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Idiopathic Amblyopia
Idiopathic Amblyopia Gunter K. von Noorden, M.D.
Two children without strabismus, anisometropia, or a history of form-vision deprivation who had normal stereoacuity were amblyopic in one eye. The amblyopia responded to occlusion treatment of the sound eye and visual acuity decreased again after cessation of therapy. There is no explanation for this amblyopia. It is possible, however, that binocularly provoked inhibition of the fovea of one eye was conditioned during infancy by an amblyopiogenie condition such as anisometropia. This inhibition may have continued to be triggered by binocular vision in these patients, even though the original obstacle to fusion was no longer apparent. AMBLYOPIA is defined as a reversible reduction of visual acuity for which no cause can be detected by the physical examination of the eye. Strabismus, uncorrected anisometropia, and severe isohypermetropia, as well as form-vision deprivation caused by cataracts, complete blepharoptosis, uncontrolled occlusion therapy, or opacities of the ocular media during infancy are recognized as causative factors. I examined two patients with amblyopia who had none of these conditions at the time of the examination and who had no history of strabismus or other ocular disorders and manifested a reversible and unilateral reduction of visual acuity in an apparently normal eye.
Case Reports Case 1 A S-year-old boy had been followed up by another ophthalmologist for several months and treated for
From the Cullen Eye Institute, Baylor College of Medicine, and the Ophthalmology Service, Texas Children's Hospital, Houston, Texas. This study was supported in part by National Institutes of Health grants EY 01120, EY 07001, and EY 02520, the Charles De Pauw Foundation for Pediatric Ophthalmology, and the Houston Delta Gamma Foundation. Reprint requests to G. K. von Noorden, M.D., Ophthalmology Service, Texas Children's Hospital, Box 20269, Houston, TX 77225.
214
©AM~RICAN
amblyopia in the right eye with glasses and by patching in the left eye. According to the referring physician, visual acuity in the right eye had been 20/100 and improved to 20/60 after one month of patching. The patient's mother indicated that his visual acuity would drop as soon as patching was discontinued. When I examined the patient, he was wearing a patch over the left eye and his visual acuity was 20/40 in the right eye and 20/20 in the left eye on the letter chart while wearing his glasses (+ 1.50 sph in both eyes). His personal history was unremarkable and there was no strabismus or other ocular disorders in his family history. A cyclogyl refraction was performed and showed R.E.: +2.50 sph + 0.50 cyl axis 105; L.E.: +2.75 sph. A complete ocular motility examination was performed and showed an esophoria of 4 prism diopters at distance and of 3 prism diopters near, without correction of the refractive error, and orthophoria at distance and near with correction. Fusional amplitudes, as tested with a rotary prism, were normal. The patient had 60 sec of arc stereopsis on the TNO random-dot test. The four-prism diopter base-out prism test was positive for foveal suppression of the right eye. Retinal correspondence was normal on the Bagolini striated glasses test and the patient fixated foveolarly and steadily with each eye when tested with the Visuscope. Results of the remainder of the ocular examination, including ophthalmoscopy, examination of the pupil, and biomicroscopy of the anterior segment, were normal. As there was no apparent cause for the amblyopia, patching was discontinued. The patient returned 3% months later. Visual acuity in the right eye had dropped to 20/50. A complete ophthalmologic examination and the refraction measurement were repeated and confirmed all of the findings that had been obtained at the first visit. Patching of the left eye during all waking hours was resumed, and six weeks later visual acuity in the right eye had reached a peak of 20/25, only to drop again to 20/S0 after two months without treatment. The patient was placed on a regimen of three to four hours of patching per day in combination with some form of visual activity such as watching television, drawing, or coloring pictures. His visual acuity in the right eye varied beJOURNAL OF OPHTHALMOLOGY 100:214-217, JULY, 1985
Vol. 100, No. 1
215
Idiopathic Amblyopia
Logvis. angle 20/20 20/25
5/25/83
20/30 20/40
Fig. 1 (von Noorden). Case 1. Response to occlusion treat-
20/50
ment.
20/60 20/80
-
OCCL.
tween 20/30 and 20/40 on subsequent visits. When the right eye' 5 visual acuity was tested under binocular conditions (American Optical Vectographic Project-OsChart), it decreased from 20/30 to 20170. The time course of his responses to treatment is summarized in Figure 1. Case 2 A 9-year-old boy had no known ocular problem until two weeks before his first visit to my office. At that time he suffered a "scratch" over the right eye while fighting with another child. His mother took him to an emergency room, where he was examined by an ophthalmologist. There was no visible ocular injury but visual acuity in the right eye was found to be reduced and the patient was referred to me for further examination. The patient's history was unremarkable and there was no family history of strabismus or other ocular disorders. The uncorrected visual acuity was 20/200 in the right and 20/20 in the left eye at distance. Cycloplegic refraction showed R.E.: -0.50 sph + 0.75 cyl axis 90; L.E.: +0.25 sph. The cover test was negative, and the alternating prism and cover test showed an esophoria of 2 prism diopters at distance. Fusional amplitudes, as tested with a rotary prism, were normal. The patient had 60 sec of arc stereopsis on the TNO random-dot test. Retinal correspondence was tested with the Bagolini striated glasses and the afterimage test and found to be normal. The fixation behavior was examined with a Visuscope; the. patient had foveolar unsteady fixation in the right eye and foveolar steady fixation in the left eye. The Bagolini stripe corresponding to the right eye was seen by the patient as having a hole in its center,
PARTIAL OCCL.
indicating foveal suppression of that eye.' The patient also gave a foveal suppression response for the right eye on the four-prism diopter base-out prism test. Results of a complete ophthalmologic examination, including ophthalmoscopy, examination of the pupils, and biomicroscopy of the anterior segments, were negative. Additional tests performed on this patient are listed in the Table. One week later, the entire examination was repeated and confirmed the findings that had been obtained at the first visit. Full-time patching of the left eye was started. Only six weeks later, visual acuity in the right eye had recovered to 20/50-2 and oscillated between 20/50 and 20/60 for the next 25% months, during which time the patch was worn for most of the day. Treatment was then discontinued as the boy was 11 years old and no further improvement seemed likely. Visual acuity remained 20/60 for another 6% months, but when the patient returned IV2 years later it had dropped to its pretreatment level of 20/200. The time course of treatment results is summarized in Figure 2. Additional tests were performed on both patients on subsequent visits. These included the Pulfrich effect," a test for aniseikonia," computed tomography of the skull, and a comprehensive neuro-ophthalmologic examination. The results of these and other tests are summarized in the Table.
Discussion In discussing these cases with several colleagues, I gained the impression that they are not unique.
216
July, 1985
AMERICAN JOURNAL OF OPHTHALMOLOGY
Log vis. angle
20/20 20/25 20/30 20/40 20/50
Fig. 2 (von Noorden). Case 2. Response to occlusiontreat-
2/28/80 1/18/82
20/60
4/7/82 (11 vI
20/80
\'16~
20/100
2O/2001_--..L..
-. . I-. - - . . I-. - - -I~- -
./ oecL. 1980
merit.
10/21/82
1981
1982
However, a survey of the literature failed to produce a description of patients similar to those under study. Since the differential diagnosis between amblyopia without apparent cause, hysteria, malingering, or a disease affecting the afferent visual pathway may be difficult, the present patients ate of more than theoretic interest. In searching for the cause of amblyopia, one must first rule out the possibility that these patients had a subclinical small-angle strabismus, causing inhibition of the fovea of the minimally deviating eye and
"
if
1984
thus amblyopia. The complete normalcy of the motility examination results, including normalcy of stereoacuity, militates against this possibility. Parks! has described a "primary monofixation syndrome" and mentioned the absence of bifoveal fusion, normal peripheral fusion, reduced stereoacuity, monocular facultative scotoma, a negative cover test, and small degrees of amblyopia. However, analysis of his data shows that most patients had either a small-angle manifest esotropia with anomalous retinal correspondence or an absence of amblyopia. Only two TABLE
SUMMARY OF TESTS TESTS
4.6. base-out prism test Visual acuity tested
CASE 1
CASE 2
Positive for scotoma R.E. Reduced in R.E.
Not tested
60 sec
60 sec
Normal
Normal Foveolar unsteady
Positive for scotoma R.E.
under binocular conditions Stereoacuity (TNO) Retinal correspondence Fixation behavior of
Foveolar steady
amolyoplc eye Aniseikonia. Computed tomographic
Absent Negative
Absent Negative
scan of skull Cover test Spontaneous Pulfrich
Negative·
Negative
Present
Absent
Normal
Normal
effect Neuro-ophthalmologic examination
Vol. 100, No. 1
217
Idiopathic Amblyopia
(Cases 43 and 96) of the 100 patients described by Parks' had clinical characteristics remotely similar to those observed in the patients reported herein, but their amblyopia was mild (20/40 in the worse eye) and there was no indication that it responded to treatment. Thus, it cannot be excluded that the two patients described by Parks may have had a mild but irreversible organic visual defect in one eye. Lang" analyzed 120 patients with primary microstrabismus. Most had a distinctive eye movement on the cover test (that is, a manifest esotropia), and in the eight patients without such movement, fixation was either eccentric or other features that were not found in our patients, such as anomalous retinal correspondence, were present. Thus, none of the patients in Lang's series are comparable with the patients described in this study. The observations that visual acuity improved in both instances after occlusion treatment of the fixating eye and deteriorated again after periods of binocular vision, and that visual acuity of the amblyopic eye decreased further when tested under binocular conditions of seeing (Case I), clearly imply the presence of foveal inhibition of one eye that was provoked by binocular stimulation. Strabismus, microstrabismus (according to Lang"), or the primary monofixational syndrome (according to Parks") could be excluded as causative factors of this inhibition. A significant anisometropia, a frequent cause of amblyopia, was also absent at the time of examination. Basic aniseikonia, that is, aniseikonia presumably due to a difference of the distribution of the spatial values of the retinal elements, has been identified as another obstacle to fusion," but it was not present in my patients. Thus, the cause of amblyopia in these two children remains elusive with regard to known arnblyopiogenic mechanisms. One may speculate however that anisometropia may have been present during infancy. Inhibition of the fovea of one eye evoked by anisometropia may still be active, although it serves no apparent useful purpose now as the eyes have become isometropic. It
is of interest in this regard that clinically significant astigmatic refractive errors? and anisometropia" have been reported to disappear spontaneously as a child grows older. The findings of a spontaneous Pulfrich effect in one of our patients (Case 1) and of normal stereoacuity in both cases are also supportive of this theory, as both phenomena have been associated previously with anisometropic amblyopia. 2,9 Another more remote but possible cause for amblyopia in these children is that anomalies of binocular vision that are too subtle to be detected by current diagnostic means cause inhibition of the foveal function of one eye.
References 1. von Noorden, G. K: Present status of sensory testing. In Symposium on Strabismus. Transactions of the New Orleans Academy of Ophthalmology. St. Louis, C. V. Mosby, 1978, p. 56. 2. Tredici, T. D., and von Noorden, G. K: The Pulfrich effect in anisometropic amblyopia and strabismus. Am, J. Ophthalmol. 98:499, 1984. 3. Awaya, 5., Sugawara, M., and Horibe, F.: The "new aniseikonia test" and its clinical application. Acta Soc. Ophthalmol. [pn. 86:217, 1982. 4. Parks, M. M.: The monofixation syndrome. Trans. Am. Ophthalmol. Soc. 67:609, 1969. 5. Lang, J.: Mikrostrabismus. In Naumann, G. O. H., Merte, H. J., Hollwich, F., and Gloor, B. (eds.): Bucherei des Augenarztes, 2nd ed. Stuttgart, F. Enke Verlag, 1982, pp.59-66. 6. von Noorden, G. K: Burian-von Noorden's Binocular Vision and Ocular Motility. Theory and Management of Strabismus, 2nd ed. St. Louis, C. V. Mosby, 1980, p. 135. 7. Mohundra, I., Held, R., Gwiazda, J., and Brill,S.: Astigmatism in infants. Science 202:329, 1978. 8. Cantolino, S. J., and von Noorden, G. K: Heredity in microtropia. Arch. Ophthalmol. 81:753, 1969. 9. Avilla, C. W., and von Noorden, G. K: Limitation of the TNO random dot stereotest for visual screening. Am. Orthopt. J. 31:87, 1981.
Two children without strabismus, anisometropia, or a history of form-vision deprivation who had normal stereoacuity were amblyopic in one eye. The amblyopia responded to occlusion treatment of the sound eye and visual acuity decreased again after cessation of therapy. There is no explanation for this amblyopia. It is possible, however, that binocularly provoked inhibition of the fovea of one eye was conditioned during infancy by an amblyopiogenie condition such as anisometropia. This inhibition may have continued to be triggered by binocular vision in these patients, even though the original obstacle to fusion was no longer apparent. AMBLYOPIA is defined as a reversible reduction of visual acuity for which no cause can be detected by the physical examination of the eye. Strabismus, uncorrected anisometropia, and severe isohypermetropia, as well as form-vision deprivation caused by cataracts, complete blepharoptosis, uncontrolled occlusion therapy, or opacities of the ocular media during infancy are recognized as causative factors. I examined two patients with amblyopia who had none of these conditions at the time of the examination and who had no history of strabismus or other ocular disorders and manifested a reversible and unilateral reduction of visual acuity in an apparently normal eye.
Case Reports Case 1 A S-year-old boy had been followed up by another ophthalmologist for several months and treated for
From the Cullen Eye Institute, Baylor College of Medicine, and the Ophthalmology Service, Texas Children's Hospital, Houston, Texas. This study was supported in part by National Institutes of Health grants EY 01120, EY 07001, and EY 02520, the Charles De Pauw Foundation for Pediatric Ophthalmology, and the Houston Delta Gamma Foundation. Reprint requests to G. K. von Noorden, M.D., Ophthalmology Service, Texas Children's Hospital, Box 20269, Houston, TX 77225.
214
©AM~RICAN
amblyopia in the right eye with glasses and by patching in the left eye. According to the referring physician, visual acuity in the right eye had been 20/100 and improved to 20/60 after one month of patching. The patient's mother indicated that his visual acuity would drop as soon as patching was discontinued. When I examined the patient, he was wearing a patch over the left eye and his visual acuity was 20/40 in the right eye and 20/20 in the left eye on the letter chart while wearing his glasses (+ 1.50 sph in both eyes). His personal history was unremarkable and there was no strabismus or other ocular disorders in his family history. A cyclogyl refraction was performed and showed R.E.: +2.50 sph + 0.50 cyl axis 105; L.E.: +2.75 sph. A complete ocular motility examination was performed and showed an esophoria of 4 prism diopters at distance and of 3 prism diopters near, without correction of the refractive error, and orthophoria at distance and near with correction. Fusional amplitudes, as tested with a rotary prism, were normal. The patient had 60 sec of arc stereopsis on the TNO random-dot test. The four-prism diopter base-out prism test was positive for foveal suppression of the right eye. Retinal correspondence was normal on the Bagolini striated glasses test and the patient fixated foveolarly and steadily with each eye when tested with the Visuscope. Results of the remainder of the ocular examination, including ophthalmoscopy, examination of the pupil, and biomicroscopy of the anterior segment, were normal. As there was no apparent cause for the amblyopia, patching was discontinued. The patient returned 3% months later. Visual acuity in the right eye had dropped to 20/50. A complete ophthalmologic examination and the refraction measurement were repeated and confirmed all of the findings that had been obtained at the first visit. Patching of the left eye during all waking hours was resumed, and six weeks later visual acuity in the right eye had reached a peak of 20/25, only to drop again to 20/S0 after two months without treatment. The patient was placed on a regimen of three to four hours of patching per day in combination with some form of visual activity such as watching television, drawing, or coloring pictures. His visual acuity in the right eye varied beJOURNAL OF OPHTHALMOLOGY 100:214-217, JULY, 1985
Vol. 100, No. 1
215
Idiopathic Amblyopia
Logvis. angle 20/20 20/25
5/25/83
20/30 20/40
Fig. 1 (von Noorden). Case 1. Response to occlusion treat-
20/50
ment.
20/60 20/80
-
OCCL.
tween 20/30 and 20/40 on subsequent visits. When the right eye' 5 visual acuity was tested under binocular conditions (American Optical Vectographic Project-OsChart), it decreased from 20/30 to 20170. The time course of his responses to treatment is summarized in Figure 1. Case 2 A 9-year-old boy had no known ocular problem until two weeks before his first visit to my office. At that time he suffered a "scratch" over the right eye while fighting with another child. His mother took him to an emergency room, where he was examined by an ophthalmologist. There was no visible ocular injury but visual acuity in the right eye was found to be reduced and the patient was referred to me for further examination. The patient's history was unremarkable and there was no family history of strabismus or other ocular disorders. The uncorrected visual acuity was 20/200 in the right and 20/20 in the left eye at distance. Cycloplegic refraction showed R.E.: -0.50 sph + 0.75 cyl axis 90; L.E.: +0.25 sph. The cover test was negative, and the alternating prism and cover test showed an esophoria of 2 prism diopters at distance. Fusional amplitudes, as tested with a rotary prism, were normal. The patient had 60 sec of arc stereopsis on the TNO random-dot test. Retinal correspondence was tested with the Bagolini striated glasses and the afterimage test and found to be normal. The fixation behavior was examined with a Visuscope; the. patient had foveolar unsteady fixation in the right eye and foveolar steady fixation in the left eye. The Bagolini stripe corresponding to the right eye was seen by the patient as having a hole in its center,
PARTIAL OCCL.
indicating foveal suppression of that eye.' The patient also gave a foveal suppression response for the right eye on the four-prism diopter base-out prism test. Results of a complete ophthalmologic examination, including ophthalmoscopy, examination of the pupils, and biomicroscopy of the anterior segments, were negative. Additional tests performed on this patient are listed in the Table. One week later, the entire examination was repeated and confirmed the findings that had been obtained at the first visit. Full-time patching of the left eye was started. Only six weeks later, visual acuity in the right eye had recovered to 20/50-2 and oscillated between 20/50 and 20/60 for the next 25% months, during which time the patch was worn for most of the day. Treatment was then discontinued as the boy was 11 years old and no further improvement seemed likely. Visual acuity remained 20/60 for another 6% months, but when the patient returned IV2 years later it had dropped to its pretreatment level of 20/200. The time course of treatment results is summarized in Figure 2. Additional tests were performed on both patients on subsequent visits. These included the Pulfrich effect," a test for aniseikonia," computed tomography of the skull, and a comprehensive neuro-ophthalmologic examination. The results of these and other tests are summarized in the Table.
Discussion In discussing these cases with several colleagues, I gained the impression that they are not unique.
216
July, 1985
AMERICAN JOURNAL OF OPHTHALMOLOGY
Log vis. angle
20/20 20/25 20/30 20/40 20/50
Fig. 2 (von Noorden). Case 2. Response to occlusiontreat-
2/28/80 1/18/82
20/60
4/7/82 (11 vI
20/80
\'16~
20/100
2O/2001_--..L..
-. . I-. - - . . I-. - - -I~- -
./ oecL. 1980
merit.
10/21/82
1981
1982
However, a survey of the literature failed to produce a description of patients similar to those under study. Since the differential diagnosis between amblyopia without apparent cause, hysteria, malingering, or a disease affecting the afferent visual pathway may be difficult, the present patients ate of more than theoretic interest. In searching for the cause of amblyopia, one must first rule out the possibility that these patients had a subclinical small-angle strabismus, causing inhibition of the fovea of the minimally deviating eye and
"
if
1984
thus amblyopia. The complete normalcy of the motility examination results, including normalcy of stereoacuity, militates against this possibility. Parks! has described a "primary monofixation syndrome" and mentioned the absence of bifoveal fusion, normal peripheral fusion, reduced stereoacuity, monocular facultative scotoma, a negative cover test, and small degrees of amblyopia. However, analysis of his data shows that most patients had either a small-angle manifest esotropia with anomalous retinal correspondence or an absence of amblyopia. Only two TABLE
SUMMARY OF TESTS TESTS
4.6. base-out prism test Visual acuity tested
CASE 1
CASE 2
Positive for scotoma R.E. Reduced in R.E.
Not tested
60 sec
60 sec
Normal
Normal Foveolar unsteady
Positive for scotoma R.E.
under binocular conditions Stereoacuity (TNO) Retinal correspondence Fixation behavior of
Foveolar steady
amolyoplc eye Aniseikonia. Computed tomographic
Absent Negative
Absent Negative
scan of skull Cover test Spontaneous Pulfrich
Negative·
Negative
Present
Absent
Normal
Normal
effect Neuro-ophthalmologic examination
Vol. 100, No. 1
217
Idiopathic Amblyopia
(Cases 43 and 96) of the 100 patients described by Parks' had clinical characteristics remotely similar to those observed in the patients reported herein, but their amblyopia was mild (20/40 in the worse eye) and there was no indication that it responded to treatment. Thus, it cannot be excluded that the two patients described by Parks may have had a mild but irreversible organic visual defect in one eye. Lang" analyzed 120 patients with primary microstrabismus. Most had a distinctive eye movement on the cover test (that is, a manifest esotropia), and in the eight patients without such movement, fixation was either eccentric or other features that were not found in our patients, such as anomalous retinal correspondence, were present. Thus, none of the patients in Lang's series are comparable with the patients described in this study. The observations that visual acuity improved in both instances after occlusion treatment of the fixating eye and deteriorated again after periods of binocular vision, and that visual acuity of the amblyopic eye decreased further when tested under binocular conditions of seeing (Case I), clearly imply the presence of foveal inhibition of one eye that was provoked by binocular stimulation. Strabismus, microstrabismus (according to Lang"), or the primary monofixational syndrome (according to Parks") could be excluded as causative factors of this inhibition. A significant anisometropia, a frequent cause of amblyopia, was also absent at the time of examination. Basic aniseikonia, that is, aniseikonia presumably due to a difference of the distribution of the spatial values of the retinal elements, has been identified as another obstacle to fusion," but it was not present in my patients. Thus, the cause of amblyopia in these two children remains elusive with regard to known arnblyopiogenic mechanisms. One may speculate however that anisometropia may have been present during infancy. Inhibition of the fovea of one eye evoked by anisometropia may still be active, although it serves no apparent useful purpose now as the eyes have become isometropic. It
is of interest in this regard that clinically significant astigmatic refractive errors? and anisometropia" have been reported to disappear spontaneously as a child grows older. The findings of a spontaneous Pulfrich effect in one of our patients (Case 1) and of normal stereoacuity in both cases are also supportive of this theory, as both phenomena have been associated previously with anisometropic amblyopia. 2,9 Another more remote but possible cause for amblyopia in these children is that anomalies of binocular vision that are too subtle to be detected by current diagnostic means cause inhibition of the foveal function of one eye.
References 1. von Noorden, G. K: Present status of sensory testing. In Symposium on Strabismus. Transactions of the New Orleans Academy of Ophthalmology. St. Louis, C. V. Mosby, 1978, p. 56. 2. Tredici, T. D., and von Noorden, G. K: The Pulfrich effect in anisometropic amblyopia and strabismus. Am, J. Ophthalmol. 98:499, 1984. 3. Awaya, 5., Sugawara, M., and Horibe, F.: The "new aniseikonia test" and its clinical application. Acta Soc. Ophthalmol. [pn. 86:217, 1982. 4. Parks, M. M.: The monofixation syndrome. Trans. Am. Ophthalmol. Soc. 67:609, 1969. 5. Lang, J.: Mikrostrabismus. In Naumann, G. O. H., Merte, H. J., Hollwich, F., and Gloor, B. (eds.): Bucherei des Augenarztes, 2nd ed. Stuttgart, F. Enke Verlag, 1982, pp.59-66. 6. von Noorden, G. K: Burian-von Noorden's Binocular Vision and Ocular Motility. Theory and Management of Strabismus, 2nd ed. St. Louis, C. V. Mosby, 1980, p. 135. 7. Mohundra, I., Held, R., Gwiazda, J., and Brill,S.: Astigmatism in infants. Science 202:329, 1978. 8. Cantolino, S. J., and von Noorden, G. K: Heredity in microtropia. Arch. Ophthalmol. 81:753, 1969. 9. Avilla, C. W., and von Noorden, G. K: Limitation of the TNO random dot stereotest for visual screening. Am. Orthopt. J. 31:87, 1981.