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Heritability of ocular component dimensions in mice phenotyped using depth-enhanced swept source optical coherence tomography

Ling Wang, Boris Považay, Yen Po Chen, Bernd Hofer, Wolfgang Drexler and Jeremy Guggenheim

Researchers based at Cardiff University, U.K. and the Medical University of Vienna, Austria have taken advantage of the extended depth range delivered by swept source OCT to measure the eye size of mice with unprecedented precision [1].

Measurement of eye size in humans is a standard medical procedure carried out before cataract removal surgery, which is perhaps the most commonly performed surgical operation in the world. The eye measurements are acquired using a laser Doppler interferometry (LDI) technique [2] closely related to time domain OCT.

The length of the eye along its visual axis determines the refractive error of the eye. Myopia (nearsightedness) results when the axial length of the eye is too long relative to the optical power of the cornea and crystalline lens. Because high-degree myopia is an important risk factor for sight-threatening conditions such as retinal detachment and retinal degeneration, researchers from Cardiff University have been studying the genetics of myopia to try and understand how it can be prevented. Since mice can be raised under carefully controlled conditions and bred to produce large families, they are a valuable model for pinpointing specific genes involved in regulating eye size. However, instruments based on the time domain LDI principle lack the accuracy needed for genetic studies of mouse eye size [3], as mouse eyes are only ~3 mm in length compared to ~23 mm in humans.

The respiration rate in mice is approximately 2.5 Hz. This produces to a cyclic shift in eye position that leads to measurement errors in time domain LDI. To overcome this limitation, researchers from the Medical University of Vienna designed a swept source OCT instrument that provides 512 depth scans in 18.3 ms, which is fast enough to provide B-scans (cross-sectional images) of the mouse eye free from motion artefacts [4]. A key feature of the approach is the use of the fast dispersion-encoded, full-range (DEFR) algorithm to double the usable depth range.  In standard swept source OCT, complex conjugate mirror artefacts are seen, centred on the position of the zero-delay. DEFR suppresses these to provide a scan depth of 2 x 5 mm at −101 to −71 dB sensitivity, for a single scan of 2048 samples/depth scan with 0.43 nm line width. The light source operates at 1056 nm (with a tuning range of 70 nm) providing deep penetration of ocular tissues. To ensure that images are reproducibly aligned with respect to the optical axis of the mouse eye, alternating B-scans are acquired in the horizontal and vertical meridians (corresponding to transverse and sagittal planes through the eye). Real-time video display of these B-scans permits precise alignment. To enhance the signal strength, 50 horizontal and 50 vertical B-scans are digitally registered, and averaged.

The repeatability of swept source OCT for measuring ocular component dimensions in mice is superior to all previous measurement methods [1]. In a proof-of-principle study using a set of parent and offspring mice, the first heritability measurements of mouse ocular component dimensions have been obtained, which demonstrate that inter-individual differences in eye size are primarily controlled by genetics.

Presentation

 
 

References

  1. Wang, L., Považay, B., Chen, Y.P., Hofer, B., Drexler, W. and Guggenheim, J.A. (2011) Heritability of ocular component dimensions in mice phenotyped using depth-enhanced swept source optical coherence tomography. Exp. Eye Res. in press.
  2. Hitzenberger, C.K., Drexler, W., Dolezal, C., Skorpik, F., Juchem, M., Fercher, A.F. and Gnad, H.D. (1993) Measurement of the axial length of cataract eyes by laser-Doppler interferometry. Invest. Ophthalmol. Vis. Sci. 34, 1886-1893.
  3. Schmucker, C. and Schaeffel, F. (2004) In vivo biometry in the mouse eye with low coherence interferometry. Vision Res. 44, 2445-56.
  4. Wang, L., Hofer, B., Chen, Y.-P., Guggenheim, J.A., Drexler, W. and Povazay, B. (2010) Highly reproducible swept-source dispersion encoded full-range biometry and imaging of the mouse eye. J. Biomed. Opt. 15, 046004.

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