• Users Online: 567
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 1-10

A study to evaluate and compare the effect of amblyopia on both nerve fiber layer thickness and ganglion cell complex in either anisometropic or strabismic individuals


Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

Date of Submission28-Jun-2019
Date of Decision07-Jan-2020
Date of Acceptance08-Jan-2020
Date of Web Publication20-Apr-2020

Correspondence Address:
MD Abd Elmagid M Tag Eldin
Department of Ophthalmology, Faculty of Medicine, Al-Azhar University, Cairo, 11765
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_62_19

Get Permissions

  Abstract 


Background Anisometropia and high refractive errors are very annoying problems. Anisometropic amblyopia is one of the most common forms of amblyopia. Typical treatment includes refractive correction with glasses or contact lenses combined with occlusion. Anisometropic amblyopia is often detected later than other forms of amblyopia, because vision is generally good in the fellow eye, the eyes are typically orthotropic, and the child functions well with the use of the sound eye. A large fraction of the cases results from strabismus with constant unilateral fixation, which leads to amblyopia in the deviating eye. Amblyopia generally does not develop if fixation alternates, providing each eye with similar access to higher visual centers, or if strabismic deviation is intermittent (as a result of fusional vengeance or incomitance), so that there are periods of normal binocular interaction that preserve the integrity of the visual system. The visual system is sensitive to the effects of abnormal visual experience only during a limited time in infancy and childhood; this is referred to as the critical period or the sensitive period.
Objective This study used SD-optical coherence tomography to compare retinal nerve fiber layer (RNFL) thickness and ganglion cell complex in amblyopic and fellow eyes of patients of varied ages. Twenty patients (10 patients with anisometropic amblyopia and 10 patients with strabismic amblyopia) with unilateral amblyopia underwent SD-optical coherence tomography examination for both amblyopic and follow eyes.
Results and conclusion The study showed that there was no significant difference in RNFL between amblyopic and fellow eyes in the two groups of anisometropic and strabismic amblyopia. There was a statistically significant difference in ganglion cell complex thickness measurements between amblyopic eyes and fellow eyes in the two groups of anisometropic and strabismic amblyopia. There was a statistically significant difference between the two groups of patients regarding means of average RNFL thickness in the fellow eyes and means of inferior RNFL thickness in the fellow eyes.

Keywords: evaluation, comparative, nerve fiber layer, thickness, ganglion cell complex, amblyopia


How to cite this article:
Tag Eldin AM, Hudieb AE. A study to evaluate and compare the effect of amblyopia on both nerve fiber layer thickness and ganglion cell complex in either anisometropic or strabismic individuals. Sci J Al-Azhar Med Fac Girls 2020;4:1-10

How to cite this URL:
Tag Eldin AM, Hudieb AE. A study to evaluate and compare the effect of amblyopia on both nerve fiber layer thickness and ganglion cell complex in either anisometropic or strabismic individuals. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 May 30];4:1-10. Available from: http://www.sjamf.eg.net/text.asp?2020/4/1/1/282865




  Introduction Top


Amblyopia is a developmental defect of the brain’s visual pathway; it is the most frequent cause of unilateral poor visual acuity (VA) in children, with an incidence of 0.5–3.5% in preschool and school-age children. Amblyopia develops gradually owing to vision deprivation and/or abnormal binocular interaction, with absence of pathological conditions of the eye or the visual pathway in the brain, and usually presents itself in children within the age of 6–8 years and persists lifelong [1].

Etiology of amblyopia includes but is not limited to the following:
  1. Refractive amblyopia: uncorrected refractive errors are considered the most common cause of amblyopia.
    1. Anisometropic amblyopia: it is caused by a difference in refractive error between the two eyes which may be as little as 1.0 D sphere. The more ametropic eye receives a blurred image, in a mild form of visual deprivation. It is frequently associated with micro-strabismus and may coexist with strabismic amblyopia [2].
    2. Isoametropic amblyopia: it occurs when both eyes are amblyopic from a significant yet similar refractive error [2].
    3. Meridional amblyopia: amblyopia caused by significant astigmatism [2].
  2. Strabismic amblyopia: it results from abnormal binocular interaction where there is continued monocular suppression of the deviating eye [2].
  3. Deprivation amblyopia: deprivation amblyopia is the least common and typically most severe form of amblyopia and develops when the visual axis is obstructed. Various causes of stimulus deprivation include eyelid ptosis, cornea opacities, cataracts, and vitreous hemorrhage among others [2].


Reverse amblyopia

Reverse amblyopia is a result of penalization of the sound eye with patching or atropine during amblyopia treatment of the original amblyopic eye. The type of amblyopia and its severity not only adversely affects VA but also binocularity, contrast sensitivity, grating acuity, and central versus eccentric fixation [2].

The mechanism of development of amblyopia involves affecting various levels of the visual pathway. It has been reported that shrinkage of cells in the lateral geniculate nucleus that receive input from the amblyopic eye and a shift in the dominance pattern in the visual cortex could be one of those effects (Huynh et al., 2009) [3].

However, some other pathological mechanisms are still considered to be controversial such as involvement of the retina (Huynh et al., 2009, Kanski, 2011) [3],[4],[5].

This controversy persists till our current day especially after modern advances in neuro-anatomy and neuro-physiology have reopened the possibility that there is some retinal dysfunction in amblyopia (Von Noorden and Crawford, 1992) [6].

Optical coherence tomography (OCT) is a noninvasive test in which the thickness of the retinal nerve fiber layer (RNFL) is measured (Yen et al., 2004) [7].

According to a study conducted in 2017, it was concluded by using OCT that the unilateral amblyopic eyes had thicker RNFL compared with unamblyopic eyes. Retinal variations between different types of the amblyopia differ from one type to another. Moreover, it was concluded that the age of the study subjects may alter prognosis and treatment of the condition. Despite being conducted very recently, the study researchers recommended emphasizing those conclusions by conducting further studies [5].

Therefore, in this study, OCT was used to compare RNFL thickness and ganglion cell complex (GCC) in amblyopic and fellow eyes of patients of varied ages.


  Aim Top


The aim was to compare RNFL thickness and GCC in amblyopic and fellow eyes of patients of varied ages using OCT.


  Patients and methods Top


Study design

This was a cross-sectional prospective study.

Population of study

A prospective observational clinical study was conducted on 20 patients with unilateral amblyopia (strabismic or anisometropic amblyopia). OCT examination was done for both the amblyopic and sound eyes.

The patients were divided into two groups:
  1. Group A: 10 patients with anisometropic amblyopia.
  2. Group B: 10 patients with strabismic amblyopia. The patients were selected from those attending the outpatient clinics of the ophthalmology department in National Institute of Diabetes and Endocrinology, Cairo, Egypt, where examinations and imaging also took place.


Inclusion criteria

The following were the inclusion criteria:
  1. Patient with strabismic or anisometropic amblyopia only.
  2. The VA difference between the amblyopic and normal eyes was at least two lines of Snellen acuity.


Exclusion criteria

The following were the exclusion criteria:
  1. Previous intraocular surgery.
  2. Any intraocular pathology (history of cataract, glaucoma, retinal disorders, or laser treatment).


Methods

All patients had undergone a detailed eye examination including the following:
  1. Anterior segment examination using slit lamp to exclude anterior segment abnormalities or media opacity.
  2. Cycloplegic refraction.
  3. VA: uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) using Snellen charts.
  4. Cover–uncover test to determine strabismic type.
  5. Prism cover test measures the angle of deviation in strabismic patients.
  6. Intraocular pressure measurement by applanation tonometry.
  7. Slit-lamp biomicroscopy and fundus examination to exclude posterior segment abnormalities.
  8. OCT imaging using SD-OCT. A RS-3000 Advance model has a 5-µm depth resolution in tissue and 20-µm transverse resolution. Each A-scan of this instrument had a depth of 2 mm and comprised 512 pixels, providing a digital depth sampling of 3.9 µm per pixel. For wide-area three-dimensional (3D) imaging in the posterior pole, raster scanning over a 9×9-mm square area centered on the foveal center was conducted with a scan density of 512 A-scans (horizontal)×128 B-scans (vertical). For cpRNFL imaging, raster scanning over a 6×6-mm square area centered on the optic disc center was conducted with a scan density of 512 A-scans (horizontal)×128 B-scans (vertical). It took 1.6 s to obtain a single 3D data set. Imaging was performed by the researcher and a well-trained examiner after pupillary dilatation, with the examiner rejecting any scans with motion artifacts, poor centration, incorrect segmentation, poor focus, or missing data.


Measurements

Automated measurements of GCC and RNFL thickness were performed, and thickness and significance maps for GCC and RNFL thickness were generated using in-built software of the RS-3000. The GCC thickness was measured between the internal limiting membrane and the outer boundary of the inner plexiform layer. RNFL thickness was measured in a circle 3.45 mm in diameter consisting of 256 A-scans, which were positioned automatically around the optic disc in each 3D data set.

The parameters from the GCC map are as follows:
  • Average GCC (average GCC thickness for the whole area).
  • Superior GCC (average GCC thickness for the superior half of the area).
  • Inferior GCC (average GCC thickness for the inferior half of the area).


Ethical considerations

  1. No harmful maneuvers were performed or used.
  2. An informed consent was taken from all the participants before taking any data or doing any investigations.
  3. Explanation of the study aim was done in a simple manner to be understood by nonmedical professions.
  4. The researcher only has access to the data used in this study. Study data will not be used without patients’ approval.
  5. Participants will be allowed to be informed about the study results.
  6. Participants were entitled right to withdraw from the study at any time without giving any reasons.


Statistical analysis

Statistical analysis was done on a personal computer using SPSS, version 25 (SPSS is statistical analysis software, IBM Company, Chicago, USA).

Data were collected from the imaging equipment (OCT) on CDs, entered and tabulated on SPSS, and then analyzed using appropriate statistical tests. Descriptive analysis: continuous data are described using mean and SD, and Bar charts with SEs were used to graphically illustrate the difference in means between the two groups of patients.

To test for normality of the data, the Shapiro–Wilk test for normality was applied to choose best comparative analysis tests ([Table 1]).
Table 1 Test of normality for all variables within the anisometropic amblyopia group of patients

Click here to view


Comparative analysis: the two groups of patients were compared regarding means of VA measurements, means of RNFL thickness measurements, and GCC thickness measurements in both fellow and amblyopic eyes. For normally distributed data, Student (unrelated/independent samples) t test was used to determine statistical significance of difference between the means. For not normally distributed data, Mann–Whitney U test was used.

Within each group, fellow and amblyopic eyes were compared regarding the same aforementioned parameters. For normally distributed data, paired (related) t test was used to determine statistical significance of difference between the means. For not normally distributed data, Wilcoxon’s rank test was used.

Correlations were made between UCVA and BCVA of amblyopic eyes with RNFL and GCC thickness measurements in the same eye using Spearman’s coefficient. P value less than or equal to 0.05 are considered statistically significant.


  Results Top


Descriptive analysis

  1. Sample descriptive regarding age were described in terms of mean and SD.
  2. Bar charts representing means and SDs were used to graphically illustrate the difference in means between the two treatment groups.


Testing for normality

To test for normality of the data, the Shapiro–Wilk test for normality was applied to choose best data descriptive presentation parameters and comparative analysis tests ([Table 2] and [Table 3]).
Table 2 Test of normality for all variables within the strabismic amblyopia group of patients

Click here to view
Table 3 Descriptive analysis of the age of each group of patients (anisometropic and strabismic)

Click here to view


The mean age of the sample subjects within the anisometropic group is 32.14 years old (±17.5). This higher than the mean age of the sample subjects within the strabismic group (27.6±21) ([Table 4]).
Table 4 Descriptive analysis of visual acuity measurements according to each group of patients (anisometropic and strabismic) and results of the nonparametric Mann–Whitney U test to compare between them

Click here to view


There is a statistically significant difference in means of UCVA of amblyopic eye between the two groups of patients.

There are no statistically significant differences between the two groups of patients regarding mean UCVA of fellow eyes, BCVA of amblyopic eyes, and BCVA of fellow eyes ([Table 5]).
Table 5 Descriptive analysis of retinal nerve fiber layer measurements by optical coherence tomography according to each group of patients (anisometropic and strabismic) and comparison between them

Click here to view


There is a statistically significant difference between both groups of patients regarding means of average RNFL thickness in fellow eyes and means of inferior RNFL thickness in fellow eyes. There is no statistically significant difference between the two groups of patients regarding means of superior RNFL thickness in fellow eyes and average, superior, and inferior RNFL thickness in amblyopic eyes ([Table 6]).
Table 6 Descriptive analysis of ganglion cell complex measurements by optical coherence tomography according to each group of patients (anisometropic and strabismic) and results of the Student’s t test to compare between them

Click here to view


There are no statistically significant differences between the two groups of patients regarding means of GCC thickness measurements ([Table 7]).
Table 7 Comparison between retinal nerve fiber layer measurements by optical coherence tomography of amblyopic and fellow eyes within the anisometropic group of patients

Click here to view


There are no statistically significant differences between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of RNFL thickness measurements ([Table 8]).
Table 8 Comparison between ganglion cell complex measurements by optical coherence tomography of amblyopic and fellow eyes within the anisometropic group of patients

Click here to view


There is a statistically significant difference between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of inferior GCC thickness measurements.

There are no statistically significant differences between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of average and superior thickness measurements ([Table 9]).
Table 9 Comparison between retinal nerve fiber layer measurements by optical coherence tomography of amblyopic and fellow eyes within the strabismic group of patients

Click here to view


There are no statistically significant differences between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of RNFL thickness measurements ([Table 10]).
Table 10 Comparison between ganglion cell complex measurements by optical coherence tomography of amblyopic and fellow eyes within the strabismic group of patients

Click here to view


There is a statistically significant difference between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of superior GCC thickness measurements.

There are no statistically significant differences between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of average and inferior thickness measurements ([Table 11]).
Table 11 Correlation between visual acuity measurements and retinal nerve fiber layer and ganglion cell complex measurements by optical coherence tomography in amblyopic eyes in anisometropic group of patients

Click here to view


There is a statistically significant moderate positive correlation between BCVA of amblyopic eye and GCC thickness measurements within the anisometropic groups of patients ([Table 12]).
Table 12 Correlation between visual acuity measurements and retinal nerve fiber layer and ganglion cell complex measurements by optical coherence tomography in amblyopic eyes strabismic group of patients

Click here to view


There is a statistically significant strong positive correlation between UCVA and BCVA of amblyopic eye within the strabismic groups of patients.


  Discussion Top


In this study, we measured RNFL and GCC thickness in amblyopic and fellow eyes with SD-OCT. We divided the patients into two groups: anisometropic and strabismic amblyopic.

Regarding VA between groups there is a statistically significant difference in means of UCVA of amblyopic eye between the two groups of patients. There are no statistically significant differences between the two groups of patients regarding means UCVA of fellow eyes, BCVA of amblyopic eyes, and BCVA of fellow eyes.

Retinal nerve fiber layer between groups

  1. There is a statistically significant difference between the two groups of patients regarding means of average RNFL thickness in fellow eyes and means of inferior RNFL thickness in fellow eyes.
  2. There is no statistically significant difference between the two groups of patients regarding means of superior RNFL thickness in fellow eyes and average, superior, and inferior RNFL thickness in amblyopic eyes.


Ganglion cell complex between groups

There are no statistically significant differences between the two groups of patients regarding means of GCC thickness.

Retinal nerve fiber layer within group − anisometropic

There are no statistically significant differences between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of RNFL thickness measurements.

Retinal nerve fiber layer within group − strabismic

There are no statistically significant differences between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of RNFL thickness measurements.

Ganglion cell complex within group − anisometropic

There is a statistically significant difference between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of inferior GCC thickness measurements.

There are no statistically significant differences between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of average and superior thickness measurements.

Ganglion cell complex within group − strabismic

There is a statistically significant difference between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of superior GCC thickness measurements.

There are no statistically significant differences between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of average and inferior thickness measurements.

Correlations

There is a statistically significant moderate positive correlation between BCVA of amblyopic eye and GCC thickness measurements within the anisometropic groups of patients.

There is a statistically significant strong positive correlation between UCVA and BCVA of amblyopic eye within the strabismic groups of patients.

As mentioned earlier, the controversy about involvement of the retina in the pathogenesis of amblyopia persists till as soon as the year 2017.

In our study also, results came up with variations regarding the different measurements.

Our results were similar to the studies that reported no statistically significant differences between normal eyes and amblyopic eyes (whether anisometropic or strabismic) regarding RNFL thickness.

For example, Ersan et al. [8] conducted a study that compared patients with strabismus (35 patients) and patients with anisometropia (30 patients) were compared with their fellow eyes and age-matched and sex-matched healthy eyes (40 participants). The study concluded that amblyopia is not associated with a decrease in RNFL thickness in strabismic or anisometropic amblyopia.

According to Ersan et al. [8], in the anisometropic group, the inter-eye differences in RNFL thickness parameters seemed to be related to the refraction differences between the amblyopic eyes and their fellow eyes. Our study might have touched base with such hypothesis as it revealed statistically significant moderate positive correlation between BCVA of amblyopic eye and GCC thickness measurements within the anisometropic groups of patients.

The same study also concluded that RNFL thickness did not differ between strabismic amblyopic, anisometropic amblyopic, and control eyes (P>0.05). This is similar to our findings regarding means of superior RNFL thickness in fellow eyes and average, superior, and inferior RNFL thickness in amblyopic eyes.

In contrast to these results, Kasem and Badawi [5] (Auckland, New Zealand) found out that the unilateral amblyopic eyes were prone to have a higher CMT and thicker global RNFL compared with those of the sound fellow eyes.

Regarding thickness of GCC, our study results conclude that there is a statistically significant difference between amblyopic eyes and fellow eyes within the strabismic group of patients regarding means of superior GCC thickness measurements. This finding is similar to what Tugcu et al. [9] reported that patients with strabismic amblyopia presented with significant reduction in GCC thickness.

On the contrary, Araki et al. [10] concluded in their study that there was no significant difference in thickness between amblyopic and fellow eyes regarding both types: anisometropic and strabismic.

In addition, Szigeti et al. [11] used TD-OCT image segmentation methodology involving the entire macular area, extracting seven retinal layers.

They enrolled 38 patients (mean age, 32.4±17.6 years; range, 6–67 years) with unilateral amblyopia. A total of 17 patients had strabismic amblyopia, 11 patients had anisometropic amblyopia, and 10 patients had combined amblyopia (strabismus and anisometropia).

There was significant changes in the GCC layer in the pericentral region and in the OPL layer calculated for the total macula and measured in the peripheral region.The great variability in the results of the studies in question was stated by a systematic review by Avram [12] of 30 clinical trials regarding amblyopia evaluation with OCT. The research articles analyzed were published between 2006 and 2016 and were identified on PubMed database.

Avram [12] found that 19 research studies focused on macular and nerve optic changes, seven on choroidal changes, and six on retinal changes after occlusion. The results were discussed according to the type of amblyopia, alteration of macular thickness, optic nerve changes, GCC changes, and alteration of choroidal thickness.

Avram [12] concluded that the results were of great variability, and it seemed that macula and choroid involvement is more frequently suggested compared with optic nerve involvement.


  Conclusion Top


Our study is done to compare the RNFL thickness and GCC in amblyopic and fellow eyes using SD-OCT.

The study showed there was no significant different in RNFL between amblyopic and fellow eyes in two groups of anisometropic and strabismic amblyopia.

There was a statistically significant difference between amblyopic eyes and fellow eyes within the anisometropic group of patients regarding means of inferior GCC thickness measurements.

There was a statistically significant difference between the two groups of patients regarding means of average RNFL thickness in fellow eyes and means of inferior RNFL thickness in fellow eyes.

There is a statistically significant moderate positive correlation between BCVA of amblyopic eye and GCC thickness measurements within the anisometropic groups of patients.

We recommend that further research studies in addition to histopathological studies with a greater number of patients are required to confirm these findings. Moreover studies that correlate RNFL and GCC thickness with functional outcome after treatment (amblyopic therapy) are needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Andalib D, Javadzadeh A, Nabai R, Amizadeh Y. Macular and retinal nerve fiber layer thickness in unilateral anisometropic or strabismic amblyopia. J Pediatr Ophthalmol Strabismus 2013; 50:218–221.  Back to cited text no. 1
    
2.
Hess RF. Amblyopia: site unseen. Clin Exp Optom 2001; 84:321–336.  Back to cited text no. 2
    
3.
Huynh SC, Samarawickrama C, Wang XY, Rochtchina E, Wong TY et al. Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study. Ophthalmology 2009; 116:1604–1609.  Back to cited text no. 3
    
4.
Kanski JJ. Clinical ophthalmology a systemic approach. 7th ed. Edinburgh: Elsevier Ltd; 2011.  Back to cited text no. 4
    
5.
Kasem MA, Badawi AE. Changes in macular parameters in different types of amblyopia: optical coherence tomography study. Clin Ophthalmol (Auckland, NZ) 2017; 11:1407–1416.  Back to cited text no. 5
    
6.
Von Noorden GK, Crawford ML. The lateral geniculate nucleus in human strabismic amblyopia. Invest Ophthalmol Vis Sci 1992; 33:2729–2732.  Back to cited text no. 6
    
7.
Yen MY, Cheng VY, Wang G. Retinal nerve fiber layer thickness in unilateral amblyopia. 2004; 45:2224–2230.  Back to cited text no. 7
    
8.
Ersan I, Zengin N, Bozkurt B, Özkagnici A. Amblyopia. J Pediatr Ophthalmol Strabismus 2013; 50:113–117.  Back to cited text no. 8
    
9.
Tugcu B, Araz-Ersan B, Kilic M, Erdogan ET, Yigit U, Karamursel S. The morpho-functional evaluation of retina in amblyopia. Curr Eye Res 2013; 38:802–809.  Back to cited text no. 9
    
10.
Araki S, Miki A, Yamashita T, Goto K, Haruishi K, Ieki Y, Kiryu J. A comparison between amblyopic and fellow eyes in unilateral amblyopia using spectral-domain optical coherence tomography. Clin Ophthalmol 2014; 8:2199–2207.  Back to cited text no. 10
    
11.
Szigeti A, Tátrai E, Szamosi A, Vargha P, Nagy ZZ, Németh J et al. A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation. PLoS ONE 2014; 9:3–4.  Back to cited text no. 11
    
12.
Avram E. Can optical coherence tomography redefine amblyopia? Rom J Ophthalmol 2017; 61:95–100.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Aim
Patients and methods
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed210    
    Printed20    
    Emailed0    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]