Diagnosing glaucoma

Unmet needs for diagnosing glaucoma

In this video, Professor Anthony King discusses the unmet needs for diagnosing glaucoma, highlighting the benefits of developing screening strategies and improving patient education.

Considering the importance of early diagnosis, yet the difficulty in achieving it, reliable diagnosis of early-stage glaucoma remains an unmet clinical need¹

Given that the glaucoma disease process begins up to 20 years before diagnosis is possible, in which time irreversible vision loss may have already occurred, there is a need to develop techniques to diagnose glaucoma earlier, when treatment has a higher chance of improving clinical outcomes^2,3. While glaucoma is associated with increased intraocular pressure (IOP)⁴, and a primary treatment goal is to reduce IOP in order to prevent further optic nerve damage⁴, measuring changes in IOP and using those measurements to inform diagnosis, treatment and monitoring is problematic for several reasons.

Early glaucoma diagnosis with high specificity and sensitivity

Following age, elevated IOP is the strongest risk factor for primary open angle glaucoma⁵. However, research indicates that no single value of IOP is sufficiently sensitive or specific enough to detect glaucoma. For instance, although high IOP is a risk factor for glaucoma, high IOP in isolation is not indicative of glaucoma. Conversely, a person with normal IOP values can have glaucoma. IOP alone – in the absence of optic disc examination or visual field test – is therefore not an effective screening tool, and elevated IOP has been found to be a poor case-finding test for glaucoma^5,6.

While IOP measurements can help inform diagnosis, treatment and management of glaucoma, one-off IOP measurements taken in clinical practice can be problematic for the following reasons¹.

Diurnal variation

• IOP fluctuates throughout the day due to the circadian rhythm, with maximum and minimum levels typically occurring at daybreak and at the end of the afternoon, respectively. Given these peak fluctuations occurring outside standard clinic hours, it is difficult to detect the presence of increased IOP in this setting⁴
• If appointment times vary between clinic visits, IOP readings may be incomparable¹
• Although IOP variations in glaucomatous eyes tend to be higher than in healthy eyes, IOP can vary by as much as 5 mmHg per day in healthy eyes and be unrelated to disease progression or eye damage⁴

Factors influencing IOP

The following factors can influence IOP levels^1,4:

• Ocular factors (e.g. accommodation)
• Extraocular muscle action or blinking
• Corporal factors (e.g. physical exercise and blood pressure, body position, Valsalva manoeuvres)
• External factors (e.g. atmospheric pressure, tight neck ties)
• Some systemic medications
• The methods or observer measuring IOP in the clinic can affect the measurement obtained.

These factors suggest the need for devices that continuously monitor IOP levels, not only to gain insight into the range of IOP levels the optic nerve is exposed to, but also to monitor a patient’s response to treatment¹.

Other issues related to sensitivity and specificity that affect reliable early diagnosis¹:

• Research suggests that the sensitivity of current biomarkers can be improved in order to more accurately diagnose early disease. Examples include macular ganglion and nerve fibre layer imaging, and alternative visual field-testing protocols. However, few novel techniques have been explored to date.
• Glaucoma exists within a range of age-related neurodegenerative conditions which are also associated with retinal nerve fibre layer thinning, such as Parkinson’s and Alzheimer’s disease. Differentiating between these conditions can be difficult, and patients with Parkinson’s or Alzheimer’s disease may be misdiagnosed as having glaucoma and unlikely to benefit from IOP-lowering therapy further complicates the diagnosis of glaucoma.

The impact of socioeconomic factors and patient education on glaucoma

Several research studies indicate that a relationship exists between socioeconomic factors and glaucoma^7-10. According to a study of the global health burden of glaucoma, socioeconomic differences contributed to inequalities of provision of glaucoma care between countries¹¹. While early treatment can prevent glaucoma-related vision loss and change the disability adjusted life years burden, differences in access to healthcare and the difficulties associated with diagnosis – given that chronic glaucoma is largely asymptomatic in its early stages – are key unmet needs in glaucoma^11,12. Low levels of glaucoma awareness across the world impact the use of eyecare services, further contributing to the lack of early detection¹².

Affordable, effective screening approaches for glaucoma

In order to identify people at risk of losing visual function, affordable and effective screening approaches are required. Highly accurate glaucoma diagnosis based on one photograph has been achieved thanks to automated grading of optic disc photographs. Low-cost, widespread glaucoma diagnosis may be achieved by using fundus imaging with grading assisted by artificial intelligence. However, further research is needed to determine how to best apply these tools¹.

Considering the impacts of glaucoma when diagnosis is delayed, improvements in detection are needed, with calls for a proactive screening strategy to be implemented. While mass glaucoma screening has been cited as cost-prohibitive, China and India have reported population-based screenings that were cost-effective¹².

Figure 1 highlights key unmet needs in glaucoma diagnosis.

Figure 1. Unmet needs in glaucoma diagnosis. IOP, intraocular pressure.

Screening and diagnostic strategies for glaucoma

References

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