Management of amblyopia
Jaime Tejedor
Dept Ophthalmology
Hospital Ramón y Cajal
C Colmenar km 9100
Madrid 28034
Spain
Phone: 34-913369008
Fax: 34913369023
Email: jtejedor.hrc@salud.madrid.org
As the scientific understanding of amblyopia advances and clinical evidence accumulates, new standards of practice are beginning to emerge. Current evidence suggests that a gradual and measured approach will achieve excellent results, minimising unnecessary interventions in children with anisometropic and strabismic amblyopia. PEDIG conducts large randomised controlled trials and observational studies. Typically, 50-80 investigators participate in each individual study, to evaluate the effectiveness of current practices under real world conditions. The studies involve the standardised assessment of visual outcomes using masked assessors. However, they do not involve monitoring of adherence to the prescribed regimens and therefore may more closely resemble the situations encountered in clinical practice.
Refractive correction alone is adequate for many patients
A number of studies indicate that optical correction alone may be effective in many cases. The studies also indicate that in those unresponsive to optical correction the next reasonable step is to start patching the fellow eye two hours a day or use twice weekly atropine drops to the fellow eye. However, if a plano lens is used in addition to atropine, careful monitoring of visual acuity of the fellow eye is necessary to avoid inducing reverse amblyopia. In one observational study, PEDIG investigators found that refractive correction alone brought about a mean improvement of 2.9 lines of vision in the affected eye of 84 amblyopic children, aged three to seven years, with previously untreated anisometropic amblyopia. In addition, mean visual acuity improved from 20/80 to 20/40, and 78 per cent of patients gained two or more lines of visual acuity, 60 percent gained three or more lines, but even more importantly there was a resolution of amblyopia in 27 percent of patients. Similar improvement occurred among patients with strabismic amblyopia. In patients with strabismic amblyopia alone there was a mean gain of 2.2 lines and among those with combined strabismic and anisometropic amblyopia there was a mean gain of 2.6 lines, with refractive correction alone. Most of the improvement occurred in the first 10-15 weeks of treatment but some patients continued to improve for up to 30 weeks. The severity of amblyopia did not appear to influence outcome. The amount of vision gained was similar among those with severe amblyopia and moderate amblyopia.“Optical treatment of amblyopia” or ‘refractive adaptation’ can completely address amblyopia in some children – making patching or atropine unnecessary. We can
therefore conclude from the spectacle studies, regardless of whether amblyopia is anisometropic or strabismic, to treat refractive error first and follow until visual acuity stops improving.
Low dose patching is often effective
The PEDIG studies have shown that in cases where spectacle correction does not bring about an adequate response, patching may result in further improvements. They also suggest that prescribing full-time patching is unlikely to achieve better results than prescribing part-time patching, when used as initial therapy, even in cases of severe amblyopia. In a randomised study involving 189 patients with moderate amblyopia who underwent prescribed patching for either two hours a day or six hours a day, the two treatment groups had identical improvement throughout the study. Mean visual acuity in both groups was 20/63 at baseline, 20/40 at five weeks and 20/32 at four months. The practical conclusion from this study is to start with two hours a day of occlusion in cases of moderate amblyopia and increase the intensity of the patching if there is an inadequate response. Similarly, the results of another PEDIG study, which involved 175 patients, indicate that patching prescribed for six hours a day may be as effective as prescribing full-time patching in children with severe amblyopia. In the randomised trial, there was a mean improvement of 4.7 lines in the full-time patching group and 4.8 lines in the six-hour patching group. In such cases the practical conclusion is to start with six hours a day patching and increase the intensity of treatment if there is an inadequate response.
Another study suggested that the activities patients engage in during low dose patching would have no bearing on visual improvement. The study involved 425 patients aged three to seven years with amblyopia ranging from 20/40 to 20/400 who underwent patching for two hours a day while engaging in either near or distance activities. After 17 weeks there was no statistically significant difference between the two groups in terms of visual improvement. The mean visual acuity of the amblyopic eyes in both groups improved from mean pretreatment of 20/80 to 20/40 after treatment. In this study, children with severe amblyopia were also included, and were also prescribed patching two hours a day. Among these children with severe amblyopia (20/100 to 20/400), there was a mean improvement of 3.6 lines at 17 weeks and six patients had a complete resolution of their condition. There is no justification for specific instructions regarding what to do when patched, other than something that takes their mind off it. And there is a role for two hours a day as initial therapy even in severe amblyopia.
Atropine may be as effective as patching
Atropine appears to be as effective as patching and finds higher acceptance among some parents, according to another PEDIG study. The study involved children with moderate amblyopia, visual acuity 20/40 to 20/100, who underwent either patching for at least six hours a day or daily administration of one drop of atropine every morning. At their six-month assessments the amblyopic eyes of the two treatment groups achieved similar improvements of visual acuity, with mean gains of 3.16 lines in the patching group and 2.84 in the atropine group. The proportion achieving a visual acuity of 20/30 or better, more than three lines of improvement, was 79 per cent in the patching group and 74 per cent in the atropine group. In another PEDIG study that compared daily and weekend atropine, 47 per cent of the patients in the daily group and 53 per cent in the weekend group had an amblyopic eye acuity that was either 20/25 or better or the same as or better than the sound eye acuity, suggesting that there was no advantage of daily atropine over two days a week. Yet another PEDIG study showed that adding a plano lens to atropine therapy (as initial therapy) had limited benefit over atropine alone, but found that even severe amblyopia can respond to atropine. Among 60 children three to six years of age with visual acuity of 20/125 to 20/400 in their amblyopic eye, mean visual acuity improved 4.5 lines with atropine-only and 5.1 lines with atropine plus a plano lens. Nevertheless, the more intense regimen of adding a plano lens to atropine resulted in a reduction of visual acuity in the sound eye of more than one line in 17 per cent of patients, compared to only four per cent in the group receiving atropine alone. And although all eyes returned to baseline, two patients in the atropine plus plano lens group underwent active treatment for reverse amblyopia. So if a plano lens is used in addition to atropine, careful monitoring of visual acuity is needed to avoid inducing reverse amblyopia. Previous PEDIG studies have focused on initial amblyopia therapy. Ongoing PEDIG studies are evaluating the effectiveness of adding therapy in cases where amblyopia has not completely responded to initial therapy. One current study is evaluating ramping-up patching (from two to six hours a day) and a second current study is evaluating adding a plano lens to atropine.
Results require cautious interpretation
Although the PEDIG studies provide useful information towards designing a protocol for the treatment of amblyopia, they leave many questions unanswered. For an ideal level of evidence, a wellrun, completed randomised controlled trial with solid statistical evidence that can be clinically translated in significant new data is the recognised way to go. This is a difficult goal to achieve and it is with these qualifiers that one has to always look at data generated by clinical trials. The PEDIG studies on amblyopia are no exception to that. Questions that arise from the PEDIG reports include the effect of investigator discretion at various stages of these studies as well as the influence of patients’ compliance, and the influence of past treatment on the trial’s success. On atropine usage, the PEDIG reports show a good acceptance, but it is also essential to know if this conclusion can be widely applied to families of different cultures, or different ethnical background. We also do not know yet what the systemic effect of long term atropine are on the patients, blood pressure included; the anecdotal evidence certainly warrants a closer look into that. Also, still unspecified is the influence of the refractive error on the effectiveness of atropine penalisation.
A significant concern arises regarding the frequent choice of subnormal visual acuity levels as success targets in the PEDIG studies on amblyopia treatment. And finally, we do not know the effect of long term success of the slower initial response to treatment that is the characteristic of the less aggressive approaches suggested by the PEDIG results.
The surgical option
For patients whose amblyopia has not responded to conventional treatment, refractive surgery has emerged as an option to bring about further visual improvements rendering them more amenable to refractive and occlusive response. Treating paediatric patients with LASEK over the past 12 years for refractory anisometropic amblyopia, the procedure results in an overall improvement in BCVA and in stereopsis with excellent stability achieved for targeted refraction and minimal to no haze. In a study involving 53 patients with a mean age of 8.4 years who underwent LASEK after failing all other treatments, the refractive difference between the two eyes was reduced from a preoperative value of 6.89 D to 1.8 D. All clinicians should consider this therapy for children where traditional methods fail.In another study treating with hyperopic LASIK in children with amblyopia and strabismus aged eight to 16 years. He told the symposium that in 76 of 95 amblyopic eyes he has treated with hyperopic LASIK, the condition was resolved by six to 12 months after surgery and after the same follow-up period only 12 patients had strabismus, compared to 82 preoperatively. Paediatric LASIK simultaneously treats refractive amblyopia and accommodative strabismus in cases of hyperopia and hyperopic astigmatism.
Implantation of a phakic IOL can resolve amblyopia and strabismus in about a third of patients with high unilateral myopia, without excessive risk to the intraocular structures of the growing eye.
Better outcome measures are needed
Whatever treatment is used, a more robust definition of amblyopia and more appropriate outcome measures than are currently used will be necessary to determine their efficacy. Current definitions and outcome measures are not adequate because they do not reflect a physiological sense of visual pathway function and they do not promote understanding of function or the science of the condition. The standard definition of amblyopia is reduced visual function in one eye relative to the other not immediately improved by refractive correction. The measure of success in treating the condition is generally the amount of visual improvement in the affected eye. In a physiological sense, a successful outcome is achievement of that condition which is best suited to promote a normal or optimal visual development and function,
and that means equal visual input. Thus, optimum outcome for amblyopia therapy is when vision of amblyopic eye equals that of the fellow eye. However, a true cure for amblyopia requires more than just an improvement of visual acuity in the affected eye. Amblyopia involves defects in several other aspects of vision that are affected by abnormal neural development and abnormal neural processing of visual stimuli. In particular, in primate studies of amblyopia where one eye is deprived of visual stimulation, there develops an imbalance between the parvocellular pathway, which seems to be concerned primarily with perception of colour and fine detail, and the magnocellular pathway which is more involved with the visual perception of large moving objects. The two pathways work in parallel with each other, and primate studies show that when compared to normal lateral geniculate bodies, those of animals whose eyes were occluded from birth have parvocellular cells that are smaller relative to magnocellular cells for both the amblyopic and the fellow eyes.
Electrophysiological studies of patients with strabismic amblyopia show abnormalities of visual evoked potentials which are different for coloured and moving stimuli, suggesting that such patients also have different changes in their m agnocellular and parvocellular pathways. This raises the questions of whether some children fail to respond to patching because of an imbalance between these pathways and whether we should be looking selectively to stimulate magnocellular or parvocellular pathways as part of amblyopia treatment.
References
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