We evidence evolution of photonic-based solutions for cutaneous interventions, where laser-induced optical breakdown (LIOB) and laser-induced thermal breakdown (LITB) have recently emerged.
This study aimed to demonstrate distinct histological- and clinical effects of LIOB versus LITB, where LIOB relies on tight focusing of sub-nanosecond pulses at 1064nm, a wavelength not relying on presence of exogenous chromophore, which is not the case for LITB. 
Ex vivo human skin, facial and the buttock areas of human participants were treated with a proprietary LIOB prototype (1064nm, sub-nanosecond pulse, 0.15mJ energy below the skin surface) at several depth and surface coverages. Time-dependent (1h, 1, 3, 7 and 30 days post treatment) biopsies were taken from the buttocks for histological (H&E, MBTC, Resorcin-Fuchsin stains) and immuno-histochemical analysis. 
Clinical results were improvement of facial wrinkles and acne scars at fully acceptable sensations without administering anaesthesia. 
Histological examination revealed LIOB-induced highly-reproducible intradermal micro-lesions with damaged collagen (1h post treatment) but fully intact epidermis, basement membrane, and surrounding dermis (MBTC staining). Damaging of the dermal resident cells (fibroblasts, macrophages, mast cells) resulted in the initiation of the inflammation response (1h post treatment), which triggered extracellular matrix remodeling (staining for collagen III, strongest at the periphery of the lesions 3 days after treatment). At 30 days post treatment dermis was more filled with finer collagen fibers. 
By focusing laser in the epidermis, LIOB resulted in isolated epidermal cavities with abundant erythrocytes and leukocytes just below the epidermis and the onset of healing reaction (1h post treatment).
In conclusion, unlike LITB, LIOB does not require any endogenous chromophores. LIOB micro-lesions can be created in both epidermis and dermis independently, thereby addressing multiple needs in dermatology, provided triggered molecular cascades, phenotypes of involved immune cells, dynamics of the local inflammatory response are further investigated.

Unravelling laser-induced optical breakdown technology (LIOB) for cutaneous interventions: connecting molecular targets and clinical effect