The Education Committee carefully selects presentations from the WGC-2019 for your benefit. This month Xinghuai Sun introduces the sessions: New Frontiers in Medical Management and The Many Pressures of Glaucoma.
New frontiers in glaucoma
- Ciliary Muscle: A New Target For Glaucoma Therapy?
Professor Paul L. Kaufman discussed the anatomy and physiology of ciliary muscle, how aging affects ciliary muscle, and where we could target future therapy. Ciliary muscle connects with various structures of the outflow pathway. Prostaglandins act through MMP-3 and collagens to improve outflow facility. Animal study showed sustained IOP reduction with prostaglandin pathway gene therapy which could be a potential new area for therapy. The posterior tendons of ciliary muscle connect to the ora serrata, which form an elastic network extending from the TM to optic nerve region and may make the optic nerve more susceptible to glaucomatous damage. Aging reduces accommodation and ciliary muscle mobility, which could reduce the ability of TM self-cleaning effect. Professor Kaufman concluded that the ciliary muscle remains a target-rich environment for glaucoma (both outflow pathways) and for presbyopia.
- Rho-kinase Inhibitor: Japanese experience
Professor Makoto Aihara talked about ROCK inhibitor ophthalmic solutions, and results of clinical trials for Ripasudil 0.4% (GLANATEC) in Japan. ROCK inhibitor can reduce the resistance of conventional outflow pathway through both quick and short action and slow and long action mechanisms. Phase 3 clinical trials have shown good IOP-lowering effect for GLANATEC, either as monotherapy or add-on therapy. Long-term study showed additional IOP-lowering effect possibly through the slow and long action mechanism. Conjunctival hyperemia, conjunctivitis and blepharitis are the most common side effects with GLANATEC. Conjunctival hyperemia is usually transient. Conjunctivitis and blepharitis are more common after long-term administration. In the real-world clinical use of GLANATEC, the drug demonstrated significant IOP-lowering effect, and no specific safety issues were observed.
- Pharmacogenomics (aka biomarkers): A Way to Optimize Glaucoma Management?
Professor Sayoko E. Moroi talked about reflections on current event-based treatment and next translational steps on genetics, glaucoma & risk factors. Current event-based treatment reacts with IOP lowering to changes in disc or field. There are now numerous data of biobanking including genotypes, proteomics, phenotypes (clinical data), and environmental exposures. She suggested progress toward precision medicine to prevent glaucoma-related blindness. In the field of precision-based glaucoma, we should discover biomarkers for outcomes (medical Rx & surgery) with large datasets, understanding mechanisms of clinical risk factors (IOP, thin cornea, low perfusion pressure, steroid responder, etc), and understandomg mechanisms of aging, oxidative stress, autophagy and the role of environmental exposures.
- Nitric Oxide and Glaucoma
Professor Robert N. Weinreb presented to us the normal physiology and signaling pathway of NO, NO signaling dysfunction in glaucoma and its role in glaucoma therapy. The normal signaling pathway of NO is involved in both IOP regulation and hemodynamics of the eye. POAG eyes have reduced NOS activity. Disruption of NO signaling pathway increases IOP in animal models. For the therapeutic role of NO, Professor Weinreb presented that greater intake of dietary nitrate can lower POAG risk and systemically administered NO donors reduced IOP in humans. Clinical studies of a new medication, Latanoprostene Bunod, were also presented in this talk. Lastly, Professor Weinreb discussed the potential role of neuroprotection, independent of or separately from IOP lowering, through enhancing nitric oxide signaling.
- Meditation and Glaucoma
Professor Tanuj Dada talked about how meditation could affect glaucoma management. Glaucoma is related to increased plasma cortisol level, and meditation can counter the stress response and reduce plasma cortisol level. There is trans-synaptic neurodegeneration in the brain of glaucoma patients, and neuroimaging studies showed neurogenesis effect, enhancing blood flow and brain oxygenation with meditation in adult brain. Autonomic nervous system disturbance is common in glaucoma, especially NTG, and meditation can increase parasympathetic activity and decrease sympathetic activity. Other possible mechanisms that meditation help manage glaucoma were also discussed. As a conclusion, Professor Dada recommended mediation as adjunctive therapy for glaucoma patients.
The Many Pressures of Glaucoma
- Blood pressure and glaucoma
Dr. Michael Kook discussed blood pressure, IOP and the relationship between autoregulation. Glaucoma is considered as one type of end organ damage, which refers to damage in major organs supplied by the circulatory system. Insufficient blood flow, primarily determined by perfusion pressure and vascular resistance, has been shown to be associated with visual field deterioration in glaucoma. Epidemiological studies showed that both hypertension and hypotension can increase the prevalence of glaucoma and the effect is different in different age groups. Nocturnal systemic hypotension is also an important risk factor for glaucoma progression. Dr. Michael Kook concluded that blood pressure plays an important role in glaucoma, and both untreated and overtreated hypertension must be recognized. Nocturnal blood pressure dips, particularly diastolic pressure dips, may be more relevant than systolic blood pressure dip for glaucoma progression. Twenty-four-hour blood pressure monitoring should be considered in progressive patients despite well-controlled IOP.
- Does Intracranial Pressure Matter in Glaucoma?
Dr. Ningli Wang talked about the role of intracranial pressure in glaucoma. Studies about intracranial pressure and glaucoma, especially normal tension glaucoma, were discussed in the talk. NTG patients have lower BMI, smaller retrobulbar optic nerve subarachnoid space, and lower ICP. Lower ICP induces glaucomatous neuropathy in primate animals and human. Short-term lowering of CSF pressure was associated with disturbance of axonal transport and reduction of artery and venous diameters. Dr. Wang also hypothesized that rebalancing translaminar cribrosa pressure difference (TLPD) through focal lamina cribrosa defect (LCD) may be beneficial and this was partly supported by their clinical study in a group of NTG patients. Dr. Wang concluded that ICP does play a crucial role in glaucoma besides IOP. Many systematic parameters associated with ICP like BP, BMI, estrogen should be noticed in clinical practice.
- Why Does IOP Fluctuate?
Dr. Arthur Sit talked about IOP fluctuation and its relevance in glaucoma. IOP variation appears to be a risk factor for glaucoma in certain suspectable populations. Variations of IOP can be a risk factor in patients with low mean IOP compared to high mean IOP, and in medically treated patients rather than surgically treated patients. Body position and head position can affect IOP levels and this may be due to changes in episcleral venous pressure. Regarding circadian rhythm of IOP, peak IOP often occurs during the night, even though aqueous humor production is reduced. This may be related to body position changes and reduced outflow facility, especially in uveoscleral pathway, during the nighttime. Monitoring and managing these variations of IOP are important clinical questions for glaucoma management.
- Continuous Monitoring of IOP
Dr. Kaweh Mansouri talked about new techniques in continuous monitoring of IOP. Traditional IOP measuring techniques, including Goldmann applanation tonometry (GAT), only measure a static value in a sitting position. It may be the lowest value of all the circadian periods. Triggerfish contact lens sensor from Sensimed measures circumferential changes around the limbus and circumferential changes reflect IOP changes. The 24-hour rhythm and timing of peak with Triggerfish correlate well with pneumotonometry, while amplitude does not. Another new device, the Goldfish contact lens sensor, can measure absolute IOP values and bench tests have shown promising results. Implantable sensors iares another way for continuous IOP monitoring, and can be implanted in the eye as part of cataract surgery or glaucoma surgery. Dr. Kaweh Mansouri concluded that new techniques should meet the criteria including being safety, accurate, and providing high frequency of measurements. It should be also cheap so that most patients can benefit from them.
- Managing Pressures in Clinical Practice
Dr. Yvonne M Buys talked about her experiences of how to manage patients clinically. Among all the risk factors for glaucoma, IOP is still the only modifiable risk factor. All clinical studies collectively prove that lowering IOP does lower the rate of progressive visual field loss and lower the risk of developing glaucoma in ocular hypertension. The target pressure can be different in different areas for practice. We need to individualize the treatment paradigm, considering both the severity of disease and life expectancy. We can get to the target through eyedrops, laser, and also expanding area of surgical options. Considering MIGS, there are still no good guidelines about where to fit them in the regimen. This is because current evidence for MIGS are still poor partly due to the poorly designed clinical studies. Dr. Buys suggested that we should follow the WGA guidelines about how to perform a good clinical study. There are other factors that need to be considered. For example, we should consider reducing posture effect for patients with progressive glaucoma and good IOP. Finally, “sometimes good enough is not enough.“ We should really try to get a low pressure in progressive glaucoma despite treatment.