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Also known as Ketorolac 0.45% ophthalmic solution
Ketorolac 0.45% · 1 trial · 1 indication
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.
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.
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.
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.
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.
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).
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| Adult Type II Diabetics - No Diabetic Retinopathy (DR) | OTHER | 23 Adult type II diabetic patients with no diabetic retinopathy as a control group. |
| Adult Type 2 Diabetics-Proliferative Diabetic Retinopathy(PDR) | OTHER | 23 Adult type II diabetic patients with proliferative diabetic retinopathy as a control group. |
| 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. |
| Name | Type | Description |
|---|---|---|
| Ketorolac 0.45% ophthalmic solution | DRUG | Ketorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion. |
| Placebo - Preservative-free artificial tears | DRUG | 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 measurements | OTHER | 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 |
Inclusion Criteria: * 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 ...