Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. METHODS: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. MAIN OUTCOME MEASURES: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. RESULTS: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. CONCLUSIONS: Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.

Factors influencing the pupillary light reflex in healthy individuals.

PURPOSE: To determine the ocular anatomical factors influencing the pupillary light reactions to different wavelengths of light, measured with chromatic pupillometry. METHODS: Community-based, cross-sectional study including subjects with normal ocular health (ages 50-79 years). Direct pupillary responses to continuously increasing irradiances (6.8 to 13.8 log photons cm(-2) s(-1)) of red (631 nm) and blue (469 nm) light were measured, using a dedicated infrared pupillometer. All subjects underwent swept source optical coherence tomography (SS-OCT, CASIA SS-1000, Tomey Corporation, Nagoya, Japan) and noncontact partial coherence laser interferometry (Lenstar LS900, Haag-Streit AG, Switzerland). Univariate and multivariable regression analyses were performed to determine the anatomical features influencing pupillographic parameters. RESULTS: Among the 177 included subjects, 167 (94.4 %) were Chinese and 116 (65.5 %) female. The average baseline pupil diameter in darkness (ß = -0.080, p < 0.001) and the amplitude of the relative pupillary constriction (ß = -0.233, p = 0.006) to blue light decreased with age. The amplitude of pupillary constriction was significantly larger in patients with a thinner iris, in response to stimulation with blue (ß = -0.321, p < 0.001) and red light (ß = -0.336, p < 0.001). Other ocular parameters (i.e., lens vault, anterior chamber depth width, iris volume, iris curvature, and lens thickness) were not significantly associated with pupillometric outcomes. CONCLUSIONS: The amplitude of the pupillary light constriction to chromatic photic stimuli is reduced with increasing age and iris thickness in subjects with normal ocular health, a finding which needs to be integrated into future pupillometric studies.

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity.

PURPOSE: To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older. METHODS: Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system. MAIN OUTCOME MEASURES: Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany). RESULTS: The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters. CONCLUSIONS: In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.

Optical coherence tomography angiography in acute non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: To characterise vascular changes in eyes with acute non-arteritic anterior ischaemic optic neuropathy (NAION), using optical coherence tomography angiography (OCT-A) imaging. METHODS: This hospital-based observational case-control study included included five patients with acute NAION (6 eyes), within 7 days after onset of symptoms and 19 age-matched healthy controls (19 eyes). OCT-A (RTVue XR 100; Optovue, Fremont, California, USA), covering a 4.5×4.5 mm scan area, was used to evaluate peripapillary blood flow in cases and controls. The flow densities at the retinal and choroidal level were measured using the split-spectrum amplitude-decorrelation angiography algorithm. RESULTS: The mean age of the NAION and normal subjects was 69 (61-82) and 68 (58-82) years, respectively (p=0.3). At the acute stage, OCT-A disclosed global reduction of the mean peripapillary flow density in eyes with NAION (53.5±3.7%) compared with normal eyes (64.3±2.4%) (p<0.001). The mean vascular flow density was also reduced in the peripapillary choroid layer of eyes with NAION (53.2±7.8%) compared with controls (69.5±3.0%) (p<0.001). In patients (3 eyes) with resolution of optic disc oedema, a repeated OCT-A analysis (at 4-22 weeks) of the full segment (including retina and choroid) revealed spontaneous improvement of the average total peripapillary flow density by 8.1±2.7%. CONCLUSIONS: Using OCT-A, we revealed a global and sectorial reduction of retinal and choroidal peripapillary flow densities at the acute stage of NAION, followed by partial subsequent spontaneous recovery. Further studies are needed to establish the potential value of OCT-A for evaluating NAION and other optic neuropathies.