Treating glaucoma

Most people with glaucoma are undiagnosed and not receiving treatment. This is largely attributed to glaucoma being essentially asymptomatic until later stages of the disease. Prevalence surveys demonstrate that¹:

• in high-income countries, <50% of all detected glaucoma was diagnosed previously
• in low-income and middle-income countries, >90% of people with glaucoma are not receiving care
• up to 35% of people diagnosed with glaucoma in low-income and middle-income countries are already blind

Burton and colleagues conducted an umbrella review of systematic reviews to gain a deeper understanding of the impact of eye conditions, vision impairment and ophthalmic interventions on quality of life. While all reviews indicated poor quality of life outcomes associated with eye disease and vision loss, 75% of ophthalmic interventions had a positive impact on quality of life¹. These findings highlight the importance and the opportunity of treatment to improve outcomes for glaucoma patients. Treatment challenges in glaucoma are illustrated in Figure 1.

Figure 1. The unmet needs in glaucoma treatment^1-7.

Glaucoma treatment challenges

Greater access to treatment

While early treatment can prevent glaucoma-related vision loss and change the disability adjusted life years burden, a lack of access to healthcare is a key unmet need in glaucoma^8,9. Social determinants such as educational opportunities, gender inequity and urbanisation have a major impact on vision loss and access to eye care¹. For glaucoma specifically, research has likewise revealed associations between socioeconomic factors and glaucoma^2–5. A study of the global health burden of glaucoma found that socioeconomic differences contributed to inequalities of provision of glaucoma care between countries⁸, with a study in Taiwan revealing that patient education is a key driver of patient adherence to topical glaucoma medication⁸. Low levels of glaucoma awareness across the world impact the use of eyecare services, further contributing to the lack of early detection and the possible benefits associated with timely treatment interventions⁹.

The World Health Organization has outlined that quality healthcare is that which is equitable, safe, effective, people-centred, timely, integrated and efficient¹. Unfortunately, for people living in low-income and middle-income countries and in underserved high-income countries, barriers to quality eye healthcare are particularly common and include cost, shortages of well-trained personnel, and lack of access to quality services, appropriate and well-maintained equipment and consumables¹. It has been demonstrated that services such as community outreach vision screening improve equity for women, older people and marginalised communities in glaucoma¹.

Effective treatments to prevent progression and restore function

High-quality clinical trials have demonstrated that lowering intraocular pressure (IOP) slows – and sometimes stops – glaucoma progression¹. However, safe and effective implementation of this treatment remains a challenge in all resource settings. For example, current treatment of long-term topical ocular hypotensive drugs demonstrates poor compliance and high ongoing costs in low-income countries and middle-income countries¹. Similarly, while laser trabeculoplasty has shown effectiveness in resource-scarce settings and can be administered in one session, it rarely provides lifetime IOP control¹.

The pharmacological agents currently available to treat glaucoma aim to reduce IOP either by increasing drainage from the eye, or by reducing aqueous production. However, some glaucoma patients will experience glaucoma progression despite a reduction in IOP or will present with progressive glaucoma but with IOP levels within reference ranges. Therefore, there is an unmet need for pharmacological treatment strategies that are IOP-independent and protect against glaucomatous neurodegeneration^6,7.

More minimally invasive surgical options

Although operations such as trabeculectomy have been part of common surgical practice for decades, they are technically challenging, complex, and require extensive training to undertake competently and manage the risks involved¹⁰. Further, the significant IOP-lowering effect of trabeculectomy is not required for all patients. Surgical interventions that are less complex and require less training would allow more patients to be managed surgically. The expansion of surgical interventions from traditional filtering surgery to angle-based and suprachoroidal procedures, often undertaken in conjunction with cataract surgery, has expanded the surgical options for treatment of glaucoma. There is an unmet need for more surgical options that provide long-term IOP-lowering effects^7,11,12.

Monitoring people with glaucoma

Monitoring patients’ response to glaucoma treatment is challenging in resource-limited settings and more remote communities; however, home-based monitoring using existing widely available technologies may soon be available. In addition, vision centres staffed with mid-level ophthalmic personnel supported by remote ophthalmologic support may provide appropriate ongoing monitoring and support for glaucoma patients in remote settings¹.

Along with rapid technological improvements, it is expected that a new care model for glaucoma detection and management will emerge, and unnecessary blindness being prevented through a combination of earlier detection, effective long-term IOP-lowering treatments and remote monitoring¹.

Rehabilitation

Recognising general challenges presented by rehabilitation, the World Health Organization has called for vision rehabilitation services to be provided as part of eye care. In order to provide person-centred support, including cultural, economic and social participation, partnerships with labour, social services and education are required¹.

Early detection and treatment of glaucoma can prevent progression and avoid blindness¹³

On average, people with glaucoma are treated for 20 years¹⁴

Lowering intraocular pressure (IOP) is the only proven way to preserve visual function^6,15. Topical medications or laser trabeculoplasty may be used as initial treatment for most forms of open angle glaucoma, with surgery a consideration for those patients with advanced visual field loss at presentation⁶. In people with ocular hypertension or with glaucoma in the absence of high IOP or severe damage, multiple IOP measurements may be worth considering before beginning IOP-lowering therapy⁶.

Target IOP for glaucoma

Determining target IOP

The aim of glaucoma therapeutic management is to lower the IOP of each eye to reduce the rate of visual field deterioration enough to maintain the patient’s quality of life. Therefore, it is important to set a target IOP as a treatment goal at diagnosis. The target IOP is the upper limit of the IOP that the healthcare professional considers is in alignment with this therapeutic aim⁶.

Because there is no singular target IOP level appropriate per patient, it needs to be determined for every eye of every patient – typically as a specific pressure level or percentage reduction. In newly diagnosed patients this would include consideration of the patient’s age, baseline IOP and the stage of their disease⁶.

When determining the individual target IOP, consider the factors outlined in Figure 2.

Figure 2. Factors to consider when determining the appropriate target IOP (Adapted⁶). ^*Family history, patient preference, adverse consequences of treatment, status of the other eye and central corneal thickness should also be considered. IOP, intraocular pressure.

Table 1 outlines target IOPs that may be sufficient/required at various stages of glaucoma.

Table 1. Suggested target IOPs for each stage of glaucoma^6,16. IOP, intraocular pressure.

Adjusting target IOP

It is important to review the target IOP regularly, and to modify the target if disease progression occurs or if ocular or systemic comorbidities develop⁶. According to the European Glaucoma Society⁶:

• if disease progression occurs after treatment or during follow-up, consider lowering the target IOP
• if glaucoma is stable during follow-up and the target IOP is reached, re-evaluate the patient as needed
• if glaucoma is stable during follow-up and the target IOP is not reached, consider a higher target IOP or add treatment, and re-evaluate the patient

Pharmacological treatment options for glaucoma

IOP-lowering drugs have been available since 1875; however, despite their longstanding availability, consideration of their side effects remains key. According to the European Glaucoma Society, it is preferable to prescribe/administer the least amount of medication possible to achieve the desired response and minimise side effects⁶.

When considering pharmacological treatment options for a patient, the following factors should be considered^6,17:

• Possible side effects
• Systemic therapy
• Comorbidities
• Adherence to treatment
• Cost
• Availability
• Life expectancy
• Patient preferences
• Drug interactions with other medications

A treatment can be considered effective when the IOP reduction on treatment is similar to the published range for the drug in a comparable population. Evaluation of efficacy may be assisted by uniocular drug trial⁶.

The following drug classes are ranked in order of the amount of IOP reduction they can achieve⁶:

• Prostaglandin analogues
• Non-selective β-blockers
• Rho kinase inhibitors
• Alpha adrenoceptor agonists
• Selective β-blockers
• Topical carbonic anhydrase inhibitors

Aside from cases of severe disease and very high IOP, initiating treatment with monotherapy is recommended⁶. Prostaglandin analogues (PGAs) are commonly recommended as first choice treatment of open angle glaucoma and are also recommended as first choice treatment of primary angle closure glaucoma following interventions to widen the anterior chamber angle⁶. PGAs are recommended thanks to their efficacy, safety profile and once-daily dosing. Although they provide additional IOP-lowering when combined with most other IOP-lowering drugs, combining two different PGAs is not recommended⁶.

If initial therapy is not tolerated or is ineffective, it is recommended that the patient switches to another monotherapy (any class) rather than adding a second drug. Laser trabeculoplasty can also be considered⁶.

If monotherapy is tolerated and effective, but is failing to reduce IOP to target, an additional drug of a different class can be considered. If available, fixed combination therapy is optimal to avoid potential issues with adherence and increased exposure to preservatives, which may occur with multiple topical treatments⁶. Although fixed and unfixed combinations generally demonstrate clinical equivalency, combination therapy is only recommended as first choice treatment when a single agent may not achieve target IOP, such as in cases of very high IOP and/or advanced glaucoma⁶.

In Europe, most fixed combinations contain a β-blocker, with the most common being a prostaglandin analogue with β-blocker. Systemic side effects may be associated with β-blockers so should be used with caution, particularly in patients with relevant contraindications⁶.

Examples of fixed combination formulations that contain β-blockers include^6,18-30:

• pilocarpine/timolol
• dorzolamide/timolol
• latanoprost/timolol
• brimonidine/timolol
• timolol/brinzolamide
• bimatoprost/timolol
• travoprost/timolol
• brinzolamide/timolol
• tafluprost/timolol

Examples of fixed combination formulations that do not contain β-blockers include^6,31-33:

• brimonidine/brinzolamide
• netarsudil/latanoprost

In patients whose IOP is not controlled adequately by two agents, a third agent can be considered. If IOP control continues to be inadequate on three agents, incisional or laser surgery may be considered⁶.

In all decisions about treatment and management of glaucoma, it is important to involve the patient and, if treatment efficacy is uncertain, temporary withdrawal of IOP-lowering medication with re-evaluation of untreated IOP can be considered⁶.

Common IOP-lowering drugs

Tables 2–8 outline common IOP-lowering drugs including compounds, mode of action, contraindications and side effects.. Note that not all drugs listed are available in Europe. For more information about compounds and whether they are approved for use in your region, refer to local guidelines.

Table 2. Prostaglandin analogues: compounds, mode of action, contraindications and side effects^6,21,34-40.

Table 3. β-receptor antagonists: compounds, mode of action, contraindications and side effects⁶. COPD, chronic obstructive pulmonary disease.

Table 4. Carbonic anhydrase inhibitors: compounds, mode of action, contraindications and side effects⁶.

Table 5. Alpha-2 selective adrenoceptor agonists: compounds, mode of action, contraindications and side effects⁶.

Table 6. Rho kinase inhibitors: compounds, mode of action, contraindications and side effects^6,41,42.

Table 7. Parasympathomimetics (cholinergic drugs): compounds, mode of action, contraindications and side effects⁶. TM, trabecular meshwork.

Table 8. Osmotics: compounds, mode of action, contraindications and side effects⁶.

When reviewing treatment options for glaucoma patients, local toxicity is worth consideration, as preservatives in topical drug formulations can cause/exacerbate pre-existing ocular surface diseases such as dry eye. Benzalkonium chloride is the most common preservative found in glaucoma medications, and long-term use can result in a diminished success rate of filtering surgery. Therefore, when treating patients with ocular surface diseases, consider alternative options such as preservative-free formulations⁶.

Surgical and other options to treat glaucoma

Open angle glaucoma

Trabeculectomy is the most common surgical procedure used in glaucoma and is recommended as initial surgical treatment for open angle glaucoma, in which case augmentation with antifibrotic agents is recommended (provided the ophthalmologist is familiar with antifibrotic use). In many cases, long-term IOP control is achieved, and its long-term success is reportedly high in unoperated eyes⁶. Trabeculectomy is indicated when other therapeutic options have failed to control glaucoma or are unsuitable, and where topical medications and/or laser are unlikely to achieve target IOP. Interestingly, preservation of visual field does not differ significantly whether a patient with mild disease is initially treated with medication or laser or trabeculectomy. However, initial surgery may be more appropriate in advanced glaucoma. Long-term risks include accelerated cataract progression, blebitis/endophthalmitis, and hypotony which could threaten vision^6,16.

Other surgical options are also established including non-penetrating surgery such as viscocanalostomy and deep sclerectomy^43,44. Newer minimally invasive techniques such as gonioscopy-assisted transluminal trabeculotomy (GATT) and subconjunctivally placed micro-shunts are gaining popularity^45-47.

Angle closure glaucoma

When reviewing surgical treatment options for primary angle closure glaucoma, it is important to consider the spectrum of disease and whether cataract is present^6,16,48.

• In people aged <50 years and at high risk (e.g. high hyperopia and those requiring repeated pupil dilation for retinal disease), laser peripheral iridotomy (LPI) and surgery combined with medical treatment should be considered
• For primary angle closure suspects (PACS), LPI is recommended for high-risk individuals
• In primary angle closure glaucoma (PACG) or PAC, LPI is recommended as first-line treatment
• In patients with early to moderate PACG and co-existing cataract, lens extraction is recommended as the initial treatment option
• For patients with phakic and PACG, phacoemulsification +/− glaucoma surgery is recommended with reference to angle status and disc and field damage

For more information on treatment:

Click here to view the NICE guidelines’ treatment recommendations for people with chronic open angle glaucoma

Click here to view the NICE guidelines’ treatment recommendations for people with ocular hypertension

Emerging technologies to help treat and manage glaucoma

In this video, Professor King describes how artificial intelligence, developments in genetic technologies, and new treatment options such as neuroprotective medications, may transform how glaucoma is treated and managed in the future.

Given the projected increase in global glaucoma prevalence over the coming decades, there is a need to deliver more services to more people, and to develop innovative treatment strategies¹. Developments in technology, including artificial intelligence, telemedicine, mobile health, distance learning and low-cost retinal cameras, may help deliver high-quality, affordable, and more equitable eye health services to more people in more geographical areas, and is projected to lead to improvements in eye health over the next ten years1. In addition, the development of neuroprotective treatments that may supplement or indeed replace IOP-lowering treatment are an exciting prospect for the many people at risk of glaucoma¹⁴.

Figure 3 highlights key considerations for patient management.

Figure 3. Considerations for patient management^1,6. IOP, intraocular pressure.

Eye care in primary care settings

In many countries, general primary healthcare staff assess, treat and refer people who experience issues with their vision. While training manuals and other supports have been developed to enable the delivery of primary eye care by primary healthcare staff, experiences are mixed because of knowledge and skill gaps, lack of equipment and lack of ongoing support. In some low and/or middle-income countries, mid-level ophthalmic personnel are permanently based in primary healthcare facilities. For example, in The Gambia ophthalmic nurses work in large district health centres, bridging primary health care with secondary services¹.

In middle-resource and high-resource settings, specialised personnel typically provide primary eye care. Within community settings of high-income countries, primary eye care is commonly provided by optometrists, eye health specialists or ophthalmologists in the public and private sector, with access to sophisticated diagnostic equipment¹.

These differences in eye care delivery within primary care highlight the challenges and opportunities to deliver higher quality eye care to people within the primary care setting.

Tailoring glaucoma treatment to the patient

When managing people with or at risk of glaucoma, their wellbeing and quality of life are of primary importance. Wellbeing and quality of life are impacted by visual function, costs and side effects of treatments, and the psychological impacts of having a progressive sight-threatening condition. Quality of life is largely determined by binocular visual function or the visual function of the best eye, while progression rates of each eye (separately) help determine treatment. Target intraocular pressure (IOP), follow-up frequency and treatment intensity should be balanced against the risk of loss of quality of life due to glaucoma⁶.

It is therefore important that glaucoma treatment is tailored to the patient on the basis of their individual needs, personal preferences, general health status and the rate of progression.

The following patient-specific features may influence glaucoma management⁶:

• IOP at baseline and IOP reduction achieved
• Family history
• Severity
• Diagnosis and type
• Life expectancy and comorbidities

Patient information needs in glaucoma

When managing people with glaucoma, it is important to be aware of their information needs and any information gaps. Patients may experience anxiety at diagnosis, and throughout management of their glaucoma. Information deficits can add to anxiety, whereas providing information can help support patients, enabling them to engage in self-care and lifestyle changes, helping ensure more effective overall management of their condition⁶.

Consider the following key information gaps when managing people with glaucoma⁶:

• Provide information to patients on the diagnosis and management of their glaucoma and for any treatments they may be requiring
• Uncertainty about driving regulations and when patients may need to notify authorities of their vision loss
• Patients can have difficulty understanding the specifics of their visual field loss – providing accurate information can help them develop strategies to manage the impacts of changes to their visual field, such as using fall-prevention techniques
• Given that patients are commonly treated for decades, and in that time their ability to manage their condition will change, it may be difficult for them to adhere to their treatment – consider regular check-ins on their ability to instil their eye drops, drop instillation training where necessary, and training to enhance adherence
• While trabeculectomy or other glaucoma surgery may be routine for a surgeon, such prospects may be very confronting for a patient – consider providing patients with the information they need to feel informed about surgical options and give patients adequate time to consider and understand the options available
• For various reasons, patients may be uncomfortable to ask HCPs about their condition – it is important to invite them to ask questions during every appointment, or to encourage them to bring a list of written questions, or a support person
• Refer patients where possible to glaucoma patient support organisations where they can receive further information and support from peers

For professional support when managing people with or at risk of glaucoma, ophthalmologists and other healthcare professionals can refer to guidelines such as:

• The European Glaucoma Society’s Terminology and Guidelines for Glaucoma
• The Preferred Practice Pattern Guidelines in Ophthalmology published by the American Academy of Ophthalmology
• National Institute for Health and Care Excellence Glaucoma guideline
• The Asia-Pacific Glaucoma Society’s Asia Pacific Guidelines