|Year : 2019 | Volume
| Issue : 2 | Page : 74-81
Optical coherence tomography-based comparison of retinal nerve fiber layer thickness and macular thickness in amblyopic and fellow eyes
Abdulghaffar T.T Abdulghaffar1, Abdelkhalek Al-Saadany2, Asmaa M Ibrahim2
1 Department of Ophthalmology, Ministry of Health, Mansoura University, Dakahlia, Egypt
2 Department of Ophthalmology, Menoufia University, Menoufia, Egypt
|Date of Submission||26-Oct-2018|
|Date of Acceptance||13-Jan-2019|
|Date of Web Publication||24-Jul-2019|
Abdulghaffar T.T Abdulghaffar
Sherbin-Al Gish Street above Alexandria Bank, −Dakahlia 35661
Source of Support: None, Conflict of Interest: None
Objectives The aim of the present study was to compare the retinal nerve fiber layer thickness (RNFLT), macular thickness, and ganglion cell layer thickness between amblyopic and fellow eyes using spectral domain optical coherence tomography (OCT).
Patients and methods Seventy-six patients were included in the study (32 males and 44 females; age range, 18–40 years; mean age, 27.21±8.25 years). Detailed medical history of all patients was obtained. All patients underwent detailed ophthalmologic and fundoscopic examination by slit-lamp biomicroscopy, visual acuity by Landolt’s chart, cycloplegic refraction, ocular alignment, applanation tonometry, and OCT imaging by spectral domain OCT (Cirrus-5000 OCT).
Results There was no significant difference between the amblyopic and fellow eyes regarding central macular thickness, average macular thickness, or ganglion cell complex thickness. By further secondary analysis aiming to compare subgroups according to the refractive status, only the RNFLT was significantly lower in the amblyopic eyes compared with the fellow eyes in the myopic amblyopic subgroup only. Other OCT values were not significantly different in other amblyopic eyes versus fellow eyes in different subgroups.
Conclusion There was no significant correlation between amblyopia and OCT parameters. However, OCT revealed a significant reduction in the mean RNFLT in myopic amblyopic eyes only compared with their fellow eyes. Axial length may be more influential than amblyopia.
Keywords: amblyopia, anisometropia, macular thickness, optical coherence tomography, retinal nerve fiber layer, strabismus
|How to cite this article:|
Abdulghaffar AT, Al-Saadany A, Ibrahim AM. Optical coherence tomography-based comparison of retinal nerve fiber layer thickness and macular thickness in amblyopic and fellow eyes. Delta J Ophthalmol 2019;20:74-81
|How to cite this URL:|
Abdulghaffar AT, Al-Saadany A, Ibrahim AM. Optical coherence tomography-based comparison of retinal nerve fiber layer thickness and macular thickness in amblyopic and fellow eyes. Delta J Ophthalmol [serial online] 2019 [cited 2020 Sep 19];20:74-81. Available from: http://www.djo.eg.net/text.asp?2019/20/2/74/263414
| Introduction|| |
Amblyopia can be defined as ‘reduced best-corrected visual acuity (BCVA) in one or both eyes caused by abnormal visual experience during visual development.’ It may be caused by sensory deprivation, image blur from refractive errors, strabismus, or a combination of these factors .
Amblyopia is usually associated with changes in the distribution of ocular dominance patterns in the visual cortex, cell shrinkage in the lateral geniculate body, and optic nerve hypoplasia .
Retinal nerve fiber layer (RNFL) is considered a very sensitive indicator of early glaucoma, preceding other structural and functional changes of glaucomatous damage . However, it remains a questionable topic in amblyopia study ‘Does RNFL thickness and macular thickness differ in amblyopic eyes or not?’
Owing to its excellent ability to assess the RNFL thickness and macular thickness, optical coherence tomography (OCT) has much improved the ability to diagnose and follow-up glaucoma and other optic neuropathies .
OCT is a noncontact, noninvasive imaging method similar to ultrasound, but it uses light instead of sound and measures optical rather than acoustic or radiowaves, and hence the term ‘optical’ . OCT image in vivo has a high resolution similar to a histologic section by light microscopy in vitro . It is based on correlation techniques .
The aim of the current study was to investigate the effect of amblyopia on RNFLT, macular thickness, and ganglion cell complex (GCC) thickness by comparing amblyopic OCT measurements with normal values of fellow eye. This issue may help to update OCT normative database by taking into consideration different eye conditions, which may help to avoid both overdiagnosis and misdiagnosis of early glaucoma, as the RNFL is considered a very sensitive indicator of early glaucoma preceding other detectable structural and functional glaucomatous changes.
| Patients and methods|| |
This prospective study was performed at the Department of Ophthalmology, at Menoufia University Hospital, and Tiba Ophthalmic Center, Shebin-Alkom, on 76 patients aged between 18 and 40 years with unilateral amblyopia who presented to the outpatient clinic for examination.
In this study, amblyopia was diagnosed if there was missing of two or more lines of Landolt’s chart. So the patient with BCVA less than or equal to 6/12 was considered amblyopic provided that there was no ocular pathology.
Exclusion criteria included evidence of ocular pathology such as poor clarity of refracting media including corneal opacity, cataract, and vitreous hemorrhage; posterior segment diseases ‘retinal and optic disc diseases including glaucoma and intraocular tumors’; medical systemic disorders, such as diabetes mellitus, hypertension, and vascular disorders affecting the retina; very high degrees of refractive errors; active external eye diseases including corneal disorders and history of trauma; or previous ophthalmic surgery.
The study was approved by the Ethical Committee of the Faculty of Medicine, Menoufia University. An informed consent was signed by all participants before being enrolled in the study.
All patients underwent detailed ophthalmologic and fundoscopic examination by slit-lamp biomicroscopy, intraocular pressure measurement by applanation tonometery, visual acuity measurement by Landolt’s chart and refractive error measurement by autorefractometer using cycloplegic refraction by instillation of cyclopentolate 1% eye drops.
The spectral domain OCT Cirrus (Cirrus-5000 OCT; Zeiss Corporation, Oberkochen, Germany) was used to measure the RNFLT and macular thickness.
RNFL was assessed by obtaining average thickness of the RNFL (mean RNFLT). Macular thickness was assessed by obtaining three parameters: central macular thickness (CMT), average macular thickness, and thickness of the ganglion cell layer and inner plexiform layer ‘GCC’ ([Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7]). Cirrus normative database matched the average anatomic age and ethnical diversity values and obtained clearance from the United States Food and Drug Administration .
|Figure 2 Early treatment diabetic retinopathy study (ETDRS) grid is automatically centered on the fovea with fovea finder. Retinal thickness values from internal limiting membrane to retinal pigment epithelium in microns are compared with normative data.|
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|Figure 4 Ganglion cell analysis: sector maps dividing the elliptical annulus of the thickness map into six regions. Values are compared with normative data and expressed in thickness table showing average and minimum values compared with normative data.|
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|Figure 6 Key parameters compared with normative data are displayed in a table format.|
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Measurements were taken by macular cube 512×128 scan to express both the macula and GCC prints, and optic disc cube 200×200 scan expressing RNFL and optic nerve head analysis print  ([Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7]). Any signal strength less than 5/10 was excluded.
Results were collected, tabulated, and statistically analyzed by an IBM compatible personal computer with SPSS statistical package (Released 2015, IBM SPSS statistics for Windows, version 23.0; SPSS Inc., Armonk, New York, USA).
Two types of statistical analyses were done: descriptive statistics was expressed in number, percentage, mean, and SD, and analytic statistics, for example, Mann–Whitney’s test, was used for comparison of quantitative variables between two groups of not normally distributed data, and χ2 test was used to study association between qualitative variables. Whenever any of the expected cells were less than five, Fisher’s exact test was used.
Two-sided P value of less than 0.05 was considered statistically significant.
| Results|| |
A total of 76 patients (152 eyes) aged between 18 and 40 years, with a mean of 27.21±8.25 years, participated in this study (32 males and 44 females).
Seventy-six eyes were amblyopic, whereas the other 76 eyes were not amblyopic, with BCVA of more than 6/12 and were considered as ‘fellow eyes.’
Of 152 eyes, 14 (9.2%) eyes were strabismic, 30 (19.7%) eyes were myopic, 28 (18.4%) eyes were hyperopic, 76 (50%) eyes were astigmatic, and 18 (11.8%) eyes were emmetropic.
Myopia was observed in 24 amblyopic eyes and six fellow eyes, whereas hyperopia was observed in 18 amblyopic eyes and 10 fellow eyes. Astigmatism was detected in 34 amblyopic eyes and 42 fellow eyes.
Amblyopic eyes showed significantly higher strabismus, whereas emmetropia was significantly higher in the fellow eyes.
Misalignment was the amblyogenic factor in the 14 strabismic cases (not anisometropia), whereas the other 62 eyes showed anisometropia as the cause of amblyopia.
Strabismus, myopia, and hyperopia were significantly higher in the amblyopic eyes, but astigmatism was not. However, when we applied further analysis to the astigmatic cases, cylindrical power was significantly higher in the amblyopic eyes than in the fellow eyes.
In the myopic amblyopic cases, the mean spherical refraction was −5.75±0.90 and −0.83±1.03 D in the amblyopic and fellow eyes, respectively. In the hyperopic cases, the mean spherical refraction was 3.96±1.47 and 1.57±0.85 D in the amblyopic and fellow eyes, respectively. We observed significant difference in the mean spherical power between amblyopic and fellow eyes in the two subgroups (myopic and hyperopic), whereas the difference was minimal among the patients with astigmatic amblyopia (0.39±2.02 and 0.31±1.27 D in amblyopic and fellow eyes, respectively). However, by analyzing data of the cylindrical refractive power only in amblyopic cases caused by astigmatism, a significant difference was found between amblyopic eyes and fellow eyes, with a mean cylindrical power of −1.85±2.05 and −0.65±1.23 D in amblyopic and fellow eyes, respectively.
By converting to logMAR, the mean uncorrected visual acuity (UCVA) was 0.98±0.30 and 0.43±0.33 in the amblyopic and fellow eyes, respectively. However, the mean BCVA by logMAR was 0.68±0.43 and 0.08±0.13 in the amblyopic and fellow eyes, respectively. Comparison of UCVA and BCVA on the basis of logMAR revealed a significant difference between the two subgroups. Fellow eyes showed significantly better UCVA and BCVA values, when compared with the amblyopic eyes.
No significant difference was observed between amblyopic eyes and fellow eyes regarding CMT, average macular thickness, and GCC thickness ([Table 1]).
|Table 1 Comparison between amblyopic and fellow eyes regarding the optical coherence tomography parameters|
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The amblyopic eyes were further subdivided according to refractive error into three subgroups: myopic amblyopics, hyperopic amblyopics, and astigmatic amblyopics.
In myopic amblyopia group, the mean RNFLT in the amblyopic eyes was significantly lower than the fellow eyes. No other OCT significant measurements were detected in any subgroup of the amblyopic eyes compared with the fellow eyes ([Table 2]).
|Table 2 Comparison between amblyopic and fellow eyes refractive subgroups regarding the optical coherence tomography parameters|
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| Discussion|| |
OCT scan offered an accurate method to investigate the retinal changes in amblyopia cases. However, studies have yielded conflicting results.
In this study, we compared the thickness of the GCC, RNFL, and macula of the amblyopic eyes with that of the normal fellow eyes using Cirrus spectral domain OCT. Comparison yielded no difference between all parameters of the amblyopic and fellow eyes.
Some previous studies yielded results similar to the current study. For instance, Wang and Taranath reported no significant difference in all parameters, with the mean macular thickness in the amblyopic and the fellow eyes of 256.2±26.8 and 255.1±22.9 μm, respectively, and RNFLT in the amblyopic and the fellow eyes of 103.4±12.0 and 103.4±17.2 μm, respectively. However, this study was limited to ‘children’ with anisometropic hyperopic amblyopia only .
Another example is the study of Yakar and colleagues, which reported no significant difference in the CMT, which was 266.9±23.2 and 263.9±22.84 μm, whereas the RNFLT was 111.9±12.9 and 109.7±9.42 μm in the amblyopic and fellow eyes, respectively. Unlike the previous study, this one was limited to ‘adults’ with anisometropic hyperopic amblyopia .
The conclusion Repka and colleagues reached was similar to the previous results but with various types and degrees of refractive errors and a wide age range, not confined to certain type of refractive error or children only. They concluded that the RNFLT was ‘insignificantly’ thicker in the hyperopic amblyopic eyes .
Additionally, two other studies were limited only to unilateral strabismic amblyopia and reported no difference between amblyopic and normal fellow eyes as a control group: the study of Xu et al.  and the study of Zarei et al. , which had the same results but with the use of scanning laser polarimetry.
In the current study, the mean CMT was 244.65±18.13 μm in the amblyopic eyes versus 243.89±21.58 μm in the fellow eyes, and the mean average macular thickness was 268.89±12.62 μm in the amblyopic eyes versus 268.15±13.70 μm in the fellow eyes. No significant difference was observed between the two groups regarding the CMT values.
Dickmann and colleagues reported that only macular and foveolar thickness values were slightly higher in the ‘strabismic’ amblyopic eyes than in the fellow (sound) eyes (MT was 267±14 and 253±14 μm in the amblyopic and fellow eyes, respectively), but such difference was not observed in the anisometropic amblyopic group (MT was 257±20 and 256±18 μm in the amblyopic and fellow eyes, respectively). The study compared amblyopic and fellow eyes with a control group, and was limited to a small sample size (40 cases, 20 for each subgroup), with inclusion of a wide age range (5–56 years) . The same was the result of Andalib et al.  study, except for comparing amblyopic eyes with fellow eyes.
Another one was by Firat and colleagues, who concluded that the macular thickness of the amblyopic eyes was higher than the normal fellow eyes, although the difference was not statistically significant. They compared three groups: 36 amblyopic eyes, 36 fellow eyes, and 32 eyes of normal emmetropics as a control group. Their study had a limitation owing to the small sample size (only 36) and also narrow age range (5–23 years) .
On the contrary, El-Hifnawy et al.  reported increased macular thickness at the central subfield region, and outer nuclear layer thickening at the fovea in amblyopic eyes, concluding a possible involvement of photoreceptors.
The discrepancy between these previously mentioned studies and the current study regarding CMT presumably is a result of biodiversity in races, different sample sizes, different ages of the participants, and differences between OCT devices regarding technology and database.
In this current study, the mean GCC thickness was 81.10±5.34 and 80.73±5.08 μm in amblyopic and fellow eyes, respectively. No significant difference was observed between the two groups regarding the GCC values. Two other studies investigated the GCC: the study of Celik et al.  and the study of Firat et al. . Both studies were consistent with the current study asserting that amblyopia does not affect either GCC, macula, or RNFLT values.
According to this present study, RNFLT was 86.07±8.15 and 87.31±7.01 μm in the amblyopic and fellow eyes, respectively. No significant difference was observed between the two groups regarding the mean RNFLT values.
In the present study, on comparing the amblyopic eyes versus the fellow eyes according to refractive error type, a decreased RNFLT was observed in the ‘myopic’ amblyopic eyes only, compared with the fellow eyes of the same subgroup. The mean RNFLT value in the myopic subgroup was 81.50±5.86 and 85.50±6.34 μm in the amblyopic and fellow eyes, respectively, with a statistically significant difference.
Yoon and colleagues reported increased RNFLT in amblyopic eyes compared with fellow eyes. However, the study was limited by small a sample size (31 cases) and young age of patients (5–12 years). In addition, they only investigated patients with anisometropic hyperopic amblyopia . Moreover, Wu and colleagues found a significant thickening in the RNFL in hyperopic eyes (P=0.02) and so in the mean macular foveolar thickness (P<0.01), but not the CMT in the middle three circles: 1, 3, and 6 mm. The study was also limited to a small sample size, young age (between 5 and 16 years), and patient type (only anisometropic hyperopic amblyopia) .
However, Alotaibi and Al Enazi  reported that there was no effect on macula but only RNFL was ‘thicker’ in amblyopic cases, with no further analysis to differentiate between the results according to the amblyogenic factors. We also noticed that the hyperopic cases were highly more compared with myopic cases among the refractive ‘anisometropic’ patient group (25/93 hyperopic and 8/93 myopic) and were limited to children only (5–12 years).Yen et al.  noticed a statistically significant ‘thickening’ in the RNFL among refractive amblyopic eyes but not strabismic ones. The study was limited to a small sample size with more hyperopic cases in the refractive amblyopic group (13/18=72.2%). However, no further analysis was done to separate myopic from hyperopic eyes.
Lastly, our finding ‘RNFL thinning in myopic amblyopics’ may support Tekin et al. , hypothesis, who concluded that there was an inverse correlation between axial length and RNFLT. According to that study, when the axial length increases, which is one of the characteristic of myopia, the RNFLT decreases. They compared more myopic eyes with other fellow eyes, finding out that the mean RNFLT was 89.24±12.84 and 94.75±10.81 μm in more myopic versus other fellow eyes, respectively.
When further analysis has been applied to separate between amblyopic myopic eyes (n=18) and overall myopic eyes (n=42), the difference between RNFLT values increased to be 84.22±10.06 and 93.56±6.51 μm in ‘myopic’ amblyopic eyes and fellow eyes, respectively. The clear explanation for this was that myopic eyes − when compared with the fellow eyes − have higher axial length, because a high degree of anisometropia was the amblyogenic factor. Tekin et al.  reported significant ‘P value’ in both groups; however, it was less significant in myopic nonamblyopic eyes than ‘0.007’ but still significant any way. This result may offer an interesting explanation to all previously mentioned studies, reporting increased RNFLT in hyperopic amblyopia, as amblyopic eyes are smaller (having shorter axial length). This explanation suggests that amblyopia is not the main factor affecting the RNFLT and other possible retinal changes. In contrast, it sheds light on the axial length, being the main candidate factor affecting the RNFLT and to a lesser extent the amblyopic condition. This suggestion could be confirmed by further studies comparing retinal parameters before and after amblyopia therapy to detect the exact role of amblyopia. Moreover, studies comparing axial length to same retinal parameters could help in confirming this hypothesis.
There are several limitations to the current study. The first one is the sample size, as it was confined only to 76 amblyopic cases. Another limitation is the effect of refractive error (wide spherical range from +4 to −6 D) and the last one is the absence of controlled group to represent a reference to avoid any alterations that may occur to the normal fellow eye in patients with amblyopia.
| Conclusion|| |
No relation was found between amblyopia and OCT parameters of the macula and nerve fiber layer. However, there was a significant thinning in the RNFL of only myopic amblyopic eyes versus normal fellow ones. So, we recommend more studies and further investigation on larger sample size, myopic nonamblyopic eyes, and amblyopic eyes responding to treatment before and after amblyopia therapy.
It is important to detect which affects the retina more, amblyopia or axial length, in other words, the structural or functional factor.
Funding source: Self-funding (completely funded by the corresponding author Abdulghaffar Taha Taha Abdulghaffar) as it is submitted for partial fulfillment of the Master Degree in Ophthalmology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]