- Email: [email protected]
Severe reverse amblyopia with atropine penalization
Journal Pre-proof Severe reverse amblyopia with atropine penalization Abdelrahman M. Elhusseiny, MD, Carolyn Wu, MD, Sarah MacKinnon, MSc, OC(C), David G. Hunter, MD, PhD PII:
S1091-8531(20)30014-8
DOI:
https://doi.org/10.1016/j.jaapos.2019.12.001
Reference:
YMPA 3130
To appear in:
Journal of AAPOS
Received Date: 3 November 2019 Revised Date:
1 December 2019
Accepted Date: 4 December 2019
Please cite this article as: Elhusseiny AM, Wu C, MacKinnon S, Hunter DG, Severe reverse amblyopia with atropine penalization, Journal of AAPOS (2020), doi: https://doi.org/10.1016/j.jaapos.2019.12.001. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Severe reverse amblyopia with atropine penalization Abdelrahman M. Elhusseiny, MD, Carolyn Wu, MD, Sarah MacKinnon, MSc, OC(C), and David G. Hunter, MD, PhD Author affiliations: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts Funding support: Children’s Hospital Ophthalmology Foundation Inc, Boston, Massachusetts. Submitted November 3, 2019. Accepted December 4, 2019. Correspondence: David G. Hunter, MD, PhD, Department of Ophthalmology, Fegan 4, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115 (email: [email protected]). Word count: 1,241
We report 2 cases of refractory reverse amblyopia that developed after instillation of 1-4 drops of atropine. Risk factors appear to include age <4, large-angle esotropia, and lack of adherence to spectacle wear. Atropine penalization is as effective as occlusion therapy for treatment of moderate amblyopia in children.1-3 Although reverse amblyopia is a recognized risk, most cases respond to treatment and occur when combined with optical penalization after months of treatment.4,5 We present 2 cases of children with amblyopia who presented to Boston Children’s Hospital and were treated with atropine penalization. In both cases fixation preference reversed soon after initiation of treatment. Case 1 A 2.6-year-old healthy white girl presented with a large-angle esotropia and amblyopia of the right eye. The esotropia was first noted 1 year earlier, and she was seen by an outside ophthalmologist 6 months before presentation. Available records and parental report indicate a left eye fixation preference. Spectacle correction (+4.00 D in each eye) was prescribed at that time, but the child would not wear the glasses. On presentation at our institution, she had an esotropia of 50∆ (Figure 1A). Her best-corrected visual acuity was 20/70 in the right eye and 20/30 in the left eye using single LEA symbols. She had a strong left eye fixation preference. Cycloplegic retinoscopy was +4.00 D in the right eye and +4.00 D in the left eye. Dilated fundus examination of both eyes was normal. Daily atropine (1%) penalization6 was initiated to treat the right eye amblyopia. There was continued nonadherence with spectacle wear. After 4 days, the parents noted a fixation switch to the right eye and self-discontinued the atropine. At the follow-up examination 6 weeks later, the girl had a right eye fixation preference (Figure 1B). Best-corrected visual acuity was 20/50 in the right eye and <20/500 in the left eye.
Magnetic resonance imaging (MRI) of the brain and orbits was normal except for a Chiari I malformation. Atropine was formally discontinued and patching of the right eye initiated, but adherence to treatment was limited. After 4 months, best-corrected visual acuity in the left eye was only partially improved to 20/200; she underwent strabismus surgery in the left eye for residual esotropia. After 3 years of inconsistent patching and atropine, best-corrected visual acuity was 20/20 in the right eye and 20/60 in the left eye. Case 2 A 3.2-year-old healthy white girl with no prior eye examinations presented with an 8-month history of intermittent crossing of the eyes that seemed to be worsening over time. On examination, she had an esotropia of >65∆, with a strong right eye fixation preference (Figure 1C). Uncorrected visual acuity was 20/20 in the right eye and 20/50 in the left eye using isolated Allen cards. Cycloplegic retinoscopy was +2.25 D in the right eye and +3.50 D in the left eye. Dilated fundus examination of both eyes was normal. Full hyperopic correction was prescribed and amblyopia treatment initiated; the parents were given the options of patching and atropine, with a 4- to 6-week follow-up examination recommended. They initially attempted to patch the right eye 3 hours daily for 2 weeks; however, the patient would wear neither the patch nor her glasses, and the parents decided to try atropine penalization. After a single dose of atropine, the parents noted a fixation switch to the left eye and self-discontinued the drop. They did not return for follow-up until 3 months later, when the child demonstrated a strong left eye fixation preference (Figure 1D). Best-corrected visual acuity was reduced to <20/400 in the right eye and remained 20/50 in the left eye. MRI of the brain and orbits was normal. Atropine was formally discontinued, and patching of the left eye was initiated, but adherence to treatment was limited. After 3 months, best-corrected visual acuity in the right eye remained 5/400. The child
underwent bilateral medial rectus recessions for persistent esotropia. Two months after surgery, visual acuity had improved to 20/125 in the right eye, but nonadherence to spectacle wear and amblyopia treatment continued. Five months later (10 months after development of reverse amblyopia), visual acuity remained at 20/150 in the right eye and 20/40 in the left eye. The patient was lost to follow-up thereafter. Discussion Although atropine penalization is as effective as patching for the treatment of moderate amblyopia,6,7 there are concerns regarding the increased risk, vis-à-vis occlusion therapy, of reverse amblyopia. In the first Amblyopia Treatment Study (ATS) comparing atropine with patching for moderate amblyopia,6 visual acuity in the sound eye was decreased from baseline in 24% of the atropine group (47/194) compared to 8% of the patching group (17/208) at the 6month visit. Visual acuity in the sound eye returned to baseline in all but 5 patients in the atropine group and 2 in the patching group; in those patients, sound eye visual acuity remained 1 line worse than baseline. In an ATS study comparing atropine augmented with a plano lens with atropine alone for moderate amblyopia,8 visual acuity in the sound eye was decreased from baseline in 17% of the atropine+plano group (15/88) compared with 4% of the atropine-only group (3/84) at the 18-week visit. Visual acuity in the sound eye returned to baseline in all patients except for 1 patient, whose sound eye visual acuity remained 1 line worse than baseline. Hainline and colleagues4 found that the risk for developing reverse amblyopia was highest in highly hyperopic (average spherical equivalent, +5.00 D) patients under 4 years of age with strabismic amblyopia on daily atropine, but visual acuity of the sound eye returned to baseline in all 8 patients who developed reverse amblyopia. Although most reported cases of atropine-induced reverse amblyopia have been
reversible, Patil and colleagues9 described a 4-year-old patient who developed refractory reverse amblyopia after 3 months of treatment with daily atropine ointment; adherence to spectacle wear was not reported. After 1 year of treatment, visual acuity in the sound eye did not improve beyond 20/60. In our case series, neither patient recovered visual acuity completely in the previously preferred eye. Both patients (and that of Patil and colleagues9) were ≤4 years of age and had a large-angle esotropia. The cause of such a profound response to brief exposure to atropine in these patients is not clear. High refractive error is known to increase the risk of reverse amblyopia in atropine penalization4; this was exacerbated in our patients by nonadherence to spectacle wear. We further speculate that, considering that amblyopia can improve in some cases after esotropia repair,10 the angle of esotropia was large enough in these 2 cases that the nonfixating eye was essentially occluded by the nose and epicanthal fold on that side, enhancing the response to atropine. Both patients had moderate amblyopia and were young enough that their visual system had sufficient plasticity to enhance vulnerability to reverse amblyopia. Finally, poor adherence to spectacle wear may have been a marker for poor compliance in general, contributing to the poor response to treatment of the reverse amblyopia. Based on our experience and our review of the literature, we hypothesize that patients <4 years of age with large-angle strabismus, high refractive error, moderate amblyopia, and poor adherence to spectacle wear may be at unusually high risk for developing reverse amblyopia after as little as a single dose of atropine. Larger case series would be required to confirm the association, but until more data is available, we recommend careful monitoring of treatment response in patients with this clinical profile.
References 1.
Simons K. Amblyopia characterization, treatment, and prophylaxis. Surv Ophthalmol 2005;50:123-66.
2.
Wu C, Hunter DG. Amblyopia: diagnostic and therapeutic options. Am J Ophthalmol 2006;141:175-84.
3.
Daw NW. Critical periods and amblyopia. Arch Ophthalmol 1998;116:502-5.
4.
Hainline BC, Sprunger DC, Plager DA, et al. Reverse amblyopia with atropine treatment. Binocul Vis Strabismus Q 2009;24:25-31.
5.
Morrison DG, Palmer NJ, Sinatra RB, Donahue S. Severe amblyopia of the sound eye resulting from atropine therapy combined with optical penalization. J Pediatr Ophthalmol Strabismus 2005;42:52-3.
6.
A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268-78.
7.
A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology 2003;110:1632-7; discussion 7-8.
8.
Pediatric Eye Disease Investigator Group. Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial. Arch Ophthalmol 2009;127:22-30.
9.
Patil PA, Meenakshi S, Surendran TS. Refractory reverse amblyopia with atropine penalization. Oman J Ophthalmol 2010;3:148-9.
10.
Lam GC, Repka MX, Guyton DL. Timing of amblyopia therapy relative to strabismus surgery. Ophthalmology 1993;100:1751-6.
Legends FIG 1. Fixation switch after brief atropine penalization in 2 patients. Patient 1 with left eye fixation preference at presentation (A) and switch to right eye fixation preference after home administration 4 drops of atropine over 4 days (B). Patient 2 with right eye fixation preference at presentation (C) and switch to left eye fixation after home administration of 1 drop of atropine (D).
S1091-8531(20)30014-8
DOI:
https://doi.org/10.1016/j.jaapos.2019.12.001
Reference:
YMPA 3130
To appear in:
Journal of AAPOS
Received Date: 3 November 2019 Revised Date:
1 December 2019
Accepted Date: 4 December 2019
Please cite this article as: Elhusseiny AM, Wu C, MacKinnon S, Hunter DG, Severe reverse amblyopia with atropine penalization, Journal of AAPOS (2020), doi: https://doi.org/10.1016/j.jaapos.2019.12.001. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2020, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.
Severe reverse amblyopia with atropine penalization Abdelrahman M. Elhusseiny, MD, Carolyn Wu, MD, Sarah MacKinnon, MSc, OC(C), and David G. Hunter, MD, PhD Author affiliations: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts Funding support: Children’s Hospital Ophthalmology Foundation Inc, Boston, Massachusetts. Submitted November 3, 2019. Accepted December 4, 2019. Correspondence: David G. Hunter, MD, PhD, Department of Ophthalmology, Fegan 4, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115 (email: [email protected]). Word count: 1,241
We report 2 cases of refractory reverse amblyopia that developed after instillation of 1-4 drops of atropine. Risk factors appear to include age <4, large-angle esotropia, and lack of adherence to spectacle wear. Atropine penalization is as effective as occlusion therapy for treatment of moderate amblyopia in children.1-3 Although reverse amblyopia is a recognized risk, most cases respond to treatment and occur when combined with optical penalization after months of treatment.4,5 We present 2 cases of children with amblyopia who presented to Boston Children’s Hospital and were treated with atropine penalization. In both cases fixation preference reversed soon after initiation of treatment. Case 1 A 2.6-year-old healthy white girl presented with a large-angle esotropia and amblyopia of the right eye. The esotropia was first noted 1 year earlier, and she was seen by an outside ophthalmologist 6 months before presentation. Available records and parental report indicate a left eye fixation preference. Spectacle correction (+4.00 D in each eye) was prescribed at that time, but the child would not wear the glasses. On presentation at our institution, she had an esotropia of 50∆ (Figure 1A). Her best-corrected visual acuity was 20/70 in the right eye and 20/30 in the left eye using single LEA symbols. She had a strong left eye fixation preference. Cycloplegic retinoscopy was +4.00 D in the right eye and +4.00 D in the left eye. Dilated fundus examination of both eyes was normal. Daily atropine (1%) penalization6 was initiated to treat the right eye amblyopia. There was continued nonadherence with spectacle wear. After 4 days, the parents noted a fixation switch to the right eye and self-discontinued the atropine. At the follow-up examination 6 weeks later, the girl had a right eye fixation preference (Figure 1B). Best-corrected visual acuity was 20/50 in the right eye and <20/500 in the left eye.
Magnetic resonance imaging (MRI) of the brain and orbits was normal except for a Chiari I malformation. Atropine was formally discontinued and patching of the right eye initiated, but adherence to treatment was limited. After 4 months, best-corrected visual acuity in the left eye was only partially improved to 20/200; she underwent strabismus surgery in the left eye for residual esotropia. After 3 years of inconsistent patching and atropine, best-corrected visual acuity was 20/20 in the right eye and 20/60 in the left eye. Case 2 A 3.2-year-old healthy white girl with no prior eye examinations presented with an 8-month history of intermittent crossing of the eyes that seemed to be worsening over time. On examination, she had an esotropia of >65∆, with a strong right eye fixation preference (Figure 1C). Uncorrected visual acuity was 20/20 in the right eye and 20/50 in the left eye using isolated Allen cards. Cycloplegic retinoscopy was +2.25 D in the right eye and +3.50 D in the left eye. Dilated fundus examination of both eyes was normal. Full hyperopic correction was prescribed and amblyopia treatment initiated; the parents were given the options of patching and atropine, with a 4- to 6-week follow-up examination recommended. They initially attempted to patch the right eye 3 hours daily for 2 weeks; however, the patient would wear neither the patch nor her glasses, and the parents decided to try atropine penalization. After a single dose of atropine, the parents noted a fixation switch to the left eye and self-discontinued the drop. They did not return for follow-up until 3 months later, when the child demonstrated a strong left eye fixation preference (Figure 1D). Best-corrected visual acuity was reduced to <20/400 in the right eye and remained 20/50 in the left eye. MRI of the brain and orbits was normal. Atropine was formally discontinued, and patching of the left eye was initiated, but adherence to treatment was limited. After 3 months, best-corrected visual acuity in the right eye remained 5/400. The child
underwent bilateral medial rectus recessions for persistent esotropia. Two months after surgery, visual acuity had improved to 20/125 in the right eye, but nonadherence to spectacle wear and amblyopia treatment continued. Five months later (10 months after development of reverse amblyopia), visual acuity remained at 20/150 in the right eye and 20/40 in the left eye. The patient was lost to follow-up thereafter. Discussion Although atropine penalization is as effective as patching for the treatment of moderate amblyopia,6,7 there are concerns regarding the increased risk, vis-à-vis occlusion therapy, of reverse amblyopia. In the first Amblyopia Treatment Study (ATS) comparing atropine with patching for moderate amblyopia,6 visual acuity in the sound eye was decreased from baseline in 24% of the atropine group (47/194) compared to 8% of the patching group (17/208) at the 6month visit. Visual acuity in the sound eye returned to baseline in all but 5 patients in the atropine group and 2 in the patching group; in those patients, sound eye visual acuity remained 1 line worse than baseline. In an ATS study comparing atropine augmented with a plano lens with atropine alone for moderate amblyopia,8 visual acuity in the sound eye was decreased from baseline in 17% of the atropine+plano group (15/88) compared with 4% of the atropine-only group (3/84) at the 18-week visit. Visual acuity in the sound eye returned to baseline in all patients except for 1 patient, whose sound eye visual acuity remained 1 line worse than baseline. Hainline and colleagues4 found that the risk for developing reverse amblyopia was highest in highly hyperopic (average spherical equivalent, +5.00 D) patients under 4 years of age with strabismic amblyopia on daily atropine, but visual acuity of the sound eye returned to baseline in all 8 patients who developed reverse amblyopia. Although most reported cases of atropine-induced reverse amblyopia have been
reversible, Patil and colleagues9 described a 4-year-old patient who developed refractory reverse amblyopia after 3 months of treatment with daily atropine ointment; adherence to spectacle wear was not reported. After 1 year of treatment, visual acuity in the sound eye did not improve beyond 20/60. In our case series, neither patient recovered visual acuity completely in the previously preferred eye. Both patients (and that of Patil and colleagues9) were ≤4 years of age and had a large-angle esotropia. The cause of such a profound response to brief exposure to atropine in these patients is not clear. High refractive error is known to increase the risk of reverse amblyopia in atropine penalization4; this was exacerbated in our patients by nonadherence to spectacle wear. We further speculate that, considering that amblyopia can improve in some cases after esotropia repair,10 the angle of esotropia was large enough in these 2 cases that the nonfixating eye was essentially occluded by the nose and epicanthal fold on that side, enhancing the response to atropine. Both patients had moderate amblyopia and were young enough that their visual system had sufficient plasticity to enhance vulnerability to reverse amblyopia. Finally, poor adherence to spectacle wear may have been a marker for poor compliance in general, contributing to the poor response to treatment of the reverse amblyopia. Based on our experience and our review of the literature, we hypothesize that patients <4 years of age with large-angle strabismus, high refractive error, moderate amblyopia, and poor adherence to spectacle wear may be at unusually high risk for developing reverse amblyopia after as little as a single dose of atropine. Larger case series would be required to confirm the association, but until more data is available, we recommend careful monitoring of treatment response in patients with this clinical profile.
References 1.
Simons K. Amblyopia characterization, treatment, and prophylaxis. Surv Ophthalmol 2005;50:123-66.
2.
Wu C, Hunter DG. Amblyopia: diagnostic and therapeutic options. Am J Ophthalmol 2006;141:175-84.
3.
Daw NW. Critical periods and amblyopia. Arch Ophthalmol 1998;116:502-5.
4.
Hainline BC, Sprunger DC, Plager DA, et al. Reverse amblyopia with atropine treatment. Binocul Vis Strabismus Q 2009;24:25-31.
5.
Morrison DG, Palmer NJ, Sinatra RB, Donahue S. Severe amblyopia of the sound eye resulting from atropine therapy combined with optical penalization. J Pediatr Ophthalmol Strabismus 2005;42:52-3.
6.
A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268-78.
7.
A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology 2003;110:1632-7; discussion 7-8.
8.
Pediatric Eye Disease Investigator Group. Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial. Arch Ophthalmol 2009;127:22-30.
9.
Patil PA, Meenakshi S, Surendran TS. Refractory reverse amblyopia with atropine penalization. Oman J Ophthalmol 2010;3:148-9.
10.
Lam GC, Repka MX, Guyton DL. Timing of amblyopia therapy relative to strabismus surgery. Ophthalmology 1993;100:1751-6.
Legends FIG 1. Fixation switch after brief atropine penalization in 2 patients. Patient 1 with left eye fixation preference at presentation (A) and switch to right eye fixation preference after home administration 4 drops of atropine over 4 days (B). Patient 2 with right eye fixation preference at presentation (C) and switch to left eye fixation after home administration of 1 drop of atropine (D).