Forthcoming opportunities in keratoconus pharmacotherapy

Relevance Keratoconus (KC) is an ectatic corneal disease with a chronic progressive course. As keratectasia progresses, visual functions in young working-age individuals steadily decline; for this reason, the main goal of treatment for KC is to stabilize keratectasia. To date, all known treatment methods aimed at stopping the progression of KC are exclusively surgical, seem to be very energy-consuming and are not without a number of side effects and serious complications. Objective To theoretically substantiate the possibility of drug stabilization of keratectasia in KC. Material and methods To achieve this goal, available literature data on the etiopathogenesis of KC were selected, studied and analyzed. Results The Fleischer ring is a pathognomonic biomicroscopic sign of KC. It has been previously proven that the Fleischer ring is made up of pigment deposits at the level of the anterior stroma layers, Bowman's membrane and corneal epithelium, and the pigment contains iron ions. Modern methods of analytical chemistry have revealed the presence of copper and zinc ions in the projection of the Fleischer ring and the complete absence of these metal ions in the tissues of the central zone of the cornea. According to the basic principles of physical chemistry, such a redistribution of chalcophile metal ions is possible only if there is a physicochemical barrier in the corneal tissues. The essence of the physicochemical barrier is the precipitation of chemical elements in the tissues as a result of the transition of their water-soluble ions into biologically inaccessible water-insoluble compounds. As a result of the disruption of the normal migration of chemical elements in the thickness of the cornea, its central region is deprived of essential mineral elements necessary for the functioning of metal-dependent enzymes that metabolize connective tissue structures. Thus, in the absence of copper, iron and zinc ions, mineral dysmetabolism occurs in the corneal tissues, which ultimately leads to a violation of its supporting function and the development of keratectasia. In addition, with KE, violations of the acid-base and buffer properties of the lacrimal fluid and the ocular surface were revealed. Conclusion The above provisions substantiate the theoretical possibility of saturating the cornea with chalcophile metal ions, as well as modulating the state of the ocular surface, precorneal tear film, acid-base and buffer properties of the lacrimal fluid by pharmacotherapeutic methods [1–5]. This concept becomes a fundamental prerequisite for the development of eye drops that allow medicinally stopping the progression of keratectasia in KE and non-surgically stabilizing the visual functions of such patients - to carry out the so-called pharmacological, or medicinal, crosslinking. Key words: keratectasia; copper; zinc; tear acidity; eye drops; pharmacological crosslinking; medicinal crosslinking