Optical Coherence Tomography Measurement of Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Unilateral Amblyopic Eyes View PDF

Amblyopia is unilateral or less commonly bilateral reduction of best corrected visual acuity that cannot be attributed directly to the effect of any structural abnormality of the eye or posterior visual pathway [1].
Amblyopia caused by abnormal visual experience early in life resulting from one of the following: strabismus, anisometropia or high bilateral refractive error or stimulus deprivation [2,3]. It is responsible for more unilateral reduced vision of childhood onset than all other causes combined [4]. It affect 2-6% of general population [5,6].
Amblyopia is diagnosed In the absence of an organic lesion, (till now there is no structural changes in the amblyopic eye can be found to be helpful for diagnosis), a difference in best corrected visual acuity of two Snellen lines or more (or >1 log unit) is indicative of amblyopia. Visual acuity in amblyopia is usually better when reading single letters than letters in a row. This ‘crowding’ phenomenon occurs to a certain extent in normal individuals but is more marked in amblyopes and must be taken into account when testing preverbal children [7].
The neural sites that are influenced by visual deprivation are still under investigation. Nevertheless, it has been reported by several studies on humans and animals that, during the neonatal period, visual deprivation has an effect on the growth of cells in the lateral geniculate body that receives input from the amblyopic eye and a shift in the dominance pattern in the visual cortex [8,9]. Amblyopia occurs during the period when the neuronal network between the retina and the cerebral cortex is developing and maturing. Thus this condition is frequently developed during the first 2-3 years of the postnatal period; however, it may be developed up to the age of 8–9 years. Amblyopia is curable if treated early [10].
During fetal development, there is a rapid decline in cell density in the retinal ganglion cell layer toward the end of gestation. In humans, the total population of cells in the ganglion cell layer is highest (2.2-2.5 million cells) between approximately weeks 18 and 30 of gestation [11]. After this, the cell population declines rapidly to (1.5-1.7 million cells). The number of axons in the human optic nerve also decreases during gestation. At 16-17 weeks of gestation; the estimated number of axons was 3.7 million. The number of axons in the human adult optic nerve is 1.1 million. If amblyopia affects the process of postnatal reduction of ganglion cells; RNFL thickness may be affected more than that in the normal eye [12].
Several techniques to evaluate the RNFLT, such as red-free ophthalmoscopy, scanning laser polarimetry (SLP) and optical coherence tomography (OCT) have been described [10]. OCT is a noninvasive, noncontact technique that measures RNFLT [13]. The RNFLT measured by OCT corresponds to the RNFLT measured histologically [14]. Because OCT is based on near-infrared interferometry, the thickness measurement is not affected by refractive status or axial length of the eye, or by light changes in nuclear sclerotic cataract density [15].

To compare RNFL thickness between normal and amblyopic eyes by OCT technique looking for any structural abnormality in the amblyopic eye.

A case control hospital-based study was performed at Al-Sadder Medical city, Al-Najaf city. A total of 30 patients (14 female with 16male) in a (12-40) years old, range of 29 years, who were diagnosed with unilateral amblyopia, 10 of them with strabismic amblyopia and the others 20 patients with anisometropic amblyopia included in this study for a period started on January, till September 2014.

Since our research is intended to measure peripapillary retinal nerve fiber layer thickness of amblyopic eye as measured by OCT and compare it with the other normal fellow eye.

After taking informed consent from the patients, detailed history was obtained from each patient. Full ophthalmologic examination was performed for both eyes for all patients, as the fellow eye taken as a control group, examination include: visual acuity and best corrected visual acuity (measured with Snellen’s chart adjusted at 6 m), refraction; slit lamp biomicroscopy, intraocular pressure measurement using Airbuff tonometer (Topcon®), extra ocular movement, dilated fundoscopic examination and oct examination for peripapillary retinal nerve fiber layer thickness. Patient with organic eye disease, history or evidence of intraocular surgery, those with myopic retinal degenerations, history of glaucoma, cataract, retinal disorders or laser treatment and patient not cooperative for oct examination were excluded from the study.

After obtaining informed consent, the pupils were dilated with 1 drop of 1% tropicamid eye drop. RNFL thickness was measured 30 minute later. The oct system used in this study was oct model 2000 (3d oct, TOPCON, at AL.HAKEEM hospital) .To measure RNFL thickness, the examiner focused a scanning baem on the fundus with infrared sensing camera, RNFL 3.45 mm centered on optic disc area was used for RNFL thickness measurement for each eye.

In this study, measurements from total areas were obtained in micrometer units. Average superior, inferior, nasal and temporal RNFL thickness was detected by the circular scan. All OCT measurements were performed by the same technician. In every case, the right eye was always measured first, followed by the left eye.

Data analyzed by SPSS version 20 {statistical package for social science version 20}. Mean and standard deviation were used. T-test was used to compare between normal and amblyopic eyes, graphs used as needed. Result considered significant when p-value is equal or less than 0.05.

At the end of this study, there were 30 patient with unilateral amblyopic eyes (14 female and 16 male) 20 of them with anisometropic amblyopia and 10 with strabismic amblyopia. Mean age for patients with anisometropia was (24.8 years ± 9.7) with range of 29 years, Maximum 40 years and Minimum 11 years.

Mean age for patients with squint was (19.1 years ± 8.9) with range of 29 years, Maximum 39 years and Minimum 10 years as shown in table 1.

Study showed that the superior and inferior peripapillary RNFL thickness in anisometropic amblyopic eyes are significantly thinner than the other normal eyes with p-value 0.02 and 0.03 respectively (Tables 2 and 3), while the nasal and temporal peripapillary RNFL thickness are not significant statistically with p-value more than 0.05, as shown in table 4.

Table 1: General features of study sample.

Table 2: Basic clinical data for patient with anisometropic amblyopia.

Table 3: Basic clinical data for patient with strabismic amblyopia.

Table 4: Comparison by mean and SD between normal and amblyopic eyes for patients with anisometropia with p-value.

Table 5: Comparison by mean and SD between normal and amblyopic eyes for patients with squint with p-value.

While in strabismic amblyopia the inferior peripapillary RNFL thickness is significantly thinner than the other normal eyes with p-value 0.05 while the superior, nasal and temporal peripapillary RNFL thickness are not significantly different than the other normal eyes with p-value more than 0.05, as shown in table 5.

Amblyopia may have different effects at various levels of the visual pathway. Receiving input from the amblyopic eye causing atrophy for the cells in the lateral geniculate nucleus has been reported. Several experiments have demonstrated that light deprivation can cause modifications of retinal ganglion cells, such as cell loss, mean nuclear volume diminution in ganglion cell cytoplasm, internal plexiform layer thinning in rats and cats, and reduction in optic nerve size area in mice [16-18].

In many studies, retinal changes were investigated using imaging devices. Several OCT studies have investigated the RNFL in amblyopia. OCT studies of RNFL thickness in amblyopia reported different findings [18].

Repka MX, et al. (2009) measured the thickness of the peripapillary RNFL in amblyopic and fellow eyes with OCT in anisometropic amblyopia [19]. They found no meaningful difference in the RNFL thickness. Altintas O, et al. (2005) reported that the RNFL thickness was 2.5µm thicker in amblyopic eyes but that this difference was not statistically significant in both types of amblyopia [20]. Study was done in Turkey by 21. Yuksel N, et al. published in 2005, the study reveal no statistical difference in peripapillary RNFL thickness between amblyopic and sound eye in both anisometropic and strabismic amblyopia [21]. A study was done by Dickman A, et al. in 2012 and concludes there is no difference in thickness in anisometropic amblyopia, while in strabismic amblyopia; the amblyopic eye was significantly thicker than the sound eyes [22]. Study was done by Abtaibi AG, et al. in ALRiyadh, Saudi Arabia in 2011and concluded that peripapillary RNFL thickness was significantly thicker in amblyopic eye than the sound eyes in anisometropic amblyopia while in strabismic amblyopia was not significantly different [23]. Dickman A, et al. study at 2011, was concluded that the amblyopic eyes was significantly thicker in amblyopic than sound eye in anisometropic but not in strabimic amblyopia [24].

Similarly, Yoon SW, et al. (2005) measured the macular and peripapillary RNFL in patients with anisometropic amblyopia. They reported that the RNFL in patients with amblyopia was significantly thicker [25].

Study done by Micheal X, et al. at 2006 and concluded that peripapillary RNFL thickness was slightly thinner than the sound eyes in both anisometropic and strabismic amblyopia [26]. BaddiniCaramelli C, et al. report study at 2001and concluded that there was slight decrease in peripapillary RNFL thickness in amblyopic eye than the sound eyes [27].

In this study we compared the global and four quadrants’ RNFL thickness of amblyopic eye and other normal fellow eyes in anisometropic and strabismic amblyopia using SD-OCT (spectral domain optical coherence tomography).

We found statistically significant difference among the groups of anisometropic amblyopia in which the superior and inferior peripapillary RNFL thickness is significantly thinner than those of the normal fellow eyes with p-value 0.02, 0.03 respectively. While those of temporal and nasal peripapillary RNFL thickness are not statistically significant in which p- value more than 0.05.

In strabismic amblyopia the inferior peripapillary RNFL thickness is significantly thinner with p-value equal 0.05. While the superior, nasal and temporal peripapillary RNFL thicknesses are not significant statistically.

In this study, our result are in agreement with Micheal X, et al. (2006) [26] and with Baddini-Caramelli C, et al. (2001) [27], but are different from the result reported by Repka MX, et al. (2009) [19], Dickman A, et al. (2011) [24] and Yoon SW, et al. (2005) [25].

OCT has become a widely used tool in clinical ophthalmology. Normative data are provided automatically by OCT, but the database only includes individuals 18 years and older, limiting its use in children. There are several reports regarding the difference in the RNFL thickness between children and adults [28,29]. Possible explanations of difference from various studies include race, age, axial length, and disc area.

The differences between different versions of the device have also been found in adults, and may be due to the use of different algorithms between spectral and time domain OCT devices; making a comparison between different devices to be misleading [30,31].

Similarly, several studies on the variations of macular thickness measurements in normal subjects according to age and refractive error/ axial length have been reported. Some studies have shown reductions in macular thickness with age, whereas others have found no significant correlation. More recent studies in which the third-generation Stratus OCT was used have shown average macular thickness and macular volume to be related to refractive error/axial length in normal subjects, as in histopathologic studies [32-35].

There are several limitations to our study, namely, the small number of patients. Since, the number of patients involved in the study is small as compared to those reported in most papers; so, a larger study I warranted to confirm our results.

Our results suggest that amblyopia seems to have a significant effect on the peripapillary RNFL thickness, in strabismic and anisometropic amblyopia.

• Increasing the sample size in future studies searching the same subject may give more accurate results.
• Including OCT examination of peripapillary RNFL in treatment and fellow up of amblyopic patient need further clinical base evidence that need further research.
• Further studies, including histopathological and instrumental studies with a greater number of patients, are required to confirm the differences between amblyopic and normal eyes.

1. Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, et al. (2010) Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol 148: 143-147.
2. Von noorden GK (1967) Classification of amblyopia. AM J ophthalmol 63: 238-244.
3. Yen MY, Cheng CY, Wang AG (2004) Retinal nerve fiber layer thickness in unilateral amblyopia. Invest Ophthalmol Vis Sci 45: 2224-2230.
4. American academy (2011) Pediateric Ophthalmology and Strabismus.
5. Szigeti A, Tátrai E, Szamosi A, Vargha P, Nagy ZZ (2014) Morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation. PLoS One 9: e88363.
6. Ropper Hall G (2007) Current concept of amblyopia: A Neuro-Ophthalmology perspective. Am Orthopt J 57: 2-12.
7. Kaniski JJ, Bowling B (2011) Clinical ophthalmology systematic approach, (7^th edtn), USA.
8. Vonnoorden GK, Crawford MCJ, Levacy RA (1983) lateral geniculate nucleus in human anisometropic amblyopia. Invest Ophth Vis Sci 24: 788-790.
9. Vonnoorden GK, Crawford MCJ (1992) lateral geniculate nucleus in human strabismus amblyopia. Invest Ophthalmol Vis Sci 33: 2729-2732.
10. Alotaibi AG, Al Enazi B (2011) Unilateral amblyopia: Optical coherence tomography findings. Saudi J Ophthalmol 25: 405-409.
11. Provis JM, van driel Billson FA, Russell P (1985) Development of human retina, pattern of cell distribution and redistribution in the ganglion cell layer. J Comp Neurol 233: 429-451.
12. Greenfield DS, Knighton RW, Huang XR (2000) Effect of corneal polarization on assessment of retinal nerve fiber layer thickness by scanning laser polarimetry. AMJ ophthalmol 129: 715-722.
13. Yoon SW, Park WH, Baek SH, Kong SM (2005) Thicknesses of macular retinal layer and peripapillary retinal nerve fiber layer in patients with hyperopic anisometropic amblyopia. Korean J Ophthalmol 19: 62-67.
14. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, et al. (1991) Optical coherence tomography. Science 254: 1178-1181.
15. Schuman JS, Pedut-Kloizman T, Hertzmark E, Hee MR, Wilkins JR, et al. (1996) Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmol 103: 1889-1898.
16. Barnes GR, Li X, Thompson B, Singh KD, Dumoulin SO, et al. (2010) Decreased gray matter concentration in the lateral geniculate nuclei in human amblyopes. Investigative ophthalmology & visual science. 2010 Mar 1;51(3):1432-8. Invest Ophthalmol Vis Sci 51: 1432-1438.
17. Yalcin E, Balci O (2014) Peripapillary RNFL thickness, foveal thickness in hypermetropic anisometropic amblyopia. Clin Ophthalmol 8: 749-753.
18. Firat PG, Ozsoy E, Demire S, Cumurcu T, Gunduz A (2013) Evaluation of peripapillary retinal nerve fiber layer, macula and ganglion cell thickness in amblyopia using spectral optical coherence tomography. Int J Ophthalmol 6: 90-94.
19. Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, et al. (2009) Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol 148: 143-147.
20. Altintas O, Yüksel N, Ozkan B, Caglar Y (2005) Thickness of the retinal nerve fiber layer, macular thickness, and macular volume in patients with strabismic amblyopia. J Pediatr Ophthalmol Strabismus 42: 216-221.
21. Dickman A, Petroni S , Perrota V Parreilla R, Aliberti S, et al (2012) Measurement of retinal nerve fiber layer thickness, macular thickness, and foveal volume in amblyopic eyes using spectral-domain optical coherence tomography. J AAPOS 16: 86-88.
22. Abtaibi AG, AL Enazi B (2011) Unilateral amblyopia optical coherence tomography finding. Saudi J Ophthalmol 25: 405-409.
23. Dickmann A, Petroni S, Perrotta V, Salerni A, Parrilla R, Aliberti S, et al (2011) A morpho-functional study of amblyopic eyes with the use of optical coherence tomography and microperimetry. J AAPOS 15: 338-341.
24. Yoon SW, Park WH, Baek SH, Kong SM (2005) Thicknesses of macular retinal layer and peripapillary retinal nerve fiber layer in patients with hyperopic anisometropic amblyopia. Korean J Ophthalmol 19: 62-67.
25. Repka MX, Goldenberg-Cohen N, Edwards AR (2006) Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol 142: 247-251.
26. Baddini-Caramelli C, Hatanaka M, Polati M, Umino AT, Susanna R Jr (2001) Thickness of the retinal nerve fiber layer in amblyopic and normal eyes: a scannig laser polarimetry study. JAAPOS 5: 82-84.
27. Parikh RS, Parikh SR, Sekhar GC, Prabakaran S, Babu JG, (2007) Normal age-related decay of retinal nerve fiber layer. Ophthalmol 114: 921-926.
28. Huynh SC, Wang XY, Rochtchina E, Mitchell P (2006) Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old children: findings by optical coherence tomography. Ophthalmol 113: 1583-1592.
29. Leung CK, Chiu V, Weinreb RN, Liu S, Ye C, et al. (2011) Evaluation of retinal nerve fiber layer progression in glaucoma: a comparison between spectral-domain and time-domain optical coherence tomography. Ophthalmol 118: 1558-1562.
30. Knight OJ, Chang RT, Feuer WJ, Budenz DL (2009) Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmol 116: 1271-1277.
31. Eriksson U, Alm A (2009) Macular thickness decreases with age in normal eyes: a study on the macular thickness map protocol in the Stratus OCT. Br J Ophthalmol 93: 1448-1452.
32. Manassakorn A, Chaidaroon W, Ausayakhun S, Aupapong S, Wattananikorn S (2008) Normative database of retinal nerve fiber layer and macular retinal thickness in a Thai population. Jpn J Ophthalmol 52: 450-456.
33. Lam DS, Leung KS, Mohamed S, Chan WM, Palanivelu MS, et al. (2007) Regional variations in the relationship between macular thickness measurements and myopia. Invest Ophthalmol Vis Sci 48: 376-382.
34. Wu PC, Chen YJ, Chen CH, Chen YH, Shin SJ, et al. (2008) Assessment of macular retinal thickness and volume in normal eyes and highly myopic eyes with third-generation optical coherence tomography. Eye (Lond) 22: 551-555.