease. 6. The primary E R G changes are photo pic. 7. In central retinal disease, as in periph eral retinal disease, the more visual cells in volved, the greater the changes in the E R G . 690 Mullett Street (26).
APPENDIX
In this report five stimuli from the standard procedure are included for comparison. The stimuli L016, D04, D016, DR16, L04 20/ second are obtained utilizing a Grass PS2 photic stimulator. The intensities refer to the dial set tings of the machine. The red filter is of plastic (Grass) and its transmission is restricted to wavelengths above 590 millimicrons. L016 is the maximum stimulus given in a light adapted state with no filter. L04 20/second is a subfusion flicker at inten sity 4, no filter. D04 and DO 16 are given after five minutes dark adaptation ; 4 and 16 refer to the dial set tings. DR (red) 16 is a red light given during dark adaptation at intensity 16. The L016 and L04 20/second stimuli are srbjected to computer analysis. REFERENCES
1. Ruedemann, A. D., Jr., and Noell, W. K. : A contribution to the electroretinogram of retinitis pigmentosa. Am. J. Ophth., 47:564 (Jan. Pt. II) 1959. 2. Ruedemann, A. D., Jr. : The electroretino gram in hereditary visual cell degeneration. Tr. Am. Acad. Ophth. Otolaryng., 63:142, 1959. 3. ■ : The electroretinogram in chronic methyl alcohol poisoning in human beings. Tr. Am. Ophth. Soc, 59:480, 1961. 4. Ruedemann, A. D., Jr., and Noell, W. K. : The electroretinogram in central retinal dgeneration. Tr. Am. Acad. Ophth. Otolaryng., 65:576, 1961. 5. Noell, W. K. : Personal communication.