Education Committee Highlights WGC-2019 -part 1

The Education Committee carefully selects presentations from the WGC-2019 for your benefit. This month Pradeep Ramulu kicks off the 2019 videos and introduces the following sessions: A holistic view on glaucoma: A case based approach and Fuelling the power house.

A holistic view on glaucoma: A case based approach
Randy Craven discussed the reasons for, and approach to, pigmentary glaucomas occurring for reasons other than pigment dispersion syndrome. Any cause of pigment release can obstruct conventional outflow through the TM, leading to IOP elevation. Secondary pigment dispersion syndromes can occur for reasons such as trauma, herpetic infections and chronic atropine use, but are most often found with IOL-related issues, including sulcus IOLs (especially one-piece lenses) and piggyback IOLs. Gonioscopy before and after dilation is important in IOL-related pigment dispersion to confirm haptic positions, and UBM may be considered for this purpose as well. Initial treatment options for IOL-related pigment dispersion are to either dilate or constrict the pupil based on which is most likely to minimize iris chaffing given the eye anatomy. In cases where medical treatment fails, Dr. Craven gives examples of how the IOL can be modified or repositioned to prevent further pigment release, and reduce IOP.Challenges in pseudoexfoliative (PXF) glaucoma were discussed by Gauti Johannesson. Dr. Johannesson reviewed the aggressive course which often accompanies PXF glaucoma, as demonstrated by the Early Manifest Glaucoma Trial (EMGT). Challenges in managing PXF include lens related issues (i.e. lens/IOL dislocation) and more complications at the time of cataract surgery. Using various patient examples, he discusses both the pros of early cataract surgery (i.e. enjoying the IOP-lowering effect), and also the cons of early cataract surgery (more time for IOL displacement later), suggesting that early cataract surgery is generally a good idea. He also discusses whether additional challenges are present which guide how the patient should be managed medically by their primary doctor, suggesting that no additional health checks or screening exams are required.

Anthony Hall, a uveitis expert from Melbourne, discussed the epidemiology, etiology, and treatment options in uveitic glaucoma. Data are reviewed showing that roughly 20-30% of patients followed for uveitis clinic will present with significant IOP elevation after 10 years of follow-up, with particularly high rates of associated glaucoma in eyes with uveitis due to Posner-Schlossman, viral infections, toxoplasmosis, and JIA. In one study, even higher rates of glaucoma were noted, with 6% of eyes developing glaucoma annually, and nearly 2% of eyes going blind from glaucoma annually. Dr. Hall describes the various mechanisms of glaucoma in uveitis, broadly dividing mechanisms into open vs. closed angle mechanisms. Steroid response also plays a role in uveitic glaucoma, and data are reviewed suggesting that with enough steroids, most patients will demonstrate an IOP rise. Regarding the management of glaucoma, caution should be given to OCT imaging, as uveitis can be associated with RNFL thickening. Regarding treatment, Dr. Hall emphasizes that proper treatment of the inflammation is critical, and suggests that fears regarding prostaglandin therapy are overblown. He also reviews the broad array of surgical treatments, including trabeculectomy and tube shunt surgery.

Stephanie Watson discussed a common and often vexing aspect of glaucoma care: ocular surface disease. The causes of ocular surface disease are many (medication use, prior surgery, etc), and are important to identify to direct treatment optimally. Aspects of treatment include eliminating medication toxicity, ensuring healthy tears, controlling inflammation, dealing with persistent epithelial defects, and fixing the eyelids. Medication toxicity can be minimized by reducing exposure to BAK. Inflammation treatment depends on the severity of disease, and can include steroids in more advanced disease. Fluorometholone is discussed as a particularly attractive option given its high potency relative to its propensity to raise the IOP. Special situations are discussed where ocular surface disease are common, including corneal grafts, vernal and atopic keratoconjunctivitis, and aniridia. Approaches to optimal medication use are presented, with an emphasis on non-preserved medications, combination therapy, and avoidance of unnecessary medications, particularly prostaglandins.

Sheila Marco discusses principles for the optimal management of traumatic glaucoma. Glaucoma from trauma can occur for many reasons, including hyphema, angle recession, lens-related issues, and ghost cells. Risks for developing glaucoma (as well as the proposed mechanisms of glaucoma) are reviewed, including hyphema or cyclodialysis occurring with injury, greater degrees of angle recession, phacodonesis, and heavy trabecular pigmentation. Dr. Marco discusses management strategies for hyphema, which can raise IOP in the early period after injury, including optimal medical therapy, and when surgery should be considered. The variable timing of presentation with angle recession was discussed, and specific pearls for treating angle recession glaucoma were presented, such as avoidance of pilocarpine therapy and laser trabeculoplasty.

Thasarat Vajaranant presented several pearls regarding the treatment of glaucoma during pregnancy. While glaucoma is not a common condition in pregnancy, few guidelines exist about treating glaucoma during pregnancy, and many practitioners have limited experience with this condition. While IOP typically reduces during pregnancy, in glaucoma patients, VF progression and/or IOP elevation is not uncommon (almost 20%). Recommendations for medication therapy during pregnancy are given, including particular caution regarding treatment over the first trimester, attention to medication concentration, punctal occlusion, attention to risk classification systems, and appropriately tailoring therapy during the period of lactation. Options for lowering IOP with procedures (laser trabeculoplasty or surgery) are also presented, and recommendations are given regarding when and how surgery should be done to minimize risks to the fetus.

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Fuelling the powerhouse
This session focused on the importance of the mitochondria in glaucoma, and how this information relates to the pathophysiology of glaucoma and possibility of treatment.

Ian Trounce discussed the possibility of mitochondrial therapeutics for optic nerve dysfunction. Dr. Trounce first described the mitochondrial life cycle and where therapies might be helpful (i.e. mitophagy, the process by which cells remove damaged mitochondria). The potential importance of mitochondria in glaucoma is suggested by the numerous mitochondrial genetic mutations producing optic atrophy. Also, in peripheral cell lines, POAG show a deficiency in mitochondrial Complex I (as demonstrated by reduced rates of ATP synthesis). More recently, smaller genetic studies have suggested that specific mitochondrial DNA haplotypes are associated with a reduced risk of glaucoma. While no mitochondrial therapeutics are in practice, studies in mice have suggested that modulation of mitochondrial vulnerability using Vitamin B3 prevents glaucoma in aged mice. Thus, further work is necessary to determine the key aspects of mitochondrial function which might be modified as part of therapy, and testing potential therapies in both animal and human models.

Ted Garway Heath discussed a more clinical approach to how to study the role of mitochondria in human glaucoma. Conceptually, the potential importance of mitochondria in glaucoma is supported by the heavy reliance of RGC axons on mitochondria due to the high energy demands created by axon potential generation, particularly in the unmyelinated portion of the optic nerve. Other important cells may be heavily reliant on mitochondria, including glial cells and trabecular beams. The impressive genetic evidence for mitochondrial function to glaucoma is also reviewed. One very impressive study was discussed, which showed mitochondrial efficiency was much higher in ocular hypertensive patients as compared to both normal controls and patients with normal tension glaucoma patients. More recent work is also discussed which shows that mitochondrial respiratory capacity decreases with severity of glaucoma, and lower in NTG patients as opposed to those with high-tension glaucoma. Dr. Garway Heath also describes his future planned work, which will look at longitudinal changes in glaucoma progression with measures of mitochondrial function.

Nick Marsh-Armstrong discussed the relevance of mitochondria and astrocytes in the optic nerve head to glaucoma. Dr. Marsh-Armstrong showed evidence that astrocytes change morphology in glaucoma, and that they phagocytose axonal mitochondria, a phenomenon also observed in monkeys. Data are also shown in which mitophagy can be directly imaged in vivo (in Xenopus). Dr. Marsh-Armstrong then shows evidence that several optineurin mutations prevent movement of optineurin across the span of RGC axons, suggesting that it may play a role in astrocyte mitophagy of axonal mitochondria (transmitophagy).

Bang Bui discussed the impact of aging on the optic nerve, starting out by sharing the striking increase in prevalence and incidence of glaucoma with age. Age not only affects the number of RGCs, but also the number of synapses and the smaller dendritic and axonal arbors. Of interest, however, RGC function does not decline much despite these age-related structural changes, suggesting that age-related compensatory mechanisms. However, these compensatory mechanisms may exert a price, as suggested by data suggesting that the same level of IOP creates greater dysfunction and slower recovery in RGCs from older mice, as compared to younger mice. Data and ongoing experiments are presented regarding the issue of whether this greater IOP susceptibility with age is the result of vascular parameters or tissue factors (i.e. changes in stiffness).

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