Nonlinear optical photodynamic therapy (NLO-PDT) of the cornea

A method of nonlinear optical photodynamic therapy of a cornea, the method comprising:

• pretreating the cornea with a photosensitive agent, which is capable of generating free radicals within a treatment volume of the cornea upon laser irradiation;
• and providing the photodynamic therapy within the treatment volume of the cornea by:
• directing to said cornea laser irradiation by a pulsed near-infrared laser light, which provides a multiphoton beam at a predetermined intensity and having a near-infrared wavelength through a focusing objective lens of an apparatus, the multiphoton beam having a beam width and the focusing objective lens having a fixed numerical aperture;
• generating a focal volume with the multiphoton beam at a depth in the cornea by reducing an effective numerical aperture of the apparatus, compared to the numerical aperture of the focusing objective lens, to a final value between 0.16 and 0.08 by expanding the beam width impinging on the focusing objective lens, wherein the focal volume comprises is between 150 and 2500 femtoliters;
• and
• moving the focal volume in three dimensions relative to the tissue within a predetermined clinical time span, to define the treatment volume, which is larger than the focal volume.