Altered Non-Visual Photoreception in Patients With Glaucoma: Impacts on Sleep, Alertness, Mood, and Cognition

NCT07364929 | Recruiting

• 1 other identifier: DSRB 2024/00123
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

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:

• Standard indoor light (\~300 lux)
• Full-spectrum light (\~1000 lux) 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.

Conditions

Glaucoma

Keywords

light; glaucoma; brain; sleep; mood; cognition; alertness

Outcome Measures

Primary Outcomes (30)

• 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

  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)

Secondary Outcomes (15)

• Anticipatory Pupil Size

  Immediately after the procedure

• Hit Rate

  Immediately after the procedure

• False Alarm Rate

  Immediately after the procedure

• Correct Rejection Rate

  Immediately after the procedure

• Miss Rate

  Immediately after the procedure

Study Arms (2)

Patients with glaucoma

EXPERIMENTAL

Patients undergoing both control and intervention light exposure in a cross-over randomized design.

Other: Full-spectrum light exposure; Other: Standard indoor light exposure (Control)

Controls (healthy adults)

ACTIVE COMPARATOR

Healthy adults following the same procedures compared to patients with glaucoma

Other: Full-spectrum light exposure; Other: Standard indoor light exposure (Control)

Interventions

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).

Also known as: Sun-like light

Controls (healthy adults); Patients with glaucoma

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).

Controls (healthy adults); Patients with glaucoma

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with primary open-angle glaucoma (POAG), as indicated by Humphrey Visual Field (HVF) mean deviation (VFMD) scores better than -12 dB in at least one eye during their most recent clinic visit.
• Patients having spared central vision.
• Patients aged 45 to 75 years old.
• Patients with a best-corrected visual acuity better than 6/12
• English-speaking patients
• Participants aged 50 to 70 years old.
• Participants with a best-corrected visual acuity better than 6/12
• Normal ophthalmic examination
• English-speaking participants

You may not qualify if:

• Participants with myopia exhibiting a refractive error exceeding -8.00 diopters (D)
• Participants with a history of complicated previous intraocular surgery
• Participants taking alpha-adrenergic agonist eye drops or other systemic medications or drugs that could affect the pupillary response
• Participants with any past or current ocular condition (i.e., age-related retinal diseases (e.g., age-related macular degeneration), retinal pigment epithelium diseases (e.g., Best's disease), diabetic retinopathy, or other optic or generalized neuropathies, significant ocular trauma, or any eye condition affecting fixation (eg. Nystagmus)).
• Participants diagnosed with cataracts at NS3+ (Nuclear Sclerosis) and above, as well as those with Posterior Subcapsular (PSC) cataracts
• Participants with clinically diagnosed psychiatric or neurologic disorders, including cognitive impairment or dementia
• Participants with diagnosed mood disorders
• Participants engaged in night shift work within the past three months, are currently using sleeping pills, or have recently travelled across timezones within a month prior to the study
• Participants with obstructive sleep apnea
• Participants with abnormal auditory function
• Participants with impaired color vision
• Pre-menopausal women (last menstrual period \< 1 year) (If applicable)
• Patients having unilateral glaucoma, congenital glaucoma, non-glaucomatous optic neuropathy, abnormal central vision
• Diabetics on treatment

Sponsors & Collaborators

• National University of Singapore: lead
• Singapore National Eye Centre: collaborator
• Singapore Eye Research Institute: collaborator
• National University Hospital, Singapore: collaborator

Study Sites (2)

National University Hospital

Singapore, Singapore

NOT YET RECRUITING

Singapore National Eye Center

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Glaucoma

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Study Officials

• Raymond P. Najjar, PhD

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniella Mahfoud, MSc.

CONTACT

+65 65165474; daniella.mahfoud@u.nus.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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: 1. Standard Indoor Light (Control) Condition (\~300 lux) 2. Full-spectrum (Intervention) Condition (\~1000 lux) The order of exposure is randomized. Half of the participants start with the standard light, then switch to the full-spectrum light. The other half experience the reverse order. This randomization prevents order or carryover effects (for example, participants simply performing better the second time because of practice or worse because of fatigue).

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: January 23, 2026
• Study Start: September 5, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)