Diabetic RetinopathyPhase 1INSPIRENCT04505566
INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study
A Phase 1 study testing Ketorolac 0.45% ophthalmic solution and Aqueous PGE2 and inflammatory cytokines measurements in people with Diabetic Retinopathy, run by Stephen J. Kim, MD at 1 site in United States.
Trial summary
The central hypothesis is that inflammation mediators are biomarkers of both systemic diabetes and Diabetic Retinopathy (DR) progression in the aqueous and that sustained topical ketorolac application reduces/suppresses those inflammatory mediators thereby reducing the progression of Diabetic Retinopathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- Ketorolac 0.45% ophthalmic solution and Aqueous PGE2 and inflammatory cytokines measurements
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Nov 2020to 21 Apr 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aim 1 Diabetic Arm Inclusion Criteria: Adult patients age 18 years or greater with type II diabetes.
- Aim 1 Nondiabetic Control Arm Inclusion Criteria: age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole.
- Aim 2 Inclusion Criteria: Adult patients age 18 years or older with type II diabetes, with baseline moderate NPDR and HbA1c ≥ 8.
Who cannot join
- Aim 1 Diabetic Arm Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure > 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.
- Aim 1 Nondiabetic Control Arm Exclusion Criteria: Patients who are unable to comply with testing and follow-up.
- Aim 2 Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure > 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy (INSPIRE) Study
The central hypothesis is that inflammation mediators are biomarkers of both systemic diabetes and Diabetic Retinopathy (DR) progression in the aqueous and that sustained topical ketorolac application reduces/suppresses those inflammatory mediators thereby reducing the progression of Diabetic Retinopathy.
Read the detailed description
Study goals include confirming inflammation mediators are biomarkers of both systemic diabetes and DR progression in the aqueous. Like the vitreous humor, the aqueous reflects localized ocular inflammation, however, is technically easier to collect with less risk. The investigators will also determine the long-term effects of sustained ketorolac application on intraocular cytokine levels, DR progression, and diabetic macular edema (DME) incidence. The proposal is the first to use a cornea-permeable Nonsteroidal anti-inflammatory drug (NSAID) for the treatment of DR.
It is believed local inflammation control in the eye will transform future treatment options for diabetic patients facing blindness. Tracking and inhibiting local inflammatory mediators through all DR stages has the capacity to reduce or prevent disability in millions of patients per year.
164 adult type II diabetic mellitus (T2DM) patients, aged 18 years or greater will be enrolled to measure aqueous PGE2 and inflammatory cytokines. Because the pathophysiology of type I disease and the population it effects are different, type I diabetic patients will be excluded. Diabetic retinopathy is broadly categorized as nonproliferative (NPDR) and proliferative (PDR). The international Clinical Disease Severity Scale is a standard classification system consisting of two categories and five stages: the nonproliferative category, stage 1-4 and proliferative category, stage 5. Stage 1 is characterized as "no apparent retinopathy." The nonproliferative stage is further grouped into stage 2 (mild), stage 3 (moderate), and stage 4 (severe). Stage 5 is final stage, PDR.
Of the 164 patients enrolled for aqueous PGE2 and inflammatory cytokine measurements, the diabetic participants corresponding to stages 1, 3, and 5 will be classified as patients with no DR (23 patients), with PDR (23 patients), and with moderate NPDR (118 patients). The 118 participants with moderate NPDR will be randomized for Aim 2 described below.
In addition, 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will be enrolled as controls.
Aim 1 of this project is to measure aqueous PGE2 and inflammatory cytokines during DR progression.
Aim 2 of this project is two-fold:
- Investigate the long-term effects of daily topical application of ketorolac on PGE2 and cytokine levels.
- Determine how topical application of ketorolac influences DR progression and development of DME.
- Conditions
- Diabetic Retinopathy
- Being tested
- Ketorolac 0.45% ophthalmic solution, Placebo - Preservative-free artificial tears, Aqueous PGE2 and inflammatory cytokines measurements
- Keywords
- Topical Ketorolac, Acuvail, Prevention of Diabetic Retinopathy
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketorolac 0.45% ophthalmic solutionDrug
Also called Acuvail
Ketorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.
Placebo - Preservative-free artificial tearsDrug
Also called Refresh
Preservative free artificial tears ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.
Aqueous PGE2 and inflammatory cytokines measurementsOther
After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured
| Study group | Role | What they receive |
|---|---|---|
| Adult Type II Diabetics - Moderate NPDR - Ketorolac | Experimental | 59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy and HbA1c ≥ 8 randomized to Ketorolac treatment. Receives: Drug: Ketorolac 0.45% ophthalmic solution; Other: Aqueous PGE2 and inflammatory cytokines measurements |
| Adult Type II Diabetics - Moderate NPDR - Placebo | Placebo comparator | 59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy randomized to placebo treatment. Receives: Drug: Placebo - Preservative-free artificial tears; Other: Aqueous PGE2 and inflammatory cytokines measurements |
| Adult Type II Diabetics - No Diabetic Retinopathy (DR) | Other | 23 Adult type II diabetic patients with no diabetic retinopathy as a control group. Receives: Other: Aqueous PGE2 and inflammatory cytokines measurements |
| Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR) | Other | 23 Adult type II diabetic patients with proliferative diabetic retinopathy as a control group. Receives: Other: Aqueous PGE2 and inflammatory cytokines measurements |
| Age-matched Non-diabetics | Other | We will also enroll 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole. Removed aqueous fluid that is typically discarded will instead be collected and stored at -80° C. Aqueous fluid will be tested for inflammatory markers as detailed below to provide a reference level for cross-comparison analysis. Receives: Other: Aqueous PGE2 and inflammatory cytokines measurements |
What is being measured
The primary outcome is the main question the study is designed to answer.
PGE2 level during Diabetic Retinopathy progression
Aqueous samples will be analyzed using liquid chromatography electrospray ionization tandem mass spectrometry to measure all PGE2 levels. PGE2 will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Measured: 1 year
Vascular Endothelial Growth Factor (VEGF) level during Diabetic Retinopathy progression
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure VEGF levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Measured: 1 year
Interleukin 6 (IL-6) level during Diabetic Retinopathy progression
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure IL-6 levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Measured: 1 year
Interleukin 8 (IL-8) level during Diabetic Retinopathy progression
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure IL-8 levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Measured: 1 year
Progression of Diabetic Retinopathy (DR)
To determine progression of DR, we will analyze data from the 118 diabetic patients randomized to either Ketorolac or placebo. Diabetic retinopathy progresses in discrete steps defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale (15-step scale: minimum value of 10 and maximum value of 65, with higher scores meaning a worse outcome). With each advancing level, the risk of developing DME and/or PDR increases. A 2-stage or more worsening on the ETDRS severity scale is associated with an increased risk of vision loss.
Measured: 3 years
Severity of Diabetic Retinopathy (DR)
A blinded sub-investigator will grade DR by utilizing the 15-step severity scale established by the ETDRS. A 2-step or more increase or decrease in severity scale, observed on 2 consecutive follow-up appointments, will define a change in DR (progression or improvement).
Measured: 3 years
Secondary outcomes (2)
Incidence of Diabetic Macular Edema
To determine incidence of Diabetic Macular Edema, we will analyze data from the 118 diabetic patients. An increase in macular thickness (determined by OCT as ≥ 40%) will determine development of DME.
Measured: 3 years
Progression of Diabetic Macular Edema
To determine progression of Diabetic Macular Edema, we will analyze data from the 118 diabetic patients. An increase in macular thickness (determined by OCT as ≥ 40%) will determine progression of DME.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start9 Nov 2020
- Primary completion21 Apr 2026
- Study completion21 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a 2 aim, randomized and double-masked Phase I study on topical Ketorolac for the prevention of diabetic retinopathy. 164 adult type II diabetic patients, aged 18 years or greater will be enrolled in addition to 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will also be enrolled.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stephen J. Kim, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Allergan, National Eye Institute (NEI)
- Responsible party
- Sponsor-investigator, Stephen J. Kim, MD, Vanderbilt University Medical Center
- Investigators
- Stephen J Kim, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04505566
- Sponsor's protocol ID
- 201433
- Other IDs
- 5R01EY031315-02
- Acronym
- INSPIRE
- Status last verified
- Aug 2026
- First submitted
- 31 Jul 2020
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available.
Publications
Kim SJ, Gangaputra S, Choi L, McNeer E, Sheng J. INFLAMMATORY MEDIATORS IN DIABETIC MACULAR EDEMA: A Prospective, Controlled Study. Retina. 2026 Sep 1;46(9):1513-1519. doi: 10.1097/IAE.0000000000004893.
PubMed 42246764Kim SJ, Gangaputra S, Sheng J, Patel S, Nair AA, Al Hussein Al Awamlh S, Fitzpatrick J, Cherney E, Veach L, Nicholson C. Analysis of 24 pro-inflammatory cytokines in aqueous and serum of 94 patients without diabetes. Br J Ophthalmol. 2025 Nov 20;109(12):1357-1362. doi: 10.1136/bjo-2025-327421.
PubMed 40695570
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy (INSPIRE) Study
- ClinicalTrials.gov ID
- NCT04505566
- Acronym / sponsor ID
- INSPIRE / 201433
- Conditions
- Diabetic Retinopathy
- Keywords
- Topical Ketorolac, Acuvail, Prevention of Diabetic Retinopathy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Stephen J. Kim, MDUniversity, hospital or other
- Collaborators
- Allergan, National Eye Institute (NEI)
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 21 Apr 2026 (actual)
- Study completion
- 21 Apr 2026 (actual)
- First posted
- 10 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The central hypothesis is that inflammation mediators are biomarkers of both systemic diabetes and Diabetic Retinopathy (DR) progression in the aqueous and that sustained topical ketorolac application reduces/suppresses those inflammatory mediators thereby reducing the progression of Diabetic Retinopathy.
Detailed description
Study goals include confirming inflammation mediators are biomarkers of both systemic diabetes and DR progression in the aqueous. Like the vitreous humor, the aqueous reflects localized ocular inflammation, however, is technically easier to collect with less risk. The investigators will also determine the long-term effects of sustained ketorolac application on intraocular cytokine levels, DR progression, and diabetic macular edema (DME) incidence. The proposal is the first to use a cornea-permeable Nonsteroidal anti-inflammatory drug (NSAID) for the treatment of DR.
It is believed local inflammation control in the eye will transform future treatment options for diabetic patients facing blindness. Tracking and inhibiting local inflammatory mediators through all DR stages has the capacity to reduce or prevent disability in millions of patients per year.
164 adult type II diabetic mellitus (T2DM) patients, aged 18 years or greater will be enrolled to measure aqueous PGE2 and inflammatory cytokines. Because the pathophysiology of type I disease and the population it effects are different, type I diabetic patients will be excluded. Diabetic retinopathy is broadly categorized as nonproliferative (NPDR) and proliferative (PDR). The international Clinical Disease Severity Scale is a standard classification system consisting of two categories and five stages: the nonproliferative category, stage 1-4 and proliferative category, stage 5. Stage 1 is characterized as "no apparent retinopathy." The nonproliferative stage is further grouped into stage 2 (mild), stage 3 (moderate), and stage 4 (severe). Stage 5 is final stage, PDR.
Of the 164 patients enrolled for aqueous PGE2 and inflammatory cytokine measurements, the diabetic participants corresponding to stages 1, 3, and 5 will be classified as patients with no DR (23 patients), with PDR (23 patients), and with moderate NPDR (118 patients). The 118 participants with moderate NPDR will be randomized for Aim 2 described below.
In addition, 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will be enrolled as controls.
Aim 1 of this project is to measure aqueous PGE2 and inflammatory cytokines during DR progression.
Aim 2 of this project is two-fold:
- Investigate the long-term effects of daily topical application of ketorolac on PGE2 and cytokine levels.
- Determine how topical application of ketorolac influences DR progression and development of DME.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
- Model description
- This is a 2 aim, randomized and double-masked Phase I study on topical Ketorolac for the prevention of diabetic retinopathy. 164 adult type II diabetic patients, aged 18 years or greater will be enrolled in addition to 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will also be enrolled.
| Arm | Type | Receives |
|---|---|---|
| Adult Type II Diabetics - Moderate NPDR - Ketorolac | Experimental | Drug: Ketorolac 0.45% ophthalmic solution, Other: Aqueous PGE2 and inflammatory cytokines measurements59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy and HbA1c ≥ 8 randomized to Ketorolac treatment. |
| Adult Type II Diabetics - Moderate NPDR - Placebo | Placebo comparator | Drug: Placebo - Preservative-free artificial tears, Other: Aqueous PGE2 and inflammatory cytokines measurements59 Adult type II diabetic patients with baseline moderate non-proliferative diabetic retinopathy randomized to placebo treatment. |
| Adult Type II Diabetics - No Diabetic Retinopathy (DR) | Other | Other: Aqueous PGE2 and inflammatory cytokines measurements23 Adult type II diabetic patients with no diabetic retinopathy as a control group. |
| Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR) | Other | Other: Aqueous PGE2 and inflammatory cytokines measurements23 Adult type II diabetic patients with proliferative diabetic retinopathy as a control group. |
| Age-matched Non-diabetics | Other | Other: Aqueous PGE2 and inflammatory cytokines measurementsWe will also enroll 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole. Removed aqueous fluid that is typically discarded will instead be collected and stored at -80° C. Aqueous fluid will be tested for inflammatory markers as detailed below to provide a reference level for cross-comparison analysis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Aim 1 Diabetic Arm Inclusion Criteria: Adult patients age 18 years or greater with type II diabetes.
- Aim 1 Nondiabetic Control Arm Inclusion Criteria: age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole.
- Aim 2 Inclusion Criteria: Adult patients age 18 years or older with type II diabetes, with baseline moderate NPDR and HbA1c ≥ 8.
Key exclusion criteria (3 listed)
- Aim 1 Diabetic Arm Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure > 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.
- Aim 1 Nondiabetic Control Arm Exclusion Criteria: Patients who are unable to comply with testing and follow-up.
- Aim 2 Exclusion Criteria: Patients with a history of previous vitrectomy in either eye; prior intravitreal injection within 3 months; co-existent macular, retinovascular, or inflammatory disease; history of ocular trauma; aphakia; presence of an anterior chamber intraocular lens; current use of prescription systemic NSAIDs or regular use of nonprescription NSAIDs including aspirin (defined as 4 days or more a week for at least 2 weeks a month); blood pressure > 180/110 mmHg; risk for corneal melting; and inability to comply with follow-up.
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 |
|---|---|---|
| Ketorolac 0.45% ophthalmic solutionAlso: AcuvailKetorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion. | Drug | Adult Type II Diabetics - Moderate NPDR - Ketorolac |
| Placebo - Preservative-free artificial tearsAlso: RefreshPreservative free artificial tears ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion. | Drug | Adult Type II Diabetics - Moderate NPDR - Placebo |
| Aqueous PGE2 and inflammatory cytokines measurementsAfter topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured | Other | Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR), Adult Type II Diabetics - Moderate NPDR - Ketorolac, Adult Type II Diabetics - Moderate NPDR - Placebo, Adult Type II Diabetics - No Diabetic Retinopathy (DR), Age-matched Non-diabetics |
Primary outcome
PGE2 level during Diabetic Retinopathy progression
Time frame: 1 year
Aqueous samples will be analyzed using liquid chromatography electrospray ionization tandem mass spectrometry to measure all PGE2 levels. PGE2 will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Vascular Endothelial Growth Factor (VEGF) level during Diabetic Retinopathy progression
Time frame: 1 year
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure VEGF levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Interleukin 6 (IL-6) level during Diabetic Retinopathy progression
Time frame: 1 year
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure IL-6 levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Interleukin 8 (IL-8) level during Diabetic Retinopathy progression
Time frame: 1 year
Aqueous samples will be analyzed using a microparticle bead-based multiplex assay will be used to measure IL-8 levels. VEGF will be measured every 4 months during 1 year of study to determine whether their mean mediator levels associate with DR severity stage using a linear mixed effects model. The DR severity stage will be included as a continuous or categorical variable, and potential confounding factors as well as baseline measurements for each inflammatory mediator, will be adjusted in the analysis.
Progression of Diabetic Retinopathy (DR)
Time frame: 3 years
To determine progression of DR, we will analyze data from the 118 diabetic patients randomized to either Ketorolac or placebo. Diabetic retinopathy progresses in discrete steps defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale (15-step scale: minimum value of 10 and maximum value of 65, with higher scores meaning a worse outcome). With each advancing level, the risk of developing DME and/or PDR increases. A 2-stage or more worsening on the ETDRS severity scale is associated with an increased risk of vision loss.
Severity of Diabetic Retinopathy (DR)
Time frame: 3 years
A blinded sub-investigator will grade DR by utilizing the 15-step severity scale established by the ETDRS. A 2-step or more increase or decrease in severity scale, observed on 2 consecutive follow-up appointments, will define a change in DR (progression or improvement).
2 secondary outcomes
Incidence of Diabetic Macular Edema
Time frame: 3 years
Progression of Diabetic Macular Edema
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Derived from this study: PubMed 42246764Kim SJ, Gangaputra S, Choi L, McNeer E, Sheng J. INFLAMMATORY MEDIATORS IN DIABETIC MACULAR EDEMA: A Prospective, Controlled Study. Retina. 2026 Sep 1;46(9):1513-1519. doi: 10.1097/IAE.0000000000004893.
- Derived from this study: PubMed 40695570Kim SJ, Gangaputra S, Sheng J, Patel S, Nair AA, Al Hussein Al Awamlh S, Fitzpatrick J, Cherney E, Veach L, Nicholson C. Analysis of 24 pro-inflammatory cytokines in aqueous and serum of 94 patients without diabetes. Br J Ophthalmol. 2025 Nov 20;109(12):1357-1362. doi: 10.1136/bjo-2025-327421.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available.
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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.
Stephen J Kim, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketorolac 0.45% ophthalmic solution and Aqueous PGE2 and inflammatory cytokines measurements in people with Diabetic Retinopathy, run by Stephen J. Kim, MD at 1 site in United States.
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 3 inclusion and 3 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 21 Aug 2026. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
PGE2 level during Diabetic Retinopathy progression (time frame: 1 year). The study lists 6 primary outcomes in all. 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 NCT04505566, which also lists 2 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 21 Aug 2026.