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Reports No. 1 mit one to see only the occasional extreme case of an alteration that can be detected more readily when lucifer yellow is employed as an extracellular probe. In conclusion, our results show that mechanical disruption of the intact relationship between the ROSs and the RPE and/or interphotoreceptor matrix prevents the abscission of the terminal disks under conditions in which they would normally be shed. Particularly in view of the above discussion, this finding does not necessarily mean that the RPE actively bites off the ends of ROSs by "piecemeal phagocytosis" without any participation by the rods, but it does indicate that the neural retina does not have autonomous control over the shedding of its ROS disks. Key words: photoreceptor outer segments, rod disk, retinal pigment epithelium, membrane turnover, retinal detachment Acknowledgments. We gratefully acknowledge Dean Bok's critical comments on a draft of the manuscript and Steve Bernstein's preparation of Figure 2. From the *Neuroscience Research Program and Department of Biological Sciences, University of California, Santa Barbara, the t Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, and the tDepartment of Visual Science, Indiana University, Bloomington. Supported by NSF Grant BNS-8420242 and NIH Grant EY-00888. Submitted for publication: June 27, 1985. Reprint requests: David S. Williams, Department of Visual Sciences, School of Optometry, Indiana University, Bloomington, IN 47405. References 1. White RH: The effect of light and light deprivation upon the structure of the larval mosquito eye. Ill Multivesicular bodies and protein uptake. J Exp Zool 169:261, 1968. 187 2. Williams DS and Blest AD: Extracellular shedding of photoreceptor membrane in the open rhabdom of a tipulid fly. Cell Tissue Res 205:423, 1980. 3. Young RW and Bok D: Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol 42:392, 1969. 4. O'Day WT and Young RW: Rhythmic daily shedding of outer segment membranes by visual cells in the goldfish. J Cell Biol 76:593, 1978. 5. Young RW: Shedding of discs from rod outer segments in the Rhesus monkey. J Ultrastruct Res 34:190, 1971. 6. Spitznas M and Hogan MJ: Outer segments of photoreceptors and the retinal pigment epithelium. Arch Ophthalmol 84:810, 1970. 7. Bok D and Young RW: Phagocytic properties of the retinal pigment epithelium. In The Retinal Pigment Epithelium, Zinn KM and Marmor MF, editors. Cambridge, MA, Harvard University Press, 1979, pp. 148-174. 8. Besharse JC: The daily light-dark cycle and rhythmic metabolism in the photoreceptor-pigment epithelial complex. Prog Retina Res 1:81, 1982. 9. Hollyfield JG and Rayborn ME: Membrane assembly in photoreceptor outer segments: progressive increase in 'open' basal discs with increased temperature. Exp Eye Res 34:115, 1982. 10. Besharse JC, Terrill RO, and Dunis DA: Light-evoked disc shedding by rod photoreceptors in vitro: relationship to medium bicarbonate concentration. Invest Ophthalmol Vis Sci 19:1512, 1980. 11. Currie JR, Hollyfield JG, and Rayborn ME: Rod outer segments elongate in constant light: darkness is required for normal shedding. Vision Res 18:995, 1978. 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 sodium, ouabain, and strophanthidin on the shedding of rod outer segment discs. J Comp Physiol A 154:763, 1984. 14. Matsumoto B and Besharse JC: Light and temperature modulated staining of the rod outer segment distal tips with lucifer yellow. 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 pattern electroretinograms (P-ERGs) from the eyes of 14 patients with amblyopia and 14 normal subjects. In the control group, and in normal eyes of patients, pattern electroretinograms were obtained with monocular central fixation. Amblyopic eyes were examined by monocular and binocular fixation, and the fixation point was shifted horizontally and/or vertically until the P-ERG reached its maximal amplitude. After adjusting visual fixation, there were no significant differences in amplitude between the normal and the amblyopic eyes. In addition, the differences between both eyes were compared with the right-left eye variability of the 14 normal subjects. In the amblyopic eyes, no P-ERG abnormality was observed. These results do not support previous reports of reduced P-ERG amplitudes and are in agreement with recent findings obtained under steady-state conditions. Invest Ophthalmol Vis Sci 28:187-191, 1987 The question as to what extent the retina is affected in amblyopia has remained unanswered. In amblyopic eyes, several authors1"3 have described a reduction of the first positive component of the transient pattern electroretinogram (P-ERG). Recently, Arden et al4 found in a large population of amblyopic children that the transient P-ERG amplitude was reduced in most amblyopic eyes at 2 Hz modulation. Occlusion at an earlier age reduces the P-ERG amplitude and orthoptic treatment increases it. Hess et al5'6 showed that with Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933362/ on 05/10/2017 188 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / January 1987 optimized optical focus, fixation alignment, and fixation stability for each amblyopic eye, no P-ERG abnormality was observed under steady-state conditions (8-Hz modulation). The purpose of the present investigation is to resolve the conflicting results by using stimulus conditions (checkerboard stimulus with transient conditions at 2-Hz modulation) comparable to those of Arden et al4 with optimal fixation for each individual eye. Materials and Methods. Stimulation and recording technique: An alternating checkerboard pattern was produced on a TV monitor by a Medelec pattern generator (Medelec, Ltd., Surrey, UK) and presented at a distance of 1 m. Each check subtended 41 min arc, the test field was 26° X 21°, the contrast was 97%, the mean luminance was 30 candela/m 2 , and a temporal frequency of 4 reversals per second (2 Hz) was used. The P-ERG was recorded with gold foil electrodes.7 The reference electrode was placed on the ipsilateral temple, while the ground electrode was on the contralateral temple. Signals were measured every 0.8 ms over a period of 200 ms, filtered between 1 Hz and 30 Hz and averaged 256 times by a Medelec ER94a/Sensor with artifact rejection. The amplitude between the first negative and positive peak was evaluated. Normal group and patients: 14 adults (from 18 to 34 yr; mean age, 26 yr) with normal visual acuity and 14 patients (from 9 to 60 yr; mean age, 24 yr) with amblyopia of varying severity were examined after informed consent was obtained. A full ophthalmologic examination was given to each subject to verify that there was no additional sign of ocular pathology. In Table 1, clinical details of the patients are given. Natural pupils were used and found to be of equal diameter in all subjects. Refractive errors were determined skiascopically and, in some patients, were verified by adding plus or minus lenses and noting changes of the P-ERG amplitude. In the control group, monocular P-ERGs with central fixation were recorded from both eyes. In addition, for two normal subjects the fixation point was shifted horizontally and vertically. For all patients, P-ERGs of the normal eye were obtained with monocular central fixation. Depending on the type of amblyopia (ie, strabismic or anisometropic) fixation was better with either monocular or binocular fixation. All patients were examined with both methods and the fixation point was then shifted horizontally and/or vertically until the P-ERG reached its maximal amplitude. In order to control the influence of visual evoked responses or of other distant potentials from the unoccluded normal eye during binocular fixation,8 we also recorded the P-ERG with the gold foil electrode placed on the amblyopic occluded eye, while the normal eye fixed the monitor. In this case, no measurable response Vol. 28 was obtained. Amplitudes of the P-ERG were compared by t-tests. Results. In the normal subjects, the means and standard deviations of the absolute P-ERG amplitudes were 5.14 ± 1.34 /iV for the right eyes and 5.29 ± 1.16 ixV for the left eyes. In order to compare both eyes of the normal individuals, the difference was calculated by subtracting the amplitude of the left eye response from that of the right eye. The mean and standard deviation of the differences between the two eyes were -0.15 ± 0.88 ^V. In the patients, the mean and standard deviations of the responses of normal eyes were 4.61 ± 0.92 /xV; these values were not significantly different from the responses of normal subjects. While the normal eye fixated the monitor, when recording from the occluded amblyopic eye we never obtained reproducible potentials at the peak time of the first positive component of P-ERG. Thus, during binocular fixation, potentials from the normal eye (eg, a contralateral ERG) or from the cortex (eg, VEP) which have been reported for steady-state stimulation8 were avoided. Figure 1 shows the P-ERG amplitudes of two normal individuals when the fixation point was shifted horizontally and vertically. As reported previously,9 our results confirm that under these stimulus conditions, the P-ERG has largest amplitude at the fovea and reduces as the stimulus is imaged eccentrically. The results of the P-ERG amplitudes are listed in Table 1. Depending on the clinical details, the amplitudes were larger with either monocular or binocular fixation. In Figure 2, the raw data of patient 4 are shown. With monocular fixation (curves a and b), there was a large amplitude difference between the normal right eye (4.7 /iV) and the amblyopic left eye (0.7 jiV). Because of the low visual acuity of 0.03 of this patient, his monocular fixation was accompanied by large eye movements. With binocular fixation of the center of the test field, the P-ERG increased to 1.4 jiV (curve c). In view of the large squint angle of 17.5°, we shifted the fixation point temporally up to 24° (curves d-h). The amplitudes increased up to 4.1 /iV at a fixation of 20° eccentricity (curve g) and decreased with further eccentric fixation (curve h). The temporal fixation point at 20° fixation was then shifted up or down (curves ik). A maximal amplitude of 4.4 /*V was reached with a fixation at 20° temporal and 2° above (curve j). The amplitude difference of - 0 . 3 nV between the amblyopic and the normal eye is in the normal range. It is remarkable that latenties of the P-ERG do not change with fixation eccentricity (Fig. 2). The results are shown schematically in Figures 3a and 3b. Figures 3c and 3d show other examples of patients in which the amplitude was larger than with binocular Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933362/ on 05/10/2017 189 Reporrs No. 1 Table 1. Clinical findings P-ERG amplitude faV) Patient Sex Visual Fixation Age (yr) acuity (RE/LE) eccentricity (nasal) 1 F 23 1.0/0.4 2 F 35 0.1/1.0 3 F 22 4 M 23 1.0/0.03 5 M 40 0.5/1.0 6 F 28 1.2/0.03 7 8 M M 11 19 1.0/0.3 1.2/0.1 9 M 12 1.0/0.03 10 F 24 0.63/1.0 11 F 60 0.2/1.0 12 F 18 0.07/1.2 13 M 9 0.8/0.15 14 M 14 1.0/0.6 ' 1.0/0.03 Class Strabismic, esotropia at 4 yr, no therapy Strabismic, surgery at 35 yr Strabismic, surgery at 22 yr Strabismic, esotropia at 3 yr, patching therapy Anisometropic and strabismic, first refractive correction at 7 yr Anisometropic and strabismic, first refractive correction at 11 yr, surgery at 22 yr Strabismic, 0 therapy Deprivation, congenital ptosis, surgery and patching therapy at 6yr Strabismic, patching therapy at 6 yr Strabismic, patching therapy at 6 yr Strabismic, surgery at 3 and 17 yr, diplopia Anisometropic, first refractive correction at 8 yr, patching therapy Anisometropic, first refractive correction at 8 yr Anisometropic, first refractive correction at 10 yr Amblyopic eye Squint angle Normal eye monocular Monocular Binocular 0°-4° +0°-+5° 4.1 4.9 4.9 12°-15° 0 4.7 2.8 4.8 14° 0 4.2 1.1 4.2 Optic disc + 17.5° 4.7 0.7 4.4 Central -2° 4.7 4.9 4.9 12°-14° 0 5.7 3.9 5.6 Central 8° -0.3° -6° 5.2 4.6 5.8 3.7 4.7 4.0 4° +7° 3.6 3.0 3.6 Central +0°-2° 5.8 6.3 6.6 +2°-3° +20° 5.1 4.3 3.2 3° 0 6.0 5.8 5.8 2° 0 3.0 1.9 3.3 Central 0 3.2 3.2 3.7 fixation with monocular fixation. Patient 6 had a straight eye position after surgery and the maximum of P-ERG amplitude was found with binocular fixation of the middle of the monitor. Patient 10 had a squint angle of +0°-+2°, which fits well with her amplitude maximum of P-ERG at +2°. Figures 3e and 3f give examples of patients in which the P-ERG amplitude was equal or larger with monocular fixation than with binocular fixation. Patient 5 (Fig. 3e) had a visual acuity of 0.5 in his amblyopic eye and a very unsteady binocular fixation. With monocular central fixation, his P-ERG amplitude was reproducible and reached its maximum. In all horizontal positions, patient 7 (Fig. 3f) had larger P-ERG ampli- tudes with monocular fixation. Patient 11 experienced diplopia and unsteady fixation; even with eccentric fixation corresponding to the clinical squint angle binocularly, her P-ERG amplitudes were only 3.2 nV. Monocular fixation was better, although accompanied by eye movements, and the P-ERG amplitude was 4.3 jiV. The difference in the P-ERG between the normal and amblyopic eye was -0.8 nV and was in normal range in spite of unsteady fixation. The mean and standard deviation of the absolute PERG amplitude of amblyopic eyes was 4.70 ± 0.96 nV. The mean and standard deviation of the differences between normal and amblyopic eyes was 0.09 ± 0.48 MV. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933362/ on 05/10/2017 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / January 1987 190 Discussion. Conflicting results have been reported as to whether the P-ERG is reduced in amblyopia. Several 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 Wanger et al.3 Nevertheless, we did not find any significant difference between normal eyes and amblyopic eyes when the eyes were optimally focused and aligned (ie, eccentricfixationtaken 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 central fixation, the P-ERG amplitude was greater or equal with monocularfixationthan with binocular fixation. It is indeed difficult to ensure correct fixation alignment in patients with both poor visual acuity and a large squint angle. In spite of this, we found that by careful assessment of fixation alignment, the P-ERG was normal in all types of amblyopia. Our patients covered a wide age range (from 9 to 60 yr) and our results do not support the notion that there are changes 6 go 3° 30 temporal 6° top 0c Vol. 28 6° nasal 3° 6° bottom Fig. 1. Effect of eccentric fixation on P-ERG amplitude of two normal individuals, a, Horizontal shifting, b, Vertical shifting. There were no significant differences in either the absolute amplitudes or in the relative differences of amblyopic eyes and normal eyes. Latencies of amblyopic eyes were in normal range. AE Binocular fixation Mpnocular fixation top 3 0c .d bottom r0° 6C nasal • e .f .g .h .k 14° 17° 20° 24° temporal AE Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933362/ on 05/10/2017 Fig. 2. P-ERG recordings from the normal (NE) and amblyopic eye (AE) of patient 1. Left, Monocular fixation of the normal eye (curve a) and the amblyopic eye (curve b). Middle, Horizontal fixation shift of the binocularly fixating amblyopic eye (curves c-h). Right, Vertical fixation shift of the binocularly fixating amblyopic eye at 20° temporal (curves g-j). (Inset) Points of fixation. Hv T3 3 4 limit of testf ield 4 Acknowledgments. The authors acknowledge Professor E. Dodt for continous support and encouragement and Dr. W. Skrandies for helpful discussion. 4 • . < o 191 Reports No. 1 4° 0 4 nasal Hv 8 • ^ < V 4° 2 0 bottom 12 16 20 24 temp 2 4 top .10 6 From the *Max Planck Institute for Clinical and Physiological Research, Bad Nauheim, F.R.G., and 1st University Eye Clinic, Vienna, Austria; and fSt. Marienkrankenhaus, Frankfurt, F.R.G. Submitted for publication: October 17, 1985. Reprint requests: Dr. Irene Gottlob, 1st University Eye Clinic, Spitalg-2, A-1090, Vienna, Austria. 6 References 4 tude o rv> V ^^ Q. E 6 4 2 n V 7 . 5 A( 6° 0 nasal • 6° temp 0 6° nasal • 6° temp Fig. 3. P-ERG amplitudes (ordinates) of amblyopic eyes of patients (4, 6, 10, 5, 7) plotted against horizontal or vertical eccentricity. •: normal eye; • : amblyopic eye, monocular fixation; 0: amblyopic eye, binocular fixation. at the retinal level caused by long-term disuse (see Arden and Wooding4) in functional amblyopia. Thus, we are in agreement with thefindingsof Hess et al5'6 of a normal P-ERG response in amblyopic eyes. Key words: amblyopia, pattern electroretinogram, electrophysiology 1. Sokol S and Nadler D: Simultaneous electroretinograms and visual evoked potentials from adult amblyopes in response to pattern stimuli. Invest Ophthalmol Vis Sci 18:848, 1979. 2. Arden GB, Vaegan, Hogg CG, Powell DJ, and Carter RM: Pattern ERGs are abnormal in many amblyopes. Trans Ophthalmol Soc UK 308:82, 1980. 3. Wanger P and Person HE: Oscillatory potentials, flash and pattern-reversal electroretinograms in amblyopia. Acta Ophthalmol 62:643, 1984. 4. Arden GB and Wooding SL: Pattern ERGs in amblyopia. Invest Ophthalmol Vis Sci 26:88, 1985. 5. Hess RF and Baker CL: Assessment of retinal function in severely amblyopic individuals. Vision Res 24:1367, 1984. 6. Hess RF, Baker CL, Verhoeve JN, Tulunay Keesey U, and France TD: The pattern evoked electroretinogram: its variability in normals and its relationship to amblyopia. Invest Ophthalmol Vis Sci 26:1610, 1985. 7. Arden GB, Carger RM, Hogg C, Siegel IM, and Margolis S: A gold foil electrode: extending the horizons for clinical electroretinography. Invest Ophthalmol Vis Sci 18:421 1979. 8. Seipel WH and Siegel IM: Recording the pattern electroretinogram: a cautionary note. Invest Ophthalmol Vis Sci 24:796, 1983. 9. Hess RF and Baker CL: Human pattern-evoked electroretinogram. 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 astigmatism. The axis of greatest power is usually in the orientation orthogonal to the most common type found in Caucasian adults, with-the-rule astigmatism. We now find that Chinese infants also have a high incidence of astigmatism relative to adults, but its orientation is orthogonal to that of Caucasian infants. The source of this racial difference is not clear. It is unlikely to be due to the most obvious difference, the structure of the eyelids. Invest Ophthalmol Vis Sci 28: 191-194,1987 The high incidence of astigmatism in human infants has been rediscovered in recent years.1"4 Three different techniques, near retinoscopy,2 cycloplegic retinoscopy,3 and photo-refraction,4 all demonstrate it. They agree that the predominant axis of negative cylindrical power is vertical, that is, against-the-rule astigmatism. These studies were all performed in the United States and the subjects were all Caucasians. Recently a visiting investigator from the People's Republic of China (LiLuo Fang) joined the M.I.T. Infant Vision Laboratory. Herfluencyin Chinese allowed us to work with Chinese parents and their Chinese infants. To our surprise, we discovered that these infants had an incidence of astigmatism equal to that of Caucasians, but with the predominant axis in the orthogonal orientation, that is, with-the-rule astigmatism. Materials and Methods. Near retinoscopy was used by FT to refract 45 Caucasian infants (both parents were Caucasian), 22 Chinese infants (both parents were Chinese), 47 Caucasian adults, and 40 Chinese adults. The Chinese subjects were recruited by Dr. Fang, pri- Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933362/ on 05/10/2017