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Individual Differences in the Post-Illumination Pupil Response to Blue Light: Assessment without Mydriatics

View Article: PubMed Central - PubMed

ABSTRACT

Melanopsin-containing retinal ganglion cells play an important role in the non-image forming effects of light, through their direct projections on brain circuits involved in circadian rhythms, mood and alertness. Individual differences in the functionality of the melanopsin-signaling circuitry can be reliably quantified using the maximum post-illumination pupil response (PIPR) after blue light. Previous protocols for acquiring PIPR relied on the use of mydriatics to dilate the light-exposed eye. However, pharmacological pupil dilation is uncomfortable for the participants and requires ophthalmological expertise. Hence, we here investigated whether an individual’s maximum PIPR can be validly obtained in a protocol that does not use mydriatics but rather increases the intensity of the light stimulus. In 18 participants (5 males, mean age ± SD: 34.6 ± 13.6 years) we evaluated the PIPR after exposure to intensified blue light (550 µW/cm2) provided to an undilated dynamic pupil. The test-retest reliability of the primary PIPR outcome parameter was very high, both between day-to-day assessments (Intraclass Correlation Coefficient (ICC) = 0.85), as well as between winter and summer assessments (ICC = 0.83). Compared to the PIPR obtained with the use of mydriatics and 160 µW/cm2 blue light exposure, the method with intensified light without mydriatics showed almost zero bias according to Bland-Altman plots and had moderate to strong reliability (ICC = 0.67). In conclusion, for PIPR assessments, increasing the light intensity is a feasible and reliable alternative to pupil dilation to relieve the participant’s burden and to allow for performance outside the ophthalmological clinic.

No MeSH data available.


Related in: MedlinePlus

The change in pupil diameter of the left eye throughout the light exposure protocol in three different conditions. The traces represent the population mean pupil diameter, with the semi-transparent areas indicating the 95%-confidence interval, for each of the three conditions (red trace: the condition including 160 µW/cm2 blue light with the use of mydriatics (160My+), green trace: the condition including 160 µW/cm2 blue light with the pupil in its natural state (160My−), blue trace: the condition including 550 µW/cm2 blue light with the pupil in its natural state (550My−)). The bottom bar indicates the light exposure sequence, which was equal for all three condition (black = dark, red = monochromatic red light and blue = monochromatic blue light).
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biology-05-00034-f001: The change in pupil diameter of the left eye throughout the light exposure protocol in three different conditions. The traces represent the population mean pupil diameter, with the semi-transparent areas indicating the 95%-confidence interval, for each of the three conditions (red trace: the condition including 160 µW/cm2 blue light with the use of mydriatics (160My+), green trace: the condition including 160 µW/cm2 blue light with the pupil in its natural state (160My−), blue trace: the condition including 550 µW/cm2 blue light with the pupil in its natural state (550My−)). The bottom bar indicates the light exposure sequence, which was equal for all three condition (black = dark, red = monochromatic red light and blue = monochromatic blue light).

Mentions: The previously established pupillometry procedures have been described elsewhere [16]. In brief, the right eye was exposed to an illumination protocol, while the left eye was continuously recorded using a custom-made infrared pupillometry set-up. The surface of the light source was 16 × 10 cm and the distance between the illuminated eye and the light stimulus was 5 cm. The light exposure protocol consisted of the following five 5-min intervals: baseline dark, monochromatic red light (635 nm) to maximize the pupil response after blue light, dark [35], monochromatic blue light (465 nm), and post-blue dark (Figure 1). These longer stimulus durations allow for more specific assessment of the melanopsin-signaling pathway because of the low sensitivity and slow kinetics of ipRGCs [3,36]. Previous research showed that light adaption of ipRGCs was completed after 5 min of light exposure, probably saturating the ipRGCs response [37]. From the baseline and post-blue pupil diameter two PIPR outcome parameters were calculated, the (1) PIPR-mm and the (2) PIPR-% [38,39]. We previously showed that these PIPR measurements have very high within-subject test-retest reliability [16].PIPR-mm = baseline pupil diameter − post-blue pupil diameter(1)PIPR-% = 100 * PIPR-mm/baseline pupil diameter(2)


Individual Differences in the Post-Illumination Pupil Response to Blue Light: Assessment without Mydriatics
The change in pupil diameter of the left eye throughout the light exposure protocol in three different conditions. The traces represent the population mean pupil diameter, with the semi-transparent areas indicating the 95%-confidence interval, for each of the three conditions (red trace: the condition including 160 µW/cm2 blue light with the use of mydriatics (160My+), green trace: the condition including 160 µW/cm2 blue light with the pupil in its natural state (160My−), blue trace: the condition including 550 µW/cm2 blue light with the pupil in its natural state (550My−)). The bottom bar indicates the light exposure sequence, which was equal for all three condition (black = dark, red = monochromatic red light and blue = monochromatic blue light).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037353&req=5

biology-05-00034-f001: The change in pupil diameter of the left eye throughout the light exposure protocol in three different conditions. The traces represent the population mean pupil diameter, with the semi-transparent areas indicating the 95%-confidence interval, for each of the three conditions (red trace: the condition including 160 µW/cm2 blue light with the use of mydriatics (160My+), green trace: the condition including 160 µW/cm2 blue light with the pupil in its natural state (160My−), blue trace: the condition including 550 µW/cm2 blue light with the pupil in its natural state (550My−)). The bottom bar indicates the light exposure sequence, which was equal for all three condition (black = dark, red = monochromatic red light and blue = monochromatic blue light).
Mentions: The previously established pupillometry procedures have been described elsewhere [16]. In brief, the right eye was exposed to an illumination protocol, while the left eye was continuously recorded using a custom-made infrared pupillometry set-up. The surface of the light source was 16 × 10 cm and the distance between the illuminated eye and the light stimulus was 5 cm. The light exposure protocol consisted of the following five 5-min intervals: baseline dark, monochromatic red light (635 nm) to maximize the pupil response after blue light, dark [35], monochromatic blue light (465 nm), and post-blue dark (Figure 1). These longer stimulus durations allow for more specific assessment of the melanopsin-signaling pathway because of the low sensitivity and slow kinetics of ipRGCs [3,36]. Previous research showed that light adaption of ipRGCs was completed after 5 min of light exposure, probably saturating the ipRGCs response [37]. From the baseline and post-blue pupil diameter two PIPR outcome parameters were calculated, the (1) PIPR-mm and the (2) PIPR-% [38,39]. We previously showed that these PIPR measurements have very high within-subject test-retest reliability [16].PIPR-mm = baseline pupil diameter − post-blue pupil diameter(1)PIPR-% = 100 * PIPR-mm/baseline pupil diameter(2)

View Article: PubMed Central - PubMed

ABSTRACT

Melanopsin-containing retinal ganglion cells play an important role in the non-image forming effects of light, through their direct projections on brain circuits involved in circadian rhythms, mood and alertness. Individual differences in the functionality of the melanopsin-signaling circuitry can be reliably quantified using the maximum post-illumination pupil response (PIPR) after blue light. Previous protocols for acquiring PIPR relied on the use of mydriatics to dilate the light-exposed eye. However, pharmacological pupil dilation is uncomfortable for the participants and requires ophthalmological expertise. Hence, we here investigated whether an individual’s maximum PIPR can be validly obtained in a protocol that does not use mydriatics but rather increases the intensity of the light stimulus. In 18 participants (5 males, mean age ± SD: 34.6 ± 13.6 years) we evaluated the PIPR after exposure to intensified blue light (550 µW/cm2) provided to an undilated dynamic pupil. The test-retest reliability of the primary PIPR outcome parameter was very high, both between day-to-day assessments (Intraclass Correlation Coefficient (ICC) = 0.85), as well as between winter and summer assessments (ICC = 0.83). Compared to the PIPR obtained with the use of mydriatics and 160 µW/cm2 blue light exposure, the method with intensified light without mydriatics showed almost zero bias according to Bland-Altman plots and had moderate to strong reliability (ICC = 0.67). In conclusion, for PIPR assessments, increasing the light intensity is a feasible and reliable alternative to pupil dilation to relieve the participant’s burden and to allow for performance outside the ophthalmological clinic.

No MeSH data available.


Related in: MedlinePlus