Short-term Photopic Negative Response Changes Seen After Lowering Intraocular Pressure

Doctor helps the patient and gives the eye drops
Researchers noted an optimized PhNR protocol detected short-term improvements in some glaucoma patients after applying IOP-lowering medications.

Researchers using an optimized protocol to measure inner retinal function using the photopic negative response (PhNR) detected short-term improvements in some participants with glaucoma after a reduction of intraocular pressure (IOP). However, the majority of participants showed no change, according to findings published in Investigative Ophthalmology & Visual Science.

This study was designed to evaluate whether PhNR can dependably detect short-term inner retinal function changes soon after topical IOP reduction in patients with glaucoma, and to compare the corresponding changes using standard automated perimetry (SAP). The treatment group had 47 participants starting a new or additional IOP-lowering therapy for glaucoma, and the control group had 39 participants with stable glaucoma. Baseline and follow-ups (3±2 month) measurements for visual field, IOP, electroretinograms (ERGs), and retinal nerve fiber layer thickness were recorded. To record PhNR, an optimized protocol was developed using a portable ERG device. Also analyzed were the PhNR saturated amplitude (Vmax), Vmax ratio, semi-saturation constant (K), and Naka-Rushton function slope.

A significant IOP reduction was seen in the treatment group compared with the control group (28±3% vs 2±3%; P <.0001). No significant interaction was seen for PhNR Vmax (F₁,₈₃=2.099, P =.15), but a significant difference was seen between the 2 time points (F₁,₈₃=5.689, P =.019). In the post hoc analysis using Sidak’s multiple comparisons test, a significance difference was seen between baseline and 3 months in the treatment group but not in the control group (mean difference, 1.23 µV; 95% CI, 0.24-2.22 vs 0.30 µV; 95% CI, 0.78-1.38). Neither group had significant differences in K or slope of the Naka-Rushton function (K: F₁,₈₁=3.363, P =.07; slope: F₁,₈₁=0.00, P =1.00); these were not further analyzed.

In the treatment group, improvement beyond test–retest variability was seen in 8 of 47 participants (17%) compared with 1 of 39 (3%) in the control group (P =.007, X² test). The majority of participants did not show a significant change, and no correlation was seen between PhNR Vmax change and baseline IOP or the degree of IOP change. Study investigators suggest that a group of treatment-naïve participants may show a greater change in retinal function, but this was beyond the current study’s scope. Additionally, a 3-month time point for follow-up may be insufficient for detectable change to be captured in some participants. Future longitudinal studies with additional follow-ups are needed.

Study investigators concluded that “our optimized protocol for measuring the PhNR using the RETeval device was able to detect short-term improvements in inner retinal function in a proportion of participants following IOP reduction. Although only a small proportion improved, such short-term changes in PhNR may provide a means for detecting improvement or deterioration in RGC function, and this approach merits further investigation for its utility in longitudinal glaucoma monitoring and the assessment of new treatments.”


Tang J, Hui F, Hadoux X, et al. Short-term changes in the photopic negative response following intraocular pressure lowering in glaucoma. Invest Ophthalmol Vis Sci. 2020;61(10):16. doi: 10.1167/iovs.61.10.16