Targeted preventive measures and advanced approaches in personalised treatment of glaucoma neuropathy

Abstract

Glaucoma is a major cause of vision loss worldwide with nearly 8 million people bilaterally blind from the disease. This number is estimated to increase over the next 10 years. The key to preventing blindness from glaucoma is effective diagnosis and treatment. The classical glaucoma treatment focuses on intraocular pressure (IOP) reduction. Better knowledge of the pathogenesis has opened up additional therapeutical approaches often called non-IOP lowering treatment. Whilst most of these new avenues of treatment are still in the experimental phase, others are already used by some physicians. These new therapeutic approaches allow a more personalised patient treatment. Non-IOP lowering treatment includes improvements of ocular blood flow, particularly blood flow regulation. This can be achieved by improving the regulation of ocular blood flow (improving autoregulation) by drugs such as carbonic anhydrase inhibitors, magnesium or calcium channel blockers. It can also be improved by decreasing blood pressure over-dips. Blood pressure can be increased by an increase in salt intake or in rare cases by treatment with fludrocortisone. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting Endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Suppression of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Upregulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head. Reduction of oxidative stress especially at the level of mitochondria also seems to be protective. This can be achieved by gingko, dark chocolate, polyphenolic flavonoids occurring in tea, coffee or red wine and anthocyanosides found in bilberries as well as by ubiquinone and melatonin. This review describes the individual mechanisms which may be targeted by non-IOP lowering treatment based on our pathogenic scheme.

Fig. 1

Normal optic disc. a Normal optic disc in a healthy person (left), in the eye of a cadaver (middle), and a histological section (right). b Glaucomatous atrophy of the optic disc. The eye of the patient is shown on the left, of a cadaver in the middle and a histological section in the right

Fig. 2

The pathogenetic scheme of GON. The pathogenetic scheme by Flammer and Mozaffarieh [1], depicts the individual mechanisms that may be targeted by non-IOP lowering treatment. The numbers in red correspond to the section numbers in the manuscript

Fig. 3

Magnesium inhibits the effect of endothelin-1 (ET-1). Relaxing effect of increasing concentrations of MgSO₄ and MgCl₂ added to endothelial-precontracted porcine ciliary arteries (−10⁻⁸ M). NaCl, which has the same osmolarity as MgSO₄, did not evoke a relaxation

Fig. 4

Short-term effect of nifedipine. Mean defect of visual field test (Octopus program G1) at baseline and 60 min after intake of 20 mg sustained- release nifedipine in a) improvement in patients with digital vasospasm, and b) no change in patients without digital vasospasm. When treatment was continued for 12 months, the improvement in the group with vasospasm was still detectable (not shown here)

Fig. 5

a Drainage of aqueous humor. Aqueous humor (green) drains through the trabecular meshwork into Schlemm’s canal. b Trabecular meshwork of a healthy individual. c Trabecular meshwork of a glaucoma patient