Groth, Sylvia L. BA; Harrison, Andrew MD; Grajewski, Alana L. MD; Lee, Michael S. MD
Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota.
Address correspondence to Michael S. Lee, MD, Department of Ophthalmology, University of Minnesota, 420 Delaware Street, Southeast, MMC 493, Minneapolis, MN 55455-0501; E-mail: firstname.lastname@example.org
Supported by unrestricted grant from Research to Prevent Blindness, New York, NY.
The authors report no conflicts of interest.
Background: Optical coherence tomography (OCT) provides useful structural information that can augment functional data. Newer spectral-domain technology provides faster and higher resolution images than time-domain machines. Although each measures the same structures, the values systematically differ. We evaluated eyes with longstanding no light perception (NLP) visual acuity secondary to optic atrophy using spectral-domain OCT to determine minimum retinal nerve fiber layer (RNFL) thickness.
Methods: The authors conducted a retrospective, cross-sectional chart review study to identify patients with NLP acuity for 8 months or more and having a good quality Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) to measure the RNFL thickness. An unpaired t test compared the eyes with a previously published data set measured with time-domain OCT.
Results: Eleven eyes from 10 patients were examined with the Spectralis OCT. The mean duration of documented NLP acuity was 3.72 ± 1.20 years. The mean RNFL thickness was 34.18 ± 2.66 μm (95% confidence interval, 28.26–40.11 μm). Mean RNFL thickness was significantly thinner on this spectral-domain OCT than previously published values on time-domain OCT (34.18 vs 45.42 μm, P = 0.004).
Conclusion: Using the Spectralis OCT, mean RNFL thickness for NLP eyes due to optic atrophy is 28–40 μm. This provides clinicians useful information when considering how aggressively to manage patients with optic nerve disease.
Optical coherence tomography (OCT) has revolutionized imaging in ophthalmology (1), with the technology steadily improving since its debut in 1991 (2). This noncontact device has become invaluable in correlating structural status with visual function and in guiding management decisions. Third-generation time-domain optical coherence tomography (TD-OCT) machines achieve axial resolution of 10–15 μm, whereas newer spectral-domain optical coherence tomography (SD-OCT) can delineate structures more clearly with an axial resolution of 5–7 μm (3). There are 3 major spectral-domain machines currently available: Cirrus (Carl Zeiss Meditech, Dublin, CA), Spectralis (Heidelberg Engineering, Heidelberg, Germany), and RTVue (Optovue, Inc, Fremont, CA).
Significant differences exist between mean retinal nerve fiber layer (RNFL) thickness measurements obtained by TD-OCT and SD-OCT. Several studies have shown that in normal eyes, measurement of RNFL thickness is thinner with SD-OCT compared with TD-OCT (4–6). These differences are most apparent with the Cirrus and Spectralis machines, where normal mean RNFL measures 98.7 and 107 μm, respectively, compared with 110.1 μm using the time-domain Stratus (Carl Zeiss Meditech) (3). This also is true in patients with glaucoma. Compared with TD-OCT, SD-OCT results show thinner RNFL thickness in more advanced cases of glaucoma and thicker RNFL thickness in less severe cases (4).
The purpose of this study was to evaluate RNFL thickness using Spectralis OCT in eyes with longstanding no light perception (NLP) vision secondary to optic atrophy. We compared our results to those of Chan and Miller (7), who measured a similar patient population using TD-OCT.
MATERIALS AND METHODS
After obtaining institutional review board approval from the University of Minnesota, patients were identified by retrospective chart review. For inclusion, patients met the following criteria: 1) NLP for 8 or more months in at least one eye; 2) seen in the ophthalmology clinic between July 2009 and September 2011; 3) visual loss secondary to optic atrophy; and 4) RNFL thickness measured by Spectralis OCT. Patients were excluded for poor quality OCT images, NLP acuity for less than 8 months, and visual acuity of light perception or better. In cases with bilateral blindness, both eyes were included for study.
RNFL thickness was measured in each eye using the Spectralis OCT in the FoDi (fovea-to-disk) alignment mode. A 3.4-mm circle was centered on the optic nerve. An unpaired t test was used to compare our data with that of Chan and Miller (7). A Pearson correlation coefficient was calculated for the duration of NLP vision compared with RNFL thickness.
Thirteen eyes from 11 patients were identified. One eye was excluded for visual acuity of light perception and another for a decentered scan, leaving 11 eyes from 10 patients for analysis (Table 1). There were 3 male and 7 female patients with a mean age of 43.6 ± 6.75 years. The mean duration of documented NLP acuity was 3.73 ± 1.20 years (range, 8 months to 11 years). Mean RNFL thickness among NLP eyes was 34.18 ± 2.67 μm. Compared with the data from Chan and Miller (7), mean RNFL thickness measured significantly thinner using the SD-OCT than TD-OCT (34.18 vs 45.42 μm, P = 0.004). Correlation of duration of NLP to RNFL thickness was r = −0.123 (P = 0.7184). The fellow eyes in the 9 patients with unilateral NLP included 2 with no clinical evidence of disease (mean thickness = 90.0 μm), 4 with clinical evidence of disease, and 3 in which OCT was not performed on the fellow eye. No comparisons were made on these eyes.
TD-OCT uses interferometry to measure structures with high resolution. This technique requires a moving reference mirror to evaluate the changes in reflectivity over time of light waves beamed through tissue. Up to 400 axial scans are generated per second. SD-OCT provides simultaneous measurement of changes in light reflectivity and the relative amplitude frequencies within the backscattered light (4). SD-OCT is able to capture images much faster and at a significantly higher resolution with 40,000 scans per second (heidelbergengineering.com).
A large number of studies in patients with glaucoma have evaluated RNFL thickness using both TD-OCT and SD-OCT with substantial differences reported (3–6). These 2 types of OCT measure RNFL thickness differently. OCT 3, a time-domain machine, measures the RNFL thickness with an automated segmentation algorithm that detects the internal limiting membrane boundary to the boundary between the reflective RNFL and less reflective ganglion cell body layer (8). SD-OCT measures RNFL thickness with a software algorithm that delineates the RNFL boundaries. In normal eyes, this usually results in thinner measurements of RNFL thickness. However, specifically in glaucoma, the measurements can be either thicker or thinner compared with time-domain machines, based on the severity of the disease. The reason for this difference likely relates to the breakdown of segmentation algorithms in advanced optic nerve disease. Possibly, SD-OCT scans identify a deeper outer boundary when assessing a thin nerve so that the measured RNFL appears thicker than on TD-OCT. Spectral-domain machines use less smoothing effect, which might also lead to thicker measurements (4).
With both TD-OCT and SD-OCT, mean RNFL thickness for normal eyes is approximately 100 μm (Cirrus: 98.68 μm; Spectralis: 106.59 μm; RTVue: 112.78 μm). Knowledge of the minimum RNFL thickness can improve clinical management as one attempts to determine the degree of optic nerve damage (3). Despite knowing the upper limits of normal RNFL thickness, the lower limit has been less well studied. We found the lower limit of mean RNFL to be 34 μm with a 95% confidence interval of 28.26–40.11 μm using the Spectralis machine. Chan and Miller (7) determined the minimum thickness of RNFL in eyes with NLP from optic atrophy to be 45.42 μm using the Stratus TD-OCT. This is significantly thicker than our results (P = 0.004). Among severely glaucomatous eyes, SD-OCT measurements of RNFL thickness are thinner compared with TD-OCT (4,9). In this patient group, the RNFL measures even thinner with the Spectralis compared with the Cirrus (9), which may relate to differences in data acquisition protocols.
There are a number of factors that will affect the minimum RNFL thickness in NLP eyes secondary to optic atrophy. Several structures add to the thickness of the RNFL besides ganglion cell axons. Glial cells make up approximately one-fifth of the cross-sectional area of the primate RNFL (10). Retinal blood vessels, gliosis, and dead or non-functioning ganglion cell axons contribute to RNFL thickness (7,10–12). Finally, the residual thickness of the RNFL measurement may represent an artifact of OCT software. These factors, in part, explain the thinner measurement of RNFL thickness with SD-OCT, which uses newer software with higher resolution imaging.
We recognize the limitations of our study, including the small number of eyes studied and the fact that it was retrospective. Additionally, it is unknown how long it takes for the RNFL atrophy to establish its nadir. Despite these limitations, we believe our results are valid and that clinicians should recognize that the minimum mean RNFL thickness using Spectralis OCT is 28–40 μm (95% confidence interval).
1. Baumal CR. Clinical applications of optical coherence tomography. Curr Opin Ophthalmol. 1999;10:182–188.
2. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG. Optical coherence tomography. Science. 1991;254:1178–1181.
3. Seibold LK, Mandava N, Kahook MY. Comparison of retinal nerve fiber layer thickness in normal eyes using time-domain and spectral-domain optical coherence tomography. Am J Ophthalmol. 2010;150:807–814.
4. Knight OJ, Chang RT, Feuer WJ, Budenz DL. Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology. 2009;116:1271–1277.
5. Arthur SN, Smith SD, Wright MM, Grajewski AL, Wang Q, Terry JM, Lee MS. Reproducibility and agreement in evaluating retinal nerve fibre layer thickness between Stratus and Spectralis OCT. Eye (Lond). 2011;25:192–200.
6. Wolf-Schnurrbusch UE, Ceklic L, Brinkmann CK, Iliev ME, Frey M, Rothenbuehler SP, Enzmann V, Wolf S. Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Invest Ophthalmol Vis Sci. 2009;50:3432–3437.
7. Chan CK, Miller NR. Peripapillary nerve fiber layer thickness measured by optical coherence tomography in patients with no light perception from long-standing nonglaucomatous optic neuropathies. J Neuroophthalmol. 2007;27:176–179.
8. Giaconi JA, Law SK, Coleman AL, Caprioli J. Optic nerve: optical coherence tomography. In: Pearls of Glaucoma Management. Berlin, Germany: Springer-Verlag, 2010:45–49.
9. Tan BB, Natividad M, Chua KC. Comparison of retinal nerve fiber layer measurement between 2 spectral domain OCT instruments. J Glaucoma. 2012;21:266–273.
10. Ogden TE. Nerve fiber layer of the primate retina: thickness and glial content. Vision Res. 1983;23:581–587.
11. Cursiefen C, Holback LM, Schlotzer-Schrehardt U, Naumann GO. Persisting retinal ganglion cell axons in blind atrophic human eyes. Graefes Arch Clin Exp Ophthalmol. 2001;239:158–164.
12. Sihota R, Sony P, Gupta V, Dada T, Singh R. Diagnostic capability of optical coherence tomography in evaluating the degree of glaucomatous retinal nerve fiber damage. Invest Ophthalmol Vis Sci. 2006;47:2006–2010.