Progression of brain changes in glaucoma

Glaucoma is one of the leading causes of irreversible blindness worldwide. The
traditional view of glaucoma is that of an eye disease in which an elevation of
intraocular pressure (IOP) causes the death of retinal ganglion cells (RGCs)
through simple mechanical stress, leading to characteristic visual field (VF)
defects. However, between 30-39% of glaucoma patients in Western countries have
normal IOP on presentation, a condition referred to as normal-tension glaucoma
(NTG). Furthermore, ocular hypertension (OHT) commonly exists as an independent
entity in the complete absence of glaucomatous retinal changes.

This lack of consistency in the relationship between IOP and glaucomatous
retinal changes challenges our conventional view of glaucoma. One proposed
hypothesis is that glaucoma is potentially a neurodegenerative disease of the
whole brain, with retinal glaucomatous changes being an extension of that
degeneration and not a primary pathology of the retina.

Indeed, numerous MRI studies investigating structural brain changes in glaucoma
patients have found evidence of neurodegeneration in both the visual pathway
and visual cortex of glaucoma patients. Of course such degeneration could be
attributed to trans-synaptic degeneration and sensory deprivation secondary to
glaucomatous retinal damage and its subsequent functional loss. However, more
recent studies have also found structural degenerative brain changes beyond the
visual system, which cannot be attributed to glaucomatous retinal changes,
favoring the hypothesis that glaucoma is a global neurodegenerative disorder of
the whole brain.

Although glaucomatous retinal damage over time has been studied extensively
using optical coherence tomography (OCT), there is a complete lack of
longitudinal studies of glaucomatous brain changes. To the best of our
knowledge, all studies of structural brain changes in glaucoma patients have
been cross-sectional in nature so far. The proposed study intends to
investigate structural brain changes of glaucoma patients using anatomical MRI
in a longitudinal manner.

The primary objective is to study glaucomatous structural brain changes in a
longitudinal manner, and how it relates to visual functional loss and
glaucomatous retinal changes over time.

Historical cohort study

There are no direct risks associated with the proposed study.
The planned ophthalmological examination is akin to the standard examination
one receives on a visit to an ophthalmologist, which involves no risks.
The MRI scanners which will be used have a magnetic field strength of 3 Tesla,
which is a very common field strength used extensively in both clinical
practice and research. No side effects have been reported so far with the use
of such scanners.