Quantitative Analysis of Retinal Nerve Fiber Layer Thickness of Normal Children and Adolescents

Han-Cheul Ahn; Hyuk-Woo Son; Jae Suk Kim; Joo Hwa Lee

doi:10.3341/kjo.2005.19.3.195

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Ahn, Son, Kim, and Lee: Quantitative Analysis of Retinal Nerve Fiber Layer Thickness of Normal Children and Adolescents

Original Article

Korean Journal of Ophthalmology

Korean Journal of Ophthalmology 2005; 19(3): 195-200.

Published online: 30 September 2005

DOI: https://doi.org/10.3341/kjo.2005.19.3.195

Quantitative Analysis of Retinal Nerve Fiber Layer Thickness of Normal Children and Adolescents

Han-Cheul Ahn, MD¹, Hyuk-Woo Son, MD², Jae Suk Kim, MD¹, Joo Hwa Lee, MD¹

¹Department of Ophthalmology, Sanggye Paik Hospital, Inje University, College of Medicine, Seoul, Korea.

²Han Kook Eye Clinic, Seoul, Korea.

Reprint requests to Joo Hwa Lee, MD. Department of Ophthalmology, Sanggye Paik Hospital, Inje University, College of Medicine, #761-1 Sanggye 7-dong, Nowon-gu, Seoul 139-707, Korea. Tel: 82-2-950-1096, Fax: 82-2-935-6904, joohlee@sanggyepaik.ac.kr

Received 12 May 2005 Accepted 29 August 2005

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To determine the normal range of retinal nerve fiber layer (RNFL) thickness of normal children and adolescents by optical coherence tomography (OCT).

Methods

This study analyzed 144 eyes of 72 normal children and adolescents by OCT III (Zeiss-Humphrey, San Leandro, CA., USA) and the results were compared with the RNFL thickness of Korean adults.

Results

The mean RNFL thickness of the 72 normal children and adolescents was 105.53±10.33 µm. The mean values for left and right eyes were 104.28±7.68 µm and 106.79±12.98 µm, respectively. There was no significant difference in mean RNFL thickness between the 4 quadrants of the left and right eyes (p=0.926). Additionally, the mean RNFL thickness showed a similar size pattern regardless of age (p=0.99). RNFL thickness was found to be greater in adults than in children or adolescents, although the difference was not statistically significant (p=0.295. Likewise, no significant difference was found with gender (p=0.822) or in the pattern of RNFL thickness of 12 sectors between children and adults (p=0.08).

Conclusions

This study reports RNFL thickness, as determined by OCT, for normal children and adolescents. We found this measurement method to be suitable for the early diagnosis of glaucoma and to the examination of its progression in these subjects. The findings could be used as clinical parameters for adolescent glaucoma.

Keywords: Adolescent glaucoma, Optical coherence tomography, Retinal nerve fiber layer thickness

Glaucoma is a disease with visual field defects due to irreversible damage of optic nerves by mechanical factors such as high intraocular pressure (IOP) and endogenous factors such as reduced blood flow. Glaucoma is usually asymptomatic in the early stage and at the late stage, when visual field defects have progressed substantially, visual acuity impairment or the symptom of visual field contraction begins to appear. Therefore, early diagnosis and appropriate treatment are very important. The measurement of IOP, the perimetry and optic disc examination are the most basic tests for the early diagnosis of glaucoma; however, the ease of detection may vary depending on the age, gender, race, time of measurement, and examiners, and these basic tests are not very helpful in the early detection of normal tension glaucoma. The visual field examination has the problem that the visual field impairment is only detectable after a substantial loss of the retinal nerve fiber layer (RNFL), which therefore limits its effectiveness in the early diagnosis of glaucoma.1-4 The optic disc examination using ophthalmoscope varies widely depending on the examiner, and since in normal eyes the individual variation of the optic disc shape is large, this examination, although it suitable as a glaucoma screening test, cannot contribute decisively to the early and definite diagnosis of glaucoma.5

It has been shown that changes of the optic disc or in the vicinity of the disc and RNFL defects precede the visual acuity impairment.5-12 Therefore, since RNFL photographs and the objective optic disc examination allow the detection of structural changes that can be detected prior to the visual acuity impairment and thus allow the initiation of treatment at the appropriate time, they may contribute to the prevention of optic nerve damage by glaucoma. Particularly, as RNFL defects appear earlier than changes of the optic disc, Tuulonen et al. have reported that RNFL photography is useful as a screening test for glaucoma.13,14

Optical Coherence Tomography (OCT) is a test that marks the level of reflection from the retina with different colors according to the level and thus obtains a section image. Since this test uses a beam instead of sound, the resolution is excellent and minute tissue can be assessed. By measuring differences in the amount of reflected beam according to the characteristic of each tissue, the histological characteristic of the tissue can be determined and, by connecting the tested points, a one-dimensional picture of the retina is obtained. In addition, OCT has the advantage of not contacting the eyes of the subjects directly.

The objectivity and reproducibility of OCT have been proven by Schuman et al. However, the RNFL thickness of normal eyes has not been widely analyzed by OCT, and particularly, in Korean, it has been applied only to adults. No investigation has been carried out to analyze the normal RNFL thickness in children and adolescents. Therefore, although the incidence of glaucoma at this age is low, the normal RNFL thickness value that could be used as a reference in children and adolescents suspected of having glaucoma of glaucomatous nerve fiber defects remains unknown.15,16 It is thus required to characterize the normal range of RNFL thickness measured by OCT that could be applied to the early diagnosis of pediatric as well as adolescent glaucoma patients.

Hence, on subjects from 9 to 18 years old, the normal range of RNFL thickness was analyzed by examining the RNFL by OCT to obtain basic information for the early diagnosis and follow up examination of glaucoma.

Materials and Methods

The test was performed on 144 eyes of 72 normal children and adolescents who visited our hospital from September 2003 to October 2004. All patients underwent the visual acuity test, refraction test, IOP test, slit lamp examination, optic disc examination using ophthalmoscope, and OCT III (Zeiss-Humphrey, San Leandro, CA., U.S.A).

Normal eyes were defined as IOP under 21 mmHg as measured by Goldman tonometer, a cup-disc ratio by direct ophthalmoscope of less than 0.4 or the difference between the two eyes of less than 0.1, a refractive error of between +3 diopters and -6 diopters, and the absence of systemic diseases such as diabetes or hypertension, abnormal findings in the anterior segment or the retina, a history of trauma or eye surgery and a family history of glaucoma.

Prior to OCT test, both eyes of the subjects were made mydriasis with 1% tropicamide and 2.5% phenylephrine hydrochloride. The two methods available to suppress the ocular movement by fixing the macular through blinking at an aimed beam are internal fixation and external fixation relative to the opposite eye. In our study, the internal fixation method was used.

Of the data obtained by OCT, the mean RNFL thickness, and the average thicknesses of both the right and left eyes in the four quadrants (superior, inferior, temporal, and nasal) were obtained. The results were compared with the average value of RNFL thickness of Korean normal adults as reported by Lee et al. in the journal of the Korean Ophthalmological Society in 1999. Lee and colleagues used internal fixation in 66 eyes of 66 normal adults without ophthalmologic problems to obtain an OCT measurement of the RNFL thickness with the vicinity of the optic nerve indicated by a 3.4-mm diameter, circular beam. In addition, the significance of the difference of RNFL thickness according to gender and age was examined in the test group of the present study. Finally, the significance of the thickness difference with normal adults was examined in 12 sectors.

Statistical analysis was performed using the SPSS/PC (Sigmaplot 2000) statistics program, student t test and ANOVA. P values less than 0.05 were considered to be statistically significant.

Results

The study was performed on 144 eyes of 72 normal children and adolescents; 33 male and 39 female. The mean age was 12.60±2.13 years (range, 9-18 years), 11.81±2.44 for males and 13.38±2.93 for females. The males were slightly younger than the females, but the difference was not significant. The average refraction abnormality was -3.15±2.2 diopters, and the average IOP was 14.25±1.35 mmHg (Table 1).

The average RNFL thickness of the normal children and adolescents, measured using OCT with a 3.4-mm diameter, circular beam, was 105.53±10.33 (m overall. The averages of the left and right eyes were 104.28±7.68 µm and 106.79±12.98 µm, respectively. The superior, inferior, nasal and temporal quadrants of the left eye were 132.75±16.42 µm, 130.92±15.04 µm, 63.65±14.10 µm, and 90.47±20.45 µm, and of the right eye were 132.73±23.90 µm, 133.34±25.32 µm, 75.62±13.62 µm, and 85.00±14.93 µm, respectively. The results were thickest in the superior and inferior quadrants for both eyes (Table 2).

There were no significant differences between the left and right eyes, nor between the four quadrants (Fig. 1) (p=0.926). In children and adolescents, the average RNFL thickness showed little variation with age (Table 3, Fig. 2) (p=0.99).

The RNFL thickness was thicker in adults, but the difference was not statistically significant (Table 4, Fig. 3) (p=0.295). In none of the four quadrants was there any significant difference in RNFL thickness according to gender (Table 5, Fig. 4) (p=0.822). There was no significant difference in RNFL thickness in any of the 12 sectors between the adults and the children and adolescents (Table 6, Fig. 5) (p=0.08).

Discussion

Glaucoma is a disease that leaves permanent visual field defects if not detected early and treated appropriately, and, in severe cases, it can cause blindness. Therefore, early diagnosis is critical, and in patients with the progressed disease it is important to prevent further damage of the visual function through careful examination of the disease progression.

To diagnose glaucoma and observe the disease progression, IOP measurement, optic disc examination, and visual field examination, etc., have all been applied. However, each test method has its limitations in terms of diagnostic value and usefulness. IOP varies even daily depending on the measurement time, and the sensitivity of the optic nerve against IOP shows individual variation. Hence, it is difficult to determine the borderline value between normal and glaucomatous eyes, as the factors influencing the value are diverse and its usefulness is low in glaucoma with ocular hypertension or normal tension glaucoma.

In optic disc examination by fundus examination, and disc stereo photographs, etc., the evaluation of the cup-disc ratio is subjective, it is difficult to detect early changes of the optic disc, and, in normal eyes, the shape of the optic disc in individuals varies widely. Therefore, to differentiate between the normal disc and the glaucomatous disc, a substantial limitation is present.

The visual field examination is automatic, and its diagnostic value has been improved by the computerized automatic perimetry; nevertheless, as it is a psychological physical test in which accompanied variables react, its shortcoming is that it is greatly influenced by the patient condition. Particularly, it has the problem that visual field defects can be detected only after a substantial progression of the loss of the optic nerve axon, and therefore it is limited for the early diagnosis of glaucoma.1-4

Several investigators have shown that the RNFL defect precedes the visual field defect, and recently Quigley et al. have reported that in glaucomatous optic nerve damage, the RNFL damage due to the damage of the retinal ganglion cells could become an important marker for the impairment of ocular function,5-7,17-19 and that such reduction of the RNFL thickness precedes the optic disc change.2,13,14,17-19 In addition, for the detection of the extremely early glaucomatous change, numerous studies reported the greater importance of the continuous retinal nerve fiber examination compared to the continuous optic disc examination.2,10,14,20 In regard to the measurement assessment of such RNFL, since it was first attempted by Hoyt et al21,22 in 1973 by red-free fundus photography, in 1987, Takamoto and Schwarts20 measured the RNFL thickness using stereophotogrammetry, and in the same year, Caprioli et al23 applied computerized measurement values to assess the RNFL surface contour. However, in most cases although RNFL defects were detectable based on subjective interpretation and resolution, their quantitative measurement remained difficult.

In contrast with the above described techniques, OCT can generate one-dimensional images of the retina, from which the RNFL thickness can be measured directly. The automated computer algorithm quantitates the RNFL thickness and the thickness of the entire retina as a red and strongly reflected layer on the boundary between the retina and vitreous, and it shows the thicknesses of the superior, inferior, temporal and nasal quadrants, the clock hour sections and the entire retina. Since OCT is based on 840 nm interferometry, it is not influenced by the refraction state or the optic axis, nor by the level of nuclear sclerosis in cataract or similar opacity of the ocular media. However, posterior subcapsular cataract or cortical cataract may mediate an influence on OCT.15

In our study, the RNFL thickness, as assessed by OCT, in normal children and adolescents was thicker in the superior and inferior quadrants of both eyes. The thickness was smaller than that of normal Korean adults as reported by Lee et al,16 but the difference was not statistically significant (p=0.295). Nevertheless, the version of OCT that was used by Lee et al. for the calculation of the normal range of RNFL thickness in adults was different from the OCT method that we used, which may have introduced errors in the direct comparison between the two groups. In normal adults, it has been reported that the RNFL becomes thinner with increased age. Nonetheless, no significant change of the thickness according to age was detected across our age range of 9 years to 18 years. Since no significant difference according to gender in the children and adolescents was detected, it was considered acceptable to interpret the results regardless of gender, as in adults. In the 12 sectors of the continuous graph, a pattern similar to adults was obtained, and it is thus thought that a normal range similar to that of adults may be obtained by collecting more data and subsequently quantitating the results.16

Visual field defects in the paracentral area could not reveal the absence of glaucomatous damage,10,14 and the RNFL is thinnest in the area which concurred to visual field defects, according to Schuman et al.15 Nevertheless, despite the optic disc and the visual field in the vicinity both being normal, the finding that the site of the RNFL damage concurred with the visual field defect in the paracentral area, and that the RNFL thickness was highly correlated to physical findings such as visual field defects, enabled normal and glaucomatous eyes to be differentiated by measuring RNFL thickness with OCT. Hence, by analyzing the RNFL thickness directly with OCT, prior to the appearance of typical glaucomatous findings such as visual field defect, optic disc cupping, and RNFL defect, etc., the early diagnosis and detection of glaucoma are possible, which will help to reduce the damage of ocular function due to glaucoma.

Therefore, based on the results of our study it is considered that OCT can not only play a role in supplementing previous IOP measurement, visual field examination, and optic disc analysis, etc., but it may also be useful for the early diagnosis, study and analysis of glaucoma in Korean children and adolescents. However, to increase the diagnostic specificity and sensitivity, efforts should be made to obtain the RNFL thickness over a wider range of normal Korean children and adolescents by applying OCT, and furthermore, direct comparison and analysis of RNFL thickness values of pediatric and adolescent glaucoma patients may be required. In addition, future study should focus on defining the standard database of the RNFL thickness in each group, using larger study populations than this study, and examining the change of the glaucomatous RNFL thickness in all age groups including children and adolescents.

In this study, we measured the RNFL thickness in normal Korean children and adolescents with OCT. We found this method to be applicable to the early diagnosis of glaucoma and to the examination of its progression in pediatric and adolescent glaucoma patients.

Figures and Tables

Fig. 1

Mean retinal nerve fiber layer (RNFL) thickness of each quadrant in the left and right eyes.

Fig. 2

(A) Mean retinal nerve fiber layer (RNFL) thickness according to age (right eye). (B) Mean retinal nerve fiber layer (RNFL) thickness according to age (left eye).

Fig. 3

Mean retinal nerve fiber layer (RNFL) thickness of subjects and adults.

^*Lee JH, Ahn CS, Lee DY. Quantification of Retinal Nerve Fiber Layer Thickness in the Normal Subjects Using Optical Coherence Tomography. J Korean Ophthalmol Soc 1999;40:2804-15.

Fig. 4

Mean retinal nerve fiber layer (RNFL) thickness according to gender.

Fig. 5

Mean retinal nerve fiber layer (RNFL) thickness of 12 sectors.

^*Lee JH, Ahn CS, Lee DY. Quantification of Retinal Nerve Fiber Layer Thickness in the Normal Subjects Using Optical Coherence Tomography. J Korean Ophthalmol Soc 1999;40:2804-15.

Table 1

Study characteristics (N=72)

^*mean value.

Table 2

Mean retinal nerve fiber layer thickness

p=0.926.

Table 3

Mean retinal nerve fiber layer thickness (µm) according to age

^*ANOVA

Table 4

Mean retinal nerve fiber layer thickness of subjects and adults

: p value=0.295.

^*Lee JH, Ahn CS, Lee DY. Quantification of Retinal Nerve Fiber Layer Thickness in the Normal Subjects Using Optical Coherence Tomography. J Korean Ophthalmol Soc 1999;40:2804-15.

Table 5

Mean retinal nerve fiber layer thickness according to gender

^*Intraocular pressure, ^†Refractive error, ^‡Superior, ^§Inferior, ^∥ t-test.

Table 6

Mean retinal nerve fiber layer thickness (µm) of 12 sectors

p value=0.08.

^*Lee JH, Ahn CS, Lee DY. Quantification of Retinal Nerve Fiber Layer Thickness in the Normal Subjects Using Optical Coherence Tomography. J Korean Ophthalmol Soc 1999;40:2804-15.

Notes

This work was supported by the 2004 Inje University research grant.

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