May 2008
Volume 49, Issue 5
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Anatomy and Pathology/Oncology  |   May 2008
Overlapping of Retinal Nerve Fibers in the Horizontal Plane
Author Affiliations
  • Jin Wook Jeoung
    From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;
  • Tae-Woo Kim
    From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;
    Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea; and the
  • Kyung Bok Kang
    Kong Eye Center, Seoul, Korea.
  • Jong Joo Lee
    From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;
  • Ki Ho Park
    From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;
  • Dong Myung Kim
    From the Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea;
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1753-1757. doi:10.1167/iovs.07-1408
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      Jin Wook Jeoung, Tae-Woo Kim, Kyung Bok Kang, Jong Joo Lee, Ki Ho Park, Dong Myung Kim; Overlapping of Retinal Nerve Fibers in the Horizontal Plane. Invest. Ophthalmol. Vis. Sci. 2008;49(5):1753-1757. doi: 10.1167/iovs.07-1408.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To describe a previously unreported overlapping trajectory of retinal nerve fibers over other retinal nerve fibers in the horizontal plane, and to report on the incidence of this anatomic variation.

methods. This study included 1410 eyes of 1018 subjects with one or more localized retinal nerve fiber layer (RNFL) defects detected by using red-free fundus photography. All red-free fundus photographs were reviewed, and eyes with overlapping retinal nerve fibers in the horizontal plane were selected. Overlapping nerve fibers were defined as fibers with a trajectory nonparallel to the adjacent fibers, according to the red-free fundus photographs.

results. Overlapping of retinal nerve fibers was detected in 33 eyes of 30 subjects. The estimated incidence of overlapping retinal nerve fibers was 2.3% (95% confidence interval [CI], 1.6%–3.1%) per eye and 2.9% (95% CI, 1.9%–4.0%) per subject. For all 33 eyes, a localized arcuate RNFL defect was observed in the inferotemporal quadrant and was partially overlapped by relatively straight nerve fibers. Optical coherence tomography confirmed the overlying retinal nerve fibers and showed a decrease in the RNFL thickness at the corresponding location of the adjacent RNFL defect.

conclusions. Overlapping retinal nerve fibers were identified in the horizontal plane in 33 eyes. In those eyes, the localized RNFL defect was partially obscured by the overlying nerve fibers, leading to an unusual appearance of the RNFL defect. Awareness of this anatomic variation may help clinicians to avoid overlooking RNFL defects that are obscured by overlapping bundles.

Ganglion cell axons converge on the optic nerve in an organized pattern. Axons from the nasal, superior, and inferior retina have relatively straight courses. Those arising from the temporal retina arc, above or below the macular region, enter the superior temporal and inferior temporal portions, respectively, of the optic nerve in an arcuate pattern. Those arising in the macular region pass directly to the temporal edge of the optic nerve, forming the papillomacular bundle. 1  
Axon depth within the retinal nerve fiber layer (RNFL) is based on the original location of the ganglion cell nucleus. Axons from the peripheral retina tend to run deeper in the nerve fiber layer and enter the outer edge of the neuroretinal rim of the optic nerve. Those from ganglion cells located closer to the posterior pole are more superficial in the nerve fiber layer and enter the optic nerve toward the inner edge of the neuroretinal rim. 2 Thus, there is overlapping of axons in the axial plane. However, in the horizontal plane, it is generally considered that nerve fibers run parallel without overlapping in their trajectory from the retina to the optic nerve, 3 4 as depicted in many glaucoma textbooks (for example, Refs. 5 6 7 ). 
The present study describes an overlapping trajectory of retinal nerve fibers in the horizontal plane as they approach the optic nerve head. To the best of our knowledge, such an overlapping trajectory of retinal nerve fibers has not been described. 
Materials and Methods
Eyes with one or more localized RNFL defects detected by red-free fundus photography were consecutively enrolled from the database of patients who were examined for glaucoma between January 2006 and March 2007 at the Seoul National University Bundang Hospital. A localized RNFL defect was defined as a well-outlined, dark, wedge-shaped area in the bright striated pattern of the surrounding healthy RNFL with its tip touching the optic disc border. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Seoul National University Bundang Hospital. 
Before the study, all patients underwent a complete ophthalmic examination, including visual acuity, refraction, central corneal thickness, slit lamp biomicroscopy, gonioscopy, Goldmann applanation tonometry, dilated stereoscopic examination of the optic disc, red-free fundus photography, optical coherence tomography, and standard automated perimetry. 
Red-free fundus photographs of the included patients were reviewed, and eyes with overlapping retinal nerve fibers in the horizontal plane were selected. Overlapping nerve fibers were defined if red-free fundus photography revealed the RNFL defect covered with overlying nerve fiber bundles having a trajectory nonparallel to the adjacent fibers. Eyes with a history of intraocular surgery other than uncomplicated cataract surgery, secondary causes for elevated intraocular pressure (e.g., corticosteroid use, iridocyclitis, or trauma), and other retinal diseases that might affect the interpretation of red-free fundus photographs were excluded. 
Medical records of the selected subjects with overlapping RNFL were reviewed and data regarding gender, age, laterality, refractive error, baseline intraocular pressure without ocular hypotensive medication, and central corneal thickness were collected. 
Red-Free Fundus Photography
Red-free fundus photographs were acquired with a digital camera (model EOS D60; Canon, Tochigiken, Japan) after maximum pupil dilation. Sixty degree, wide-angle views of the optic disc, carefully focused on the retina using the built-in split-line focusing device and centered between the fovea and the optic disc were obtained and reviewed on an LCD monitor. 8 9  
Optical Coherence Tomography
Eyes were measured with the peripapillary Fast RNFL program of the Stratus OCT (Carl-Zeiss Meditec, Dublin, CA) after a pupillary dilation to a minimum diameter of 5 mm. The imaging lens was positioned 1 cm from the eye to be examined and adjusted independently until the retina was in focus. The internal fixation target was used owing to its higher reproducibility. 10 Data were analyzed with the Stratus system software (ver. 4.0). To measure the thickness of the nerve fiber layer at the location of interest, optical coherence tomography in the linear scanning mode was performed, in addition to the routine fast RNFL program in some cases in which the overlapping nerve fibers were observed in red-free fundus photographs. 
Visual Field Testing
Visual field analysis was performed with the Swedish Interactive Threshold Algorithm (SITA) standard of the visual field perimeter (Humphrey Field Analyzer II 750; Carl-Zeiss Meditec, Dublin, CA) with the central full-threshold program 24-2. Only reliable visual field results were included (i.e., fixation losses, false positives, and false negatives all ≤25%). 
Results
The study involved 1435 eyes of 1034 subjects with one or more localized RNFL defects detected using red-free fundus photography. Of those, 25 eyes were excluded due to a history of vitrectomy (23) or uveitis (2), which resulted in a final sample of 1410 eyes of 1018 subjects. 
Of the 1410 eyes, overlapping of retinal nerve fibers was detected in 33 eyes of 30 subjects. The estimated prevalence of overlapping retinal nerve fibers was 2.3% (95% confidence interval [CI], 1.6%–3.1%) per eye and 2.9% (95% CI, 1.9%–4.0%) per subject. Three subjects had overlapping retinal nerve fibers in both eyes. The mean age (years) ± SD of the subjects was 51.8 ± 11.0 years (range, 33–74 years), and there were 15 men and 15 women. Twenty-eight (84.8%) eyes were myopic, and the mean refractive error was −1.00 ± 1.70 D (range, −4.75 to +2.00 D; Table 1 ). Univariate analysis found that the frequency of overlapping nerve fibers was not associated with age (P = 0.13; odds ratio [OR], 0.98; 95% CI, 0.95–1.01), gender (P = 0.30; OR, 1.51; 95% CI, 0.70–3.24), refractive error (P = 0.41; OR, 0.94; 95% CI, 0.80–1.09), intraocular pressure without medication (P = 0.67; OR, 1.03; 95% CI, 0.90–1.18), or central corneal thickness (P = 0.55; OR, 1.00; 95% CI, 0.99–1.02). 
For all 33 eyes, overlapping retinal nerve fibers were detected only in the inferotemporal quadrant. They were relatively straight and overlying the adjacent arcuate RNFL defect (Figs. 1 2 3) . Optical coherence tomography (OCT) confirmed the overlying nerve fibers and the measured RNFL thickness was decreased in the corresponding location of the RNFL defect (Figs. 1B 1C) . The circular 360° OCT scans on the peripapillary RNFL also demonstrated a decrease in the RNFL thickness at the corresponding location of the RNFL defect (Fig. 1D)
The RNFL defect associated with overlapping retinal nerve fibers could be divided into two subgroups according to its appearance. In the first subgroup (12 eyes of 12 subjects), the arcuate RNFL defect was divided by the overlapping bundles running over the defect. In that subgroup, red-free fundus photography revealed both a crescent-shaped and a horn-shaped RNFL defect (Figs. 2A 2B 2E 2F 3B) . In the second subgroup (21 eyes of 19 subjects), the RNFL defect was partially obscured by relatively straight nerve fibers. The RNFL defect appeared crescent-shaped in this subgroup (Figs. 2C 2D 3A)
Discussion
The distribution of axons within the RNFL has been relatively well identified. Axons from ganglion cells located temporal to the fovea are divided into a superior and inferior arcade by the horizontal raphe extending from the macula into the temporal periphery of the retina. 11 Along their trajectory, retinal nerve fibers are believed not to overlap in the horizontal plane, thereby preserving a retinotopic organization. However, the present study of 1410 eyes found that 33 had overlapping retinal nerve fibers in the horizontal plane. We believe this finding has anatomic and clinical significance. 
The RNFL contains retinal ganglion cell axons covered by astrocytes and bundled by processes of Müller cells. Retinal nerve fibers are ophthalmoscopically visible as bright and fine striations in the inner retinal layer that fan off the optic disc into the retinal periphery. 12 13 14 All striations of interest in the present study had this fanning-off appearance according to red-free fundus photography, indicating they were retinal nerve fibers. Moreover, OCT showed that the tissues observed in red-free photographs were located in the RFNL, further indicating that these fibers were a deviant set of nerve fiber bundles. 
Overlapping RNFL was observed only in the inferotemporal quadrant. The reasons underlying this exclusivity are presently unknown. Given that retinal nerve fiber bundles are most abundant in the inferior temporal area, 15 we can speculate that some fibers may have undergone an aberrant trajectory during development due to crowding of the bundles. 
Studies have shown that localized RNFL defects can be detected ophthalmoscopically if more than 50% of the thickness of the RNFL is lost. 16 It is suggested that retinal ganglion cells located in the deep and middle layer of the RNFL are mainly involved in the early period of disease. 14 Our cases are in line with this suggestion by showing damage to the deep layer of the RNFL, with the superficial overlying layer left undamaged. 
The present identification of overlapping RNFL may have clinical significance. Using red-free photography, clinicians usually look for a defect that is geometrically complete, either arcuate or sectoral depending on the location. However, in patients with overlapping retinal nerve fibers, the RNFL defect may present as an unusual shape, being separated or partially obscured by the overlying bundles. Such a presentation may lead clinicians to interpret the defect as an artifact, particularly in early RNFL defect cases. 
The present study of overlapping nerve fibers involved only eyes with localized RNFL defects. In our experience, overlapping nerve fibers are recognizable only when associated with RNFL defects that provide background contrast. Thus, the incidence shown in the present study is a rough estimate and does not represent the exact incidence in the general population. It is possible that the incidence calculated in this study was an underestimate, because previously existing overlapping nerve fibers may have disappeared in some eyes as the RNFL atrophy progressed. Thus, the incidence of this anatomic variation in the general population remains to be explored. 
In summary, the present study details 33 cases of overlying trajectory of retinal nerve fibers in eyes with RNFL defects. In these cases, localized arcuate RNFL defects were partially obscured by the overlying nerve fibers. Awareness of this anatomic variation may help clinicians avoid overlooking RNFL defects that are obscured by overlapping bundles. 
 
Table 1.
 
Demographic and Clinical Characteristics for Eyes with Overlapping Retinal Nerve Fibers in the Horizontal Plane
Table 1.
 
Demographic and Clinical Characteristics for Eyes with Overlapping Retinal Nerve Fibers in the Horizontal Plane
Characteristic Descriptive Statistic (n = 33)
Age (y) 51.8 ± 11.0
Male/female (n) 15/15
Eye involvement of overlapping retinal nerve fibers, n (%)
 Right eye 16 (53)
 Left eye 11 (37)
 Both eyes 3 (10)
Spherical equivalent (D) −1.00 ± 1.70
Intraocular pressure without medication (mm Hg) 15.2 ± 2.8
Central corneal thickness (μm)* 558.1 ± 35.9
Parameters of Humphrey C24-2 SITA-Standard
 Mean deviation (dB) −0.09 ± 2.95
 Pattern standard deviation (dB) 2.55 ± 2.49
Location of RNFL defect, n (%)
 Superotemporal and inferotemporal 9 (27)
 Superotemporal only 0 (0)
 Inferotemporal only 24 (73)
 Nasal 0 (0)
Location of overlapping retinal nerve fibers, n (%)
 Superotemporal and inferotemporal 0 (0)
 Superotemporal only 0 (0)
 Inferotemporal only 33 (100)
 Nasal 0 (0)
Figure 1.
 
Red-free fundus photograph and OCT results in case 4. (A) An arcuate RNFL defect (arrows) in the inferotemporal quadrant was partially obscured by overlapping nerve fibers (arrowheads). (B, C) OCT confirmed the overlying retinal nerve fibers (arrowhead) and showed a decrease in the RNFL thickness (arrows) at the corresponding location of the RNFL defect. (D) The circular 360° OCT scans on the peripapillary RNFL demonstrated a decrease in the RNFL thickness at the corresponding location of the RNFL defect.
Figure 1.
 
Red-free fundus photograph and OCT results in case 4. (A) An arcuate RNFL defect (arrows) in the inferotemporal quadrant was partially obscured by overlapping nerve fibers (arrowheads). (B, C) OCT confirmed the overlying retinal nerve fibers (arrowhead) and showed a decrease in the RNFL thickness (arrows) at the corresponding location of the RNFL defect. (D) The circular 360° OCT scans on the peripapillary RNFL demonstrated a decrease in the RNFL thickness at the corresponding location of the RNFL defect.
Figure 2.
 
Red-free fundus photographs for cases 6 (A), 7 (B), 9 (C), 18 (D), 22 (E), and 27 (F). For each case, an arcuate retinal nerve fiber layer (RNFL) defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected. (A, B, E, F) Red-free fundus photography revealed both a crescent-shaped and a horn-shaped defect in the inferotemporal quadrant. It appeared that the arcuate RNFL defect was divided by the overlapping bundles running over the defect. (C, D) A localized arcuate RNFL defect was observed in the inferotemporal quadrant and was partially overlapped by relatively straight nerve fibers.
Figure 2.
 
Red-free fundus photographs for cases 6 (A), 7 (B), 9 (C), 18 (D), 22 (E), and 27 (F). For each case, an arcuate retinal nerve fiber layer (RNFL) defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected. (A, B, E, F) Red-free fundus photography revealed both a crescent-shaped and a horn-shaped defect in the inferotemporal quadrant. It appeared that the arcuate RNFL defect was divided by the overlapping bundles running over the defect. (C, D) A localized arcuate RNFL defect was observed in the inferotemporal quadrant and was partially overlapped by relatively straight nerve fibers.
Figure 3.
 
Red-free fundus photographs of the right (A) and left (B) eyes in case 29. An RNFL defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected in both eyes.
Figure 3.
 
Red-free fundus photographs of the right (A) and left (B) eyes in case 29. An RNFL defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected in both eyes.
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Figure 1.
 
Red-free fundus photograph and OCT results in case 4. (A) An arcuate RNFL defect (arrows) in the inferotemporal quadrant was partially obscured by overlapping nerve fibers (arrowheads). (B, C) OCT confirmed the overlying retinal nerve fibers (arrowhead) and showed a decrease in the RNFL thickness (arrows) at the corresponding location of the RNFL defect. (D) The circular 360° OCT scans on the peripapillary RNFL demonstrated a decrease in the RNFL thickness at the corresponding location of the RNFL defect.
Figure 1.
 
Red-free fundus photograph and OCT results in case 4. (A) An arcuate RNFL defect (arrows) in the inferotemporal quadrant was partially obscured by overlapping nerve fibers (arrowheads). (B, C) OCT confirmed the overlying retinal nerve fibers (arrowhead) and showed a decrease in the RNFL thickness (arrows) at the corresponding location of the RNFL defect. (D) The circular 360° OCT scans on the peripapillary RNFL demonstrated a decrease in the RNFL thickness at the corresponding location of the RNFL defect.
Figure 2.
 
Red-free fundus photographs for cases 6 (A), 7 (B), 9 (C), 18 (D), 22 (E), and 27 (F). For each case, an arcuate retinal nerve fiber layer (RNFL) defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected. (A, B, E, F) Red-free fundus photography revealed both a crescent-shaped and a horn-shaped defect in the inferotemporal quadrant. It appeared that the arcuate RNFL defect was divided by the overlapping bundles running over the defect. (C, D) A localized arcuate RNFL defect was observed in the inferotemporal quadrant and was partially overlapped by relatively straight nerve fibers.
Figure 2.
 
Red-free fundus photographs for cases 6 (A), 7 (B), 9 (C), 18 (D), 22 (E), and 27 (F). For each case, an arcuate retinal nerve fiber layer (RNFL) defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected. (A, B, E, F) Red-free fundus photography revealed both a crescent-shaped and a horn-shaped defect in the inferotemporal quadrant. It appeared that the arcuate RNFL defect was divided by the overlapping bundles running over the defect. (C, D) A localized arcuate RNFL defect was observed in the inferotemporal quadrant and was partially overlapped by relatively straight nerve fibers.
Figure 3.
 
Red-free fundus photographs of the right (A) and left (B) eyes in case 29. An RNFL defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected in both eyes.
Figure 3.
 
Red-free fundus photographs of the right (A) and left (B) eyes in case 29. An RNFL defect (arrows) and overlapping nerve fiber bundles (arrowheads) were detected in both eyes.
Table 1.
 
Demographic and Clinical Characteristics for Eyes with Overlapping Retinal Nerve Fibers in the Horizontal Plane
Table 1.
 
Demographic and Clinical Characteristics for Eyes with Overlapping Retinal Nerve Fibers in the Horizontal Plane
Characteristic Descriptive Statistic (n = 33)
Age (y) 51.8 ± 11.0
Male/female (n) 15/15
Eye involvement of overlapping retinal nerve fibers, n (%)
 Right eye 16 (53)
 Left eye 11 (37)
 Both eyes 3 (10)
Spherical equivalent (D) −1.00 ± 1.70
Intraocular pressure without medication (mm Hg) 15.2 ± 2.8
Central corneal thickness (μm)* 558.1 ± 35.9
Parameters of Humphrey C24-2 SITA-Standard
 Mean deviation (dB) −0.09 ± 2.95
 Pattern standard deviation (dB) 2.55 ± 2.49
Location of RNFL defect, n (%)
 Superotemporal and inferotemporal 9 (27)
 Superotemporal only 0 (0)
 Inferotemporal only 24 (73)
 Nasal 0 (0)
Location of overlapping retinal nerve fibers, n (%)
 Superotemporal and inferotemporal 0 (0)
 Superotemporal only 0 (0)
 Inferotemporal only 33 (100)
 Nasal 0 (0)
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