Glaucoma severity linked to pupil response
Functional and structural glaucoma severity was associated with impaired intrinsically photosensitive retinal ganglion cell function, according to a study published in Investigative Ophthalmology and Visual Science.
“The significant association between PIPR [postillumination pupil response] and glaucoma severity shown in our study was consistent with the findings of four previous clinical studies that revealed associations between impaired ipRGC [intrinsically photosensitive retinal ganglion cell] function and glaucomatous damage, such as RNFL [retinal nerve fiber layer] thinning and visual field defects,” Tadanobu Yoshikawa, MD, PhD, of Nara Medical University and Yoshikawa Eye Clinic in Japan, and colleagues wrote.
Yoshikawa and colleagues conducted a cross-sectional analysis of the LIGHT study, which included 148 patients with glaucoma, and assessed ipRGC function by PIPR using pupil diameter after exposure to blue and red light.
After adjusting for multiple variables, investigators determined that worsening in visual field mean deviation (MD) was associated with higher blue six-second PIPR amplitude, while thinner RNFL thickness was associated with higher blue six-second PIPR amplitude, lower net PIPR change and lower net PIPR.
Comparison of 35 patients with nonsevere glaucoma (mean age, 68 years; 37% men) and 113 patients with severe glaucoma (mean age, 71 years; 50% men) revealed that the severe glaucoma group had a significantly higher prevalence of oral medication use (antihistamines and dopaminergic drugs) and history of cataract surgery vs. the nonsevere group (P = .036 and .004, respectively). Initial pupil size during blue light stimulus in the severe glaucoma group also was larger than the nonsevere group (P = .015).
Further, analyses of the visual field MD were inversely correlated with blue 6-second PIPR amplitude (P < .001) and positively correlated with net PIPR change (P = .044), while RNFL thickness was inversely correlated with blue 6-second PIPR amplitude (P < .001) and positively correlated with net PIPR change (P = .004) and net PIPR (P = .012).
“Our results indicate a possible circadian misalignment in patients with glaucoma through impaired ipRGC function,” the authors concluded.
Perspective
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For decades rods and cones were thought to be the only photoreceptors in the retina. About 20 years ago a population of ipRGCs were identified. Although ipRGCs represent a small subset (1%) of retinal ganglion cells, these cells are important to controlling circadian rhythm, pupillary light reflexes and sleep.
Glaucoma is characterized by progressive retinal ganglion cell loss, and studies have shown that glaucoma disrupts circadian rhythm. Yoshikawa and colleagues are helping elucidate the mechanism of the influence of glaucoma on circadian disruption by better understanding the connection between ipRGC function and glaucoma.
They found a significant association between impaired ipRGC function and the structural and functional severity of glaucoma. Further, they found that impaired ipRGC function decreases melatonin secretion in patients with glaucoma, which may possibly promote clinical manifestations of circadian disruption such as sleep disturbance, mood disorders and blood pressure variability.
While this research is directed more toward understanding how glaucoma affects circadian rhythm, there are lessons for those of us in clinical glaucoma care. This article has motivated me to discuss easily overlooked problems like poor sleep with my glaucoma patients. Also this article reminds me that a close working relationship with other providers can ensure the overall wellbeing of our patients.
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