Visual Field Improvement After the Initiation of Intraocular Pressure–Lowering Therapy

Patients were selected from the United Kingdom Glaucoma Treatment Study, a randomized, triple-masked, multicenter, placebo-controlled clinical trial. Patients with newly diagnosed open-angle glaucoma who had not been treated were randomized into two groups. The purpose of the study was to determine whether the visual field (VF) improved after the initiation of treatment in patients with newly diagnosed mild open-angle glaucoma (MD; less than −6 dB). A group of 202 patients was treated with latanoprost, and the other group of 205 patients was given a placebo. The eye with the worse VF mean deviation at baseline was treated.

Patients received eye drops (latanoprost or placebo) for approximately 2.5 months between their eligibility and baseline visits. The baseline intraocular pressure (IOP) was 14.7 mm Hg in the treated group and 18.8 mm Hg in the control group. The "mean (SD) IOP reduction from baseline was 4.8 (4.2) and 1.0 (3.6) mmHg in the treated and placebo groups, respectively." The baseline VF MD was −4.4 dB in the placebo group and −4.2 dB in the treated group. The "mean (SD) change in MD was almost the same for the treated (−0.03 [1.45] dB) and placebo (+0.08 [1.72] dB) groups (P = .47)," which indicates that "any improvement in MD was the same for the treated and placebo groups." The authors then excluded locations with values below 15 dB and considered the effect at subsets of locations that improved between eligibility and baseline visits, as well as the central 16 locations of the 24-2 VF grid, and did not find any VF improvement between treated and untreated patients. They concluded that "there was no evidence for VF improvement in the participants allocated to the treatment group compared with those in the placebo group."

Reddingius et al acknowledged that the limitations of their study were that it only looked at the medical lowering of the IOP and did not include surgical IOP reduction. Furthermore, patients with an IOP of >35 mm Hg were excluded from the study. The authors noted that other studies have shown VF improvement after surgical intervention; however, these studies either had no control arm, had a poor agreement among expert clinicians when the VFs were evaluated, or did not randomize the patients. This is in marked contrast to their study, which was placebo-controlled and triple-masked. The authors indicated that VF improvement after IOP lowering might require larger IOP changes.

The authors have nicely shown that VF sensitivity does not improve in patients within a 3-month term after the initiation of medical IOP lowering compared with those randomized to placebo. Furthermore, their comment that "the study shows that improvement in VF after the initiation of IOP-lowering treatment is unlikely, certainly in eyes with normal to moderately increased pre-treatment pressures" might be appropriate for patients who have been followed for 3 months but not long-term. Katz et al, using masked observers, showed that, in their series of patients followed for 10 years, approximately one-third (16 of 51) of eyes with glaucoma with at least a 30% lowering of IOP with treatment, in contrast to none of those with less than a 20% lowering of IOP after treatment, had reversible optic disc cupping.¹ The Collaborative Initial Glaucoma Treatment Study enrolled 607 patients with an average MD of 5.4 dB and IOP of 27.5 mm Hg and followed them for an average of 7.2 years. Of note, "at 1, 3, and 5 years after treatment initiation, the percentages showing loss (6.6%, 10.9%, and 14.5%, respectively) and improvement (7.5%, 12.7%, and 13.9%, respectively) differed minimally and were not statistically significant (P > .20)." Additionally, "patients with the lowest maximum IOPs (≤13 mm Hg) had, on average, 18.7% of visits, showing a substantial gain in MD compared with 13.4%, 10.6%, and 8.0% in those with maximum IOPs of 14 to 17 mm Hg, 18 to 21 mm Hg, and ≥22 mm Hg."²

Caprioli hypothesized that a combination of low IOP could result in increased vascular perfusion, reviving the ischemic retinal ganglion cells. Specifically, "there is a group of ganglion cells that may be sick but not dead and can be revived." Additionally, "this repair may be considered neurorescue and may already be available in the form of treatment by robust IOP reduction."³

I commend Reddingius et al for their rigorous triple-blind study. Unfortunately, their study, being of short duration, lost track of the forest because of the trees. Their work would be more clinically significant if their patients could be evaluated over a longer period of time.

References

1. Katz LJ, Spaeth GL, Cantor LB, et al. Reversible Optic Disk Cupping and Visual Field Improvement in Adults With Glaucoma. Am J Ophthalmol. 1989;107(5):485–492. https://www.ajo.com/article/0002-9394(89)90492-3/abstract
2. Musch DC, Gillespie BW, Palmberg PF, et al. Visual Field Improvement in the Collaborative Initial Glaucoma Treatment Study. Am J Ophthalmol. 2014;158(1):96–104. https://www.ajo.com/article/S0002-9394(14)00190-1/abstract
3. Caprioli J. Glaucoma: A Disease of Early Cellular Senescence. Invest Ophthalmol Vis Sci. 2013;54(14).ORSF60– ORSF67. https://iovs.arvojournals.org/article.aspx?articleid=2127414