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| Name | Class |
|---|---|
| Singapore National Eye Centre | OTHER_GOV |
| Singapore Eye Research Institute | OTHER |
| National University Hospital, Singapore | OTHER |
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The goal of this study is to understand how light sensitivity in the eye affects sleep, mood, alertness, and cognition in adults with glaucoma compared to healthy individuals aged 45-75 years.
The main questions it aims to answer are:
Researchers will compare patients with glaucoma and age-matched healthy controls to see if differences in light sensitivity can explain changes in non-visual light responses (i.e., sleep, mood, alertness, and cognition) and whether full-spectrum light exposure can enhance alertness and wellbeing.
Participants will:
Complete eye exams and baseline questionnaires about their sleep, daytime sleepiness, mood, and wellbeing.
Wear a wrist-worn device for 8-16 days to record their sleep patterns and light exposure.
Visit the laboratory for cognitive and attention tests following exposure to two lighting conditions (randomized, cross-over):
This study will help researchers understand how glaucoma affects the brain beyond vision and explore whether light-based interventions can improve quality of life for people living with glaucoma.
Glaucoma is a chronic eye disease that damages retinal ganglion cells (RGCs), leading to progressive loss of vision. Recent evidence suggests that glaucoma may also affect a special subset of RGCs called intrinsically photosensitive retinal ganglion cells (ipRGCs), which contain the light-sensitive pigment melanopsin. These cells are critical for regulating non-visual responses to light, such as sleep, mood, alertness, and cognition, by sending light signals from the eye to various regions of the brain.
Patients with glaucoma often report sleep disturbances, fatigue, and mood changes, yet the biological mechanisms behind these symptoms are not fully understood. It remains unclear whether such non-visual effects result from damage to ipRGCs or from other disease-related factors. Understanding this relationship is important for improving the overall wellbeing and quality of life of individuals living with glaucoma.
This study will therefore investigate how glaucoma affects non-visual responses to light and whether brief, safe exposure to full-spectrum light can improve alertness, sleepiness, and mood. The study combines observational and interventional components to comprehensively assess the link between light perception, brain function, and behavior in glaucoma.
Study Design and Procedures
A total of 120 participants will take part in the study:
Each participant attends two study visits:
Visit 1 is done at the clinics (National University Hospital / Singapore National Eye Center) and covers the following:
Participants are given a wrist-worn actigraphy device to record their daily sleep-wake cycles and light exposure for 8-16 days at home, along with a sleep diary.
Visit 2 is done at the laboratory (National University of Singapore - Eye N' Brain Research Platform). After completing actigraphy, participants return for detailed testing of attention, cognition, and vigilance following exposure to two lighting conditions:
Participants undergo two sessions of exposure to each of these lights (separated by a period of standard light during which they perform different versions of the MoCA test).
The timing of the visit is individualized based on each participant's sleep/wake cycle. Participants go through the sessions in a cross-over manner and the order of lighting conditions will be randomized to control for order effects.
Following light exposure, the following cognitive tasks are employed while doing eye tracking and cognitive pupillometry:
Subjective rating scales of mood, wellbeing, and sleepiness are administered before and after each lighting condition and after cognitive assessment to monitor fluctuations throughout the session.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with glaucoma | Experimental | Patients undergoing both control and intervention light exposure in a cross-over randomized design. |
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| Controls (healthy adults) | Active Comparator | Healthy adults following the same procedures compared to patients with glaucoma |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Full-spectrum light exposure | Other | Participants will be exposed to a full-spectrum white light designed to replicate the spectral quality of natural daylight while maintaining safe, indoor intensity levels. The light source delivers an illuminance of approximately 1000 lux and is free of ultraviolet and infrared wavelengths. Each participant will undergo two periods of light exposure, intermittently, during the laboratory visit at the Eye N' Brain Research Platform (NUS). |
| Measure | Description | Time Frame |
|---|---|---|
| Subjective Sleep Quality | Sleep quality is assessed using the Pittsburgh Sleep Quality Index (PSQI), a validated self-report questionnaire measuring subjective sleep quality, sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction over the past month. Higher scores indicate poorer sleep quality. | Baseline (Visit 1) |
| Subjective Daytime Sleepiness | Daytime sleepiness is assessed using the Epworth Sleepiness Scale (ESS), a validated questionnaire evaluating the likelihood of dozing in common daytime situations. Higher scores indicate greater daytime sleepiness. | Baseline (Visit 1) |
| Depressive Symptoms | Depressive symptoms will be assessed using the Patient Health Questionnaire-9 (PHQ-9), a validated self-report questionnaire measuring the frequency and severity of depressive symptoms over the past two weeks. Higher scores indicate greater depressive symptom severity. | Baseline (Visit 1) |
| Global Cognitive Function | Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), a standardized screening tool evaluating executive function, attention, memory, language, and visuospatial abilities. | Baseline (Visit 1) |
| Global Cognitive Function during light exposure | Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), a standardized screening tool evaluating executive function, attention, memory, language, and visuospatial abilities. Alternate validated versions will be used across visits to minimize learning effects. | Immediately after the procedure |
| Median Reaction Time |
| Measure | Description | Time Frame |
|---|---|---|
| Anticipatory Pupil Size | Anticipatory pupil size will be assessed using an eyetracker measuring pupil size throughout PVT and oddball tasks. Anticipatory pupil size will be quantified by median pupil size prior stimulus onset. | Immediately after the procedure |
| Hit Rate |
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Inclusion Criteria:
Patients with glaucoma must meet all of the inclusion criteria to participate in this study.
Healthy controls must meet all of the inclusion criteria to participate in this study:
Exclusion Criteria:
All subjects (patients and controls) meeting any of the exclusion criteria at baseline will be excluded from participation:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daniella Mahfoud, MSc. | Contact | +65 65165474 | daniella.mahfoud@u.nus.edu |
| Name | Affiliation | Role |
|---|---|---|
| Raymond P. Najjar, PhD | National University of Singapore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National University Hospital | Not yet recruiting | Singapore | Singapore |
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| ID | Term |
|---|---|
| D005901 | Glaucoma |
| ID | Term |
|---|---|
| D009798 | Ocular Hypertension |
| D005128 | Eye Diseases |
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In this study, the cross-over model refers to the way each participant experiences both lighting conditions (control light and intervention light). Each participant (whether patient or healthy control) takes part in two experimental sessions during their laboratory visit:
This randomization prevents order or carryover effects (for example, participants simply performing better the second time because of practice or worse because of fatigue).
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| Standard indoor light exposure (Control) | Other | Participants will be exposed to a standard indoor light with an illuminance of approximately 300 lux. Each participant will undergo two periods of light exposure, intermittently, during the laboratory visit at the Eye N' Brain Research Platform (NUS). |
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Median reaction time will be assessed using a laboratory-based auditory Psychomotor Vigilance Task (aPVT). Participants will respond to auditory stimuli presented via headphones by pressing a key on a keyboard while viewing a fixation display on a monitor. Reaction time is defined as the interval between stimulus onset and the participant's button press. The primary outcome measure is the median reaction time calculated across all valid trials within the task. |
| Immediately after the procedure |
| Vigilance Lapses | Vigilance lapses will be assessed using a laboratory-based auditory Psychomotor Vigilance Task (aPVT). Participants will respond to auditory stimuli presented via headphones by pressing a key on a keyboard while viewing a fixation display on a monitor. Omission lapses are defined as trials in which no response is registered within the predefined response window following stimulus onset. The outcome measure is the total number of omission lapses across all valid trials. | Immediately after the procedure |
| Long Reation Time Lapses | Long reaction time lapses will be assessed using a laboratory-based auditory Psychomotor Vigilance Task (aPVT). Participants respond to auditory stimuli by pressing a key on a keyboard. A long reaction time lapse is defined as any trial in which the reaction time exceeds two times the participant's median reaction time for the task. The outcome measure is the total number of long reaction time lapses across all valid trials. | Immediately after the procedure |
| Anticipatory Responses | Anticipatory responses will be assessed using a laboratory-based auditory Psychomotor Vigilance Task (aPVT). Participants respond to auditory stimuli by pressing a key on a keyboard. An anticipatory response is defined as a button press occurring before stimulus onset, reflecting premature responding. The outcome measure is the total number of anticipatory responses across all valid trials. | Immediately after the procedure |
| Sustained Attention Variability | Additional reaction time metrics will be derived from the auditory Psychomotor Vigilance Task (aPVT) to characterize response speed distribution and variability. These metrics include reaction time slope across trials, fastest reaction times (e.g., fastest 10%), slowest reaction times (e.g., slowest 10%), and measures of intra-individual reaction time variability. These outcomes provide complementary information on vigilance stability and performance dynamics beyond central tendency measures. | Immediately after the procedure |
| Associative Learning | Associative Learning is assessed using a computerized variant of the Digital Symbol Substitution Task (DSST). Associative learning is quantifies by the proportion of correct responses across all trials (accuracy). | Immediately after the procedure |
| Processing Speed | Processing speed is assessed using a computerized variant of the Digital Symbol Substitution Task (DSST). Processing speed is quantifies by the median reaction time taken across trials to judge if the presented combination is correct or incorrect (button press). | Immediately after the procedure |
| Visual Attention Allocation | Visual attention allocation during the Digit Symbol Substitution Task (DSST) is assessed using eye tracking. Predefined areas of interest (AOIs), including the reference symbol-number set and the presented test pair, will be used to quantify visual strategy. Outcome measures include the number and sequence of visits to each AOI and the proportion of viewing time spent within each AOI across valid trials. | Immediately after the procedure |
| Eye-Movement Behavior | Eye-movement behavior during the Digital Symbol Substitution Task (DSST) will be assessed using video-based eye tracking. Metrics will characterize visual exploration and oculomotor behavior and include fixation count and duration, saccade frequency and amplitude, and related summary measures averaged across valid trials. | Immediately after the procedure |
| Selective Attention | Cognitive processing of infrequent auditory stimuli will be assessed using a laboratory-based auditory oddball task. Auditory tones will be presented via headphones while participants view a fixation display on a monitor and respond using a keyboard. Accuracy is defined as the proportion of correctly detected target tones and correctly ignored non-target tones across all trials. | Immediately after the procedure |
| Auditory Discrimination Performance | Auditory discrimination performance will be assessed using an auditory oddball task. Sensitivity (d') will be calculated based on hit rates (correct detection of target tones) and false alarm rates (responses to non-target tones). Higher d' values indicate greater ability to discriminate infrequent target tones from frequent non-target tones. | Immediately after the procedure |
| Task-Evoked Pupillary Responses | Task-evoked pupillary responses will be recorded during performance of the auditory Psychomotor Vigilance Task (aPVT) as well as the oddball task using eye-tracking pupillometry. Changes in pupil size measured during task performance, following stimulus presentation and participant response, will be quantified as indicators of cognitive effort and alertness. Outcome measures include pupil dilation amplitude and response dynamics averaged across valid trials. | Immediately after the procedure |
| Pupillary Responses to Shapes | Changes in pupil size during image presentation will be quantified as physiological correlates of the perceived features of a shape, independent of physical luminance. | Immediately after the procedure |
| Objective sleepiness | Objective sleepiness will be assessed using a computerized time estimation task. Participants will be instructed to press a button when they believe that a specified time interval has elapsed (10 seconds, 20 seconds, 30 seconds, 60 seconds, and 120 seconds). Time estimation accuracy will be quantified as the difference between the estimated and actual interval duration across trials. | Immediately after the procedure |
| Risk Taking Behavior | Risk-taking behavior is assessed using the Balloon Analogue Risk Task (BART), a computerized decision-making task. Adjusted average pumps is calculated as the mean number of pumps on balloons that do not burst (i.e., excluding balloons that explode), providing an index of risk-taking propensity. | Immediately after the procedure |
| Subjective Sleepiness, Mood, and Wellbeing | Change in subjective sleepiness, mood, and wellbeing assessed using the Stanford Sleepiness Scale (SSS) and Likert scales before each light exposure (baseline), immediately after exposure (acute effect), and following cognitive assessments (sustained effect). | Immediately after the procedure |
| Sleep Quantity | Night time sleep quantity (minutes) will be collected through actigraphy watches given to participants. | 8-16 days in between the visits |
| Sleep Efficiency | Night time sleep efficiency (%) calculated as the amount of time spent asleep (in minutes) by the total amount of time in bed (in minutes) will be measured using actigraphy watches given to participants. | 8-16 days between the visits |
| Phasic Pupil Constriction to Blue Light | Phasic pupil constriction to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Phasic pupil constriction to blue light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a blue light stimulus. It is calculated as a percentage change from baseline. | Baseline (Visit 1) |
| Phasic Pupil Constriction to Red Light | Phasic pupil constriction to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Phasic pupil constriction to red light refers to the rapid, transient decrease in pupil diameter that occurs immediately after the onset of a red light stimulus. It is calculated as a percentage change from baseline. | Baseline (Visit 1) |
| Maximum Pupil Constriction to Blue Light | Maximum pupil constriction to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Maximum pupil constriction to blue light refers to the greatest reduction in pupil diameter observed following the onset of a blue light stimulus. It is calculated as a percentage change from baseline. | Baseline (Visit 1) |
| Maximum Pupil Constriction to Red Light | Maximum pupil constriction to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Maximum pupil constriction to red light refers to the greatest reduction in pupil diameter observed following the onset of a red light stimulus. It is calculated as a percentage change from baseline. | Baseline (Visit 1) |
| Pupil Constriction Latency to Blue Light | Maximum pupil constriction to blue light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Constriction latency is defined as the time from blue light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds. | Baseline (Visit 1) |
| Pupil Constriction Latency to Red Light | Maximum pupil constriction to red light will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. Constriction latency is defined as the time from red light onset to the first detectable decrease in pupil diameter relative to baseline. It is measured in seconds. | Baseline (Visit 1) |
| Post-illumination Pupillary Responses | Post-illumination pupillary responses (PIPR) will be quantified using chromatic pupillometry with a handheld chromatic pupillometer. PIPR refers to the sustained pupil constriction that persists after the termination of a light stimulus. | Baseline (Visit 1) |
Hit Rate assessed using a laboratory-based auditory oddball task. Auditory tones will be presented via headphones while participants view a fixation display on a monitor and respond using a keyboard. Hit rate is defined as the proportion of correctly detected target tones relative to the total number of target tones presented during the auditory oddball task. |
| Immediately after the procedure |
| False Alarm Rate | False alarm rate is assessed using a laboratory-based auditory oddball task. Auditory tones will be presented via headphones while participants view a fixation display on a monitor and respond using a keyboard. False alarm rate is quantified as the proportion of responses made to non-target tones relative to the total number of non-target tones presented during the auditory oddball task. | Immediately after the procedure |
| Correct Rejection Rate | Correct rejection rate is assessed using a laboratory-based auditory oddball task. Auditory tones will be presented via headphones while participants view a fixation display on a monitor and respond using a keyboard. Correct rejection rate is defined as the proportion of non-target tones for which no response is made (i.e., correctly ignored non-target tones) relative to the total number of non-target tones presented during the auditory oddball task. | Immediately after the procedure |
| Miss Rate | Miss rate is assessed using a laboratory-based auditory oddball task. Auditory tones will be presented via headphones while participants view a fixation display on a monitor and respond using a keyboard. Miss rate is quantified as the proportion of target tones for which no response is made (i.e., missed targets) relative to the total number of target tones presented during the auditory oddball task. | Immediately after the procedure |
| Visual Behavior During Time Estimation Task | Eye-movement behavior during the time estimation task will be assessed using video-based eye tracking. Metrics will characterize visual behavior during interval estimation and include fixation count and duration, saccade frequency, and related summary measures averaged across trials. | Immediately after the procedure |
| Secondary Risk Taking Metrcis | Additional performance metrics from the Balloon Analogue Risk Task (BART) will be derived to further characterize task behavior and outcomes. These metrics include the number of balloon explosions, total earnings accumulated, and related summary measures averaged across trials. These outcomes provide complementary information on risk-reward decision-making beyond the adjusted average pump count. | Immediately after the procedure |
| Reward Seeking Behavior | Reward seeking behavior is assessed using the Balloon Analogue Risk Task (BART), a computerized decision-making task. The number of trilas played will be quantified as a metric reflecting reward seeking behavior. | Immediately after the procedure |
| Risk/Reward-Related Visual Behavior | Eye-movement behavior during the Balloon Analogue Risk Task (BART) will be assessed using video-based eye tracking. Metrics will characterize visual behavior during decision-making and include areas visited (count and duration), fixation count and duration, saccade frequency, and related summary measures averaged across trials. | Immediately after the procedure |
| Daytime average light levels (lux) | Daytime average light levels (lux) collected using wearable light sensors. | 8-16 days between the visits |
| Daytime average melanopic lux | Daytime average melanopic lux collected using wearable light sensors. | 8-16 days between the visits |
| Time spent outdoors | Calculated time spent outdoors collected using the wearable light sensors. | 8-16 days between the visits |
| Nighttime average melanopic lux | Nighttime average melanopic lux collected using wearable light sensors. | 8-16 days between the visits |
| Time spent over 250 or other melanopic EDI threshold during daytime | Time spent over 250 or other melanopic EDI threshold during daytime measured using the wearable light sensor | 8-16 days between visits |
| Time spent under 10 or other melanopic EDI threshold during nighttime | Time spent below 10 melanopic lux or other thresholds during nighttime measured using the wearable light sensor | 8-16 days between visits |
| Singapore National Eye Center | Recruiting | Singapore | Singapore |
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