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The Changing Landscape of Glaucoma

2T CPD in Australia | 0.5CD in New Zealand | 1 July 2018
Figure 4. Punctate epitheliopathy associated with topical glaucoma medication use

By Dr. Simon Skalicky

Ten major changes over the past 10 years have significantly altered and improved the delivery of glaucoma healthcare. These changes have come about thanks to a growing understanding of glaucoma risk factors and pathogenesis, along with technological innovations, therapeutic advances, and a more informed approach to patient education. The next 15–20 years look promising for people with, and at risk of, this blinding disease.

LEARNING OBJECTIVES

1. Understand the changing indications for glaucoma surgery in light of MIGS and the need for it to be considered when planning cataract surgery for glaucoma patients
2. Appreciate the impact of technology on glaucoma clinical care, the role of SLT as an alternative to topical medical therapy and the role of patient education
3. Understand the concept of managing ocular hypertension and the role of OCT scanning in glaucoma diagnosis and monitoring
4. Recognise how to manage glaucoma patients with dry eye syndrome and the influence of diet and lifestyle on glaucoma.

Over the last decade the way experts understand and treat glaucoma has changed dramatically. The textbook approach to glaucoma 10 years ago would have omitted reference to standard concepts of today, such as Minimally Invasive Glaucoma Surgery (MIGS), optical coherence tomography (OCT) progression analysis, collaborative care models and dietary modifications. Progress has occurred thanks to a series of technological innovations, altered trends in service delivery, changes in thinking and therapeutic advances; all leading to a substantial paradigm shift in glaucoma management. Below is a list of 10 ways in which the standard of clinical care for glaucoma has altered over the last 10 years.

MINIMALLY INVASIVE GLAUCOMA SURGERY

MIGS represents a broad group of small surgical devices characterised by minimal conjunctival dissection, short operating times, rapid recovery and a good safety profile.

This is a rapidly expanding field with transtrabecular devices (eg. Istent Inject, Figure 1A) increasingly performed in conjunction with cataract surgery. Other devices are available with a growing body of supportive data, such as:

  • the Cypass, which creates a cyclodialysis cleft and drains to the suprachoroidal space (Figure 1B),
  • Hydrus, a fenestrated curved tube that enters, passes through and dilates Schlemm’s canal (Figure 1C), and
  • Xen Gel Implant, a soft collagen implant that is inserted, ab interno, from the anterior chamber into the subconjunctival space creating a bleb (Figure 1D).

Figure 1A. iStent inject

 

Figure 1B. iCypass

 

Figure 1C. Hydrus

 

Figure 1D. Xen gel implant

The result of this disruptive technology is that glaucoma surgery, long relegated to advanced disease recalcitrant to medical therapies, can now be offered much earlier in the disease course owing to its improved safety profile. The potential for glaucoma to shift from a primarily medically to surgically treated disease is here, although currently being limited by Medicare which restricts MIGS devices to use with  cataract surgery. The exception is the Xen, which in many ways is more similar to traditional filtration surgery than to other MIGS devices. It is permitted for stand alone use, and is increasingly used as an alternative to trabeculectomy.1 Xen appears to be highly effective, reducing glaucoma medication and resulting in an average IOP of 12mmHg. It does, however, produce a bleb, and can result in bleb-related complications like a trabeculectomy: fibrosis (sometimes requiring multiple needlings), blebitis, over drainage and dysasthesia.

With various MIGS devices (iStent, Hydrus, Cypass) available in conjunction with cataract surgery, cataract management among glaucoma patients has become more involved than just a few years ago; we now must decide whether MIGS should be used, and which device to use. We used to be satisfied with the 1-2mmHg intraocular pressure (IOP) lowering of cataract surgery alone. Now the goal posts have shifted, and MIGS should really be considered with phaco for all patients with glaucoma. Because of the Medicare restrictions, not offering MIGS could be a missed opportunity.

This is most relevant for patients with problems in IOP control, adherence or ocular surface disease. iStent, with its excellent safety profile and no substantial increased risks to cataract surgery, should be strongly  considered.2 While the data comparing MIGS head-to-head is lacking, it seems that larger devices, such as the Cypass, should be considered in more advanced glaucoma, or for patients on multiple topical medications in whom the iStent is less likely to render them medication-free.3 Cypass appears to lower
the IOP 2mmHg on top of the effect of cataract surgery, with additional reduction in topical medication load. Complications such as transient uveitis, hyphaema, IOP spike or transient myopic shift can all occur with the Cypass.

SELECTIVE LASER TRABECULOPLASTY AS FIRST LINE GLAUCOMA THERAPY

With growing confidence, Selective Laser Trabeculoplasty (SLT) is used as a primary treatment for ocular hypertension or open angle glaucoma (Figure 2).

Figure 2. SLT

SLT uses brief (three nanosecond) pulses of diffuse (400 μm spot size) laser at 532nm (frequency doubled Q-switched Nd: YAG laser) to provide selective thermolysis to only pigmented endothelial trabecular meshwork (TM) cells. The short and diffuse pulses prevent heat transfer and spares adjacent cells and tissues from coagulative or disruptive damage, which is seen with argon laser trabeculoplasty (ALT).4 SLT modifies cellular activity and cytokine release causing greater aqueous outflow through the TM.5 SLT is generally performed as an office based procedure resulting in an average 25 per cent IOP reduction with 70–75 per cent success rate, lasting on average, three to four years.6

This challenges the widely practiced paradigm of topical IOP lowering drops as first line care for ocular hypertension and glaucoma. Our previously held tenets, that laser should be used only when drops fail, is too restrictive. Today, many patients do not want the bother of daily medications, the challenge of maintaining adherence and perseverance (and the stress of failure to adhere), and the discomfort and ocular surface disease associated with regular topical medications.

Indeed, while the evidence has progressively mounted for the safety and efficacy of SLT,7 so too are we learning more about the failures of topical medical therapy. SLT is frequently quoted to be less effective on subsequent treatments than primary treatment, yet new evidence suggests repeat 360 degrees. SLT is as effective as initial 360 degrees treatment.8,9,10 In many ways, topical medical therapy lets us down: the drug
tachyphylaxis impairs reliable long term IOP control; persistence and adherence is generally suboptimal, and drops do not reliably prevent progression to advanced glaucoma. Additionally, these drops can result in long term, irreversible structural changes to the ocular surface, exacerbated by preservatives (leading to chronic blepharitis and dry eye syndrome).11

Compared to SLT, ALT was more destructive (Figure 3), and could cause nasty complications such as an intractable rise in IOP. This is why, in the past, it was appropriate to reserve ALT only for cases in which drop therapy had failed. SLT has fewer, minor complications (generally a red, irritated or inflamed eye that settles in days), but its safety profile is generally very good, and can be used early in glaucoma or ocular hypertension (OHTN) with good effect.

Figure 3. ALT vs. SLT

OCULAR SURFACE DISEASE AND GLAUCOMA:

BETTER TREATMENTS, MORE DROP OPTIONS AND ALTERNATIVES

Ocular surface disease is commonly associated with glaucoma, and present in up to 20–60 per cent of glaucoma patients.12 Glaucoma management, especially based on preserved topical therapy, often exacerbates ocular surface disease (Figure 4). Today there is a greater awareness of the need to not only optimise IOP control, but to do so in a way that is relatively gentle on the ocular surface. The tools are here to do so: as discussed above, alternative treatments like SLT and MIGS are gentler on the ocular surface.

Preservatives are important to prevent build-up of pathogens within opened drop bottles, but are tough on the ocular surface when used long term. Combination topical medications, ‘gentler’ preservatives and preservative free topical preparations help reduce the burden of dry eye syndrome. The strongest preservative is probably Benzalkonium chloride (BAK), a soaplike quaternary ammonium, found in many common ophthalmic drops. Today alternative preservatives to BAK are available. Polyquad, found in Travatan, is a quaternary ammonium like BAK, but with a much larger molecule and hence not internalised by epithelial cells. Purite, found in Alphagan P, is a preservative that breaks down on contact with air. However, many patients using alternative preservatives to BAK or preservative free medications still suffer from dry eye syndrome, indicating that BAK is not the only culprit; dry eye syndrome is a multifactorial condition.

In current practice there is a greater emphasis on ocular surface health among glaucoma patients involving lid hygiene, preservative-free lubricants, dietary supplements, targeted anti-microbial treatments and in select cases punctual plugs and cyclosporin. Most importantly we now understand that if a patient is clearly suffering from their topical glaucoma drops, asking them to persist with those drops is no longer necessary. There are many alternative options they can pursue to control the IOP and improve their quality of life.13

OCT DIAGNOSIS AND MONITORING FOR GLAUCOMA AND OCT ANGIOGRAPHY

OCT structural analysis is increasingly used for glaucoma diagnosis and monitoring. As visual field (VF) defects only manifest once 30–50 per cent of the retinal ganglion cells are lost,14 structural OCT analysis provides much earlier and more sensitive diagnosis. As a result of this widespread technology, we are diagnosing glaucoma earlier than ever before.

This impressive technology is rapidly evolving – refinements include macular ganglion cell and inner plexiform layer analysis, the use of Bruch’s membrane opening (BMO) as a point of reference for disc analysis, and improved algorithms for detecting progression.15 OCT progression analysis provides invaluable aid to glaucoma monitoring and treatment planning, allowing key decisions to be made long before significant visual loss occurs (Figure 5).16

Figure 5. OCT progression analysis of the RNFL; left superior RNFL thinning

Interpretation of OCT findings in glaucoma is now critical; false positives are common and findings in myopia or macular disease are difficult to interpret. We must learn to distinguish ‘red-disease’ (OCT abnormal findings but otherwise healthy discs) and ‘green-disease’ (normal OCT analysis despite other clear signs of glaucoma). Combining information from different structural measurements, such as retinal nerve fibre layer (RNFL) thickness, macular-ganglion cell layer, macularinner plexiform layer, may improve the diagnostic accuracy of OCT.

OCT-angiography, evaluating calibre and flow of small vessels in the optic nerve head and superficial macula, is an exciting development and shows promise to detect early glaucomatous changes.17

OCULAR HYPERTENSION – NOT TO BE IGNORED

As we use OCT to detect glaucomatous damage earlier, the distinction between ocular hypertension (OHTN) and glaucoma shifts. What we previously called OHTN is in fact early glaucoma that we lacked the tools to detect.

Furthermore, it is conceivable that glaucomatous damage might be occurring even earlier than we can detect on today’s tools (OCT); damage on an ultrastructural, cellular level, for which detection is beyond our current imaging modalities. For these reasons, the old tenet “don’t treat ocular hypertension, wait for visual field loss before treatment” often does not hold up in today’s practice. OHTN can be considered as the very beginning of a journey that ultimately leads to visual loss and incapacity; the earlier we intervene the better (Figure 6). Treating OHTN to reduce future glaucomatous damage needs to be considered case by case, in light of glaucoma risk factors: family history, myopia, thin central corneae, systemic vasculopathy or suspicious disc findings (Figure 7).18 This does not apply for OHTN associated with very thick central  corneae, which is probably ameasurement artefact.

 

Figure 6. The glaucoma continuum

 

Figure 7. Results from the Ocular Hypertension Treatment Study

Treating OHTN with SLT, as opposed to drops, is appropriate. In many ways the risk/benefit analysis of topical drop therapy treatment for OHTN does not stack up, as the side effects and problems with drop treatment are worse than the condition. This is not the case of SLT, which is overall better tolerated and has a lesser impact on daily life than drops.13,19 For many patients who understand the future implications of glaucoma, have seen relatives lose vision, and are unhappy with raised IOPs, there is a strong desire to be proactively preventative; SLT makes a lot of sense for them.

EXTERNAL DRAINAGE TUBE DEVICES

An external drainage tube device, such as the Molteno, Baerveldt or Ahmed tube, is a form of glaucoma filtration surgery typically reserved for cases in which the trabeculectomy has failed previously, or is likely to fail. Tubes are not new, but today are being used more frequently and earlier in our surgical algorithms, as an alternative to primary or revision trabeculectomy. In the past they were rarely performed, instead reserved for a select few glaucoma surgical cases. The advantage of the larger plate models (e.g. Baerveldt) is that the plate is placed under the recti muscles (typically lateral and superior) allowing a much broader area of drainage and lower chance of bleb encystment (Figure 8).

Figure 8. Baerveldt glaucoma drainage device

Supported by robust evidence (such as the Tube v Trabeculectomy study,20 the Primary Tube v Trabeculectomy study21 and Ahmed v Baerveldt study22) we are using tubes more commonly for cases in
which the trabeculectomy is likely to scar and fail. We are also using them more commonly for failed trabeculectomy while performing revision or redotrabeculectomies less frequently.

COLLABORATIVE CARE FOR GLAUCOMA IN AUSTRALIA

Optometry and ophthalmology in Australia are today working closely together to provide a mutually agreeable and safe model of collaborative glaucoma care; this would have been inconceivable a generation ago. This is to the credit of both professions, and addresses the wider need to provide optimal healthcare to all  Australians despite limited healthcare resources.

Following a RANZCO sponsored Collaborative Care Referral pathway and a memorandum of understanding
between RANZCO and Specsavers, the path is now clear for wider expansion and closer collaboration between our professions.23 Creating meaningful key performance indicators, monitoring data and quantitative evaluation of the model are steps underway to enhance this.

The bedrock of collaborative care is communication. Digital correspondence, with the possibility of an electronic referral footprint and pooled resources on a dedicated e-platform, should enhance closer collaboration and improve patient care.

DIGITAL DISRUPTION – GLAUCOMA E-HEALTH PROMOTION

E-health and smart phone technology has allowed some tantalising opportunities in glaucoma care. Apps to remind patients of appointments, pre-programmed drop reminders and health self monitoring systems are just the beginning. Tablet and smart phone based means of vision testing allow glaucoma to be diagnosed and monitored potentially out of clinics, providing a greater reach and penetrance of glaucoma services.24

This, combined with glaucoma awareness campaigns based on social media, will hopefully improve the appalling 50 per cent rate of undiagnosed glaucoma in our community. In recent months we have all witnessed the dark side of ‘big i-brother’ – Cambridge Analytica and Facebook, for example – but using social media to better target glaucoma screening and awareness campaigns, and deliver much needed
glaucoma education to patients via digital links, is a fascinating paradigm shift.

Organisations such as Glaucoma Australia (GA) are beginning to enter into this uncharted territory. GA is exploring IT solutions to better connect with glaucoma patients and their families. GA is building a sophisticated, informative and interactive website, with tailored entry portals for patients, optometrists, ophthalmologists and pharmacists. This is linked with a strong social media presence, which was put to good effect for World Glaucoma Week this year to promote glaucoma awareness and encourage screening.

One exciting opportunity is via new software interface platforms, like Oculo. Using this platform, if patients provide consent, an electronic contact with GA is generated when they are referred on Oculo by their optometrist as a glaucoma patient or suspect. They are invited electronically to the GA webpage, and social media and email for subsequent patient contact is then possible. The issue of family risk (and encouraging their relatives to be screened) is addressed. This approach requires an interface between clinicians and IT experts to be fine tuned to ensure we are capturing the right patients.

NUTRITION, LIFESTYLE AND GLAUCOMA

Ten to 15 years ago, there was little evidence for the impact of nutrition on glaucoma. Today, thanks to large population studies such as the Nurses Health Study, we know that diet can influence glaucoma, and we
must counsel our patients accordingly. A diet rich in nitrates (found in green leafy vegetables) is protective against glaucomatous vision loss.25 Further evidence suggests that low levels of niacin (vitamin B3) is associated with glaucoma, and that high-dose vitamin B3 might even confer some neuroprotection.26,27
B3 is found plentifully in turkey, chicken, peanuts, mushrooms, liver and tuna, and of course Vegemite! Omega-3 fatty acids, found in oily fish (eg. salmon) and chia, has been shown to lower rates of glaucoma.28

Other lifestyle factors, such as smoking, obesity or inactivity can increase the risk of glaucoma.29,30 One curious study found that exposure to dog antigens reduced glaucoma risk and cat antigens increased glaucoma risk (Figure 9).31 The pathogenesis explaining this association is far from clear, but suggests a role of chronic inflammation (possibly of the ocular surface) in the development of glaucoma.

Figure 9. ‘Daisy’ Skalicky. Will she prevent her master getting glaucoma?

A PATIENT CENTRED APPROACH TO GLAUCOMA CARE

In previous times it was acceptable for patient care to be didactic. However, this generation of patients wants to know more about their disease, and be actively informed about the holistic management of their glaucoma. The onus is now on specialists to communicate better and in a more modern fashion to our patients and with each other. Knowledgeable patients lead to best health outcomes.32 Patients need expert support and direction to accurate information, as much distress and misinformation can come from relying on Dr. Google.

In glaucoma, key predictors for management success are participation in regular clinical monitoring and adherence to treatment. Education about the nature of glaucoma, its prognosis, the need for ongoing monitoring and treatment improve the patient’s knowledge, engagement and experience, and outcomes.33,34

THE FUTURE

Contemplating all these changes, it is easy to imagine how glaucoma may change further in the near future. While nothing is certain, here is what glaucoma management may look like in the next 15–20 years:

  • Improved genetic knowledge to target screening and identify individuals at risk of developing glaucoma.
  • Genetic assessments to better identify patients who will respond well to particular treatments.
  • Novel therapeutic agents, developed from stem cells, that target neuroprotective pathways.
  • Better structure/function correlation linking visual field with OCT structural parameters improving diagnosis and progression analysis.
  • Machine learning (eg. artificial neural networks) to allow automated glaucoma diagnosis and monitoring for visual field, disc photos and OCT analysis.
  • An online referral pathway improving digital footprinting of referral patterns. This information will enhance the link among patients, referrers and glaucoma specialists and improve retention to monitoring programs.
  • Patient self-owned health database (eg on an online blockchain protected dataset, or a government sponsored database like ‘MyHealth’) will allow better consistency and pooling of medical records and monitoring of data.
  • Continued development of new glaucoma surgical devices. While the current MIGS offer wonderful opportunities, none reach the ultimate ‘10-10-10’ goal in glaucoma surgery, set by Professor Sir Peng Khaw: a procedure that takes 10 minutes, resulting in an IOP of 10mmHg and lasting 10 years. Such a procedure is necessary to impact glaucoma on a global scale. Such a procedure is likely to require external, subconjunctival drainage (like the Xen or InnFocus) and improved means of subconjunctival fibrosis control (ie. more reliable and safer than mitomycin C).
  • Better funding for targeted glaucoma screening programs that may hopefully improve the 50 per cent undetected rate. These may use clever strategies involving social media health promotion, tabletbased visual function tests and/or genetic risk profiling.

 

 

        
Dr. Simon Skalicky FRANZCO, PhD, BSc (Med), MPhil, MMed, MBBS (Hons 1) is a Victorian ophthalmologist with subspecialty skills in glaucoma and cataract. After completing medical school with first class honours, hospital residency and ophthalmology training in Australia, he undertook subspecialty fellowship training at Cambridge University in the United Kingdom where he studied glaucoma and cataract surgery. Currently he holds consultant posts at the Royal Victorian Eye and Ear Hospital and Royal Melbourne Hospital. He consults privately at Eye Surgery Associates in East Melbourne, Malvern and Vermont South.
Dr. Skalicky is widely published and actively involved in training medical students, ophthalmology registrars and glaucoma subspecialty fellows. He is an active clinical researcher in the field of glaucoma, particularly interested in evaluating glaucoma management from the perspective of the patients’ experience and their quality of life.  He is a Clinical Senior Lecturer at the Universities of Sydney and Melbourne. He is a federal Councillor and Chair of the Ophthalmology Committee for Glaucoma Australia. He is Victorian representative for the Australia and New Zealand Glaucoma Society, and on the Associate Advisory Board and Scientific Committee for the World Glaucoma Association.   
 
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' What we previously called OHTN is in fact early glaucoma that we lacked the tools to detect '