Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis)Phase 4NCT05832996

Cool vs Room-temperature Artificial Tears

A Phase 4 study testing Refresh Plus Preservative-free Lubricant Eye Drops in people with Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis) and Central Retinal Vein Occlusion With Macular Edema, run by University of Iowa at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Background and Objective: To evaluate the efficacy of cooled versus room temperature artificial tears in reducing post intravitreal injection (IVI) ocular discomfort. Patients and Methods: Patients receiving IVI were randomized to either cooled or room temperature tears intervention groups. Read more about this study

Who is it for?: Ages 18 to 105 yearsHealthy volunteers can take part
Conditions the study is for: Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis), Central Retinal Vein Occlusion With Macular Edema, Exudative Age-Related Macular Degeneration, Unspecified Eye
What is being tested?: Refresh Plus Preservative-free Lubricant Eye Drops
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 124 participants
Where: 1 siteUnited States
Study dates: 1 Mar 2022to 6 Jul 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 105 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Patients were eligible if they were receiving standard intravitreal injections for their exudative age-related macular degeneration, cystoid macular edema, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion with macular edema, or retinal neovascularization.

Who cannot join

Inability or lack of willingness to participate in the study
Active ocular infection including infectious uveitis
First time receiving intravitreal injection
Those who reported never having ocular discomfort following intravitreal injections on the pre-injection questionnaire
Less than 18 years of age

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Iowa Hospitals & Clinics - Department of Ophthalmology
Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: Randomized Controlled Study of Cooled Versus Room-Temperature Artificial Tears for Reducing Surface Irritation Following Intravitreal Injection

Background and Objective: To evaluate the efficacy of cooled versus room temperature artificial tears in reducing post intravitreal injection (IVI) ocular discomfort.

Patients and Methods: Patients receiving IVI were randomized to either cooled or room temperature tears intervention groups. Both groups rated their ocular discomfort following IVI before intervention and again after administration of cooled or room temperature tears.

Conditions: Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis), Central Retinal Vein Occlusion With Macular Edema, Exudative Age-Related Macular Degeneration, Unspecified Eye, Cystoid Macular Edema, Ocular Surface Disease, Dry Eye Sensation
Being tested: Refresh Plus Preservative-free Lubricant Eye Drops
Medical subject headings: Disease, Macular Edema, Eye Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Refresh Plus Preservative-free Lubricant Eye DropsDrug
Refresh Plus Preservative-free Lubricant Eye Drops at either 4 or 25 degree Celsius

Study groups in NCT05832996
Study group	Role	What they receive
Cooled artificial tear group	Experimental	Stored at 4 degree Celsius Receives: Drug: Refresh Plus Preservative-free Lubricant Eye Drops
Room temperature artificial tear group	Active comparator	Stored at 25 degree Celsius Receives: Drug: Refresh Plus Preservative-free Lubricant Eye Drops

What is being measured

The primary outcome is the main question the study is designed to answer.

The Efficacy of Cooled Versus Room Temperature Artificial Tears in Reducing Post Intravitreal Injection Ocular Discomfort as Measured by Pain Scale Survey.
The level of subjectively reported pain scale from 1 to 10, where 1 is minimal pain and 10 is extreme pain
Measured: with 72 hours of the intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 20226 Jul 2022

First posted27 Apr 2023
Study start1 Mar 2022
Primary completion1 Jul 2022
Study completion6 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (20)Papers the sponsor has linked to this study.
Other trials for Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Investigator
Enrolment: 124 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05832996
Sponsor's protocol ID: 202201397
Status last verified: Feb 2025
First submitted: 14 Mar 2023
Last updated: 4 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina. 2009 Jul-Aug;29(7):875-912. doi: 10.1097/IAE.0b013e3181a94f01.
PubMed 19584648
Patel SN, Gangaputra S, Sternberg P Jr, Kim SJ. Prophylaxis measures for postinjection endophthalmitis. Surv Ophthalmol. 2020 Jul-Aug;65(4):408-420. doi: 10.1016/j.survophthal.2019.12.005. Epub 2020 Jan 7.
PubMed 31923477
Grzybowski A, Kanclerz P, Myers WG. The use of povidone-iodine in ophthalmology. Curr Opin Ophthalmol. 2018 Jan;29(1):19-32. doi: 10.1097/ICU.0000000000000437.
PubMed 28984794
Swift W, Bair JA, Chen W, Li M, Lie S, Li D, Yang M, Shatos MA, Hodges RR, Kolko M, Utheim TP, Scott W, Dartt DA. Povidone iodine treatment is deleterious to human ocular surface conjunctival cells in culture. BMJ Open Ophthalmol. 2020 Sep 16;5(1):e000545. doi: 10.1136/bmjophth-2020-000545. eCollection 2020.
PubMed 32995498
Saedon H, Nosek J, Phillips J, Narendran N, Yang YC. Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections. Cutan Ocul Toxicol. 2017 Dec;36(4):343-346. doi: 10.1080/15569527.2017.1291665. Epub 2017 Feb 28.
PubMed 28166657
Laude A, Lim JW, Srinagesh V, Tong L. The effect of intravitreal injections on dry eye, and proposed management strategies. Clin Ophthalmol. 2017 Aug 16;11:1491-1497. doi: 10.2147/OPTH.S136500. eCollection 2017.
PubMed 28860698
Dohlman TH, Lertsuwanroj B, D'Amico DJ, Ciralsky JB, Kiss S. Evaluation of signs and symptoms of ocular surface disease after intravitreal injection. Acta Ophthalmol. 2019 Dec;97(8):e1154-e1156. doi: 10.1111/aos.14146. Epub 2019 Jun 25. No abstract available.
PubMed 31237739
Segal O, Segal-Trivitz Y, Nemet AY, Cohen P, Geffen N, Mimouni M. Anxiety levels and perceived pain intensity during intravitreal injections. Acta Ophthalmol. 2016 Mar;94(2):203-4. doi: 10.1111/aos.12802. Epub 2015 Jul 28. No abstract available.
PubMed 26215781
Chaturvedi R, Wannamaker KW, Riviere PJ, Khanani AM, Wykoff CC, Chao DL. Real-World Trends in Intravitreal Injection Practices among American Retina Specialists. Ophthalmol Retina. 2019 Aug;3(8):656-662. doi: 10.1016/j.oret.2019.03.023. Epub 2019 Apr 4.
PubMed 31133544
Avery RL, Bakri SJ, Blumenkranz MS, Brucker AJ, Cunningham ET Jr, D'Amico DJ, Dugel PU, Flynn HW Jr, Freund KB, Haller JA, Jumper JM, Liebmann JM, McCannel CA, Mieler WF, Ta CN, Williams GA. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014 Dec;34 Suppl 12:S1-S18. doi: 10.1097/IAE.0000000000000399.
PubMed 25489719
Kaplan RI, Drinkwater OJ, Lee RH, Chod RB, Barash A, Giovinazzo JV, Gologorsky D, Jansen ME, Rosen RB, Gentile RC. Pain Control after Intravitreal Injection Using Topical Nepafenac 0.3% or Pressure Patching: A Randomized, Placebo-Controlled Trial. Ophthalmol Retina. 2019 Oct;3(10):860-866. doi: 10.1016/j.oret.2019.04.022. Epub 2019 Apr 26.
PubMed 31221565
Rifkin L, Schaal S. Shortening ocular pain duration following intravitreal injections. Eur J Ophthalmol. 2012 Nov-Dec;22(6):1008-12. doi: 10.5301/ejo.5000147. Epub 2012 Apr 24.
PubMed 22562296
Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf. 2002;25(4):233-50. doi: 10.2165/00002018-200225040-00002.
PubMed 11994027
Fujishima H, Yagi Y, Shimazaki J, Tsubota K. Effects of artificial tear temperature on corneal sensation and subjective comfort. Cornea. 1997 Nov;16(6):630-4.
PubMed 9395871
Hu Youwei J, Chang B. Effect of cooling proparacaine 0.5% eye drops on patient's comfort during instillation. Eye (Lond). 2015 Aug;29(8):1112-3. doi: 10.1038/eye.2015.59. Epub 2015 Apr 24. No abstract available.
PubMed 25907208

Study at a glance

From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Controlled Study of Cooled Versus Room-Temperature Artificial Tears for Reducing Surface Irritation Following Intravitreal Injection
ClinicalTrials.gov ID: NCT05832996
Acronym / sponsor ID: 202201397
Conditions: Diabetic Retinopathy With Macular Edema of Both Eyes (Diagnosis), Central Retinal Vein Occlusion With Macular Edema, Exudative Age-Related Macular Degeneration, Unspecified Eye, Cystoid Macular Edema, Ocular Surface Disease, Dry Eye Sensation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 124 participants (actual)
Lead sponsor: University of IowaUniversity, hospital or other
Study start: 1 Mar 2022 (actual)
Primary completion: 1 Jul 2022 (actual)
Study completion: 6 Jul 2022 (actual)
First posted: 27 Apr 2023 (actual)
Results: Posted 4 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background and Objective: To evaluate the efficacy of cooled versus room temperature artificial tears in reducing post intravitreal injection (IVI) ocular discomfort.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 2

Arm	Type	Receives
Cooled artificial tear group	Experimental	Drug: Refresh Plus Preservative-free Lubricant Eye DropsStored at 4 degree Celsius
Room temperature artificial tear group	Active comparator	Drug: Refresh Plus Preservative-free Lubricant Eye DropsStored at 25 degree Celsius

Who may qualify

Ages: 18 to 105 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Patients were eligible if they were receiving standard intravitreal injections for their exudative age-related macular degeneration, cystoid macular edema, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion with macular edema, or retinal neovascularization.

Key exclusion criteria (5 listed)

Inability or lack of willingness to participate in the study
Active ocular infection including infectious uveitis
First time receiving intravitreal injection
Those who reported never having ocular discomfort following intravitreal injections on the pre-injection questionnaire
Less than 18 years of age

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Refresh Plus Preservative-free Lubricant Eye DropsRefresh Plus Preservative-free Lubricant Eye Drops at either 4 or 25 degree Celsius	Drug	Cooled artificial tear group, Room temperature artificial tear group

Primary outcome

The Efficacy of Cooled Versus Room Temperature Artificial Tears in Reducing Post Intravitreal Injection Ocular Discomfort as Measured by Pain Scale Survey.
Time frame: with 72 hours of the intervention
The level of subjectively reported pain scale from 1 to 10, where 1 is minimal pain and 10 is extreme pain

Results and safety

Results posted to the registry on 4 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cooled Artificial Tear Group	56	48
Room Temperature Artificial Tear Group	68	61

Primary outcome: The Efficacy of Cooled Versus Room Temperature Artificial Tears in Reducing Post Intravitreal Injection Ocular Discomfort as Measured by Pain Scale Survey.

Time frame: with 72 hours of the intervention. Mean (Standard Deviation). Unit: score on a scale

Measure	Cooled Artificial Tear Group n = 48	Room Temperature Artificial Tear Group n = 61
Value	2.21 (0.2)	1.95 (0.2)

Adverse events

Time frame: The specific period time over which adverse event data were collected was 4 months, which was the entire duration of the study. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cooled Artificial Tear Group	0 of 48 (0%)	0 of 48 (0%)	0 of 48
Room Temperature Artificial Tear Group	0 of 61 (0%)	0 of 61 (0%)	0 of 61

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19584648Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina. 2009 Jul-Aug;29(7):875-912. doi: 10.1097/IAE.0b013e3181a94f01.
Background: PubMed 31923477Patel SN, Gangaputra S, Sternberg P Jr, Kim SJ. Prophylaxis measures for postinjection endophthalmitis. Surv Ophthalmol. 2020 Jul-Aug;65(4):408-420. doi: 10.1016/j.survophthal.2019.12.005. Epub 2020 Jan 7.
Background: PubMed 28984794Grzybowski A, Kanclerz P, Myers WG. The use of povidone-iodine in ophthalmology. Curr Opin Ophthalmol. 2018 Jan;29(1):19-32. doi: 10.1097/ICU.0000000000000437.
Background: PubMed 32995498Swift W, Bair JA, Chen W, Li M, Lie S, Li D, Yang M, Shatos MA, Hodges RR, Kolko M, Utheim TP, Scott W, Dartt DA. Povidone iodine treatment is deleterious to human ocular surface conjunctival cells in culture. BMJ Open Ophthalmol. 2020 Sep 16;5(1):e000545. doi: 10.1136/bmjophth-2020-000545. eCollection 2020.
Background: PubMed 28166657Saedon H, Nosek J, Phillips J, Narendran N, Yang YC. Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections. Cutan Ocul Toxicol. 2017 Dec;36(4):343-346. doi: 10.1080/15569527.2017.1291665. Epub 2017 Feb 28.
Background: PubMed 28860698Laude A, Lim JW, Srinagesh V, Tong L. The effect of intravitreal injections on dry eye, and proposed management strategies. Clin Ophthalmol. 2017 Aug 16;11:1491-1497. doi: 10.2147/OPTH.S136500. eCollection 2017.
Background: PubMed 31237739Dohlman TH, Lertsuwanroj B, D'Amico DJ, Ciralsky JB, Kiss S. Evaluation of signs and symptoms of ocular surface disease after intravitreal injection. Acta Ophthalmol. 2019 Dec;97(8):e1154-e1156. doi: 10.1111/aos.14146. Epub 2019 Jun 25. No abstract available.
Background: PubMed 26215781Segal O, Segal-Trivitz Y, Nemet AY, Cohen P, Geffen N, Mimouni M. Anxiety levels and perceived pain intensity during intravitreal injections. Acta Ophthalmol. 2016 Mar;94(2):203-4. doi: 10.1111/aos.12802. Epub 2015 Jul 28. No abstract available.
Background: PubMed 31133544Chaturvedi R, Wannamaker KW, Riviere PJ, Khanani AM, Wykoff CC, Chao DL. Real-World Trends in Intravitreal Injection Practices among American Retina Specialists. Ophthalmol Retina. 2019 Aug;3(8):656-662. doi: 10.1016/j.oret.2019.03.023. Epub 2019 Apr 4.
Background: PubMed 25489719Avery RL, Bakri SJ, Blumenkranz MS, Brucker AJ, Cunningham ET Jr, D'Amico DJ, Dugel PU, Flynn HW Jr, Freund KB, Haller JA, Jumper JM, Liebmann JM, McCannel CA, Mieler WF, Ta CN, Williams GA. Intravitreal injection technique and monitoring: updated guidelines of an expert panel. Retina. 2014 Dec;34 Suppl 12:S1-S18. doi: 10.1097/IAE.0000000000000399.
Background: PubMed 31221565Kaplan RI, Drinkwater OJ, Lee RH, Chod RB, Barash A, Giovinazzo JV, Gologorsky D, Jansen ME, Rosen RB, Gentile RC. Pain Control after Intravitreal Injection Using Topical Nepafenac 0.3% or Pressure Patching: A Randomized, Placebo-Controlled Trial. Ophthalmol Retina. 2019 Oct;3(10):860-866. doi: 10.1016/j.oret.2019.04.022. Epub 2019 Apr 26.
Background: PubMed 22562296Rifkin L, Schaal S. Shortening ocular pain duration following intravitreal injections. Eur J Ophthalmol. 2012 Nov-Dec;22(6):1008-12. doi: 10.5301/ejo.5000147. Epub 2012 Apr 24.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Douglas Jin, MD principal investigator

University of Iowa

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Efficacy of Cooled Versus Room Temperature Artificial Tears in Reducing Post Intravitreal Injection Ocular Discomfort as Measured by Pain Scale Survey. (time frame: with 72 hours of the intervention). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05832996, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.