These agents seem to interfere with the healing that generally occurs after filtering surgery . into the perspectives available nowadays in this field. 1. Introduction Glaucoma is one of the leading causes of blindness in the world, second only to cataracts [1, 2]. It is a chronic, Mc-MMAD degenerative disease affecting the optic nerve, but insidious: in fact, when the etiopathogenetic process has started and has already damaged the nerve fibers, the symptomatology is almost silent [3, 4]. When the patient becomes aware of the visual impairment, the neural function is already compromised and the chances of recovery are significantly reduced. There is no scientific evidence of the field of visual recovery once its defect has been documented. However, a perimetric learning effect among a percentage of patients could occur, very unlikely to represent a real improvement. For these reasons, glaucoma is a disease of enormous social impact, both from the human point of view, because it is highly disabling and compromises the quality of life and autonomy of those affected , and from Mc-MMAD an economic point of view: for its clinical-therapeutic management, in fact, a substantial percentage of public healthcare expenditure is invested . The term glaucoma actually encompasses several forms of optical neuropathies with still partly obscure etiopathogenesis associated with typical visual field alterations and increased intraocular pressure [7, 8]. In reality, this last characteristic is not the rule: in recent years, the number of cases of normotensive glaucoma, Mc-MMAD which is not associated with an increment in IOP, Ednra has increased dramatically, especially in relation to the lengthening of life expectancy [9, 10]. In fact, it has long been known that only about half of the glaucoma cases have intraocular pressure above reference values [11C13]. In any case, the most accredited etiopathogenetic hypothesis would be the death of retinal ganglion cells due to mechanical stress and apoptosis following ischemic and/or chemical mechanisms, which would seem to have glutamate and NMDA receptor activation as protagonists, which would cause an exponential increase in intracellular calcium concentration, thus triggering irreversible damage to DNA and cell death [14, 15]. In light of this, it is clear that it is of great importance to study the phases of this disorder and to continually seek new preventive and therapeutic strategies . According to the current scientific panorama, the therapeutic possibilities are aimed at acting both on the initial stages of the disease and on the final outcomes, i.e., on the advanced stages of glaucoma for which the lesions are considerable and no longer reversible, but in which it is possible to intervene by enhancing the residual functions at the highest level. In this context, the aim of our manuscript is to provide a comprehensive Mc-MMAD review of the recently investigated new approaches to treat early and late stages of the disease. This literature search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . Studies reporting novel treatment strategies of glaucoma were systematically reviewed. PubMed, MEDLINE, Web of Science, and Embase databases (from inception up to 1 1 January, 2020) were searched. The electronic search method included the terms glaucoma’, novel therapies’, electrical stimulation’, micropulse’, stem cells’, exosomes’, optic nerve regeneration’, growth factors’, rehabilitation’, which were connected in various combinations by or’/’and’. The last search was carried out on 1 January, 2020. Either prospective or retrospective, both randomized and not randomized studies were considered for eligibility. No restrictions in terms of follow-up were applied. Eligible papers must have been published in peer-reviewed journals and in English, with no publication date or publication status limitations. Titles and abstracts of all identified studies were independently reviewed by two researchers (P.M. and A.N.) to assess eligibility. A full-text evaluation of all potential studies was performed later. Once studies have been selected and included, data were extracted by two independent investigators (P.M. and A.N.). When discrepancies were found, a third author (R.N.) was involved to achieve consensus. 2. Overview of the Current Evolution of Treatment Strategies In addition to the well-known hypotensive drugs, in recent years, research has focused on the development of new local and systemic drugs to be used to reduce intraocular pressure. The main innovative drugs discovered are Mc-MMAD latrunculin derivatives, ROCK inhibitors, cannabinoids, local calcium channel blockers, and.