Traditional methods to correct and rehabilitate the refractive status of children with anisometropic amblyopia include spectacles and contact lenses combined with some form of occlusion or optical penalization therapy. However, a subset of these children may not improve with these traditional forms of treatment because of aniseikonia, compliance issues, or both. This is especially true in children with concurrent medical diagnoses such as autism, cerebral palsy, developmental delay, Down's syndrome, or other associated ocular disorders including corneal, retinal, and optic nerve problems.1–5
We previously reported our experience treating myopic anisometropic amblyopia with photorefractive keratectomy (PRK)1 and laser-assisted subepithelial keratectomy (LASEK)2 and published case reports3 showing favorable visual results when children had myopic anisometropic amblyopia associated with coexisting medical and ocular pathology. Our results of treating myopic anisometropic amblyopia with laser refractive surgery have been favorable. Based on these and other reports,6–17 most recently by Tychsen et al.,6 Autrata and Rehurek,8 and Paysse et al.,12 we assessed the refractive, visual acuity, and binocular results of LASEK for anisomyopia, anisohyperopia, and anisoastigmatia in children with various levels of amblyopia secondary to anisometropic causes.
PATIENTS AND METHODS
All patients in this prospective series represented end-stage visual treatment failures in which traditional methods of optical correction and amblyopia treatment were not successful. Patients who would not or could not wear glasses and/or contact lenses and who were not successfully treated with standard amblyopia treatments (occlusion and/or pharmacologic) after 6 months were considered for laser refractive surgery to eliminate the anisometropia in the affected eye. Patients were included in the study and placed in 1 of 3 groups based on France's recently published guidelines for amblyopia risk factors.18 The groups were (1) myopic difference greater than 3.00 diopters (D), (2) astigmatic difference greater than 1.50 D, and (3) hyperopic difference greater than 3.50 D. The guidelines, which have the endorsement of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS), represent the refractive point at which anisometropic amblyopia could become a significant risk factor to a child of amblyopiogenic age.
The children were followed for at least 1 year; their refractive status, visual acuity, and binocular vision were assessed and recorded 2 and 6 months as well as 1 year after LASEK. Based on our experience with PRK and LASEK treatments in children with high refractive errors,2,3 we lasered for as high as −19.00 D of effect in this series as our upper limit for the treatment dose applied. Previous PRK and LASEK studies1–3 found that the achieved correction was much higher than targeted in any eye treated for more than −15.00 D of effect. This phenomenon has also been noted in the literature.19,20 Although the reason for the increased effect after laser treatment is unknown, it may be the result of corneal remodeling after PRK and LASEK combined with less scleral rigidity in highly myopic patients and in children in general. This phenomenon should be considered when planning the amount of laser treatment in children with myopia greater than −15.00 D, and it works favorably in children in need of refractive correction greater than −19.00 D, for example.
At each follow-up visit, complete eye examinations were performed. They included cycloplegic retinoscopy and subjective refractions, when possible; repeat anterior segment and fundus evaluations; orthoptic evaluations; and binocular vision testing. When possible, the best corrected visual acuity (BCVA) was recorded; however, many patients were in age groups or had associated disabilities that made objective visual acuity measurements impossible.
Visual acuity was measured when possible before surgery and at each postoperative follow-up using HOTV, Snellen, or Teller cards. Children who were unable to cooperate for visual testing or unable to tolerate occlusion were excluded from the BCVA analysis.
Binocular vision was measured when possible before surgery and at each postoperative follow-up visit. Macular fusion and extramacular binocular fusion were measured using the Worth 4-dot test at 3 m and 33 cm, respectively. Grading of the Worth 4-dot test was pass or fail; passing required reporting or touching 4 dots, while failure required reporting or touching 2, 3, or 5 dots. Stereoacuity was measured using the Titmus stereoacuity, Lang 1, and/or Frisby test. The stereoscopic levels achieved were divided into 3 groups: no stereopsis or fusion (Titmus fly could not be identified, >3000 sec of arc, or negative Worth 4 dot), gross stereopsis (800 to ≤3000 sec of arc), and fine stereopsis (≤800 sec of arc).
At each follow-up clinic visit, patients were evaluated and recommendations were made as needed for amblyopia with patching and/or atropine in addition to appropriate changes in glasses. Not all children required glasses after LASEK, although some still wore glasses if their nonamblyopic eye had a refractive error requiring correction. In these cases, the target laser amount in the amblyopic eye was made to balance the refractive power in the better-seeing nonamblyopic eye. Subsequent strabismus surgery, if required, was performed once the amblyopia treatment was considered optimal.
The College of Physicians and Surgeons of Alberta and the Regional Surgical Executive Committee approved the use of general anesthesia and LASEK in children in a nonhospital surgical facility. This was a requirement deemed necessary by these licensing bodies for approval of the laser treatments in a nonhospital surgical facility and may not be the standard required in other countries. All parents and legal guardians were given a detailed explanation of the procedure and the risks and benefits of the laser treatment. They all signed a consent form stating that they understood the LASEK treatment for their child. The Alberta Health Care Insurance plan (provincial government) covered payment for the LASEK procedures in all patients.
Laser-assisted subepithelial keratectomy was performed in all cases. The LASEK and general anesthesia techniques have been described in detail.1–3
Table 1 shows the breakdown of the anisometropic groups, patient characteristics, and refractive change achieved after laser treatment. The mean age of all patients was 8.4 years (range 10 months to 16 years), which is within the age for effective reversal of anisometropic amblyopia. Three children younger than 2 years had LASEK at a very early age. Two of them had extreme myopia in the amblyopic eye; 1 had LASEK at age 1 year for −10.00 D while the nonamblyopic eye was −0.50 D, and the other had LASEK at 10 months with the amblyopic eye measuring −19.50 D and the nonamblyopic eye +3.50 D. Both children had LASEK early as the anisometropia was so large that no traditional treatment alternatives were reversing the subsequent amblyopia. The third child in the younger age group was born with a corneal dermoid affecting the visual axis, inducing deprivation and anisometropic amblyopia with myopic astigmatism at an oblique angle, which was not responding to amblyopia treatment by traditional methods. When the patient was 11 months old, the dermoid was surgically removed, clearing the visual axis. When the child was 1 year old, LASEK was successfully performed to resolve the dense amblyopia resulting from deprivation and anisometropia.
The mean preoperative refractive difference between eyes (9.48 D) was larger in the myopic anisometropic group; however, the range was wide (3.50 to 23.00 D) and much larger than in the other 2 groups. One year after LASEK, all 3 groups had a refractive difference that was more appropriate to reduce the risk for amblyopia, as outlined by France.
The difference at each follow-up between the eye that had LASEK and the fellow eye in the anisomyopic group and anisoastigmatic group is shown in Figure 1 and Figure 2, respectively. Although the myopic shift and regression rate were greater in the myopic group than in the astigmatic group, both groups were at acceptable levels to avoid amblyopia. Results of the hyperopic group were not graphed as the number of patients was small (3); however, the mean difference between eyes was 5.50 D preoperatively, 2.00 D at 2 months, 1.67 D at 6 months, and 2.33 D at 1 year.
Of the 33 patients in whom visual acuity could be measured, 63.6% had improved BCVA; 57.6% achieved 3 lines or more improvement and 30.3%, more than 5 to 6 lines improvement 1 year postoperatively (Figure 3); the remainder had no change in BCVA from pre-LASEK levels. No child lost vision as a result of LASEK. In addition, 1 year after LASEK, 80% of eyes treated with LASEK were within ±3.00 D of the fellow-eye and 54% were within ±1.00 D (Figure 4).
These same 33 children were also testable for stereopsis and fusional ability. The results are shown in Table 2. Forty-two percent had positive stereopsis before LASEK, and 87% had positive stereopsis 1 year after LASEK.
No patient required repeat laser treatment.
Amblyopia is one of the most common preventable causes of visual acuity loss in children.21 The Amblyopia Treatment Studies (ATS)22–26 report excellent results in reversing amblyopia with glasses in combination with patching, atropine treatment, or both. Conversely, the ATS studies also show that a significant subset of amblyopic patients, even without coexisting medical or ocular problems, do not have successful, timely resolution of their amblyopia with standard treatment regimens. As we report in 3 previous papers,1–3 failure with traditional amblyopia treatments may be especially true in children with coexisting medical diagnoses such as autism, cerebral palsy, developmental delay, and other ocular disorders. Tychsen et al.4,5 also note the same problems in children treated with laser refractive surgery for bilateral high myopia associated with neurobehavioral disorders. All these associated problems can contribute to a child's inability to effectively wear glasses or contact lenses or be treated with occlusion or atropine. In the past, there was no other treatment option.
Amblyopia in the defocused eye caused by anisometropia or bilateral refractive error, including astigmatism or nystagmus, often responds well to glasses if the amount of anisometropia is less than 3.00 D.18,27 However, anisometropia greater than 1.50 D,18 especially myopic anisometropia, can induce dense amblyopia. Because of the large amount of aniseikonia induced when refractive error is corrected, this form of amblyopia is especially resistant to more traditional forms of amblyopia therapy. However, with improvement in vision in the amblyopic eye, aniseikonia can become the most important factor in a child's inability to wear spectacle correction once amblyopia treatment is complete. Contact lenses are another option and provide better quality vision and a larger visual field with improved contrast sensitivity.28 However, full-time contact lens use by young children with coexisting ocular or medical problems is not always optimal or possible. As we and many others1–3,8–10,14–17,29 have demonstrated, these more complex anisometropic situations may be treated more effectively with laser refractive surgery.
A major contribution to the discussion of parameters for considering a patient to be at significant risk for developing amblyopia was recently published by France.18 This paper outlines the evidence-based guidelines that are the most helpful in screening for amblyopiogenic potential. They are hyperopia greater than +3.50 D in any meridian, myopia greater than −3.00 D in any meridian, astigmatism greater than 1.50 D at 90 or 180 degrees, astigmatism greater than 1.00 D in an oblique axis, and anisometropia (spherical or cylindrical) greater than 1.50 D. Of note is the increased risk for amblyopia with oblique astigmatism, which can be an issue in patients with lid hemangiomas, for example, which are known to induce dense anisometropic amblyopia associated with oblique astigmatism. These guidelines, endorsed by AAPOS, the American Academy of Ophthalmology, the American Association of Certified Orthoptists, and the American Academy of Pediatrics, represent a major step in establishing more effective screening and treatment guidelines for professionals who treat this complex form of amblyopia. For our study, we adopted these parameters for patient selection as they represent the levels at which anisometropic amblyopia is more likely to develop and require treatment.
A few studies have evaluated laser refractive surgery in children with anisometropic amblyopia.1–3,8–10,12–15,29 These studies used laser in situ keratomileusis (LASIK), PRK, or LASEK and report all 3 techniques are safe in children in terms of general anesthesia and the eye (ie, laser procedure itself does not worsen vision). In addition, the procedures lead to no more complications than would be expected in adults. The excimer laser has consistently reduced the spherical equivalent (SE) refractive error over the long term, and the children's vision was maintained or improved. Many earlier studies included children whose age was out of the age range for treating amblyopia.8–10,13–15,29 However, even though the children were older, the overall improvement was positive in terms of achieving the targeted post-laser refraction, improvement in or stability of vision, and few to no complications from the procedure.
Recently, Roszkowska et al.30 showed that even in adults having PRK with residual anisometropic amblyopia, 82.4% of eyes had an improvement in BCVA by 1 or more lines. This again implies that in younger age groups, more likely to have effective reversal of anisometropic amblyopia, refractive laser surgery may be an effective long-term treatment alternative that would reduce the anisometropia to a level where it would no longer be amblyopiogenic, allowing more effective long-term reversal when traditional methods fail.
Similarly, our experience with PRK3 and LASEK2 in amblyopiogenic age groups in association with coexisting medical pathology1 has been positive; the procedure improved or maintained vision in patients with anisometropic amblyopia and had a positive effect of the patient's overall fusional status. In 2005, Tychsen et al.6 found that both PRK and LASEK were effective in correcting myopic anisometropic amblyopia in children. Recently, Paysse et al.12 reported 11 patients followed for 3 years who were treated with PRK for anisometropic amblyopia after conventional therapy had failed. Photorefractive keratectomy in these patients resulted in an overall improvement in vision and fusional status that was associated with a stable reduction and balance in refractive error.
In our larger series of 53 patients, the results are also positive in treating anisometropic amblyopia in children in whom traditional treatment has failed. Of note is the improvement in vision after LASEK, with 63.6% of testable patients having improvement in the BCVA and no patient developing worse vision. The SE changes in all anisometropic groups were stable; over the 1-year follow-up, 80% of treated eyes were within ±3.00 D of the fellow eye, with consistency across the myopic, hyperopic, and astigmatic anisometropic groups. As stated, this group of pediatric patients had different treatment goals than those for a typical adult group. The main goal was to keep the eyes balanced throughout the laser process. As long as significant anisometropia did not remain after LASEK, a slight overcorrection or undercorrection was not a concern. Because of the known tendency in children for a myopic shift to occur after laser treatment, we aimed for an initial post-LASEK hyperopic correction, depending on the age of the child and balancing with the fellow eye. Although complete balance of the post-LASEK refraction was always the goal, based on research of myopic anisometropia and amblyopia, an attempt was made to keep the refractive difference between the eyes within ±0.0 to ±3.0 D. Again, this allows more flexibility in treating children than in treating adults. Based on the evidence-based guidelines presented by France,18 these patients should have a better chance of maintaining long term the improvement achieved with LASEK. In addition, of 33 testable children, the 48.5% improvement in stereopsis in the entire group is an important finding, suggesting these children should function better in their environments after LASEK.
In children, a true myopic shift secondary to refractive surgery may be indistinguishable from myopic changes that occur with normal axial length changes as children grow.31,32 Goss33 found that, on average, normal phakic pediatric eyes have a myopic shift of −0.5 D per year. Gordon and Donzis31 and Moore32 report that children's eyes continue to undergo significant growth with a myopic shift until 16 to 18 years of age. This regression may be due to an axial myopic shift related to normal growth patterns in pediatric eyes or possibly destruction of Bowman's membrane during laser treatments, which initiates a more vigorous healing response. At our clinic, children who fail traditional treatment approaches are targeted early for refractive surgery to optimize the development of visuospatial vision and binocular visual function. We therefore anticipate a myopic shift and do not consider its occurrence a complication or contraindication to refractive surgery. Paysse et al.12 and Tychsen and Hoekel4 report refractive regression rates of approximately 1.00 D per year after laser surgery in children. The mean regression rate in our series was 1.46 D per year (range 0.25 to 6.00 D per year). The 6.00 D per year regression occurred in a single patient who was originally treated for −17.50 D of myopia.
Based on our previous experience with LASEK in children,2 we also made a conscious decision to use LASEK in all children in this series. Laser-assisted subepithelial keratectomy combines the advantages of PRK and LASIK while eliminating the disadvantages of these procedures. There is no chance of a child rubbing a corneal stromal flap off, as in LASIK, and the postoperative pain in children seems less after LASEK than after PRK; also, there is little potential for flap interface problems, corneal ectasia, or intraoperative complications of LASIK such as retinal detachment and optic neuropathy.8,29,34–40 Based on the results in this study and past experience with PRK and LASEK in treating patients with anisometropic amblyopia, we think elimination of the refractive component of the anisometropia provides major visual and functional improvement in children, with or without coexisting ocular and medical disorders. As our experience with this treatment improves and expands, we may soon find that laser refractive surgery evolves into a first-line treatment option, surpassing glasses and contact lenses in eliminating anisometropia and alleviating aniseikonia, leading to more effective reversal of any residual amblyopia with patching and atropine. We believe that refractive surgeons and pediatric ophthalmologists should consider laser refractive surgery as a definite surgical option in the treatment of anisometropic amblyopia.
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