Treatment Beyond IOP

New neuroprotective treatment approaches may help preserve vision in glaucoma patients where IOP-lowering strategies fail. Roibeárd O’hÉineacháin reports from the ninth World Glaucoma E-Congress

Improvement in VF MD with nicotinamide

• Greater proportion had ≥1 dB improvement in VF MD on NAM vs. placebo.

p=0.02

27%

16%

12%

4% Worsening Improvement

Treatment group

Hui F, et al. Clin Exp Ophthalmol. 2020;48(7):903–914.

A greater proportion of participants had an increase in MD by ≥1 dB from baseline following high-dose NAM compared to placebo (27% vs. 16%) and fewer patients taking high-dose NAM had a decrease by ≥1 dB compared to placebo (4% vs 12%)

PL12 = placebo group at 12 weeks Base = baseline NAM12 = NAM (vitamin B12) group at 12 weeks

Many new non-IOP-lowering therapeutic strategies show promise for glaucoma treatment, from interventions as simple as vitamin B supplementation and exercise to gene therapy designed to stimulate repair and regeneration of retinal ganglion cells.

“I think we are moving beyond IOP being the only way in which we can treat glaucoma. I think there are many promising approaches,” Professor Keith Martin MD told the virtual gathering.

As an example, he noted there is early evidence suggesting vitamin B3 modulates the vulnerability of the retinal ganglion cell mitochondria. In a study using a mouse model of glaucoma, boosting nicotinamide either by diet or supplementation was shown to be strongly protective of the dendritic trees of the RGCs and preserved vision. In addition, there was a dose-dependent effect in the mice receiving the higher doses of nicotinamide.

The findings of a recent crossover clinical trial indicate vitamin B3 supplementation may have the same neuroprotective effect in glaucoma patients, Prof Martin said. It showed after 12 weeks of vitamin B3 supplementation, patients had a statistically significant improvement in inner retinal function, as measured by their photopic negative electroretinography (ERG) response.

In addition, 27% of the patients receiving nicotinamide had more than a decibel of improvement in their visual field mean deviation, compared to only 16% in the placebo group. Furthermore, the visual field got worse in only 4% of patients in the vitamin B3 group, compared to 12% in the placebo group.

“The findings of this trial are interesting. Given that vitamin B3 is well-tolerated and has a good safety profile, the hypothesis here is that it has the potential to be combined with existing clinical therapy as a supplement,” he noted.

Recent research suggests exercise may also have a role in preventing glaucomatous neurodegeneration, he said. For example, in a study in which mice were given increased exercise, the vulnerability of the optic nerve to IOP-induced injury was restored in older mice to that of much younger mice.

The future may see the development of gene therapies for common eye diseases without single-gene defects, including glaucoma, Prof Martin said. For example, he and his associates have developed a gene therapy that upregulates brain-derived neurotrophic factor (BDNF) signalling. Their research has shown it greatly reduced optic nerve damage in a laboratory glaucoma model. The therapy is now in preclinical development by a major pharmaceutical company, with trials to begin in due course.

Keith Martin MD, FRCOphth is Professor and Head of Ophthalmology at the University of Melbourne, Australia, and Managing Director of the Centre for Eye Research, Australia. keith.martin@unimelb.edu.au