Femtosecond Lentotomy to Restore Accommodation

The use of the femtosecond laser has become well established in refractive surgery.^1-5 This technology boasts extraordinary precision and reproducibility of the cutting process, enabling the surgeon to create different 3-D structures inside transparent tissue, such as the cornea. One exciting possibility of femtosecond application is for lentotomy.

Myers and Krueger were the first to describe the clinical prospect of deeper delivery inside the eye when they proposed using photodisruption to treat the crystalline lens.⁶ They created intralenticular incisions with a 500-nanosecond laser to soften the lens tissue and reestablish its flexibility;⁷ however, focusing nanosecond laser pulses inside the lens caused bubble formation. This side effect may be dramatically reduced with ultrashort femtosecond laser pulses.^8,9

In early investigations of the treatment of enucleated porcine and human cadaver lenses, Ripken et al10 showed that cutting patterns inside the lens tissue with femtosecond laser pulses, or femtosecond lentotomy, increased the flexibility of the lens. The cutting patterns created gliding planes for the hardened lens tissue. Moreover, the flexibility of the lens increased depending on the particular cutting pattern.^10,11

METHODS
In a recent study, 10-week-old rabbits (n=15) underwent lentotomy with a 100-kHz femtosecond laser. We used a 3-D scanning device to deliver a central wavelength of 1,041 nanometers (maximum pulse energy, 3.6 µJ; pulse duration, 306 femtoseconds). Each left eye was fixed to the scanning device suction ring while the cornea was applanated by with a flat glass contact lens (Figure 1), enabling intralenticular laser pulse scanning with a resolution of 1 µm. The intralenticular laser cutting pattern was a combination of radial and annular layers, resembling a steering-wheel pattern (Figure 2).⁹

The pulse energy, which was varied between 1.2 and 1.6 µJ, was separated between 6 and 7 µm in the x-y plane and 50 µm along the optical axis. With the high repetition rate, the total laser treatment lasted 25 seconds.

RESULTS
Femtosecond lentotomy was successfully applied to the left lens of each rabbit. Figure 3 shows the cutting pattern clearly visible inside the crystalline lens immediately after laser treatment. The cut is positioned approximately 1.7 mm below the central surface of the lens. Both annular surfaces and the cylindrical cuts are visible in the form of two squares. Additionally, one of the sagittal planes is visible. The slight dipping of the annular planes is caused by the refraction of the anterior surface of the lens.

Follow-up was performed on days 1 and 14 and again at 3 months postsurgery (Figure 4). The cuts faded and are barely visible and better confined than they were immediately after surgery. The fading of the cutting pattern is best seen in the Scheimpflug images. Figure 5 shows histological analysis of the lenses directly postop and at 2 weeks and 3 months after surgery. The disruptive laser effect stays well localized and may not lead to haze in the affected lens fibrils to the whole lens.

DISCUSSION
The in vivo application of femtosecond laser pulses in rabbits verifies the generation of specific geometric patterns inside the crystalline lens. No hazardous side effects to the cornea or the lens capsule were observed. Photodisruption inside the lens tissue leads to small gas-filled bubbles that remain as small, faint opacities after the bubbles disappear. The gas bubbles vanish because the gaseous content of the bubbles dissolves.

A big challenge within these experiments was eye fixation and alignment beneath the scanner system. As a consequence, some eyes were decentered toward the lens equator. In these cases, the laser was partly shielded by the iris so that an asymmetric intralenticular cutting effect took place.

Ocular coherence tomography (OCT) images taken prior to the laser treatment provide essential information for targeting the appropriate depth at which to place the cutting pattern. Images taken immediately after the laser surgery verified that the cut was placed as intended, well below the lens capsule. Therefore, OCT localization plays an integral and essential part in the planning of any intralenticular laser treatment.

Slit-lamp analysis after treatment indicates no opacity or other cataractous change, as might be anticipated from such a treatment. Furthermore, Scheimpflug imaging verifies both the location and intensity of any opacities or other abnormalities and confirms the absence of cataractous change following bubble resolution. The extent of the cutting pattern is well visualized due to the scattering of the light by the remaining gas bubbles. The larger the gas bubbles created inside the lens become, the greater the intensity of light scattering by Scheimpflug imaging.

At 3-month follow-up, the cutting pattern appears better localized and less intense in both OCT and Scheimpflug images. Actual cataract formation, which would be visible as a progressive opacity that increases light scattering and spreading into the surrounding tissue, was not observed.¹⁴ Also, cataract formation beyond the first 3 months, seems unlikely. Krueger¹² found that lens tissue treated with a similar femtosecond laser showed no evidence of cataract formation or light scattering at 3 months.

In summary, our study showed that it is feasible to deliver in vivo femtosecond laser pulses into rabbit eyes. During the first 3 months of follow-up, no indication of cataract formation is present. Nevertheless, more in vivo studies in regard to long-term cataract formation and increase of accommodative amplitude are necessary to transfer this treatment concept into a successful clinical method for restoring accommodation.

Holger Lubatschowski, PhD, is Head of the Biomedical Optics Department, the Laser Zentrum Hannover, Hanover, Germany. Professor Lubatschowski states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +49 511 2788 279; fax: +49 511 2788 100; e-mail: H.Lubatschowski@lzh.de.

Silvia Schumacher, PhD, is a research associate at the Laser Zentrum Hannover e.V., Hanover, Germany. Dr. Schumacher states that she has no financial interest in the products or companies mentioned. She may be reached at tel: +49 511 2788 229; fax: +49 511 2788 100; e-mail: S.Schumacher@lzh.de.

Michael Fromm, MS, is a research assistant at the Laser Zentrum Hannover e.V., Hanover, Germany. Mr. Fromm states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +49 511 2788 229; fax: +49 511 2788 100; e-mail: M.Fromm@lzh.de.

Heike Hoffmann, BS, is a research associate at the Laser Zentrum Hannover e.V., Hanover, Germany. Mrs. Hoffmann states that she has no financial interest in the products or companies mentioned. She may be reached at tel: +49 511 2788 229; fax: +49 511 2788 100; e-mail: H.Hoffmann@lzh.de.

Uwe Oberheide, PhD, is Head of the Research Department, the Laserforum e.V., Cologne, Germany. Dr. Oberheide states that he no financial interest in the products or companies mentioned. He may be reached at tel: +49 221 650 722 75; e-mail: U.Oberheide@augenportal.de.

Georg Gerten, MD, is an ophthalmology consultant at the Laserforum, e.V., Cologne, Germany. Dr. Gerten states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: G.Gerten@augenportal.de.

Alfred Wegener, PhD, is the EVER Lens Section Chairman at the Department of Ophthalmology, University of Bonn, Germany. Dr. Wegener states that he has no financial interest in the products or companies mentioned. He may be reached at e-mail: a.wegener@uni-bonn.de.

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