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The Topography of the Optic Nerve and Retina: What’s Hot

Joel S. Schuman, MD

 

1)     Optic Nerve Imaging: Confocal Scanning Laser Ophthalmoscopy

a)     An illuminating laser is scanned across the retina along with the detector system.  Only a small spot is illuminated, and light can only enter the detector through a pinhole aperture.  This permits only light from the region of interest to reach the detector; all other light is blocked.  Reflections from out of focus planes are blocked by the pinhole, allowing optical sectioning of the tissue in coronal planes.

 

b)     The commercially available confocal laser scanning ophthalmoscope, the Heidelberg Retinal Tomograph (HRT II, Heidelberg Engineering, GmbH, Heidelberg, Germany) uses a diode laser for retinal and ONH illumination.

 

c)      The HRT II each produces a series of 16-64 coronal planes through the ONH.  The number of planes varies dependent on the scan depth.

 

d)     Minimum pupil size is 1 mm; image acquisition time is 0.9-1.5 seconds.

e)     The HRT II produces an excellent map of the optic nerve, delineating the cup and disc, as well as the sloping area from neuroretinal rim to cup.  The printout provides numerous parameters which can be followed.  The most valuable of these include Cup Shape Measure (the more negative the better), Rim Area and Rim Volume (the higher the better), as well as several NFL height measures.  Valuable discriminant parameters are also calculated by the software.  The most clinically useful analysis uses the Moorfield’s Algorithm, which evaluates the ONH by sector and classifies each sector and the overall ONH as within normal limits, borderline or outside normal limits.

 

f)        Patients can be followed sequentially using software to detect change over time.

g)     Limitations of CSLO

i)        Variability of measurements is <100 µm in vivo.

ii)      Because the axial resolution is only 300 µm cross‑sectional imaging of the fundus and retinal nerve fiber layer (RNFL) with confocal scanning laser ophthalmoscopes is not feasible.

iii)    Due to limited depth resolution, the substructure of the retina cannot be resolved, and only mean depth measurements can be made accurately.  Nerve fiber layer thickness cannot be determined with precision, as the posterior margin of the NFL is not easily detected using this instrumentation; however, NFL surface contour is mapped.


 

2)     Scanning Laser Polarimetry

a)     Scanning laser polarimetry (SLP) is performed with the GDx (Nerve Fiber Analyzer, NFA, Laser Diagnostic Technologies, Inc., San Diego, CA), and more recently the GDx with a variable corneal compensator (GDx VCC, see (v) below).

i)        Uses birefringence of NFL to change the polarization rotation of light illuminating eye.  NFL thickness is measured from the change in polarization called retaradance.

ii)      Reproducibility of measurements made with the NFA is about 13 µm or better.

iii)    Limitations

(1)   Several assumptions are made in order to calculate NFL thickness using this technique:

(a)   The NFL is the main source of birefringence in the retina.

(b)   Most of the light is reflected from the outer margin of the retina, and therefore, double passes the full thickness of the NFL.

(c)   The birefringence of the NFL is homogeneous.

(2)   There are birefringent structures in the eye other than the NFL, such as the lens and cornea, and their effect on polarized light may change over time, independent of the NFL.

(3)   LASIK and PRK can significantly affect GDx measurements, most likely due to changes in corneal birefringence.

iv)    The GDx device has a large normative database, and several studies have shown concordance between GDx measurements and glaucoma status; however, discrepancies are also found in increasing numbers as use of this unit becomes more prevalent.

v)      The new version of the SLP, the GDx VCC, promises to neutralize anterior segment birefringence actively, by minimizing birefringence detected on macular scanning.  Early reports support the improved discriminating power of this modified device.

 

3)     Optical Coherence Tomography (OCT)

a)     Optical coherence tomography (OCT Carl Zeiss Meditec, Dublin, CA) is a technique for high-resolution cross-sectional optical imaging of ocular structures using light.

 

b)     OCT is a noncontact, noninvasive tomographic imaging technique utilizing short coherence length light to achieve a high resolution of about 8-10 µm with high sensitivity (OCT 3). OCT 1 and OCT 2 have axial resolutions of ~10-15 µm.

 

c)      A superluminescent diode serves as the light source for an interferometer-based fiber-optic system. The light beam is scanned transversely across the eye, analogous to B-mode ultrasound, to produce a cross-sectional image of the tissue of interest, in this case the retina and optic nerve head (ONH).

 

d)     Images

i)        The OCT and video image are displayed in real time, the OCT signal being transmitted to a computer for analysis.

ii)      Image acquisition time is < 1 second.

iii)    512 A-scans are used to create a single standard OCT image.

(1)   There are 256 A-scans in each peripapillary “fast” scan.

(2)   There are 128 A-scans in each optic nerve head or macular “fast” scan.

iv)    The image displayed is a cross-section in false color, with color corresponding to the strength of the reflected signal.

e)     Patterns

i)        Scans can be taken in any geometric pattern. For glaucoma, circular scans around the ONH and linear scans across the ONH have proven most valuable.

ii)      The circular scans around the ONH produce a cylinder of information, which is unfolded and viewed in cross section. A circle diameter of 3.37 mm has proven optimal for NFL assessment in normal and glaucomatous eyes.

iii)    NFL thickness is measured directly from the scan using an automated computer algorithm. NFL and total retinal thickness are summarized by clock hour and by quadrant, as well as by overall mean thickness.

iv)    Unlike ONH analyzers and confocal scanning laser ophthalmoscopes, no reference plane is required to determine NFL thickness, since OCT provides an absolute cross-sectional measurement of retinal substructure from which the NFL thickness is calculated.

f)        Fixation

i)        Fixation is maintained by means of an internal fixation light. A beam is placed in the fovea. The difference in position between that beam and the circle around the ONH is recorded, and the same position is used on all subsequent scans.

g)     Reproducibility of Measurements

i)        Standard deviation of measurements is about 8–10 µm.

h)      Advances

i)        Advances, such as ultrahigh resolution OCT (UHR OCT, not commercially available), provide 2–3 µm resolution.

i)        Limitations

i)        There is no normative database as yet for OCT.

ii)      The technology is young, still in evolution.

iii)    One cannot obtain an OCT image with media opacities such as dense central corneal scarring, moderate to severe posterior subcapsular cataract, or dense vitreous hemorrhage.

j)        Structure and Function

i)        There is good structural and functional correlation in normal and glaucomatous eyes evaluated with OCT and other technologies; OCT may perform better than other structural measures (CSLO, SLP) or functional measures (SAP, SITA, SWAP, FDT).

k)      Normal versus Glaucoma

i)        There is a significant difference in NFL thickness between normal and glaucomatous eyes.

ii)      NFL thickness correlates with visual field defects: thinner inferiorly with superior defects, and thinner superiorly with inferior defects.

iii)    Focal NFL defects are readily seen and quantitated, and they can be followed over time.

iv)    Although there is no relationship between cup-to-disc ratio or neuroretinal rim area and aging, NFL thickness does thin with increasing age.

l)        Macular Thickness and Glaucoma

i)        Ganglion cells are specifically lost in glaucoma.

ii)      The macula is defined anatomically as that region of the retina where the ganglion cell layer is more than one cell thick.

iii)    A ganglion cell body (soma) is 15 microns or more in size.

iv)    A ganglion cell axon is 1–2 microns in size.

v)      Most ganglion cells are in the macula.

vi)    Macular OCT does not sample regions outside macula.

vii)  360 degree circumpapillary scan includes entire retina.

viii) Each axon is thinner than its cell body.

m)   Glaucoma Diagnosis

i)        Retinal nerve fiber layer thickness evaluation

ii)      Macular ganglion cell layer thickness evaluation

n)      Ultrahigh Resolution OCT

i)        New technology for improving the resolution of optical coherence tomography (OCT)

ii)      Allows enhanced imaging of retinal microstructures

iii)    Retinal anatomy and pathology evaluation

iv)    Longitudinal resolution of retinal imaging with OCT is mainly determined by the bandwidth of the low coherence light source used for imaging.

v)      Conventional ophthalmic OCT

(1)   Superluminescent diodes emit low coherence light with a 20–25 nm bandwidth at 830 nm.

(2)   Superluminescent diodes yield a 10–15 μm longitudinal image resolution (OCT 1 or OCT 2), or 8-10 μm with dispersion compensation (OCT 3).

vi)    The resolution determines the performance of OCT retinal imaging and the performance for quantifying the retinal and RNFL thickness.

vii)  This is a novel high-resolution ophthalmic OCT system for improving the longitudinal resolution of OCT by a factor of ~3x

viii) Short pulse Ti:Al2O3 laser

(1)   Pulses less than 7 fs duration

(2)   Bandwidths up to 200 nm at 800 nm center wavelength

ix)    OCT imaging in the eyes of normal volunteers and subjects with eye pathology

(1)   Longitudinal resolutions of less than 3 μm

(2)   Highest OCT resolutions achieved for retinal imaging

x)      Higher longitudinal resolution can contribute to a better visualization of intraretinal structures and pathologies.

xi)    Higher longitudinal resolution can enable increased sensitivity and specificity of retinal and RNFL thickness changes for early diagnosis.


 

REFERENCES

1. American Academy of Ophthalmology. Optic Nerve Head and Nerve Fiber Layer Analysis. Ophthalmology 1999;106:1414-1424.

 

2. Blumenthal EZ, Williams JM, Weinreb RN, Girkin CA, Berry CC, Zangwill LM. Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography. Ophthalmology 2000;107(12):2278-2282.

 

3. Bowd C, Weinreb RN, Williams JM, Zangwill LM. The retinal nerve fiber layer thickness in ocular hypertensive, normal, and glaucomatous eyes with optical coherence tomography. Arch Ophthalmol. 2000;118(1):22-26.

 

4. Bowd C, Zangwill LM, Berry CC, Blumenthal EZ, Vasile C, Sanchez-Galeana C, Bosworth CF, Sample PA, Weinreb RN. Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Invest Ophthalmol Vis Sci, 2001;42(9):1993-2003.

 

5. Drexler W, Morgner U, Ghanta RK, Kärtner FX, Schuman JS, Fujimoto JG. Ultrahigh resolution ophthalmic optical coherence tomography. Nat Med. 2001;7(4):502-507.

 

6. Greaney MJ, Hoffman DC, Garway-Heath DF, Nakla M, Coleman AL, Caprioli J. Comparison of optic nerve imaging methods to distinguish normal eyes from those with glaucoma. Invest Ophthalmol Vis Sci. 2002;43(1):140-145.

 

7. Hoh ST, Greenfield DS, Mistlberger A, Liebmann JM, Ishikawa H, Ritch R. Optical coherence tomography and scanning laser polarimetry in normal, ocular hypertensive, and glaucomatous eyes. Am J Ophthalmol. 2000;129(2):129-135.

 

8. Kim J, Schuman JS. Imaging of the optic nerve head and nerve fiber layer in glaucoma. Ophthalmol Clin North Am. 2000;13(3):383-406.

 

9. Lemij H and Schuman JS, eds. The Shape of Glaucoma. The Netherlands: Kugler Publications; 2000.

 

10. Parisi V, Manni G, Centofanti M, Gandolfi SA, Olzi D, Bucci MG. Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients. Ophthalmology 2001;108(5):905-912.

 

11. Quigley HA, Miller NR, and George T. Clinical evaluation of nerve fiber layer atrophy as an indicator of glaucomatous optic nerve damage. Arch Ophthalmol. 1980;98:1564-1571.

 

12. Schuman JS, Hee MR, Puliafito CA, et al. Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography: a pilot study. Arch Ophthalmol. 1995;113:586-596.

 

13. Schuman JS, Pedut-Kloizman T, Hertzmark E, Hee MR, Wilkins JR, Coker JG, Puliafito CA, Fujimoto JG, Swanson EA. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103(11):1889-1898.

 

14. Schuman JS, ed. Imaging in Glaucoma. New Jersey: Slack, Inc; 1997.

 

15. Soliman MA, Van Den Berg TJ, Ismaeil AA, De Jong LA, De Smet MD. Retinal nerve fiber layer analysis: relationship between optical coherence tomography and red-free photography. Am J Ophthalmol. 2002;133(2):187-195.

 

16. Weinreb RN, Berry CC, Bathija R, Sample PA. Detection of glaucoma with scanning laser polarimetry. Arch Ophthalmol. 1998;116:1583-1589.

 

17. Zangwill LM, Williams J, Berry CC, Knauer S, Weinreb RN. A comparison of optical coherence tomography and retinal nerve fiber layer photography for detection of nerve fiber layer damage in glaucoma. Ophthalmology 2000;107(7):1309-1315.

 

18. Zeimer R, Zou S, Quigley H, Jampel H. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping: a pilot study. Ophthalmology 1998;105:224-231.

 

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