Is intraocular pressure the right criterion to assess progression or success in glaucoma?

Intraocular pressure (IOP) is the surrogate for assessing glaucoma management. It is the easiest and most widely used criterion to assess progression or success of any form of treatment for glaucoma. The incontrovertible evidence provided by early randomized controlled trials (RCTs) in glaucoma has substantiated the prime status of IOP in glaucoma. Besides, it is the only modifiable risk factor. The ease of its measurement and reproducibility has made Goldman applanation tonometry (GAT) the gold standard for measuring IOP, thereby enhancing the status of IOP.

Spaeth considered it inappropriate to use IOP as the only outcome measure for management of glaucoma.[1] His reasons included it being only a risk factor of glaucoma and not the disease itself, that other factors could be causing the glaucomatous damage, and that IOP is influenced by many patient-specific factors. This led to the consideration of other criteria to assess progression or success of treatment methods in glaucoma. IOP fluctuations, the point of time at which it is measured, and the fact that IOP can be within the normal range in a patient with glaucoma make it an uncertain predictor of glaucoma progression. Therefore, the non-IOP-dependent factors and neuroprotective mechanisms gain importance but are difficult to quantify predictors of glaucoma progression.

The modern definition of glaucoma and its management give much importance to the quality of life (QoL) of the patient. However, systematic reviews have shown that patient-reported outcome measures (PROMs) lack the sensitivity to detect early, subtle structural or functional changes.[2] They are subjective and are influenced by the patient’s mood. They may be useful in advanced, symptomatic stages of the disease.[3]

The direct assessment of structure or function seems to be more appropriate than IOP in assessing the outcome of treatment. Glaucoma-related parameters like retinal nerve fiber layer (RNFL) thickness, Bruch’s membrane opening–minimum rim width (BMO-MRW), and others using the optical coherence tomogram (OCT) provide a reproducible assessment during follow-up, but they are limited by the floor effect. These parameters need to be adjusted to their own healthy ageing rates and features as ageing in the healthy population leads to a progressive decrease of glaucoma-related parameters.[4] It has been found that optical coherence tomography angiography (OCTA) parameters in the peripapillary area have a lower floor effect when compared to OCT and therefore can identify progression-related changes until later stages.[5] The sophistication of technology used for assessing structure-based progression and its cost are significant barriers in its utilization.

Visual fields which are a direct measure of visual function can be used as a clinical end point in glaucoma surgical studies. It is resource-intensive and needs frequent testing, and the psychophysical nature of the tests makes it not very popular. Visual field is also subject to long-term fluctuation which can affect the accurate estimation of its progression rates.[6] It has also been found that IOP-based criteria poorly reflect upon the visual field progression rates.

So, it would seem that it is a good idea to have a composite success criterion(a). That this amalgamation is difficult is exemplified by the fact that the very RCTs which established that lowering the IOP decreased the progression of glaucoma also showed that visual field is variably affected despite IOP being lowered to the target levels. For example, The Collaborative Normal Tension Glaucoma Study (CNTGS) showed that despite 30% lowering of the IOP, 12% patients progressed in the treatment arm and 65% showed no deterioration in the untreated arm over a follow-up period of 8 years.[7] The rates of glaucoma progression become clinically important only when the life expectancy of the patient, the severity of disease, and what daily activities need to be preserved are considered, making its estimation complex.[8]

Our need for a robust metric, in this regard, is highlighted by the results of various studies involving minimally invasive glaucoma surgery (MIGS) as they are difficult to compare and interpret.[9] Yet, the American Academy of Ophthalmology (AAO) in 2024 has defined success for (MIGS) as maintaining an IOP of 21 mm Hg and a reduction of 20% from baseline, without additional glaucoma medications, lasers, or surgeries.[10] This highlights that IOP still retains its prime position and creating consensus over using multiple metrics is difficult.

The need of the present times is to conduct research which is personalized and precise and integrates many streams of research in this topic, to create easy to use computational models which can estimate the distribution of rate of progression, be it structural or functional or both. These can be combined with other metrics such that there can be greater uniformity in reporting of results of scientific studies and clinical practice. Till a consensus is achieved to decide the best metric, we can continue to rely on IOP as one of the criteria for evaluating success of a treatment procedure in glaucoma.

About the author

Prof. Dr. Smita Narayanan

Dr. Smita Narayanan is a Professor and Head of Glaucoma Clinic at the Department of Ophthalmology, Government Medical College, Thrissur, Kerala. She is a fellowship trained Glaucoma surgeon having 25 years of experience in training undergraduate students and Ophthalmology residents. Her special interests are in General Ophthalmology, Glaucoma and Research Methodology. She was a past Editor in chief of the Kerala Journal of Ophthalmology (KJO) and is currently a member of the Editorial Board of IJO and KJO. She has received the IJO-reviewer Honor award three times in a row. She has made numerous presentations at local, state and national levels. She has also held leadership positions at local and state societies. She is an active member of the Medical education Unit and the Curriculum Committee of her institution.