Abstract
Purpose.:
To determine the effects of age, sex, spherical equivalent, axial length, anterior chamber depth, optic disc area, and central corneal thickness on perimacular inner retinal layer thickness in the normal human eye as measured by Fourier-domain optical coherence tomography (FD-OCT).
Methods.:
In this cross-sectional observational study, 182 Korean healthy subjects aged from 22 to 84 years were included. To obtain the inner retinal layer thickness, perimacular ganglion cell complex thickness, which extends from the internal limiting membrane to the inner nuclear layer, was measured by FD-OCT on one randomly selected eye of each subject. Linear regression analyses of the effects of demographic and clinical variables, including age, sex, spherical equivalent, axial length, anterior chamber depth, optic disc area, and central corneal thickness, on perimacular inner retinal layer thickness were performed.
Results.:
The mean inner retinal layer thickness for the entire population was 93.87 μm. Thinner inner retinal layer measurements were associated with older age (P = 0.010) and greater axial length (P = 0.021). Mean inner retinal layer thickness decreased by approximately 1.59 μm for every decade of age and by approximately 1.56 μm for every 1-mm greater axial length. There was no relationship between inner retinal layer thickness and sex, anterior chamber depth, optic disc area, or central corneal thickness.
Conclusions.:
Inner retinal layer thickness, as measured by FD-OCT, varies significantly with age and axial length. The effect is small but clinically relevant in the interpretation of inner retinal layer thickness measurements.
Glaucoma is a multifactorial optic neuropathy characterized by the selective loss of retinal ganglion cells (RGCs) and their respective axons.
1 –3 Because the macular region contains more than 50% of RGCs, assessing ganglion cell changes in this region, rather than measuring peripapillary retinal nerve fiber layer (RNFL) thickness, could be useful for diagnosing glaucoma.
4 –6 Recently, the Fourier-domain optical coherence tomography (FD-OCT) technique was introduced. Compared with time-domain (TD)-OCT, this technique improves depth resolution, resulting in considerably improved image quality and a greatly reduced acquisition time.
7 –9 RTVue-100 (Optovue, Inc., Fremont, CA) is a commercially available OCT device that uses FD technology. FD-OCT software enables measurements of the thickness of the macular ganglion cell complex (GCC) layer, which extends from the internal limiting membrane to the inner nuclear layer and includes the ganglion cell layer.
10
Previous studies measuring retinal thickness have demonstrated a relationship between retinal thickness and several demographic and ocular biometric factors.
11 –26 However, no studies have investigated the relationship between ganglion cell layer thickness and ocular biometric factors. Furthermore, even though ocular biometric factors are possibly related to retinal thickness, previous studies often take into consideration only axial length and refractive error.
In this study, we used GCC thickness measurements obtained by FD-OCT to evaluate the effects of demographic and ocular biometric factors on inner retinal thickness measurements in healthy subjects. In addition to axial length and refractive error, anterior chamber depth, optic disc area, and central corneal thickness measurements were taken into account.
Subjects were consecutively enrolled from the Glaucoma-Cataract Clinic of Severance Hospital, Yonsei University (Seoul, Korea) from January 2009 to June 2010. Healthy subjects were recruited both from department personnel referrals and through an advertisement posted at Severance Hospital. This study was approved by the Institutional Review Board of Severance Hospital, Yonsei University, and was performed in adherence with the Declaration of Helsinki. Informed consent was obtained from all subjects.
All subjects underwent a full ophthalmological examination including measurement of visual acuity, intraocular pressure (IOP) measurements using Goldmann applanation tonometry, slit lamp examination, gonioscopy, fundus examination with a 90D lens, and standard automated perimetry (Humphrey Field Analyzer II with Swedish Interactive Thresholding Algorithm standard 24-2; Carl Zeiss Meditec, Dublin, CA). A reliable visual field (VF) test was defined as one with <20% fixation loss and with false-positive and false-negative errors <15%. Axial ocular dimensions were measured using partial laser interferometry (IOL Master; Carl Zeiss Meditec). Noncycloplegic refraction was measured using an autorefractor (RK-3; Canon USA., Inc., Lake Success, NY) and was further refined subjectively by experienced ophthalmologists. Refraction data were converted to spherical equivalents, which were calculated using the spherical diopter (D) plus one-half the cylindrical dioptric power. Central corneal thickness was measured with ultrasound pachymetry (DGH-1000; DGH Technology Inc., Frazer, PA). After pupillary dilation to a minimum diameter of 5 mm, each eye was imaged by RTVue-100 (Optovue, Inc.) spectral-domain OCT. All measurements on a healthy subject were performed in a single day.
No subject had any history of glaucoma in a first-degree relative, history or evidence of intraocular surgery, or retinal pathologic features. All subjects had a corrected visual acuity of 10/20 or better; refractive error from +3.00 to −8.00 D, and IOP of 21 mm Hg or less on three repeated measurements taken at different times on separate visits during clinical follow-up; open angle on gonioscopy; nonglaucomatous optic nerve head without evidence of cupping, rim loss, hemorrhages, or RNFL defects; reliable normal VF test results with normal glaucoma hemifield test results; and normal mean deviation and pattern standard deviation (P > 0.05).
Exclusion criteria were IOP ≥22 mm Hg based on three measurements on different days in either eye; evidence of a reproducible VF defect in either eye; a myopic refractive error exceeding −8.00 D; intraocular surgery in the study eye; history of ocular trauma in the study eye; diabetes mellitus or neurologic diseases; vitreoretinal disease in either eye; evidence of macular abnormality in either eye; and evidence of optic nerve or RNFL abnormality in either eye.
The average thickness of the GCC was measured using RTVue-100 (Optovue, Inc.; software version 4.0.5.39), which acquires 26,000 A-scans per second and has a 5-μm depth resolution in tissue. All scans were performed by one experienced operator.
GCC parameters were obtained by the macular map (MM7) protocols, centered 1 mm temporal to the fovea. This protocol uses one horizontal line with a 7-mm scan length (934 A-scans), followed by 15 vertical lines with a 7-mm scan length and 0.5-mm interval (800 A-scans). The GCC thickness was measured from the internal limiting membrane to the inner plexiform layer boundary. Also computed were the focal loss volume, which is the integral of deviation in areas of significant focal GCC loss, and the global loss volume, which is the sum of negative fractional deviation in the entire area.
Optic disc area measurements were obtained using the nerve head map (NHM4) mode, which creates a map from en face imaging using five circular scans ranging from 2.5 to 4.0 mm in diameter (587 or 775 A-scans each) and 12 linear data inputs (3.4-mm length, 452 A-scans each).
Images with a signal strength index of <35 with overt misalignment of the surface detection algorithm or with overt decentration of the measurement circle location were excluded.
When both eyes of a patient were eligible for analysis, one eye was randomly selected for study. Independent variables were chosen based on both empiric and statistical (from univariate results) associations with GCC thickness. The demographic and clinical variables used in this study included age, sex, spherical equivalent, axial length, anterior chamber depth, optic disc area, and central corneal thickness.
Multiple linear regression analyses were performed to test whether demographic and clinical variables (independent variables) were related to average GCC thickness (dependent variable). Because the two variables—refractive error and axial length—highly correlated with one another (
r = −0.729;
P < 0.001), one or the other variable was used in two separate models. Axial length was considered more robust than refractive error because population variations in the refractive power of the cornea and lens could affect refractometry, but it likely does not affect axial length.
27 We also considered refractive error as a substitute for axial length in a second multiple linear regression model because the model including refractive error seems to be preferable in clinical settings.
Statistical analysis was performed using SPSS for Windows (version 12.0.0; SPSS Inc., Chicago, IL). P < 0.05 was considered statistically significant.
This cross-sectional study has some limitations, including a relatively small sample size. It could not accurately present the decrease in inner retinal thickness with age, and it was conducted with only Asian subjects; there may be differences among ethnic groups. Further studies using a large and more ethnically diverse population are warranted. In our study, variables that were not significant in univariate analysis were included in a multiple regression model. Therefore, an element of randomness could have influenced the multivariate analysis. The clinical implications of the finding that GCC thickness measurements decrease with age and axial length cannot be overemphasized because the coefficient of determination of the entire multivariate model was small and the confidence interval on the slope of regression was wide. The effect of aging and long axial length on GCC thickness, at 1.59 μm per decade and 1.56 μm per 1-mm, though statistically significant, is still clinically small.
In conclusion, the results of this study, which used new-generation FD-OCT scanning with improved resolution and faster scan speed, demonstrate that thin perimacular GCC thickness is significantly correlated with old age and long axial length but not with sex, anterior chamber depth, optic disc area, or central corneal thickness in ophthalmologically healthy subjects. Although the effects of age and axial length on perimacular inner retinal layer thickness are clinically small, analysis of inner retinal thickness in glaucoma should be interpreted in the context of these findings. More finely divided layer segmentation with improved resolution of FD-OCT could be informative so that only layers affected by glaucomatous damage are measured.
Disclosure:
N.R. Kim, None;
J.H. Kim, None;
J. Lee, None;
E.S. Lee, None;
G.J. Seong, None;
C.Y. Kim, None