Medical hypothesis discovery and innovation in ophthalmology

Editorial/ No abstract

Glaucoma is a chronic optic nerve disease in which the primary damage occurs to the retinal ganglion cell axons. Therapies that prevent the death of retinal ganglion cells should be theoretically beneficial. Despite promising preclinical studies, however, almost all clinical studies with pharmacological approaches for neuroprotection in neurologic and eye diseases, including glaucoma, have so far failed to show efficacy. As the evidence supporting the neuroprotective efficacy of a ketogenic diet (KD) in a number of neurodegenerative diseases continues to grow, it is conceivable that this metabolic approach might be useful in chronic glaucoma. Putative cellular mechanisms underlying the neuroprotective activity of the KD have been identified in neurological studies, including effects on energy metabolism, the GABA system, glutamate-mediated toxicity, antioxidant mechanisms, programmed cell death, anti-inflammatory mechanisms, and the production of kynurenic acid. Of note, the same mechanisms are thought to be involved in glaucoma. Given these mechanistic similarities, testing the KD for its efficacy in neurodegenerative diseases of the eye is proposed.

Tactile palpation is a simple technique that can prove useful for estimating intraocular pressure (IOP) in primary healthcare settings, mainly in the absence of equipment, for very young children, patients who are intellectually challenged, those with eyes with extremely irregular corneas, and patients with corneal prostheses. Accordingly, this technique can also aid in the diagnosis of high IOP in primary and emergency care settings. To the best of our knowledge, there is no instrument that can quantify the estimation of IOP and teach tactile examiners. This group has developed a digital instrument called the MEHDI-IOP Measurement Model to train primary healthcare workers as well as blind individuals in the estimation of IOP. In this simple instrument, elastic spheres with a specific inner pressure can be touched and the responses of candidates with regard to the estimated pressure can be graded accordingly.

Glaucoma is a leading cause of blindness worldwide, characterised by specific visual field defects due to the degeneration of retinal ganglion cells and damage to the optic nerve head (ONH). Elevated intraocular pressure (IOP) is the most important risk factor for glaucoma development. One of the clinical hallmarks of glaucomatous optic neuropathy is the excavation of the ONH, which consists of a progressive posterior displacement of the ONH surface and excavation of the pre-laminar tissues beneath the anterior-most aspect of the scleral canal, known as the anterior scleral ring. Radial optic neurotomy (RON) is a surgical technique that has been proposed for treating central retinal vein occlusion. While the original rationale of RON was the relief of increased tissue pressure within the optic nerve that results from occlusion of the central retinal vein, recent results are discussed here which suggest that by relaxing of the scleral ring of the prelaminar and laminar regions of the ONH, RON may alleviate the IOP-related connective tissue stress, and in turn, prevent the onset and reduce the progression of glaucomatous neuropathy.

For quite some time, glaucoma has been regarded as more than just intraocular pressure [IOP] elevation. Significant contribution to this conceptual improvement has risen from a better understanding of ocular blood flow, vessel wall integrity and certain advanced ideas in neuroophthalmology, for example neuroprotection. Transforming growth factor–β (TGF-β) molecule, its inhibitors and antagonists have been increasingly researched as possible new anti-glaucoma drugs for its many, pleiotropic, effects. Among those effects, enhancing fibrosis is one of the most apparent, but certain members of this cytokine’s superfamily act as anti-fibrotics. Recent scientific efforts strongly support pushing back the frontier of conventional medical treatment. Current medical approaches already use effects on blood flow and neuronal quiescence, with significant systemic side-effects. Endeavours on the ophthalmologic exploitation of selected, favourable effects of pleiotropic TGF-βs could promote TGF-β, its inhibitors or specific antibodies as new, ideal drugs in glaucoma therapy.

Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected mosquitoes. Malaria retinopathy is misdiagnosed in the clinical setting, leading to a failure to treat other life-threatening illnesses. Indeed, the problem can be severe and should be the focus in tropical ophthalmology. In this brief article, the author summarises and comments on the present hypothesis for malarial retinopathy. This hypothesis could be justified by further basic and clinical studies.