Two-photon retinal theranostics by adaptive compact laser source

To avoid a devastating effect of eye vision impairment on the information flow from the eye to our brain, enormous effort is being put during the last decades into the development of more sensitive diagnostics and more efficient therapies of retinal tissue. While morphology can be impressively imaged by optical coherence tomography, molecular-associated pathology information can be provided almost exclusively by auto-fluorescence-based methods. Among the latter, the recently developed fluorescence lifetime imaging ophthalmoscopy (FLIO) has the potential to provide both structural information and interacting pictures at the same time. The requirements for FLIO laser sources are almost orthogonal to the laser sources used in phototherapy that is expected to follow up the FLIO diagnostics. To make theranostics more effective and cheaper, the complete system would need to couple at least the modalities of low-power high-repetition-rate FLIO and precision high-pulse energy-adjustable repetition rate phototherapy. In addition, the intermediate-power high repetition rate for two-photon excitation would also be desired to increase the depth resolution. In our work, compact fiber-laser based on high-speed gain-switched laser diode has been shown to achieve adaptable/independently tunable repetition rate and energy per pulse allowing coupled fluorescence lifetime diagnostics via two-photon excitation and phototherapy via laser-induced photodisruption on a local molecular environment in a complex ex vivo retinal tissue.