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Editors Selection IGR 21-4

Prognostic factors: IOP guidelines and Glaucoma Progression

Comment by Luciano Quaranta on:

91539 Relationship between mean follow-up intraocular pressure, rates of visual field progression and current target intraocular pressure guidelines, Melchior B; De Moraes CG; Paula JS et al., British Journal of Ophthalmology, 2022; 106: 229-233

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This paper aims to investigate if treated glaucomatous eyes with intraocular pressure (IOP) within the limits of current guideline-driven target IOPs indeed experience slow rates of glaucomatous visual field (VF) progression at levels close to those occurring due to age-related decay in sensitivity, and if the impact is the same among patients of African descent (AD) and European descent (ED). The dataset was from the multi-site African Descent and Glaucoma Evaluation Study (ADAGES) collaboration¹, an observational, prospective cohort study aimed at identifying factors that account for differences in glaucoma onset and rate of progression between AD and ED glaucoma suspects or patients. For the present report, the authors included only subjects with 'manifest glaucoma' that they defined as participants with glaucomatous optic neuropathy and abnormal baseline VF tests (pattern standard deviation (PSD) with p < 5% or Glaucoma Hemifield Test result 'outside normal limits¹), with at least five visits and more than two years of follow-up and only reliable VFs. A total of 8598 24‐2 VF tests from 603 eyes of 407 patients (144 AD and 263 ED) were included, split into three groups based on baseline VF mean deviation (MD): G1 (better than −5.0 dB), G2 (−5.0 to −10 dB) and G3 (worse than −10 dB). An eye was defined as clinically stable if its VF change rate shows a MD slope higher ('more positive') than −0.1 dB/year, based on previous estimates of the age-related decay in VF sensitivity in subjects older than 50 years.² For stable eyes, the medians and IQR of the mean follow-up IOP were G1 = 15.0 mmHg (IQR: 13.1 to 17.7), G2 = 13.2 mmHg (IQR: 11.6 to 14.3) and G3 = 11.9 mmHg (IQR: 10.1 to 13.8) (p<0.01). With the goal of unraveling the relationship between existing guidelines on target IOP vs. MD progression rates, a linear least squares regression was used to calculate median MD slopes as: −0.20 dB/y (IQR: −0.43 to −0.02) for G1 < 21 mmHg, −0.19 dB/y (IQR: −0.51 to −0.01) for G2 < 18 mmHg and −0.15 dB/y (IQR: −0.47 to 0.05) for G3 < 15 mmHg (p=0.63), with no significant differences between racial groups. The authors concluded that in their sample adherence to treatment guidelines helped slow global VF progression rates at various disease stages.

The main goal of the authors was to investigate whether follow-up IOP within the limits proposed by some versions of the current guidelines could help minimize glaucoma VF progression. A relevant byproduct of these results (although its importance has not adequately been pointed out by the authors, in our opinion) is that the MD slopes were not only close to the age-related decay in sensitivity (−0.1 dB/y), but also close to MD rates (−0.17±0.6 dB/y) found in patients with treated ocular hypertension that did not progress to glaucoma during follow-up. The slow decline in the study population ( in which treatment targets were determined for each patient at the ophthalmologist's discretion, not according to any specific guidelines) is a clear piece of evidence demonstrating that, when dealing with any patient, target IOP should be individualized and continuously readjusted according to disease progression, patient age, and other individual conditions and/or risk factors.

The authors claim that the usually observed worse glaucoma prognosis among AD patients may have been largely due to healthcare access, diagnosis, and therapy adherence issues, but also may have been due to problems with statistical treatment. Another limitation is the use of a global-scale parameter such as MD as a proxy for VF progression instead of local-level parameters such as pointwise event-based endpoints. The authors also assumed linearity of MD changes over the entire follow-up period, which may hide changes in progression rates. Another possible issue is that all IOP measurements were carried out during office-hours, which does not capture possible effects of IOP variability on progression rates.

The authors have been themselves adamantly honest in acknowledging the limitations of the present study. They could have also pointed out that the obtained results were exactly as expected, since in the framework they built no other results could be realistically obtained: in the ideal IOP target ranges the disease is controlled, in an apparent tautology. However, despite these limitations, the authors were able for the first time to quantitatively estimate the VF progression rate(s) associated with these average target IOPs for patients with different severity. They also show target IOP should be individualized and continuously adjusted especially dealing with advanced disease progression. We congratulate the authors for their paper and their valuable contribution.

Target IOP should be individualized and continuously adjusted especially dealing with advanced disease progression

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