刊載於： 國際眼科雜誌(英文版) 收錄於SCIE科學文獻引用索引資料庫及PubMed生物醫學資料庫 ISSN 2222-3959 Vol.6, No. 4, Aug. 18th 2013: 487-491INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
結果：在患者中，弱視眼視力的平均VA從0.35（SD=0.16），提高至0.85（SD= 0.16），而視力VA的改善則平均為0.45（SD= 0.10，P<0.001）。360例中的233例（64.72％）弱視得到解決。解決弱視的平均時間為8.05週（SD= 4.83）或14.14堂訓練（SD=8.76）。案例當中，治療後屈光度誤差並沒有明顯改變（P =0.437）。研究發現，較佳的基礎VA可能與成功解決弱視及縮短其時間有關。
Published in: “International Journal of Ophthalmology” (English edition)
Indexed in SCI expanded and PubMed/PubMed central
Vol.6, No. 4, Aug. 18th 2013: 487-491
“Improvement of Visual Acuity in Children with Anisometropic
Amblyopia Treated with Rotated Prisms Combined with Near Activity”
Chao-Chyun Lin, MD1, Po-Liang Chen, MD2
Aim: To evaluate the efficacy of a new modality for improving visual acuity (VA) in pediatric patients with anisometropic amblyopia.
Methods: Retrospective and interventional case series. Medical records of 360 children with anisometropic amblyopia treated with a modality that included rotated prisms, plus lenses, and near activities from January 2008 through January 2012 were analyzed. Characteristics such as improvement of VA and contrast sensitivity in amblyopic eyes and resolution of amblyopia (VA ≤0.1 logMAR or a difference of ≤2 lines in logMAR between the eyes) were assessed.
Results: Among the patients, the mean VA of the amblyopic eyes improved from 0.48 logMAR (SD = 0.16) to 0.12 logMAR (SD = 0.16) and the mean VA improvement was 0.36 logMAR (SD = 0.10, P < 0.001). Resolution of amblyopia was achieved in 233 of 360 patients (64.72%). The mean time for resolution of amblyopia was 8.05 weeks (SD = 4.83) or 14.14 sessions (SD = 8.76). Among the study group, refraction error did not change significantly after treatment (P = 0.437). We found that better baseline VA may be related to success and shorten the time to amblyopic resolution.
Conclusions: VA and contrast sensitivity improved with rotated prisms, correcting lenses, and near activities in children with anisometropic amblyopia. The VA improvement by this modality was comparable to other methods. However, the time to resolution of amblyopia was shorter with this method than with other modalities. Rotated prisms combined with near acuity could provide an alternative treatment in children with anisometropic amblyopia who can’t tolerant traditional therapy method like patching.
Amblyopia is a disorder that consists of functional abnormalities, such as visual acuity (VA) reduction, contrast sensitivity impairment, spatial distortion, abnormal spatial interaction, and contour interaction. Refractive amblyopia, either anisometropia or isometropia, results from relative high refractive errors in one or both eyes that cause blurred retinal images. The presumed mechanism is vision pattern deprivation. The affected eye provides a more blurred image to the retina and brain and amblyopia develops. Children carry the risk of developing amblyopia if the condition is untreated within their critical period. Previous studies show optimal spectacle correction is a major component in improving visual function in patients with anisometropic amblyopia.1,2 In addition, patching, or penalization of the sound eye, is a major used as an adjunct to the anisometropic amblyopia therapy.
In addition to patching, penalization, and refractive correction, there are a handful of methods to treat anisometropic amblyopia. Perceptual learning improves visual performance by repeating basic tasks3,4 and showed comparable effects in amblyopic therapy with patching.5–9
However, the social stigma and anxiety of patching in elder children limited its compliance and thus its useful application. On the contrast, perceptual learning would be less efficient in younger children than elders. Therefore, in this study, we evaluated the efficacy of a new modality that combines rotated prisms, lenses, and near activities treating pediatric patients with anisometropic amblyopia.
MATERIALS AND METHODS
The study protocol complied with the requirements of the Institutional Review Board. Medical records of pediatric patients who underwent amblyopic therapy by this modality between January 2008 and January 2012 in the ophthalmology department of Lin Amblyopic Eye Center were reviewed.
Patients were recruited into this study if they met the inclusion criteria. The major inclusion criteria were age from 3 to 11 years, visual acuity (VA) worse than 0.3 logMAR or at least two lines of difference between the eyes in children with anisometropic amblyopia, and without existence of strabismus or other ocular diseases that could result in reduced VA. Anisometropia was defined as a difference of ≥1.00 D in the myopic, hyperopic, or astigmatic refractive error between the patient’s eyes. Correction of refractive error was accepted in this study. Spectacles were prescribed by two ophthalmologists (Chao-Chyun Lin, MD and Po-Liang Chen, MD). We excluded patients if they did not meet the definition for amblyopia or failure during the follow-up period, and concurrent amblyopia treatment, such as cycloplegics, patching, or other perceptual learning tasks.
The new modality we used contains two sets of lenses for “flippers” in our visual training program. Set A was constructed with a 0.5 D plus lens and a 5.0 D prism (alternative base-in or base-down); set B included a +1.0 D plus lens with a 2.0 D basein prism.
When eligible patients performed their training for near activities at a distance between 2.5 and 3.0 meters, such as watching television, this modality switched to only set A for function. The training program, which lasted for 50 minutes, consisted of using the 0.5 D plus lens and 5.0 D base-down prism for six seconds followed by the 0.5 D plus lens and 5.0 D base-in prism for another nine seconds (Table 1; Figure 1).
In another type of training performed at closer distances ranging from 30 to 60 cm, sets A and B were worked together for 50 minutes while we added a 1.50 D plus lens in front of the eye for reading or doing homework (distance 30 cm) and a 0.5 D plus lens for playing computer games (distance 60 cm). In the initial six seconds of this training, there was only the set A lens with a 0.5 D plus lens and 5.0 D base-down cylinders. In the following 14 seconds, sets A and B were used together with a 1.5 D plus lens with 7.0 D base-in prism (0.5 D plus lens with 2.0 D base-in prism in set A and +1.0 D plus lens with 5.0 D base-in prism in set B). Net effects for different purposes differed according to the additional plus lens (Table 1).
Visual training using this modality was conducted twice a week in our outpatient department. The VA, contrast sensitivity, and cycloplegic refraction error were recorded for each patient at the beginning of the study, every four sessions during the study and at the end of the study.
The primary endpoint in this study was a difference in VA of less than 2 lines difference or a VA better than 0.1 logMAR in amblyopic eye. The secondary endpoint was that the amblyopic eye did not gain >0.1 logMAR improvement in six consecutive sessions.
Reliable measurements of VA, refraction error, and contrast sensitivity were recorded. VA was measured by logMAR VA testing (Chart 2210; Precision Vision, La Salle, IL, USA). Refraction error was checked by retinoscopy after the instillation of 0.1% cyclopentolate eye drops. Contrast sensitivity was recorded at the beginning and end of the study.
Data were analyzed using SPSS software (version 13.0 for Windows; SPSS Inc., Chicago, IL, USA). Student’s t-test was used for comparing characteristics before and after treatment. P < 0.05 was considered significant. Regression analysis was adopted to evaluate the factors concordant with improvement of the VA and amblyopia resolution among the patients.
There were 380 children who attended this study. Twelve children were excluded because they could not complete training course and six children loss of follow-up. In total, we report the results of 360 children with anisometropic amblyopia. In the group, there were 20 children with myopic amblyopia, 60 with hypermetropic amblyopia, 75 with astigmatic amblyopia, and 205 with mixed refractive amblyopia. In our study, the mean age was 6.43 years (SD = 1.40) and the baseline mean refraction error in spherical equivalent was –1.06 D (SD = 0.67). The mean VA of the amblyopic eyes at baseline was 0.48 logMAR (SD = 0.16). The baseline characteristics of these patients are listed in Table 2.
Patients were classified into success or failure groups according to the resolution of their amblyopia. The criteria for success were amblyopia that resolved with a final VA ≤0.1 logMAR in the amblyopic eye or an interocular VA difference ≤2 lines in logMAR. As a result, there were 233 patients in the success group. The overall success rate in this new modality was 64.72%. The mean VA of the amblyopic eyes improved significantly from 0.48 logMAR at baseline to 0.12 logMAR after VA stabilized with a mean improvement of 0.36 logMAR (SD = 0.10). The mean time to resolution of amblyopia was 8.05 weeks ranging from 5.0 to 24.0 weeks (SD = 4.83). The mean number of sessions of visual training to resolution was 14.14 sessions (ranging from 6 to 50 sessions, SD = 8.76) (Table 3). The mean difference in refraction error before and after treatment was –0.39 D without significance (SD = 0.67, P = 0.437). The better baseline VA was related to success and shorter of the time to amblyopic resolution (P = 0.001).
Before treatment, contrast sensitivity in these patients was below the normal limit and the peak baseline contrast sensitivity shifted to a lower frequency (Figure 2). The contrast sensitivity showed significant improvement after therapy for all spatial frequencies and improved by factors of 2.11, 1.95, 2.79, 5.20, and 4.14 at spatial frequencies of 1.5, 3. 6, 12, and 18 cycles per degree, respectively. The correlation between improvements in contrast sensitivity and VA was a factor of 0.28. Among all patients, we found that the baseline VA was the only significant factor to predict the success or failure of treatment (negative correlation, P < 0.001, R2 = 0.291). Baseline VA was also a factor for predicting faster improvement (<8 weeks).
The modality used in this retrospective study was initially designed for myopia control.10 In our prior study evaluating the short-term effect of this modality, mean reduction in refraction error of 0.28 D (SD = 0.03) was shown in the test group.10 In addition to the refraction change, we found that the contrast sensitivity also improved in our patients. Prior studies found that perceptual learning improves visual performance in amblyopic eyes4,7 and VA may also improve after contrast sensitivity improvement.8 In this study of the long-term effects of the treatment, we designed a training program that consisted of 50 minutes a session for two sessions a week. VA, contrast sensitivity, and refraction error change after treatment were analyzed.
The mainstream of refractive amblyopia therapy is refractive correction with patching, penalization, or their combination. Refractive correction alone has been proven to offer 3.9 lines of improvement during the first year in patients with bilateral moderate and severe refractive amblyopia.2 Patching and penalization are well-known adjuncts for amblyopia treatment. Although study have reviewed the efficacy and frequency of patching to increase its compliance in such patients.11However, the social stigma and anxiety of patching in elder children limited its compliance and thus its useful application. Our prior study showed comparable results between patching and perceptual learning, but most younger children felt bored when doing training.5. Therefore, we conducted this new training method for younger and older children.
The mean VA improvement in our study was 0.36 logMAR, which was compatible with previous studies. In our prior study on VA improvement by perceptual learning or patching in anisometropic amblyopic eyes, VA improvement by perceptual learning was 2.5 lines5,6 in amblyopic eyes. We believe that the different outcome in our study is attributable to different modality of visual training, or to different inclusion criteria.
Stewart and his coworkers proposed that the dose-response rate for patching in patients aged between 3 and 8 years is around 0.1 logMAR for every 120 hours of patching,13 and later they suggested that age may influence the dose-response rate in amblyopia therapy.14 According to this conclusion, it may take about 420 hours of patching to achieve a mean improvement of 0.32 logMAR. From the patching strategy in PEDIG studies, patients with moderate amblyopia (VA range from 20/80 to 20/40) should undergo a patching dose of two hours per day.11 That regimen would require nearly seven months of patching to achieve an improvement of 0.36 logMAR such as found in our study. Patients receiving the current treatment modality spent 8.05 weeks to reach resolution of refractive amblyopia. We believe that the faster resolution of five months over patching treatment is mostly attributable to this new modality.
Compliance in amblyopia therapy remains the major concern regarding its success. Loudon et al. stated that poor parental fluency in the national language, a low level of education, and poor baseline VA may lead to low compliance and then failure of therapy.15 Intense supervision of occlusion treatment and parental education greatly help to improve success rates.16 Traditional patching failed in some patients due to social stigma or anxiety, but perceptual learning may also fail because the simple tasks are too boring.5 Our treatment provided relative high compliance using this modality because of interesting tasks like playing interactive computer games, watching TV.
We thought that improvement in VA may result from several causes. First, similarly to other studies of perceptual learning, improved contrast sensitivity played a major role in improvement VA. Second, interactive activities consisting of watching favorite television programs, playing interactive computer games, and doing homework increased compliance compared with repetitive simple tasks.
Since myopia has a relatively high prevalence in East Asians of 22.4% at the age of six years and 64.1% at 12 years,17 several factors including genes, environment, or near work are thought to be involved. Near work (<30 cm) and longer working time (>30 minutes) were related to more refraction changes toward myopia18. In our study, although amblyopia treatment was performed in near activities at a distance from 30 cm to 3.0 meters, there was no significant refraction error addition noted after long-term treatment.
There were some limitations in our study. First, there was absence of a control group. Most parents requested this therapy after the failure of other therapies and were not willing to participate in the control group. Second, because this study was a retrospective, therefore, the data to do detail analysis were limited. Third, most patients enrolled in our study with moderate to mild amblyopia (most baseline VA ranged from 0.4 to 0.80 logMAR) compared with moderate to severe amblyopia in previous studies. Further perspective studies with more patients should be needed to solve these problems.
In conclusion, our study showed good results for this modality in anisometropic amblyopia therapy. VA and contrast sensitivity improved after a biweekly training program. Patients aged from 3 to 11 years with anisometroic amblyopia could achieve improvement of visual acuity or resolution of their amblyopia. This modality, which combines rotated prisms, lenses, and near activities, may provide an effective alternative for treating anisometropic amblyopia.
這個新的治療方式，包含兩組鏡片。A組鏡片的構造為0.5 D凸透鏡和5.0D稜鏡（基底朝內或朝下，二擇一）；B組則包括一個1.0 D凸透鏡與2.0 D基底朝內的稜鏡。
當符合條件的患者進行2.5至3公尺的用眼活動訓練，例如看電視時，切換至A組訓練模式。此訓練療程歷時50分鐘，包括使用0.5 D凸透鏡和5.0D基底朝下之稜鏡6秒，然後使用0.5 D凸透鏡和5.0D基底朝內之稜鏡9秒。
在另一種更近距離約30至60公分的訓練模式中，同時使用A組和B組鏡片50分鐘；如是距離約30公分的閱讀或做功課，則在眼前加上1.50 D的凸透鏡；如是距離約60公分的玩桌上型電腦遊戲，則是加上0.5D的凸透鏡。在訓練的最初6秒，只有A組鏡片的0.5 D凸透鏡和5.0D基底朝下稜鏡。接下來的14秒，A組和B組鏡片同時使用，等於1.5 D凸透鏡和7.0D基底朝內之稜鏡（A組的0.5 D凸透鏡和2.0D基底朝內稜鏡，加上B組的1.0D凸透鏡和5.0D基底朝內稜鏡）。依據不同用途增加的額外凸透鏡，會造成不同的加總影響。（表1）。
數據分析採用SPSS程式系統。 療程前後特點的分析，則是用Student’s t-test。 若P <0.05則認為是有顯著的不同。患者的弱視是否得到改善、與VA有否進步，則是通過回歸分析來評估。
共有380名兒童參與本研究。有12名兒童因無法完成訓練療程被排除，還有6名兒童因沒回來追蹤檢查而被排除。我們總共報告了360名不等視性弱視兒童的訓練結果。其中，有20名兒童有近視性弱視、60名有遠視性弱視、75名散光性弱視、和205名混合的屈光不正性弱視。本研究中，平均年齡為6.43歲（SD= 1.40）；而以球面度數來算，平均屈光不正的基準則是-1.06 D（SD= 0.67）。弱視眼的平均VA基準則是矯正視力0.3左右（SD=0.16）。這些患者的基準特徵在表2中列出。
患者依照其弱視的是否得到改善，分為成功與失敗組兩組。成功組的標準是弱視眼的最終視力≤0.1 logMAR或兩眼視差小於兩行 logMAR視力表。結果，成功組中有233名患者。此種新模式的總成功率是64.72％。弱視眼的平均VA，從0.3 (0.48 logMAR ) 進步到1.0 (0.12 logMAR )；平均進步VA為0.36 logMAR。達到弱視改善的平均時間為8.05週，最少5.0週，最多24.0週不等（SD= 4.83）。達到弱視改善的平均訓練次數為14.14次（範圍從6至50次訓練不等，SD=8.76）（見表3）。治療前後的屈光不正平均差異則為 -0.39Ð，無統計上的顯著意義（SD=0.67，P=0.437）。擁有較佳的基礎VA，與成功和在較短的時間內到弱視改善有關（P = 0.001）。
Stewart和他的同事提出，患者年齡介於3至8歲時，每120小時的遮眼，可改善視力約0.1 logMAR，其後他們又建議，年齡可能會影響遮眼在弱視治療中的成效。根據這一個結論，要達到平均0.32 logMAR視力改善，可能需約420小時的遮眼。從PEDIG研究的遮眼策略來說，中度弱視（VA介於20/80至20/40之間）的患者應接受每天2小時的遮眼。如要達到本研究中的0.36 logMAR視力改善，則約需要近7個月的遮眼治療。而以本研究來說，患者達到屈光不正性弱視的改善則只需8.05週。我們相信，本研究的特殊治療模式，正是能使弱視達到改善的時間比遮眼療法快上5個月的主要原因。