Q: What is the role of cerebrospinal fluid pressure in the
pathogenesis of glaucoma?
Glaucoma has classically been thought of as a one-pressure disease, with the only modifiable risk
factor being intraocular pressure (IOP). However, increasing experimental and clinical evidence
suggests that CSFp may be just as important. In retrospective studies on patients having undergone
lumbar puncture, patients with primary open angle glaucoma were found to have lower CSFp than
healthy controls. Interestingly, patients with normal tension glaucoma had even lower CSFp, while
patients with ocular hypertension had higher than normal CSFp.1,2
Cerebrospinal fluid bathes the central nervous system, extending along the optic nerves to the lamina
cribrosa, which acts as a barrier between two independently-pressurized compartments (IOP and
CSFp). It is now being hypothesized that a root cause of glaucoma may be due to a disturbance in the
pressure gradient across the lamina cribrosa, which has been shown to be associated with objective
findings in advanced glaucoma.3
Q: How have advances in ocular biomechanics
enhanced our understanding of glaucoma?
Investigations into the cause of glaucoma have been expanding to evaluate
not only the pressures on the optic nerve, but also the biomechanical
characteristics of an eye that dictate how it responds to a given pressure.
One of the biomechanical markers that has been implicated in glaucoma
pathogenesis is corneal hysteresis (CH). Contrary to common belief, CH
is not a static property of an eye, but rather a measure of its ability to
absorb a pressure change. Put differently, CH may help us understand the
mechanical effect of an IOP change on an eye, and possibly, its resistance or
susceptibility to nerve damage. Several studies have reported a significantly
lower CH in patients with a variety of glaucoma subtypes compared to
healthy controls, and others have correlated CH to structural change at the
optic nerve head independent of IOP.4 Further investigations into the utility
of CH and other biomechanical properties of the eye are ongoing and hold
promise for future diagnosis and management of glaucoma.
Q: What environmental factors have been
associated with an increased risk of
While socioeconomic, nutritional, and environmental factors have been
strongly linked to a number of systemic and ocular health conditions,
there is a paucity of significant evidence for direct effects of outside
factors on presence or progression of glaucoma. However, considering the
established connection between IOP and glaucoma, some of these factors
may be indirectly linked to glaucoma. Some activities which have been
documented to increase IOP include playing wind instruments, wearing
neckties, drinking coffee, and practicing certain yoga positions (e.g., a
headstand), while other activities such as exercise and ingestion of alcohol
have been posited to at least transiently reduce IOP.5 Additional factors
such as cigarette smoking and low consumption of certain dietary fats are
being investigated, but no strong evidence exists to date.
As we learn more about CSFp and its relationship to glaucoma, some
factors that cause low CSFp may garner higher interest in their relationship
to glaucoma risk. Body mass index is one physiologic parameter which has
been shown to be inversely related to CSFp, and may be linked to glaucoma
risk. Finally, body positioning and the effect of gravity on CSFp are also
factors actively being investigated for their role in glaucoma risk.
Q: At present, which glaucoma patients are most
likely to benefit from the use of MIGS?
MIGS encompasses a wide range of technologies and procedures
aimed at reducing intraocular pressure with an ab interno approach.
There are a number of gonioscopic, angle-based surgeries that attempt
to increase aqueous outflow and have various levels of effect on IOP,
either in conjunction with or independent of cataract surgery. Most MIGS
procedures are suitable for patients with mild-to-moderate primary openangle
glaucoma, and some have shown efficacy in secondary types of
glaucoma including pigment dispersion and pseudoexfoliative glaucoma.6
Because of the huge variety in procedure type and mechanism of IOP
lowering, we see an equally wide distribution of effect on IOP, and it
becomes a matter of risk-to-benefit ratio for each individual patient. In a
patient with ocular hypertension and early glaucomatous visual field loss,
choosing a trabecular bypass (iStent, Glaukos) will often achieve an IOP
goal without taking on significant risk. In patients with more significant
visual field loss failing topical therapy, diversion of aqueous to the
suprachoroidal (Cypass, Alcon) or subconjunctival space (Xen, Allergan)
may achieve lower postoperative IOP, and may balance out any perceived
increase in procedural risk.
Q: What is most promising about MIGS technology
or other ab interno glaucoma surgery?
One of the most beautiful things about MIGS procedures, in addition to
their favorable risk profiles, is the preservation of future surgical options
should the need arise. In this way, future trabeculectomy and tube shunts
are not precluded by the use of MIGS procedures. Because they work via a
variety of mechanisms, many MIGS procedures can also be complimentary
to other procedures as well. For example, the combination of a trabecular
bypass stent with endocyclophotocoagulation hits both aqueous outflow
and production and might be suitable for a patient in need of more
drastic IOP lowering than either one alone. There are many newer
technologies in the pipeline as well, which make this an exciting time to be a