Normal Pattern Electroretinograms in Amblyopia

No. 1 Reports 187

mit one to see only the occasional extreme case of an 2. Williams DS and Blest AD: Extracellular shedding of photore- alteration that can be detected more readily when lu- ceptor membrane in the open rhabdom of a tipulid fly. Cell Tissue Res 205:423, 1980. cifer yellow is employed as an extracellular probe. 3. Young RW and Bok D: Participation of the retinal pigment ep- In conclusion, our results show that mechanical dis- ithelium in the rod outer segment renewal process. J Cell Biol ruption of the intact relationship between the ROSs 42:392, 1969. and the RPE and/or interphotoreceptor matrix pre- 4. O'Day WT and Young RW: Rhythmic daily shedding of outer vents the abscission of the terminal disks under con- segment membranes by visual cells in the goldfish. J Cell Biol ditions in which they would normally be shed. Partic- 76:593, 1978. 5. Young RW: Shedding of discs from rod outer segments in the ularly in view of the above discussion, this finding does Rhesus monkey. J Ultrastruct Res 34:190, 1971. not necessarily mean that the RPE actively bites off 6. Spitznas M and Hogan MJ: Outer segments of photoreceptors the ends of ROSs by "piecemeal phagocytosis" without and the retinal pigment epithelium. Arch Ophthalmol 84:810, any participation by the rods, but it does indicate that 1970. the neural retina does not have autonomous control 7. Bok D and Young RW: Phagocytic properties of the retinal pigment epithelium. In The Retinal Pigment Epithelium, Zinn KM over the shedding of its ROS disks. and Marmor MF, editors. Cambridge, MA, Harvard University Key words: photoreceptor outer segments, rod disk, retinal Press, 1979, pp. 148-174. 8. Besharse JC: The daily light-dark cycle and rhythmic metabolism pigment epithelium, membrane turnover, retinal detachment in the photoreceptor-pigment epithelial complex. Prog Retina Acknowledgments. We gratefully acknowledge Dean Bok's Res 1:81, 1982. critical comments on a draft of the manuscript and Steve 9. Hollyfield JG and Rayborn ME: Membrane assembly in pho- Bernstein's preparation of Figure 2. toreceptor outer segments: progressive increase in 'open' basal discs with increased temperature. Exp Eye Res 34:115, 1982. From the *Neuroscience Research Program and Department of 10. Besharse JC, Terrill RO, and Dunis DA: Light-evoked disc shed- Biological Sciences, University of California, Santa Barbara, the t Jules ding by rod photoreceptors in vitro: relationship to medium bi- Stein Eye Institute, UCLA School of Medicine, Los Angeles, and the carbonate concentration. Invest Ophthalmol Vis Sci 19:1512, tDepartment of Visual Science, Indiana University, Bloomington. 1980. Supported by NSF Grant BNS-8420242 and NIH Grant EY-00888. 11. Currie JR, Hollyfield JG, and Rayborn ME: Rod outer segments Submitted for publication: June 27, 1985. Reprint requests: David elongate in constant light: darkness is required for normal shed- S. Williams, Department of Visual Sciences, School of Optometry, ding. Vision Res 18:995, 1978. Indiana University, Bloomington, IN 47405. 12. Heath AR and Basinger SF: Simple sugars inhibit rod outer segment disc shedding by the frog retina. Vision Res 23:1371, 1983. 13. Williams DS, Wilson C, Linberg K, and Fisher S: Effects of low References sodium, ouabain, and strophanthidin on the shedding of rod outer segment discs. J Comp Physiol A 154:763, 1984. 1. White RH: The effect of light and light deprivation upon the 14. Matsumoto B and Besharse JC: Light and temperature modulated structure of the larval mosquito eye. Ill Multivesicular bodies staining of the rod outer segment distal tips with lucifer yellow. and protein uptake. J Exp Zool 169:261, 1968. Invest Ophthalmol Vis Sci 26:628, 1985.

Normal Pattern Electroretinograms in Amblyopia

Irene Gortlob* and Lufz Welge-Lussenf

Checkerboard reversal stimuli were used to evoke transient findings obtained under steady-state conditions. Invest pattern electroretinograms (P-ERGs) from the eyes of 14 pa- Ophthalmol Vis Sci 28:187-191, 1987 tients with amblyopia and 14 normal subjects. In the control group, and in normal eyes of patients, pattern electroretinograms were obtained with monocular central fixation. Am- The question as to what extent the retina is affected blyopic eyes were examined by monocular and binocular fix- in amblyopia has remained unanswered. In amblyopic ation, and the fixation point was shifted horizontally and/or eyes, several authors1"3 have described a reduction of vertically until the P-ERG reached its maximal amplitude. the first positive component of the transient pattern After adjusting visual fixation, there were no significant dif- 4 ferences in amplitude between the normal and the amblyopic electroretinogram (P-ERG). Recently, Arden et al eyes. In addition, the differences between both eyes were found in a large population of amblyopic children that compared with the right-left eye variability of the 14 normal the transient P-ERG amplitude was reduced in most subjects. In the amblyopic eyes, no P-ERG abnormality was amblyopic eyes at 2 Hz modulation. Occlusion at an observed. These results do not support previous reports of earlier age reduces the P-ERG amplitude and orthoptic reduced P-ERG amplitudes and are in agreement with recent treatment increases it. Hess et al5'6 showed that with

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optimized optical focus, fixation alignment, and fixa- was obtained. Amplitudes of the P-ERG were com- tion stability for each amblyopic eye, no P-ERG ab- pared by t-tests. normality was observed under steady-state conditions Results. In the normal subjects, the means and stan- (8-Hz modulation). The purpose of the present inves- dard deviations of the absolute P-ERG amplitudes were tigation is to resolve the conflicting results by using 5.14 ± 1.34 /iV for the right eyes and 5.29 ± 1.16 ixV stimulus conditions (checkerboard stimulus with tran- for the left eyes. In order to compare both eyes of the sient conditions at 2-Hz modulation) comparable to normal individuals, the difference was calculated by those of Arden et al4 with optimal fixation for each subtracting the amplitude of the left eye response from individual eye. that of the right eye. The mean and standard deviation Materials and Methods. Stimulation and recording of the differences between the two eyes were -0.15 technique: An alternating checkerboard pattern was ± 0.88 ^V. produced on a TV monitor by a Medelec pattern gen- In the patients, the mean and standard deviations erator (Medelec, Ltd., Surrey, UK) and presented at a of the responses of normal eyes were 4.61 ± 0.92 /xV; distance of 1 m. Each check subtended 41 min arc, the these values were not significantly different from the test field was 26° X 21°, the contrast was 97%, the responses of normal subjects. While the normal eye mean luminance was 30 candela/m2, and a temporal fixated the monitor, when recording from the occluded frequency of 4 reversals per second (2 Hz) was used. amblyopic eye we never obtained reproducible poten- The P-ERG was recorded with gold foil electrodes.7 tials at the peak time of the first positive component The reference electrode was placed on the ipsilateral of P-ERG. Thus, during binocular fixation, potentials temple, while the ground electrode was on the contra- from the normal eye (eg, a contralateral ERG) or from lateral temple. Signals were measured every 0.8 ms over the cortex (eg, VEP) which have been reported for a period of 200 ms, filtered between 1 Hz and 30 Hz steady-state stimulation8 were avoided. Figure 1 shows and averaged 256 times by a Medelec ER94a/Sensor the P-ERG amplitudes of two normal individuals when with artifact rejection. The amplitude between the first the fixation point was shifted horizontally and verti- negative and positive peak was evaluated. cally. As reported previously,9 our results confirm that Normal group and patients: 14 adults (from 18 to under these stimulus conditions, the P-ERG has largest 34 yr; mean age, 26 yr) with normal visual acuity and amplitude at the fovea and reduces as the stimulus is 14 patients (from 9 to 60 yr; mean age, 24 yr) with imaged eccentrically. amblyopia of varying severity were examined after in- The results of the P-ERG amplitudes are listed in formed consent was obtained. A full ophthalmologic Table 1. Depending on the clinical details, the ampli- examination was given to each subject to verify that tudes were larger with either monocular or binocular there was no additional sign of ocular pathology. In fixation. Table 1, clinical details of the patients are given. Nat- In Figure 2, the raw data of patient 4 are shown. ural pupils were used and found to be of equal diameter With monocular fixation (curves a and b), there was a in all subjects. Refractive errors were determined large amplitude difference between the normal right skiascopically and, in some patients, were verified by eye (4.7 /iV) and the amblyopic left eye (0.7 jiV). Be- adding plus or minus lenses and noting changes of the cause of the low visual acuity of 0.03 of this patient, P-ERG amplitude. his monocular fixation was accompanied by large eye In the control group, monocular P-ERGs with cen- movements. With binocular fixation of the center of tral fixation were recorded from both eyes. In addition, the test field, the P-ERG increased to 1.4 jiV (curve c). for two normal subjects the fixation point was shifted In view of the large squint angle of 17.5°, we shifted horizontally and vertically. For all patients, P-ERGs the fixation point temporally up to 24° (curves d-h). of the normal eye were obtained with monocular cen- The amplitudes increased up to 4.1 /iV at a fixation of tral fixation. Depending on the type of amblyopia (ie, 20° eccentricity (curve g) and decreased with further strabismic or anisometropic) fixation was better with eccentric fixation (curve h). The temporal fixation point either monocular or binocular fixation. All patients at 20° fixation was then shifted up or down (curves i- were examined with both methods and the fixation k). A maximal amplitude of 4.4 /*V was reached with point was then shifted horizontally and/or vertically a fixation at 20° temporal and 2° above (curve j). The until the P-ERG reached its maximal amplitude. In amplitude difference of -0.3 nV between the am- order to control the influence of visual evoked re- blyopic and the normal eye is in the normal range. It sponses or of other distant potentials from the unoc- is remarkable that latenties of the P-ERG do not change cluded normal eye during binocular fixation,8 we also with fixation eccentricity (Fig. 2). The results are shown recorded the P-ERG with the gold foil electrode placed schematically in Figures 3a and 3b. on the amblyopic occluded eye, while the normal eye Figures 3c and 3d show other examples of patients fixed the monitor. In this case, no measurable response in which the amplitude was larger than with binocular

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Table 1. Clinical findings

P-ERG amplitude faV)

Visual Fixation Amblyopic eye Age acuity eccentricity Squint Normal eye Patient Sex (yr) (RE/LE) Class (nasal) angle monocular Monocular Binocular

1 F 23 1.0/0.4 Strabismic, esotropia 0°-4° +0°-+5° 4.1 4.9 4.9 at 4 yr, no therapy 2 F 35 0.1/1.0 Strabismic, surgery 12°-15° 0 4.7 2.8 4.8 at 35 yr 3 F 22 ' 1.0/0.03 Strabismic, surgery 14° 0 4.2 1.1 4.2 at 22 yr 4 M 23 1.0/0.03 Strabismic, esotropia Optic disc + 17.5° 4.7 0.7 4.4 at 3 yr, patching therapy 5 M 40 0.5/1.0 Anisometropic and Central -2° 4.7 4.9 4.9 strabismic, first refractive correction at 7 yr 6 F 28 1.2/0.03 Anisometropic and 12°-14° 0 5.7 3.9 5.6 strabismic, first refractive correction at 11 yr, surgery at 22 yr 7 M 11 1.0/0.3 Strabismic, 0 therapy Central -0.3° 5.2 5.8 4.7 8 M 19 1.2/0.1 Deprivation, 8° -6° 4.6 3.7 4.0 congenital ptosis, surgery and patching therapy at 6yr 9 M 12 1.0/0.03 Strabismic, patching 4° +7° 3.6 3.0 3.6 therapy at 6 yr 10 F 24 0.63/1.0 Strabismic, patching Central +0°-2° 5.8 6.3 6.6 therapy at 6 yr 11 F 60 0.2/1.0 Strabismic, surgery +2°-3° +20° 5.1 4.3 3.2 at 3 and 17 yr, diplopia 12 F 18 0.07/1.2 Anisometropic, first 3° 0 6.0 5.8 5.8 refractive correction at 8 yr, patching therapy 13 M 9 0.8/0.15 Anisometropic, first 2° 0 3.0 1.9 3.3 refractive correction at 8 yr 14 M 14 1.0/0.6 Anisometropic, first Central 0 3.2 3.2 3.7 refractive correction at 10 yr

fixation with monocular fixation. Patient 6 had a tudes with monocular fixation. Patient 11 experienced straight eye position after surgery and the maximum diplopia and unsteady fixation; even with eccentric fix- of P-ERG amplitude was found with binocular fixation ation corresponding to the clinical squint angle bin- of the middle of the monitor. Patient 10 had a squint ocularly, her P-ERG amplitudes were only 3.2 nV. angle of +0°-+2°, which fits well with her amplitude Monocular fixation was better, although accompanied maximum of P-ERG at +2°. by eye movements, and the P-ERG amplitude was 4.3 Figures 3e and 3f give examples of patients in which jiV. The difference in the P-ERG between the normal the P-ERG amplitude was equal or larger with mon- and amblyopic eye was -0.8 nV and was in normal ocular fixation than with binocular fixation. Patient 5 range in spite of unsteady fixation. (Fig. 3e) had a visual acuity of 0.5 in his amblyopic The mean and standard deviation of the absolute P- eye and a very unsteady binocular fixation. With mon- ERG amplitude of amblyopic eyes was 4.70 ± 0.96 ocular central fixation, his P-ERG amplitude was re- nV. The mean and standard deviation of the differ- producible and reached its maximum. In all horizontal ences between normal and amblyopic eyes was 0.09 positions, patient 7 (Fig. 3f) had larger P-ERG ampli- ± 0.48 MV.

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Discussion. Conflicting results have been reported 6 as to whether the P-ERG is reduced in amblyopia. Sev- eral authors1"4 used transient checkerboard stimuli at 2 Hz and described a large reduction of the P-ERG amplitude. Recently, Hess et al5'6 did not find a difference between normal eyes and amblyopic eyes with square-wave gratings that were sinusoidally reversed at 8 Hz. We used stimulus conditions similar in contrast, stimulus form, frequency, and size of checks and test field to those used by Arden et al2'4, Sokol et al1, and 3 go 30 3° 6° Wanger et al. temporal nasal Nevertheless, we did not find any significant difference between normal eyes and amblyopic eyes when the eyes were optimally focused and aligned (ie, eccentric fixation taken into account). With normal fixation, the P-ERG amplitude of most of the amblyopes was reduced; but when optimizing the fixation condition for each individual eye, the amplitude of the P-ERG increased. It was important to use fixation conditions corresponding to the clinical findings of the patients. For eyes with very low visual acuity and eccentric monocular fixation, binocular fixation generally was best (Table 1); but, in some patients with diplopia or 6° 0c 3° 6° central fixation, the P-ERG amplitude was greater or top bottom equal with monocular fixation than with binocular fixation. It is indeed difficult to ensure correct fixation Fig. 1. Effect of eccentric fixation on P-ERG amplitude of two normal individuals, a, Horizontal shifting, b, Vertical shifting. alignment in patients with both poor visual acuity and a large squint angle. In spite of this, we found that by There were no significant differences in either the careful assessment of fixation alignment, the P-ERG absolute amplitudes or in the relative differences of was normal in all types of amblyopia. Our patients amblyopic eyes and normal eyes. Latencies of am- covered a wide age range (from 9 to 60 yr) and our blyopic eyes were in normal range. results do not support the notion that there are changes Mpnocular AE fixation Binocular fixation

top Fig. 2. P-ERG recordings from the normal (NE) and 3 amblyopic eye (AE) of pa- 0c .d • e .f .g .h tient 1. Left, Monocular fix- .k ation of the normal eye (curve a) and the amblyopic bottom r C 0° 6 14° 17° 20° 24° eye (curve b). Middle, Hori- nasal temporal zontal fixation shift of the binocularly fixating amblyopic eye (curves c-h). Right, Vertical fixation shift of the binocularly fixating AE amblyopic eye at 20° temporal (curves g-j). (Inset) Points of fixation.

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limit of Acknowledgments. The authors acknowledge Professor E. Hv 4 testf ield 4 Dodt for continous support and encouragement and Dr. W. T3 • Skrandies for helpful discussion. 3 4 ^ < . • V From the *Max Planck Institute for Clinical and Physiological < o Research, Bad Nauheim, F.R.G., and 1st University Eye Clinic, 4° 0 4 8 12 16 20 24 4° 2 0 2 4 Vienna, Austria; and fSt. Marienkrankenhaus, Frankfurt, F.R.G. nasal temp bottom top Submitted for publication: October 17, 1985. Reprint requests: Dr. Irene Gottlob, 1st University Eye Clinic, Spitalg-2, A-1090, Vienna, Austria. Hv 6 .10 6 References 4 V ^^ V 1. Sokol S and Nadler D: Simultaneous electroretinograms and visual evoked potentials from adult amblyopes in response to

o rv> pattern stimuli. Invest Ophthalmol Vis Sci 18:848, 1979. tude 2. Arden GB, Vaegan, Hogg CG, Powell DJ, and Carter RM: Pattern Q. E 6 5 7 . ERGs are abnormal in many amblyopes. Trans Ophthalmol Soc UK 308:82, 1980. 4 A • • 3. Wanger P and Person HE: Oscillatory potentials, flash and pat- 2 ( tern-reversal electroretinograms in amblyopia. Acta Ophthalmol n 62:643, 1984. 6° 0 6° 6° 0 6° 4. Arden GB and Wooding SL: Pattern ERGs in amblyopia. Invest nasal temp nasal temp Ophthalmol Vis Sci 26:88, 1985. Fig. 3. P-ERG amplitudes (ordinates) of amblyopic eyes of patients 5. Hess RF and Baker CL: Assessment of retinal function in severely (4, 6, 10, 5, 7) plotted against horizontal or vertical eccentricity. •: amblyopic individuals. Vision Res 24:1367, 1984. normal eye; •: amblyopic eye, monocular fixation; 0: amblyopic 6. Hess RF, Baker CL, Verhoeve JN, Tulunay Keesey U, and France eye, binocular fixation. TD: The pattern evoked electroretinogram: its variability in nor- mals and its relationship to amblyopia. Invest Ophthalmol Vis at the retinal level caused by long-term disuse (see Ar- Sci 26:1610, 1985. 4 7. Arden GB, Carger RM, Hogg C, Siegel IM, and Margolis S: A den and Wooding ) in functional amblyopia. gold foil electrode: extending the horizons for clinical electro- Thus, we are in agreement with the findings of Hess retinography. Invest Ophthalmol Vis Sci 18:421 1979. et al5'6 of a normal P-ERG response in amblyopic eyes. 8. Seipel WH and Siegel IM: Recording the pattern electroretinogram: a cautionary note. Invest Ophthalmol Vis Sci 24:796, 1983. Key words: amblyopia, pattern electroretinogram, electro- 9. Hess RF and Baker CL: Human pattern-evoked electroretino- physiology gram. J Neurophysiol 51:939, 1984.

Orthogonal Astigmatic Axes in Chinese and Caucasian Infants

Frank Thorn,* Richard Held.f and Li-Luo

Caucasian infants are known to have a high incidence of is vertical, that is, against-the-rule astigmatism. These astigmatism. The axis of greatest power is usually in the ori- studies were all performed in the United States and entation orthogonal to the most common type found in Cau- the subjects were all Caucasians. Recently a visiting casian adults, with-the-rule astigmatism. We now find that investigator from the People's Republic of China (Li- Chinese infants also have a high incidence of astigmatism Luo Fang) joined the M.I.T. Infant Vision Laboratory. relative to adults, but its orientation is orthogonal to that of Caucasian infants. The source of this racial difference is not Her fluency in Chinese allowed us to work with Chinese clear. It is unlikely to be due to the most obvious difference, parents and their Chinese infants. To our surprise, we the structure of the eyelids. Invest Ophthalmol Vis Sci 28: discovered that these infants had an incidence of astig- 191-194,1987 matism equal to that of Caucasians, but with the predominant axis in the orthogonal orientation, that is, with-the-rule astigmatism. The high incidence of astigmatism in human infants Materials and Methods. Near retinoscopy was used has been rediscovered in recent years.1"4 Three different by FT to refract 45 Caucasian infants (both parents techniques, near retinoscopy,2 cycloplegic retinoscopy,3 were Caucasian), 22 Chinese infants (both parents were and photo-refraction,4 all demonstrate it. They agree Chinese), 47 Caucasian adults, and 40 Chinese adults. that the predominant axis of negative cylindrical power The Chinese subjects were recruited by Dr. Fang, pri-

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