The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire.

Percentage changes in the scores between baseline vs 45-day visit and baseline vs 90-day visit after daily intranasal neurostimulation are given below.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. Eye pain intensity was assessed using a numerical scale (0-10) for the most, least, and average pain in the past 24 hours and 2 weeks. Higher scores indicate severe pain of OPAS questionnaire. The percent changes in pain intensity between baseline vs 45-day and baseline vs 90-day are provided below.

IDEEL Quality of Life Questionnaire is a 27-item questionnaire, designed specifically for DED and is divided into three parts. It assesses the quality of life in three aspects of life for the previous 2 weeks: daily activities, work and feelings. The quality of life is assessed on a scale of 0-5, with zero being inability to do the activity. The score is calculated between 0 - 100 with higher scores indicating a better quality of life. Percentage change in IDEEL questionnaire subheading between baseline and day 45 and baseline and day 90 were given below.

Intraocular pressure will be measured by an applanation tonometer used on slit lamp (Goldmann) in mmHg. Change in IOP values between baseline and 90-day is provided below. A healthy eye pressure is between 10 and 21 millimeters of mercury. The differences in intraocular pressure between the baseline and day 45 visits, as well as between the baseline and day 90 visits, are presented below.

For safety analyses during the study, patient-reported adverse events that developed after intranasal neurostimulation were recorded.

Tolerability of Intranasal Neurostimulator (ITN) was evaluated by using Ocular Tolerability and Compliance Questionnaire. It assesses symptoms of discomfort in each eye after ITN use.

After daily intranasal neurostimulation, the change in the number of systemic pain medication between baseline vs 45-day visit and Baseline vs 90-day visit was evaluated.

Race and Ethnicity were not collected from any participant.

The Schirmer test was performed by placing a narrow filter-paper strip (5 x 35 mm strip of Whatman #41 filter paper) in the inferior cul-de-sac. The subject should gently close their eyes until five minutes have elapsed and the strips are removed. Aqueous tear production was measured by the length in millimeters that the strip wets during 5 minutes. The Schirmer test results range from 0 to 35 mm, with lower values indicating more severe dry eye.

Corneal Staining Score: The NEI (National Eye Institute) corneal staining score is a standardized method used to assess the extent of corneal epithelial damage, typically visualized with fluorescein dye under cobalt blue light. The cornea is divided into five equal zones. Each zone is graded on a scale from 0 to 3, based on the number and density of punctate epithelial erosions (staining spots). The scores from all five zones are summed (0-15), giving a total corneal staining score. Higher scores indicates more severe dryness.

The NEI (National Eye Institute) conjunctival staining score is used to assess damage or dryness-related staining of the bulbar conjunctiva by using lissamine green. The exposed bulbar conjunctiva is divided into six regions. Each zone is scored from 0 to 3, The scores for all six zones are summed, giving a total conjunctival staining score. The conjunctival staining score ranges from 0 to 18, with higher scores indicating more severe dry eye.

Patients marked their current pain intensity on a 10 cm horizontal visual analogue scale (VAS), with 'no pain' (0) at the left end and 'worst imaginable pain' (10) at the right end. This score was recorded as centimeter and given as 'before'. One drop of Proparacaine was then topically applied, and after 90 seconds, patients marked their pain intensity on the same scale. This second score was recorded and given as 'after'. The pain scale ranges from 0 to 10, with higher scores indicating greater pain severity.

The mean post-instillation pain intensity was subtracted from the mean pre-instillation value, divided by the mean pre-instillation intensity, and multiplied by 100 to calculate the percentage of pain change following proparacaine eyedrop instillation. Values range from -100 to 0; a value of -100 indicates that corneal pain originated entirely from peripheral corneal nerves, whereas 0 indicates that the pain originated entirely from non-ocular surface sources, such as the trigeminal ganglion or the upstream central nervous system.

Patients marked their current pain intensity on a 10 cm horizontal visual analogue scale (VAS), with 'no pain' (0) at the left end and 'worst imaginable pain' (10) at the right end. This score was recorded in centimeter and given as 'before'. One drop of cold 0.9% preservative-free saline was then topically applied, and immediately after patients marked their pain intensity on the same scale. This second score was recorded and given as 'after'. Higher scores indicate greater pain severity.

Patients marked their current pain intensity on a 10 cm horizontal visual analogue scale (VAS), with 'no pain' (0) at the left end and 'worst imaginable pain' (10) at the right end. This score was recorded in centimeters and designated as 'before'. One drop of 5% sodium chloride (Muro 128®) was then topically applied, and after twenty seconds, patients marked their pain intensity on the same scale. This second score was recorded and designated as 'after'. The pain scale ranges from 0 to 10, with higher scores indicating greater pain severity.

One drop of Proparacaine Hydrochloride Ophthalmic Solution 0.5% was topically applied in both eyes to differentiate between the peripheral versus central component of the patient's eye pain or discomfort. The level of discomfort/pain was then assessed by the visual analogue scale (VAS) questionnaire. Patients who experienced complete eye pain relief after proparacaine instillation were classified as having peripheral neuropathic corneal pain, whereas those with partial relief were classified as having mixed neuropathic corneal pain.

Patients marked their current pain intensity on a 10 cm horizontal visual analogue scale, with 'no pain' (0) at the left end and 'worst imaginable pain' (10) at the right end. This score was recorded as 'Pre-stimulation'. Each participant was asked to apply the intranasal neurostimulation device for 1 minute, and if no change in discomfort is noted, to continue for up to 3 minutes. Then patients marked their pain intensity on the same scale and recorded as 'Post-stimulation'. The pain scale ranges from 0 to 10, with higher scores indicating greater pain severity.

Pain Intensity Change Percent after Intranasal Neurostimulation was calculated by subtracting the mean post-stimulation pain intensity from the mean pre-stimulation value, then dividing by the mean pre-stimulation intensity and multiplying by 100 to obtain the percentage change. Values ranged from -100 to 100, with higher values indicating less pain reduction or pain increase after intranasal neurostimulation and a worse outcome.

The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire, with each question scored on a scale from 0 to 4, where 0 indicates 'none of the time' and 4 indicates 'all of the time.' To calculate the OSDI score, the sum of the scores from all answered questions was multiplied by 25 and then divided by the total number of questions answered. OSDI scores range from 0 to 100, with higher scores indicating more severe ocular surface symptoms and a worse outcome.

(0 = None of the time, 1 = Some of the time, 2 = Half of the time, 3 = Most of the time, 4 = All of the time)

The overall severity of pain (0 = no pain, 10 = worst pain ever)

The percentage of time spent thinking about non-eye pain (face/head) (0% = Not at all, 100% = All the time)

How much pain has interfered with/affected the following (0 = Not at all, 10 = Completely)

The final dimension of the Ocular Pain Assessment Survey's Quality of Life section assesses the percentage of time the patient spends thinking about eye pain. Scores range from 0 to 100, with higher scores indicating more time spent thinking about eye pain and greater pain severity.

The Quality of Life (QoL) section of Ocular Pain Assessment Survey (OPAS) includes 7 items: the first 6 are rated on a 0-10 scale, while the last item is scored as a percentage (0-100). To calculate the average OPAS QoL score, the percentage-based item is first converted to a 0-10 scale. Then, the sum of all answered item scores is divided by the total number of items completed. OPAS Average QoL scores range from 0 to 10, with higher scores indicating greater interference of daily activities due to ocular surface symptoms, lower QoL, and a worse outcome.

How much pain is increased when exposed to the following factors (0% = No change, 100% = Severe increase)

How often eye pain is accompanied by the following symptoms (0% = Never, 100% = All the time)

Pain relief experienced since last visit (0% = No relief, 100% = Complete relief)

The IDEEL questionnaire is a 57-item instrument and comprises three modules: dry eye impact on daily life, dry eye treatment satisfaction, and dry eye symptom bothers. In this study, the dry eye impact on daily life module was used, which consists of 27 items and assesses Quality of Life (QoL) in three aspects over the previous two weeks: daily activities, feelings, and work. Aside from the yes-or-no questions, the other questions are answered on a 0-5 Likert scale, where zero signifies an inability to perform the activity. Lower scores indicate more severe disability and worse outcome.

How often feelings are had because of dry eyes over the last two weeks (1 = All of the time, 2 = Most of the time, 3 = Some of the time, 4 = A little of the time, 5 = None of the time)

How often were the following situations experienced over the last two weeks at work because of dry eyes? (0 = All of the time, 1 = Most of the time, 2 = Some of the time, 3 = A little of the time, 4 = None of the time)

This test was done in a dimly lit room and each eye was assessed separately. The other eye was covered with an occluder to eliminate exposure to the light. The study eye was covered using a 100% opaque filter, and then the opacity of the filters was reduced in decrements of 10%. Ten graded filters were developed for this purpose; starting with the 100% opaque filter, the filter at which the patient started to feel pain/photophobia was noted. Values range 0-100; higher opacity filters reflect more photosensitivity and a worse outcome.

The VAS is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.

Post-stimulation minus pre-stimulation pain scores of all patients who underwent intranasal neurostimulation at the 45-day visit.

The Visual Analogue Scale (VAS) is a 10 cm line, with one end labeled 'no pain' (which is equivalent to a score of 0 on the numerical scale) and the other end labeled 'worst pain imaginable' (which is equivalent to a score of 10 on the numerical scale). The patient is asked to mark the scale according to the intensity of their eye pain, and the examiner measures the distance in centimeters or millimeters from the 'no pain' end of the line to score the VAS. The level of discomfort/pain before and after ITN was assessed using the VAS questionnaire (0-10). The changes in overall eye pain after ITN were recorded. Higher scores on the VAS indicate more intense pain and a worse outcome.

Post-stimulation minus pre-stimulation pain scores of all patients who underwent intranasal neurostimulation at the 90-day visit.

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

All Patients Participated 1 Day (Baseline) Visit

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

All Patients Participated 45 Day Visit

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire. Ranges: 0-10 for the "Reading and/or computer use", "Driving and/or watching TV", "General Activity", "Mood", "Sleep", "Enjoying Life/ Relationship. "Time spent thinking about pain" dimensions and 0-100. Higher scores indicate worse QoL.

All Patients Participated 90 Day Visit

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. The QoL section evaluates seven dimensions, with the first six graded using numerical rating scales (0-10) and the final question expressed as a percentage (0-100). Higher scores indicate severe pain and lower QoL in the QoL section of OPAS questionnaire.

Percentage changes in the scores between baseline vs 45-day visit and baseline vs 90-day visit after daily intranasal neurostimulation are given below.

Patients participated INSTANT study visits

The Ocular Pain Assessment Survey (OPAS) is a multidimensional questionnaire that assesses eye pain, non-eye pain, quality of life (QoL), aggravating factors, and associated factors. Eye pain intensity was assessed using a numerical scale (0-10) for the most, least, and average pain in the past 24 hours and 2 weeks. Higher scores indicate severe pain of OPAS questionnaire. The percent changes in pain intensity between baseline vs 45-day and baseline vs 90-day are provided below.

Patients participated INSTANT study visits

IDEEL Quality of Life Questionnaire is a 27-item questionnaire, designed specifically for DED and is divided into three parts. It assesses the quality of life in three aspects of life for the previous 2 weeks: daily activities, work and feelings. The quality of life is assessed on a scale of 0-5, with zero being inability to do the activity. The score is calculated between 0 - 100 with higher scores indicating a better quality of life. Percentage change in IDEEL questionnaire subheading between baseline and day 45 and baseline and day 90 were given below.

All patients participated INSTANT visits.

Intraocular pressure will be measured by an applanation tonometer used on slit lamp (Goldmann) in mmHg. Change in IOP values between baseline and 90-day is provided below. A healthy eye pressure is between 10 and 21 millimeters of mercury. The differences in intraocular pressure between the baseline and day 45 visits, as well as between the baseline and day 90 visits, are presented below.

Patients participated INSTANT study visits.

For safety analyses during the study, patient-reported adverse events that developed after intranasal neurostimulation were recorded.

All patients who underwent intranasal neurostimulation were evaluated for safety measures.

Tolerability of Intranasal Neurostimulator (ITN) was evaluated by using Ocular Tolerability and Compliance Questionnaire. It assesses symptoms of discomfort in each eye after ITN use.

All patients who underwent intranasal neurostimulation and completed Ocular Tolerability and Compliance Questionnaire.

After daily intranasal neurostimulation, the change in the number of systemic pain medication between baseline vs 45-day visit and Baseline vs 90-day visit was evaluated.

INSTANT patients participated baseline-45 Day Visit and baseline-90 Day Visit