Abstract
Purpose
To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures using eye-tracking assisted spectral domain optical coherence tomography (SD-OCT) in children with nonglaucomatous optic neuropathy.
Design
Prospective longitudinal study
Methods
Circumpapillary RNFL thickness measures were acquired with the Spectralis (Heidelberg Engineering) SD-OCT using the eye-tracking feature at two separate study visits. Children with normal and abnormal vision (visual acuity ≥ 0.2 logMAR above normal and or visual field loss) who demonstrated clinical and radiographic stability were enrolled. Intra- and intervisit reproducibility was calculated for the global average and 9 anatomic sectors by calculating the coefficient of variation and intraclass correlation coefficient.
Results
Forty-two subjects (median age 8.6 years, range 3.9 -18.2 years) met inclusion criteria and contributed 62 study eyes. Both the abnormal and normal vision cohort demonstrated the lowest intravisit coefficient of variation for the global RNFL thickness. Intervisit reproducibility remained good for those with normal and abnormal vision, although small but statistically significant increases in the coefficient of variation were observed for multiple anatomic sectors in both cohorts. The magnitude of visual acuity loss was significantly associated with the global (β = 0.026, P < .01) and temporal sector coefficient of variation (β = 0.099, P < .01).
Discussion
SD-OCT with eye tracking demonstrates highly reproducible RNFL thickness measures. Subjects with vision loss demonstrate greater intra- and intervisit variability than those with normal vision.
INTRODUCTION
Optical coherence tomography (OCT) has become an invaluable and objective tool in the management of optic neuropathies.1–7 The evolution from time-domain OCT to spectral domain OCT (SD-OCT) has not only improved image resolution and acquisition time, but now includes mechanisms to improve test-retest reliability.8–10 Specifically, some current generation SD-OCT devices provide an eye tracking feature that uses a confocal scanning laser ophthalmoscope or line scanning ophthalmoscope to accommodate for eye movements and that improves the accuracy of subsequently acquired images to be captured in the same anatomic location.11–15 The within and between visit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures have been reported most frequently using the Spectralis OCT (Heidelberg Engineering, Inc., Heidelberg, Germany) using the eye tracking feature. 11,13–15
Most studies describing the reproducibility of circumpapillary RNFL measures have examined adult subjects with glaucoma11,13 and or healthy controls.11–15 Only one study has reported the intravisit reproducibility of circumpapillary RNFL thickness measures for children with glaucoma using the Spectralis with eye tracking.11 While the data presented to date is helpful when examining healthy subjects and adults with glaucoma, it is unclear whether reproducibility measures are comparable in children with optic neuropathies other than glaucoma since the mechanism and pattern of RNFL loss differs.
The ability of SD-OCT to monitor longitudinal circumpapillary RNFL changes in glaucoma and non-glaucomatous optic neuropathies could be especially beneficial in children since their functional assessment of vision (i.e., visual acuity and visual field) relies heavily on their cooperation and cognitive abilities.16 The goal of the current study is to determine the intra- and intervisit reproducibility of RNFL thickness measurements using eye-tracking in children with non-glaucomatous optic neuropathies.
METHODS
Subjects
Children being cared for in the Neuro-Ophthalmology clinic at Children’s National Medical Center who underwent SD-OCT imaging were eligible for study enrollment. Informed consent was obtained from the parent/legal guardian before study enrollment. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board at Children’s National Medical Center. All data collected was Health Insurance Portability and Accountability Act compliant.
Subjects determined to have the following non-glaucomatous optic neuropathies were eligible for enrollment: low grade gliomas intrinsic to the visual pathway (i.e., optic pathway gliomas), extrinsic tumors involving the anterior visual pathway (i.e., craniopharyngioma, prolactinoma) and demyelinating disease. Healthy children with normal examinations and children with Neurofibromatosis type 1 who did not have an optic pathway glioma were eligible to contribute a single eye to the healthy/unaffected cohort since previous work has shown that RNFL thickness does not differ between these groups.17 Subjects were included if they met all of the following criteria: 1) two separate study visits within 12 months; 2) clinically stable disease without radiographic (i.e., tumor growth, new/worsening signal characteristics or new/worsening contrast enhancement) or clinical progression (i.e., >0.1 logMAR worsening in visual acuity or progressive visual field loss); 3) absence of examination findings suggestive of glaucoma; 4) three or more acceptable circumpapillary RNFL scans acquired at the initial study visit and a minimum of 1 scan at the follow up visit; 5) SD-OCT scan signal strength > 20 db; and 6) acquisition of the entire image volume without appreciable movement or acquisition artifact. Subjects who did not complete a second study visit or experienced clinical progression were excluded from the study. Subjects with tumors that could potentially cause vision loss in one or both eyes (i.e., optic chiasm or optic tract lesions) who demonstrated clinical progression in only one eye were excluded.
Clinical and demographic characteristics were abstracted from the subject’s clinical record. Subjects were classified as having abnormal vision is their visual acuity was ≥ 0.2 logMAR above normal for age or had visual field loss. The magnitude of visual acuity loss was calculated by subtracting the current logMAR from the normal logMAR for age. When able to cooperate, visual field loss was determined by automated or kinetic perimetry.
Image Acquisition and Analysis
All images were acquired with the Spectralis SD-OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) using the “Nsite Analytics” (version 5.6.3.0) and “TruTrack” eye-tracking. Once the patient fixates on an internal or external target allowing the optic nerve to be visualized on the infrared image, this feature permits the operator to “freeze” the image and then manually align the 3.5 mm circular scan over the optic nerve head. If the subject blinks, stops fixating or moves out of focus, the OCT acquisition will pause until proper alignment is again achieved. RNFL measures were acquired in high speed mode (768 A-scans) with an automatic real time (ART) setting of 16. RNFL thickness was measured in 9 sectors: temporal-superior, temporal, temporal-inferior, inferior, nasal-inferior, nasal, nasal-superior, superior and papillomacular bundle. The global average of all 4 quadrants was also calculated. Scans and their segmentation were reviewed by one investigator (RDR) who was blinded to all clinical information. Each scan was inspected for segmentation errors, and when necessary, was manually adjusted using the manufacturer supplied segmentation software. After the first study visit, the scan with the highest quality score, absent of image artifacts, was chosen as the reference scan for the second visit acquisitions.
Statistics
Standard descriptive statistics were used to summarize clinical and demographic characteristics. Coefficient of variation and intraclass correlation coefficient (two-way mixed-effects model) were calculated for the intra- and intervisit analysis. The coefficient of variation, calculated as the standard deviation divided by the mean, represents the variability of a measure. A lower coefficient of variation value represents less variance suggestive of more consistent measurements, whereas a higher coefficient of variation value represents greater variance among measurements. The intraclass correlation coefficient, another quantitative assessment of reproducibility, calculates the extent of congruence between individuals within a group. A higher intraclass correlation coefficient value represents greater reproducibility. Since this calculation is specific to the study population, intraclass correlation coefficient values cannot be compared across studies. Wilcoxon rank-sum test was used to compare the RNFL thickness, coefficient of variation and image quality between subjects with and without vision loss. Paired t-test using the Bonferroni adjustment for multiple comparisons (significance adjusted to P < 0.005) was used to compare the intervisit change of RNFL thickness and coefficient of variation within each cohort. Linear regression was used to evaluate the unadjusted and adjusted associations of age and tumor location (intrinsic versus extrinsic tumor) on coefficient of variation measures from the 4 anatomic quadrants (superior, nasal, inferior, temporal) and global average. Since only one eligible subject had demyelinating disease, they were included in the extrinsic tumor cohort. For subjects with normal vision in both eyes, one eye was selected for inclusion using a random number generator. Subjects with abnormal vision in both eyes could contribute two eyes, but a generalized estimating equation (GEE) was used instead of standard linear regression to account for the inter-eye correlation. The GEE model evaluated the unadjusted and adjusted associations of age, magnitude of visual acuity loss and tumor location (intrinsic tumor vs. others) on coefficient of variation measures in the abnormal vision cohort. Subjects with one eye with abnormal vision and one eye with normal vision could contribute to both vision cohorts.
RESULTS
Forty-two subjects met inclusion criteria and contributed 62 study eyes. Fifteen subjects contributed both eyes to the abnormal vision cohort while 4 subjects contributed one eye to abnormal vision cohort and one eye to normal vision cohort. Twenty subjects contributed 1 eye to the normal vision cohort. Table 1 lists the demographic and clinical characteristics for subjects with and without vision loss. Both groups had a similar interval between study visits. There was no statistical difference in scan quality between vision loss cohorts (Wilcoxon, P > .05). None of the sectors demonstrated a statistical change in RNFL thickness between visit 1 and visit 2 (see Table 2).
Table 1.
Demographic and Clinical Characteristics of Children with and without Vision Loss Undergoing Spectral-Domain Optical Coherence Tomography Using Eye-Tracking.
| Abnormal Vision (N = 22) | Normal Vision (N = 24) | |
|---|---|---|
| Age (mean/median)a | 10.7/10.2 | 8.5/8.2 |
| Range | (4.9 – 18.2) | (3.9 – 14.4) |
| Female sex – no. (%) | 14 (64) | 16 (67) |
| Race – no. (%) | ||
| White/Caucasian | 18 (82) | 19 (79) |
| Black/African American | 4 (18) | 4 (17) |
| Asian | 0 (0) | 0 (0) |
| Multiple races | 0 (0) | 1 (04) |
| Ethnicity – no. (%) | ||
| Non-Hispanic | 19(86) | 22(92) |
| Hispanic | 3 (14) | 2 (8) |
| Time between visits (mean/median)b | 4.2/2.8 | 4.2/3.3 |
| Range | (1.1 – 10.4) | (1.3 – 9.3) |
| Diagnosis – no. (%) | ||
| NF1 with OPG | 6 (27) | 9 |
| Sporadic OPG– no. (%) | 11 (50) | 6 |
| Craniopharyngioma | 2 (9) | -- |
| Prolactinoma | 1 (5) | -- |
| Langerhans Cell Histiocytosis | 1 (5) | -- |
| Demyelination | 1 (5) | -- |
| Healthy/Unaffected | -- | 9 |
| Category of Vision Loss – no.c | ||
| Abnormal visual acuity/normal visual field | 5 | -- |
| Abnormal visual field/normal visual acuity | 20 | -- |
| Abnormal visual acuity and visual field | 12 | -- |
NF1 = Neurofibromatosis type 1; OPG = optic pathway glioma
Years;
Months;
Eyes
Table 2.
Circumpapillary Retinal Nerve Fiber Layer Thickness Measures Using Eye-Tracking with Spectral-Domain Optical Coherence Tomography in Children with Optic Neuropathy.
| Sector b | Abnormal Vision (N = 37)a
|
Normal Vision (N = 25)a
|
||
|---|---|---|---|---|
| Visit 1 | Visit 2 | Visit 1 | Visit 2 | |
|
|
|
|||
| G | 63±16.7 | 64±17.5 | 97±14.9 | 97±13.8 |
| TS | 92±24.9 | 93±25.4 | 137±25.8 | 138±24.1 |
| T | 41 ± 14.4 | 41 ± 15.6 | 67 ± 13.3 | 66 ± 13.0 |
| TI | 93 ± 36.1 | 94 ± 36.9 | 143 ± 23.7 | 143 ± 22.1 |
| I | 83 ± 25.2 | 85 ± 26.2 | 124 ± 20.4 | 125 ± 19.7 |
| NI | 74 ± 22.9 | 75 ± 24.3 | 106 ± 21.1 | 108 ± 22.2 |
| N | 46 ± 20.7 | 47 ± 21.1 | 73 ± 19.4 | 73 ± 19.1 |
| NS | 74 ± 31.2 | 76 ± 31.9 | 109 ± 26.5 | 109 ± 25.5 |
| S | 83 ± 23.1 | 85 ± 23.8 | 123 ± 21.5 | 123 ± 19.4 |
| PMB | 32 ± 16.6 | 32 ± 17.8 | 49 ± 9.6 | 49 ± 9.5 |
G = global average; TS = temporal-superior; T = temporal; TI = temporal-inferior; I = inferior; NI = nasal-inferior; N = nasal; NS = nasal-superior; S = superior; PMB = papillomacular bundle;
Study Eyes
Intravisit Reproducibility
For the intravisit analysis, both the abnormal and normal vision cohort demonstrated the lowest intraclass correlation coefficient (.961 and .992, respectively) and the highest coefficient of variation (6.2% and 2.2%, respectively) in the papillomacular bundle (see Table 3). Similarly, the abnormal and normal vision cohort demonstrated the lowest coefficient of variation (1.5% and 0.7%, respectively) for the global thickness. The normal vision cohort demonstrated statistically lower coefficient of variation measures compared to the abnormal vision cohort in the global, temporal, temporal-inferior and nasal sectors (see Table 3).
Table 3.
Intravisit Intraclass Correlation Coefficient and Coefficient of Variation for Circumpapillary Retinal Nerve Fiber Layer Thickness in Children Using Spectral-Domain Optical Coherence Tomography.
| Sector | Abnormal Vision (N = 37)a
|
Normal Vision (N = 25)a
|
P Value | ||
|---|---|---|---|---|---|
| ICC (95% CI) | CV (%) | ICC (95% CI) | CV (%) | ||
|
|
|
|
|||
| G | .998 (.99, .99) | 1.5 | .998 (.99, .99) | 0.7 | .04 |
| TS | .994 (.98, .99) | 2.4 | .995 (.99, .99) | 1.4 | NS |
| T | .984 (.97, .99) | 3.1 | .997(.99, .99) | 1.2 | .03 |
| TI | .998 (.99, .99) | 2.5 | .998 (.99, .99) | 1.0 | .01 |
| I | .996 (.99, .99) | 2.0 | .998 (.99, .99) | 1.0 | NS |
| NI | .998 (.99, .99) | 2.1 | .997 (.99, .99) | 1.4 | NS |
| N | .997 (.99, .99) | 3.7 | .997 (.99, 99) | 1.4 | < 0.01 |
| NS | .997 (.99, .99) | 3.1 | .995 (.99, .99) | 2.0 | NS |
| S | .997 (.99, .99) | 1.9 | .995 (.99, .99) | 1.4 | NS |
| PMB | .961 (.93, .97) | 6.2 | .992 (.98, .99) | 2.2 | NS |
G = global average; TS = temporal-superior; T = temporal; TI = temporal-inferior; I = inferior; NI = nasal-inferior; N = nasal; NS = nasal-superior; S = superior; PMB = papillomacular bundle; ICC = intraclass correlation coefficient; CI = confidence interval; CV = coefficient of variation; NS = not significant.
Study Eyes
Intervisit Reproducibility
Both the abnormal and normal vision cohorts demonstrated lower intraclass correlation coefficient and slightly higher coefficient of variation values in the intervisit analysis (see Table 4). In the abnormal vision cohort, the lowest coefficient of variation was again demonstrated in the global measure (2.3%) and highest in the papillomacular bundle (6.6%). For the normal vision cohort, the global measure also had the lowest coefficient of variation (1.3%), but the nasal and nasal-superior sectors (3.5% and 3.6%) demonstrated the highest coefficient of variations. The normal vision cohort demonstrated statistically lower coefficient of variation measures compared to the abnormal vision cohort in the global, temporal, temporal-inferior, nasal-inferior, nasal and papillomacular bundle sectors (see Table 4).
Table 4.
Intervisit Intraclass Correlation Coefficient and Coefficient of Variation for Circumpapillary Retinal Nerve Fiber Layer Thickness in Children Using Spectral-Domain Optical Coherence Tomography.
| Sector | Abnormal Vision (N = 37)a
|
Normal Vision (N = 25)a
|
P Value | ||
|---|---|---|---|---|---|
| ICC (95% CI) | CV (%) | ICC (95% CI) | CV (%) | ||
|
|
|
|
|||
| G | .995 (.99, .99) | 2.3 | .991 (.98, .99) | 1.3 | 0.01 |
| TS | .991 (.98, .99) | 3.5 | .985 (.96, .99) | 2.4 | NS |
| T | .994 (.99, .99) | 4.0 | .987 (.97, .99) | 2.2 | < 0.01 |
| TI | .995 (.99, .99) | 3.3 | .982 (.95, .99) | 1.6 | < 0.01 |
| I | .993 (.98, .99) | 2.8 | .987 (.97, .99) | 1.7 | NS |
| NI | .990 (.98, .99) | 4.2 | .987 (.97, .99) | 2.5 | 0.01 |
| N | .992 (.98, .99) | 5.2 | .968 (.92, .98) | 3.5 | 0.03 |
| NS | .991 (.98, .99) | 4.5 | .993 (.98, .99) | 3.6 | NS |
| S | .990 (.98, .99) | 3.0 | .988 (.97, .99) | 2.7 | NS |
| PMB | .996 (.99, .99) | 6.6 | .976 (.94, .98) | 3.2 | 0.01 |
G = global average; TS = temporal-superior; T = temporal; TI = temporal-inferior; I = inferior; NI = nasal-inferior; N = nasal; NS = nasal-superior; S = superior; PMB = papillomacular bundle; ICC = intraclass correlation coefficient; CI = confidence interval; CV = coefficient of variation; NS = not significant.
Study Eyes
Both the abnormal and normal vision cohorts demonstrated an increase in coefficient of variation measures from visit 1 to visit 2 in all sectors. In the abnormal vision cohort, the coefficient of variation increase reached statistical significance for the global, temporal-superior, nasal-inferior, nasal superior and superior sectors (P < 0.005, for all comparisons). The normal vision cohort also demonstrated an increase in coefficient of variation from visit 1 to visit 2 in all sectors and reached statistical significance for the global, temporal-superior, temporal, inferior and nasal sectors (P < 0.005, for all comparisons).
Regression Analysis
The linear regression model demonstrated that the magnitude of visual acuity loss (i.e., logMAR difference from normal) was the primary predictor of global coefficient of variation (P = .009) whereas the other clinical variables (i.e., patient age and tumor location) did not significantly contribute to the model, therefore the abnormal and normal vision cohorts were analyzed separately.
Both age and tumor location (intrinsic tumor vs. extrinsic tumor) failed to demonstrate a statistically significant association with global or sector coefficient of variation in the GEE regression model for abnormal vision cohort, therefore both variables were excluded from the adjusted analysis. The magnitude of visual acuity loss (i.e., logMAR difference from normal) was significantly associated with the global (β = 0.026, P < .01) and temporal sector coefficient of variation (β = 0.099, P < .01).
The normal vision cohort failed to demonstrate a significant association between tumor location (intrinsic tumor vs. healthy/unaffected) and coefficient of variation measures in both unadjusted and adjusted analysis and was subsequently excluded. Older age was significantly associated with a higher coefficient of variation in the global (β = 0.001, P = .004) and superior sector (β = 0.003, P= .01), but not the nasal, inferior and temporal sectors (P > 0.05 for all comparisons).
DISCUSSION
Current generation SD-OCT devices are now able to provide a highly reproducible, objective measurement (i.e., circumpapillary RNFL) of the structural integrity of the anterior visual pathway.9–11,13–15,18–22 The addition of eye tracking software can now accommodate for eye movements and provide accurate image alignment during subsequent image acquisition, and thus is believed to improve reproducibility. We report good intra- and intervisit reproducibility in children with and without vision loss using the eye-tracking technology.
In our study, the intra- and intervisit coefficient of variation results demonstrated small, but statistically significant differences between subjects with and without vision loss in clinically important regions such as the global, temporal and temporal-inferior sectors. While all coefficient of variation results were below 5% in these regions for both cohorts, indicating good reproducibility, understanding the influence of vision loss on intra- and intervisit variability is important. In the abnormal vision group, the regression analysis revealed that subjects with greater visual acuity loss demonstrated higher coefficient of variation values, indicative of more variability, in the global and temporal sectors. The papillomacular bundle measures demonstrated the highest coefficient of variation for almost all comparisons, likely due to it being the thinnest section thereby making it more susceptible to differences in segmentation and movement artifacts. Slight changes in the papillomacular bundle thickness may cause large deviations in its coefficient of variation values. Therefore, clinicians should be cautious when interpreting relatively small changes in papillomacular bundle thickness.
Our intra- and intervisit coefficient of variation values in children with normal vision appear to be comparable to other investigator’s healthy control subjects who were imaged using the same SD-OCT with eye tracking.11,13,14,23 However, our subjects with abnormal vision demonstrated higher intra- and intervisit coefficient of variation values compared to adult and pediatric subjects with glaucoma.11,13 The discrepancy between studies could potentially be due to differences in the amount of RNFL loss. In the study by Ghasia and colleagues,11 their pediatric glaucoma/glaucoma suspect patients had an average global RNFL of 98 microns—much higher than our subjects with abnormal vision whose averaged 63 microns. The adult subjects with glaucoma in the study by Langenegger and colleagues13 reported the average global RNFL thickness closer to, but still higher than our subjects (71 versus 63 microns, respectively). Interestingly, another study reported that the magnitude of RNFL loss did not correlate with intervisit variability in adults with glaucoma, despite having a similar average global RNFL (i.e., 65 microns) as our subjects.23 The discrepancy between these studies and ours suggests that other clinical or technical factors can potentially influence intervisit variability.
Differences in study design may explain the variability of reproducibility results reported by investigators using the Spectralis SD-OCT.11,13,14,23 Specifically, many investigators simply have the patient reposition themselves, restart the device, lean back away from the camera or take short breaks between scans—all which are being performed on the same day.13,23 When SD-OCT images are acquired on different days, our subjects as well as the pediatric healthy controls reported by Ghasia et al,11 demonstrated an increased coefficient of variation. Serbecic et al.,14 performed follow up SD-OCT scans using eye-tracking in healthy controls on separate days and demonstrated exceptionally good coefficient of variation values (i.e., less than 1%) for all quadrants except the temporal. In our opinion, a more accurate and clinically relevant assessment of SD-OCT reproducibility occurs when imaging sessions occur on different days.
Imaging children as compared to adults may also influence reproducibility results. Since very few studies have examined the reproducibility of time-domain OCT or SD-OCT in children,11,24–26 it is difficult to determine which factors specific to children may contribute to the increased intervisit coefficient of variation. Surprisingly, our subjects with normal vision demonstrated a statistically significant positive correlation between coefficient of variation and age. We can only speculate as to why teenagers demonstrated higher coefficient of variation measures than younger children. The relationship between age and coefficient of variation was not significant in both the unadjusted and adjusted regression analysis of subjects with abnormal vision, suggesting that either the results in the normal vision group are erroneous or that the impact of vision loss obscured the influence of age. Nonetheless, the faster acquisition speed of SD-OCT and the ability of the eye-tracking feature to accommodate for eye movements and co-register subsequently acquired images to a reference scan are especially helpful when imaging uncooperative children.
A number of study limitations should be considered when interpreting our results. While our inclusion criteria required subjects to demonstrate clinical and radiographic stability, it is possible that some subjects may have experienced a subclinical decline in RNFL thickness between visits, thereby influencing the reproducibility measures. Arguing against that concern is the fact that the RNFL thickness measures for both cohorts did not significantly change nor show a trend downwards between visits (see Table 2). Secondly, we defined our abnormal vision cohort as subjects with visual acuity loss and or visual field loss. We suspect that, similar to the magnitude of visual acuity loss, the magnitude of visual field loss also contributes to the reproducibility measures. Due to a wide range of ages studied and the different visual field techniques used, we did not attempt to quantify the visual field loss and determine if it too impacts coefficient of variation and intraclass correlation coefficient values between visits. Lastly, we acquired a minimum of 3 acceptable scans at the initial visit in order to assess intra-visit variability as well as choose a high quality reference image. Only 1 acceptable scan was required during the follow up visit since it was being acquired and coregistered to the designated reference image from visit 1. While the difference in number of scans acquired between visits could influence the variance measures, acquiring 1 scan at the follow up visit is most reflective of clinical practice.
Before SD-OCT results can be used to make treatment decisions, additional research must elucidate the temporal relationship between declining vision and decreasing RNFL thickness. This will require an improved understanding of disease mechanisms and the natural history of RNFL changes after injury. Until further evidence based studies are published, clinicians should not use RNFL thickness changes to make treatment decisions, especially in patients who are clinically stable.
In conclusion, our study demonstrated that SD-OCT acquired using the eye tracking feature in young children with non-glaucomatous optic neuropathy has excellent intervisit reproducibility of RNFL measures. When assessing longitudinal changes in RNFL, the variability between visits significantly increases in the average global and temporal quadrant, as well as in subjects with more profound visual acuity loss.
Current generation spectral-domain optical coherence tomography (SD-OCT) devices include an eye tracking feature to reduce eye movement artifact as well as decrease measurement variability between visits. The reproducibility of SD-OCT circumpapillary retinal nerve fiber layer (RNFL) measures has not been well studied in children with optic neuropathy—a population that could benefit from using eye tracking. We demonstrated very good intra- and intervisit reproducibility of SD-OCT RNFL measurements in children with non-glaucomatous optic neuropathy, although those with severe vision loss demonstrated greater intervisit variability.
Acknowledgments
Funding/Support: This article was supported by the Gill Fellowship Program at The George Washington University School of Medicine (RDR), grants from the National Eye Institute/National Institutes of Health, Bethesda, Maryland (K23-EY022673, RAA), the National Institutes of Health/National Eye Institute Pediatric Research Loan repayment program (RAA), and the Gilbert Family Neurofibromatosis Institute, Washington, DC (RAA, RJP).
Other Acknowledgements: none
Biography
Ms. Raneem Rajjoub completed her Bachelor of Arts in Psychology at the George Washington University. Ms. Rajjoub is currently a second year medical student studying at the George Washington University School of Medicine and Health Sciences.
Footnotes
Financial Disclosures: None
Contribution of Authors: Design of the study (RDR, CTH, RJP, RAA), Conduct of the study (RDR, CTH, RAA); Collection, management, analysis and interpretation of the data (RAA, RDR, CTH, RJP, RAA); preparation, approval, and review of the manuscript (RDR, CTH, RJP, RAA).
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References
- 1.Kotowski J, Wollstein G, Ishikawa H, Schuman JS. Imaging of the optic nerve and retinal nerve fiber layer: An essential part of glaucoma diagnosis and monitoring. Surv Ophthalmol. 2014;59(4):458–467. doi: 10.1016/j.survophthal.2013.04.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Danesh-Meyer HV, Papchenko T, Savino PJ, Law A, Evans J, Gamble GD. In vivo retinal nerve fiber layer thickness measured by optical coherence tomography predicts visual recovery after surgery for parachiasmal tumors. Invest Ophthalmol Vis Sci. 2008;49(5):1879–1885. doi: 10.1167/iovs.07-1127. [DOI] [PubMed] [Google Scholar]
- 3.Danesh-Meyer HV, Carroll SC, Foroozan R, et al. Relationship between retinal nerve fiber layer and visual field sensitivity as measured by optical coherence tomography in chiasmal compression. Invest Ophthalmol Vis Sci. 2006;47(11):4827–4835. doi: 10.1167/iovs.06-0327. [DOI] [PubMed] [Google Scholar]
- 4.Aggarwal D, Tan O, Huang D, Sadun AA. Patterns of ganglion cell complex and nerve fiber layer loss in nonarteritic ischemic optic neuropathy by Fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53(8):4539–4545. doi: 10.1167/iovs.11-9300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Barboni P, Savini G, Valentino ML, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology. 2005;112(1):120–126. doi: 10.1016/j.ophtha.2004.06.034. [DOI] [PubMed] [Google Scholar]
- 6.Savini G, Barboni P, Valentino ML, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations. Ophthalmology. 2005;112(1):127–131. doi: 10.1016/j.ophtha.2004.09.033. [DOI] [PubMed] [Google Scholar]
- 7.Galetta KM, Calabresi PA, Frohman EM, Balcer LJ. Optical coherence tomography (OCT): imaging the visual pathway as a model for neurodegeneration. Neurotherapeutics. 2011;8(1):117–132. doi: 10.1007/s13311-010-0005-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kim JS, Ishikawa H, Gabriele ML, et al. Retinal nerve fiber layer thickness measurement comparability between time domain optical coherence tomography (OCT) and spectral domain OCT. Invest Ophthalmol Vis Sci. 2010;51(2):896–902. doi: 10.1167/iovs.09-4110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Kim JS, Ishikawa H, Sung KR, et al. Retinal nerve fibre layer thickness measurement reproducibility improved with spectral domain optical coherence tomography. Br J Ophthalmol. 2009;93(8):1057–1063. doi: 10.1136/bjo.2009.157875. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Leung CK, Cheung CY, Weinreb RN, et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a variability and diagnostic performance study. Ophthalmology. 2009;116(7):1257–1263. doi: 10.1016/j.ophtha.2009.04.013. [DOI] [PubMed] [Google Scholar]
- 11.Ghasia FF, El-Dairi M, Freedman SF, Rajani A, Asrani S. Reproducibility of Spectral-Domain Optical Coherence Tomography Measurements in Adult and Pediatric Glaucoma. J Glaucoma. doi: 10.1097/IJG.0b013e31829521db. in press. [DOI] [PubMed] [Google Scholar]
- 12.Menke MN, Dabov S, Knecht P, Sturm V. Reproducibility of retinal thickness measurements in healthy subjects using spectralis optical coherence tomography. Am J Ophthalmol. 2009;147(3):467–472. doi: 10.1016/j.ajo.2008.09.005. [DOI] [PubMed] [Google Scholar]
- 13.Langenegger SJ, Funk J, Toteberg-Harms M. Reproducibility of retinal nerve fiber layer thickness measurements using the eye tracker and the retest function of Spectralis SD-OCT in glaucomatous and healthy control eyes. Invest Ophthalmol Vis Sci. 2011;52(6):3338–3344. doi: 10.1167/iovs.10-6611. [DOI] [PubMed] [Google Scholar]
- 14.Serbecic N, Beutelspacher SC, Aboul-Enein FC, Kircher K, Reitner A, Schmidt-Erfurth U. Reproducibility of high-resolution optical coherence tomography measurements of the nerve fibre layer with the new Heidelberg Spectralis optical coherence tomography. Br J Ophthalmol. 2011;95(6):804–810. doi: 10.1136/bjo.2010.186221. [DOI] [PubMed] [Google Scholar]
- 15.Costa AM, Costa RA, Melo LA, Jr, Calucci D, Orefice JL, Cronemberger S. Influence of the eye-tracking-based follow-up function in retinal nerve fiber layer thickness using fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2013;54(3):1958–1963. doi: 10.1167/iovs.12-10884. [DOI] [PubMed] [Google Scholar]
- 16.Avery RA, Bouffet E, Packer RJ, Reginald A. Feasibility and comparison of visual acuity testing methods in children with neurofibromatosis type 1 and/or optic pathway gliomas. Invest Ophthalmol Vis Sci. 2013;54(2):1034–1038. doi: 10.1167/iovs.12-11385. [DOI] [PubMed] [Google Scholar]
- 17.Avery RA, Hwang EI, Ishikawa H, et al. Handheld optical coherence tomography during sedation in young children with optic pathway gliomas. JAMA Ophthalmology. 2014;132(3):265–271. doi: 10.1001/jamaophthalmol.2013.7649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Menke MN, Knecht P, Sturm V, Dabov S, Funk J. Reproducibility of nerve fiber layer thickness measurements using 3D fourier-domain OCT. Invest Ophthalmol Vis Sci. 2008;49(12):5386–5391. doi: 10.1167/iovs.07-1435. [DOI] [PubMed] [Google Scholar]
- 19.Mwanza JC, Chang RT, Budenz DL, et al. Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Invest Ophthalmol Vis Sci. 2010;51(11):5724–5730. doi: 10.1167/iovs.10-5222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Garas A, Vargha P, Hollo G. Reproducibility of retinal nerve fiber layer and macular thickness measurement with the RTVue-100 optical coherence tomograph. Ophthalmology. 2010;117(4):738–746. doi: 10.1016/j.ophtha.2009.08.039. [DOI] [PubMed] [Google Scholar]
- 21.Syc SB, Warner CV, Hiremath GS, et al. Reproducibility of high-resolution optical coherence tomography in multiple sclerosis. Mult Scler. 2010;16(7):829–839. doi: 10.1177/1352458510371640. [DOI] [PubMed] [Google Scholar]
- 22.Gonzalez-Garcia AO, Vizzeri G, Bowd C, Medeiros FA, Zangwill LM, Weinreb RN. Reproducibility of RTVue retinal nerve fiber layer thickness and optic disc measurements and agreement with Stratus optical coherence tomography measurements. Am J Ophthalmol. 2009;147(6):1067–1074. doi: 10.1016/j.ajo.2008.12.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Wu H, de Boer JF, Chen TC. Reproducibility of retinal nerve fiber layer thickness measurements using spectral domain optical coherence tomography. J Glaucoma. 2011;20(8):470–476. doi: 10.1097/IJG.0b013e3181f3eb64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Altemir I, Pueyo V, Elia N, Polo V, Larrosa JM, Oros D. Reproducibility of optical coherence tomography measurements in children. Am J Ophthalmol. 2013;155(1):171–176. doi: 10.1016/j.ajo.2012.06.012. [DOI] [PubMed] [Google Scholar]
- 25.Avery RA, Cnaan A, Schuman JS, et al. Reproducibility of circumpapillary retinal nerve fiber layer measurements using handheld optical coherence tomography in sedated children. Am J Ophthalmol. 2014;158(4):780–787. doi: 10.1016/j.ajo.2014.06.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Prakalapakorn SG, Freedman SF, Lokhnygina Y, et al. Longitudinal reproducibility of optical coherence tomography measurements in children. J AAPOS. 2012;16(6):523–528. doi: 10.1016/j.jaapos.2012.08.011. [DOI] [PMC free article] [PubMed] [Google Scholar]