Amblyopia is the loss of visual sensitivity related to binocularly discordant vision early in life.1 It may be caused by strabismus, anisometropia, visual deprivation, or a combination of these components, whereas anisometropia is the most common risk factor for amblyopia.1,2
In clinical practice, the diagnosis of amblyopia is essentially based on measurement of visual acuity. Along with visual acuity, contrast sensitivity and crowding phenomena are the other components of visual function that are affected in amblyopic eyes.3,4 On the other hand, possible changes in visual field, macular sensitivity, and fixation stability of amblyopic eyes have been investigated in the literature.5–10 Generalized depression of light sensitivity and central scotomas have been shown with different automated perimetry and micro-perimetry devices.5–10 However, results for location and stability of fixation were different among studies.7,8
The macular analyzer integrity assessment (MAIA) microperimetry (CenterVue) is the third generation of microperimetry instruments, which allows us to evaluate capability of fixation and sensitivity in the retina at the same time with retinal imaging created by scanning laser ophthalmoscope (SLO). In recent years, use of microperimetry in the field of macular diseases and low vision has increased.11
This study aimed to evaluate retinal sensitivity and fixation characteristics in children with anisometropic amblyopia by MAIA microperimetry and to compare the results between amblyopic and fellow eyes. The correlations between visual acuity and microperimetry parameters were also analyzed.
Patients and Methods
The study conformed to the tenets of the Declaration of Helsinki and received the approval of the Istanbul Medipol University Institutional Review Board (decision number: 10840098-604.01.01-E.64941). Written informed consent was obtained from all parents.
The study consisted of a total of 39 children (21 girls, 18 boys) with the diagnosis of anisometropic amblyopia. The selection criteria of patients were having anisometropia of 1.00 diopters (D) or greater (spherical and/or cylindrical) and a minimum difference of two Snellen lines in best corrected visual acuity (BCVA) between the eyes. The exclusion criteria were having any previous ocular surgery or trauma; having strabismus or other forms of amblyopia, optic nerve head and/or retinal diseases, or corneal disorders; and lack of cooperation at microperimetry analysis.
All patients underwent a detailed ophthalmic examination (visual acuity with Snellen charts, cover test, intraocular pressure assessment with eye tonometer [Icare], and anterior segment and dilated fundus examinations). For statistical analysis, patients' BCVA was transformed into the logarithm of the minimum angle of resolution (logMAR) scale. The spherical equivalent was measured from the cycloplegic refraction. Cycloplegia was achieved by administering cyclopentolate 1%. After cycloplegia, an autokeratorefractometry measurement (KR-8900; Topcon Medical Systems) was performed.
MAIA microperimetry was used as the micro-perimetry device. MAIA microperimetry combines retinal imaging with SLO and analyzes fixation capability and retinal sensitivity. The test was performed in a room with dim lighting without a dilated pupil. Standard test parameters including a 37-stimuli grid covering a 10° area in three side-by-side circles of 2°, 6°, and 10° of diameter with Goldmann III stimulus size, 4 asb background luminance, 36 dB dynamic range, and 4-2 threshold strategy were used during the analysis. Finally, the results of average threshold were interpreted as normal (> 28 dB), suspect (26 to 28 dB), or abnormal (< 26 dB) (Figure 1).
Sensitivity examination of the (A) amblyopic eye and (B) non-amblyopic eye of a patient. Average threshold was 26.4 dB for the amblyopic eye and 29 dB for the non-amblyopic eye.
Location and stability of fixation were evaluated by following eye motions 25 times/second and mapping the result of distribution over the SLO image. The fixation points are located within a distance of 1° and 2° and are interpreted with percentages as P1 and P2, respectively. If more than 75% of the fixation points are located within P1, the fixation is defined as “stable.” If less than 75% of the fixation points are located within P1 but more than 75% of the fixation points are located within P2, the fixation is defined as “relatively unstable.” The worse fixation pattern is “unstable” fixation, in which less than 75% of the fixation points are located within P2. Bivariate contour ellipse area (BCEA) is the area of an ellipse comprising 95% (BCEA95) and 63% (BCEA63) of fixation points depending on standard deviations of the horizontal and vertical eye positions recorded while the patient is fixating (Figure 2).
Fixation pattern of the (A) amblyopic eye and (B) non-amblyopic eye of a patient. Bivariate contour ellipse area for 63% of points (BCEA63) was 0.7°2 for the amblyopic eye and 0.4°2 for the non-amblyopic eye. Bivariate contour ellipse area for 95% of points (BCEA95) was 2.1°2 for the amblyopic eye and 1.3°2 for the non-amblyopic eye.
SPSS for Windows version 19 software (SPSS, Inc) was used for statistical analysis. The normality test was conducted by using the Shapiro-Wilk test. The Wilcoxon signed-rank test was used for comparison of average threshold and fixation indexes (P1 and P2) and BCEA for 95% and 63% of points between the amblyopic and fellow eyes. The correlations of the microperimetric parameters with BCVA were assessed with Spearman's correlation coefficient. A P value less than .05 was considered to be significant.
The patients' mean age was 10 ± 2.0 years (range: 7 to 15 years). The mean BCVA was 0.31 ± 0.16 logMAR (range: 0.15 to 0.69 logMAR) for amblyopic eyes and 0.00 ± 0.00 logMAR for fellow eyes (range: 0.00 ± 0.00 logMAR) (P < .001). The mean spherical equivalent value was +1.94 ± 5.95 D (range: −10.50 to +7.50 D) for amblyopic eyes and +2.25 ± 2.01 D (range: −0.25 to +5.50 D) for non-amblyopic eyes (P < .001). The mean values for microperimetric parameters including average threshold, fixation indexes (P1 and P2), and BCEA for 95% and 63% of points are summarized in Table 1. Average threshold value was significantly decreased in the amblyopic eyes compared to the non-amblyopic eyes (P = .003). In the fixation analysis, only P1 fixation index was significantly higher in the non-amblyopic eyes (P = .032). There was no difference between eyes for P2 fixation index and BCEA95 and BCEA63 values (P = .733, .777, and .813, respectively). The correlations of microperimetric values and visual acuity are shown in Table 2. The only significant correlation was found between P1 fixation index and visual acuity (r = −0.369, P = .005).
Mean Results of Microperimetric Parameters
Correlations of Microperimetric Parameters and Visual Acuity
In the current study, retinal sensitivity and fixation pattern of children with anisometropic amblyopia were evaluated using MAIA microperimetry. The results showed that the retinal sensitivity was significantly higher in non-amblyopic eyes compared to amblyopic eyes. In fixation analysis, P1 fixation index was also significantly higher in the non-amblyopic eyes and it was significantly correlated with visual acuity.
In addition to the decreased visual acuity, reduction in the retinal sensitivity, central scotomas, and changes in fixation stability have been shown using different microperimetry devices in amblyopic eyes.7–10 Dickmann et al7 observed an extensive decrease in retinal sensitivity and small, localized, central scotomas in both strabismic and refractive amblyopic eyes with MP-1 microperimetry. They also determined retinal nerve fiber layer and macular thicknesses, and foveal volume with stratus optical coherence tomography. Although there was no significant difference for any of these parameters, they showed a correlation between a thinner retinal nerve fiber layer and less sensitive macula in the refractive amblyopic group. Johnson10 reported decreased threshold sensitivity and larger scotoma area in the anisometropic amblyopic eyes with SLO microperimetry. The author also found reduced sensitivity in the non-amblyopic eyes compared to the control group, together with central scotoma in 80% of the non-amblyopic eyes of the patients with anisome-tropic amblyopia. Koylu et al9 evaluated eyes with severe amblyopia with visual acuity of worse than 1.0 logMAR using MP-1 microperimetry and found decreased macular sensitivity in anisometropic amblyopic eyes compared to the controls. Similar to previous research, our study showed decreased retinal sensitivity levels in the amblyopic eyes compared to the non-amblyopic eyes.
The study of Koylu et al9 investigated the fixation characteristics of adult patients with severe amblyopia and showed that fixation stability within 2° was significantly lower in amblyopic eyes of patients with anisometropic amblyopia; however, they found no significant difference within 4° compared to the healthy controls. Subramanian et al8 reported significantly larger BCEA95 for anisometropic amblyopic eyes than fellow eyes using MP-1 microperimetry in their pediatric patients. However, they showed no significant correlation between visual acuity and BCEA for anisometropic amblyopic eyes. In the current study, we found that P1 fixation index was significantly lower in the amblyopic eyes, but BCEA95 and BCEA63 values were not different between the groups. We also found a correlation between visual acuity and P1 fixation index. Conversely, Dickmann et al7 did not find a significant difference between the refractive amblyopic eye and the fellow eye, in terms of the fixation stability and location. The possible reason for the conflicting result may be because Dickmann et al7 included a limited number of patients from both pediatric and adult age groups with better visual acuity.
Molina-Martín et al12 reported normative values of MAIA microperimetry for both adults and children and showed that retinal sensitivity decreased progressively from age 20 to 70 years. Also, a more unstable fixation pattern was seen with increased age. For the children between 10 and 20 years of age, macular sensitivity was lower and fixation stability was worse compared to the young adult group. When we compared the results of our non-amblyopic eye with these normative values, we noticed decreased average threshold (28.6 vs 32.80 dB) and worse fixation stability (87.6% vs 97% for P1; 94.3% vs 100% for P2; 9.4°2 vs 3°2 for BCEA95; and 3.1°2 vs 0.3°2 for BCEA63). Including younger patients in the current study may explain this difference because Molina-Martín et al12 also found better fixation in those older than 16 years. Jones et al13 also evaluated feasibility of MAIA microperimetry in children with ages between 9 and 12 years. Similarly, mean macular sensitivity in our non-amblyopic eyes was 27.6 dB, but BCEA95 was 4.58°2, which indicates better fixation stability than our healthy eyes. Molina-Martín et al12 and Jones et al13 think that microperimetric measurement is possible in children, but due to lower sensitivities normative values should be lowered in children compared to adults. On the other hand, changes in fixation stability and scotoma areas have been observed in non-amblyopic eyes of patients with amblyopia compared to healthy controls.8,10 These findings support that amblyopia is a binocular disorder and the effects of unilateral amblyopia may not be limited to the amblyopic eye. This might be the other reason for worse values in the non-amblyopic eye of our patients.
Microperimetry is a tool that helps clinicians understand the functional status of the macula and fixation pattern. Because measuring visual acuity does not represent all functions of the visual system, microperimetric evaluation may give extra information about the total visual function of amblyopic eyes and support ophthalmologists in their management of amblyopia.
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- Dickmann A, Petroni S, Perrotta V, et al. A morpho-functional study of amblyopic eyes with the use of optical coherence tomography and microperimetry. J AAPOS. 2011;15(4):338–341. doi:10.1016/j.jaapos.2011.03.019 [CrossRef]
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- Koylu MT, Ozge G, Kucukevcilioglu M, et al. Fixation characteristics of severe amblyopia subtypes: which one is worse?Semin Ophthalmol. 2017;32(5):553–558. doi:10.3109/08820538.2015.1123739 [CrossRef]
- Johnson DA. The use of the scanning laser ophthalmoscope in the evaluation of amblyopia (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006;104:414–36.
- Molina-Martín A, Pérez-Cambrodí RJ, Piñero DP, Piñero DP. Current clinical application of microperimetry: a review. Semin Ophthalmol. 2018;33(5):620–628. doi:10.1080/08820538.2017.1375125 [CrossRef]
- Molina-Martín A, Piñero DP, Pérez-Cambrodí RJ. Normal values for microperimetry with the MAIA microperimeter: sensitivity and fixation analysis in healthy adults and children. Eur J Ophthalmol. 2017;27(5):607–613. doi:10.5301/ejo.5000930 [CrossRef]
- Jones PR, Yasoubi N, Nardini M, Rubin GS. Feasibility of macular integrity assessment (MAIA) microperimetry in children: sensitivity, reliability, and fixation stability in healthy observers. Invest Ophthalmol Vis Sci. 2016;57(14):6349–6359. doi:10.1167/iovs.16-20037 [CrossRef]
Mean Results of Microperimetric Parameters
|Parameter||Amblyopic Eye (n = 39)||Non-amblyopic Eye (n = 39)||Pa|
|AT (dB)||26.6 ± 5.9||28.6 ± 1.9||.003|
|P1 (%)||80.2 ± 20.3||87.6 ± 8.7||.032|
|P2 (%)||92.5 ± 9.6||94.3 ± 4.8||.733|
|BCEA95 (°2)||12.9 ± 17.2||9.4 ± 8.2||.777|
|BCEA63 (°2)||4.4 ± 5.6||3.1 ± 2.7||.813|
Correlations of Microperimetric Parameters and Visual Acuity