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Editors Selection IGR 8-3

Prognostic factors: Target IOP Achievement and RNFL thinning

Comment by Gustavo de Moraes on:

In this retrospective longitudinal study including 3,256 eyes of 1,923 patients ranging from suspect/mild to advanced glaucoma, Pham and colleagues investigated the relationship between rates of OCT-measured retinal nerve fiber layer (RNFL) thinning and being below (or above) target intraocular pressure (IOP). This cohort was followed for an average (SD) of 5.1 (1.7) years with 14 (8) visits with OCT scans and their mean rate of global RNFL thinning was –0.50 (1.28) μm/y. Of note, these patients had their IOP on average 2.66 (3.66) mmHg below the target set by clinicians, suggesting good pressure control during the evaluated period.

As a result, eyes with IOP above the clinician-set target experienced faster rates of RNFL thinning than eyes that were below the target pressure. Of note, the average rate of RNFL thinning was –0.44 μm/y for those below and –0.71 μm/y for those above target IOP, which correspond to rates of progression about 60% faster if the pressure is not kept below what clinicians estimated to be an acceptable value to slow or halt progression. More specifically, each mmHg increase resulted in –0.05 μm/y faster the rate of change for patients below the target IOP, while for those above target the rate was –0.14 μm/y faster. It should be emphasized, however, that the beneficial effect of lower IOP was not the same across severity levels, as the effect per mmHg reduction was greatest among moderate cases (visual field MD between −6 dB and −12 dB), followed by suspect/mild cases (MD better than -6 dB), and non-significant among eyes with more advanced disease (worse than -12 dB). The authors also identified that not only the mean IOP below target had an effect on rates of RNFL thinning, but also the percentage of visits in which the IOP remained below that target, similarly to what had been shown in the AGIS. Eyes with IOP below target in 0-25% of visits experienced rates of progression about 88% faster than those with IOP below target in 75-100% of visits, suggesting a significant role of IOP fluctuation and, possibly, compliance. Finally, a key and novel finding was that the difference between measured IOP and target IOP was a better predictor of progression than absolute IOP values.

A key and novel finding was that the difference between measured IOP and target IOP was a better predictor of progression than absolute IOP values

One important limitation of the study is that, given its retrospective design, clinicians may not be able to replicate the same methodology employed in this study to define the target IOP for each patient. Although the authors underscored that the decisions were derived from literature, we know the literature is in itself not consistent in terms of its definitions. From the figures, it can be inferred that the target for suspects was < 20 mmHg, whereas for mild, moderate, and advanced it was on average 18, 16, and 15 mmHg, respectively, with a large spread of values. For instance, among eyes with advanced glaucoma, the target IOP could range between 9 and 25 mmHg. Nonetheless, the key message that keeping the IOP below a pre-defined target has substantial impact in preventing RNFL thinning remains very solid. The absolute effect per mmHg reduction may, however, differ among clinicians.

The lack of a statistically significant effect among eyes with advanced glaucoma is well discussed in the paper and relates to a smaller sample size in that group. Two other possibilities that should also be considered are (1) the floor effect we typically see in eyes with MD worser than 12 dB (even after removing those with RNFL thickness values below 30 microns, as the authors did), which challenge our ability to measure progressive changes, and (2) the possible need for even lower target IOP among these eyes. Of course, this may not be addressed in this dataset but should be considered in future studies.

In sum, the authors should be commended for their work and for reminding clinicians of the need to establish a target IOP (or range) in all patients, modify it as needed over the course of follow-up, and to seek preserving the pressure below target at most visits.

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