Intraocular lens (IOL) implantation is the standard technique to treat cataract. Despite recent progress in surgical
procedures, posterior capsule opacification is one of the sill remaining postoperative complications of cataract surgery.
We present a novel strategy to reduce the incidence of posterior capsule opacification. A drug delivery polymer suitable
for manufacturing intraocular lenses has been developed which enables repeated drug release in a non-invasive and
controlled manner. The therapeutic molecules are attached through a UV light sensitive linkage to the polymer backbone
which is mainly responsible for the optical properties of the intraocular lenses. However, UV light can not trigger the
release of drug from the polymer due to the high absorption of the cornea. We developed linkers which enable drug
release by two-photon absorption induced cleavage of the linker structure. Since the two-photon absorption requires high
photon densities, this does not occur in ambient light conditions in daily life, but is easily triggered by focused laser
beams from a pulsed laser. In this proof-of-principle study we have employed a cyclobutane type linker and investigated
the properties of the therapeutic system with the approved drugs 5-fluorouracil and chlorambucil. The controlled drug
delivery was successfully demonstrated in vitro and additional cell tests confirmed that the device itself shows no
cytotoxicity until photochemical activation. This presented concept can provide a powerful method in ophthalmic drug
delivery.
Typical postoperative complications in cataract surgery are that refractive power and curvature of the implanted
intraocular lens (IOL) do not have optimum values, requiring the patient to wear viewing aids. This is mainly
because biometric data relevant for calculation of the IOL's shape cannot be determined with the required
precision. Hence, there is a need for methods to tune the focal length postoperatively in a non-invasive manner.
We have developed polymers where we can induce a change in refractive index by linking or cleaving bonds
between a su.ciently large number of side groups of the polymer main chain in a photoinduced cycloaddition
or cycloreversion reaction, respectively. These photoreactions lead to a change in refractive index great enough
to be interesting for the concept of in vivo tunable IOL's. The photochemical reaction can be triggered by a
two-photon process (TPA) using a pulsed laser system, i.e. the energy required for bond breaking is provided
by two photons in the visible range. This is important because light in the UV cannot induce undesired changes
of the refractive index owing to the strong UV-absorption of the cornea. Undesired changes due to light in the
visible range of the spectrum are unlikely to happen because photon density of sun light is much too low for
TPA. Due to the excellent spatial resolution that can be achieved with two-photon processes one cannot only
modify the refractive index of the entire lens but also selectively in well defined areas enabling to correct for
aberrations such as astigmatism.
Here, we present new polymers that do not only exhibit a photo induced change of refractive index great
enough to induce a change of focal length of more than two diopters in a standard IOL. These new polymers
have also significantly improved material properties with respect to the fabrication of the IOL and the TPA-sensitivities
and the light energy required to induce the refractive index change.
Before an intraocular lens (IOL) is implanted during cataract surgery, biometric data of the patient's eye have to be determined to calculate the thickness and shape of the IOL. In particular the postoperative anterior chamber depth is an important parameter to predict the correct shape of the IOL. This value, however, cannot be measured without significant uncertainities. We present a solution to this problem, describe novel polymers suitable for IOLs which refractive indices can be changed non-invasively in a photo-induced process. The focal length can be modified by about 2 D, which is sufficient to achive ideal acuteness of vision for almost all patients with implanted IOLs. The change in refractive index is accomplished by linking or cleaving bonds between a sufficiently large number of side groups of the polymer main chain in a photoinduced cyloaddition or cycloreversion, respectively. The photochemical reaction can also be triggered by a two-photon process (TPA) using a pulsed laser system, i.e. the energy required for bond breaking is provided by two photons in the visible range. Light in the UV as well as the visible range of the spectrum cannot induce undesired changes of the refractive index owing to the strong UV-absorption of the cornea and photon densities much too low for TPA, respectively. Due to the excellent spatial resolution that can be achieved with two-photon processes not only modification of the refractive index of the entire lens but also selectively in well defined areas is possible enabling the correction for aberrations such as astigmatism.
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