PCME Prevention in Patients With NPDR

May 15, 2022 updated by: Andjela Jukic, Klinički Bolnički Centar Zagreb

The Effect of Topical Corticosteroids and Topical NSAIDs Perioperatively on IL6 Levels in Aqueous Humor and on Incidence of PCME in Patients With NPDR

Pseudophakic cystoid macular edema (PCME), or Irvine-Gass syndrome, is retinal thickening of the macula, which usually develops within 3 months after surgery, with a peak incidence between 4 and 6 weeks. Despite recent improvements in surgical techniques, PCME remains one of the most common causes of visual decline following an uneventful cataract surgery. Symptoms of PCME usually are blurred vision, metamorphopsia, loss of contrast sensitivity, and central scotomas. PCME usually responds well to medical therapy or may resolve spontaneously but carries a risk of permanent vision loss or loss of contrast sensitivity. There is wide discrepancy in opinions about the most effective antiinflammatory drops for the prevention of PCME. Patients with diabetes mellitus (DM) have attracted special interest because of higher incidence of cataract and increased risk for developing CME after cataract surgery. The optimum antiinflammatory prophylaxis for PCME in patients with nonproliferative diabetic retinopathy (NPDR) remains unknown.

Purpose of this study is to determine the efficacy of topical bromfenac and topical dexamethasone on intraocular concentration of interleukin-6 (IL6) and the incidence of pseudophakic cystoid macular edema (PCME) after cataract surgery in patients with nonproliferative diabetic retinopathy (NPDR).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There is no standardized, widely-acceptable, evidence-based prophylaxis and treatment protocols to prevent macular edema after cataract surgery (PCME).

Current leading theory of pathogenesis of PCME (Irvine Gass) involves inflammation caused by surgical trauma which induces the release of inflammatory mediators like cytokines, prostaglandins and other vasopermeability factors, which disrupt the blood-retinal barrier and cause leakage from perifoveal retinal capillaries and accumulation of extracellular fluid in outer plexiform and inner nuclear layers of the retina. Diabetes is significant risk factor for developing PCME and grows proportionately with the severity of the diabetic retinopathy (DR). DR is common complication of diabetes mellitus (DM) and affects one in three persons with DM. Interleukin-6 (IL6) is associated with many intraocular inflammatory diseases such as diabetic retinopathy and macular edema acting as a pro-inflammatory cytokine. Levels of IL6 in aqueous humor are correlated with the severity of DR and the severity of DME. IL6 probably plays a crucial role in the development of inflammation after cataract surgery. Macular edema is usually monitored by spectral domain optical coherence tomography (SD-OCT) which is suitable for detecting subtle macular changes as well as follow up after treatment. OCT provides an objective measurement of macular thickness that correlates well with visual impairment and can be useful in standardizing definitions of PCME.

Prevention of PCME after cataract surgery in patients with NPDR include preoperative treatment with steroids, intravitreal injections of anti-vascular endothelial growth factors, laser treatment and topical nonsteroidal anti-inflammatory drugs (NSAIDs).

This randomized, double blinded, placebo-controlled trial will be conducted at Clinic of Ophthalmology, University Hospital Center Zagreb, Croatia. Ninety (90) eyes with mild to moderate NPDR (EDTRS classification) and cataract grade II nuclear/cortical or posterior subcapsular (Lens Opacities Classification System III) who will undergo phacoemulsification with intraocular lens implantation will be divided into three groups. Group 1 will receive topical bromfenac, group 2 will receive topical dexamethasone and group 3 will receive topical placebo, 7 days preoperatively and 3 weeks postoperatively. All patients will receive standard regimen of topical steroid-antibiotic drops postoperatively. Macular edema is defined as central foveal subfield thickness (CFT) increase of 40% from baseline. On the day of the surgery aqueous humor samples (0.1-0.2 mL) will be taken and IL6 concentration will be analyzed. Central foveal subfield thickness (CFT) will be measured with spectral domain optical coherence tomography (SD-OCT) and analyzed 7 days prior to surgery, on the day of the surgery and on 1, 7, 30 and 90 postoperative day.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
    • Grad Zagreb
      • Zagreb, Grad Zagreb, Croatia, 10000
        • KBCZagreb

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • clinical diagnosis of mild to moderate nonproliferative diabetic retinopathy (EDTRS) and
  • senile cataract grade II nuclear/cortical or posterior subcapsular (LOCS III)

Exclusion Criteria:

  • anterior segment pathology (pseudoexfoliation syndrome, corneal opacities),
  • posterior segment pathology (diabetic macular edema, previous diabetic macular edema treatment, previous retinal photocoagulation therapy, age related macular degeneration, retinal vascular diseases or history of uveitis)
  • intraoperative complications (posterior capsular rupture, vitreus loss, intraocular lens not implanted in the capsular bag),
  • postoperative complications (leaking incision, increased intraocular pressure, corneal edema or inflammation),
  • therapy for glaucoma,
  • patients on antihypertensive therapy, topical or systemic NSAIDs or steroids,
  • previous steroid responders or hypersensitivity to the NSAID drug class,
  • previous ocular trauma and intraocular surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bromfenac
Group 1 will receive topical bromfenac (0.9 mg/mL) 2x daily, 7 days before the surgery
Drug: Bromfenac Ophthalmic 0.09% Ophthalmic Solution
topical bromfenac (0.9 mg/mL) 2x daily 7 days before the surgery
Other Names:
  • Bromfenac
Procedure: Phacoemulsification surgery (PHACO)
About 0.1-0.2 mL of aqueous humor will be collected at the beginning of the cataract surgery (PHACO) through paracentesis, aqueous will then be transported in dry ice with a dedicated box to the laboratory and stored at -80C until the analysis. IL6 concentration will be analyzed with Human IL6 Quantikine Elisa kit (R&D System).
Experimental: Dexamethasone
Group 2 will receive topical dexamethasone (1mg/mL) 2x daily before the surgery
Procedure: Phacoemulsification surgery (PHACO)
About 0.1-0.2 mL of aqueous humor will be collected at the beginning of the cataract surgery (PHACO) through paracentesis, aqueous will then be transported in dry ice with a dedicated box to the laboratory and stored at -80C until the analysis. IL6 concentration will be analyzed with Human IL6 Quantikine Elisa kit (R&D System).
Drug: Dexamethasone Ophthalmic
topical dexamethasone (1 mg/mL) 2x daily 7 days before the surgery
Other Names:
  • Dexamethasone
Placebo Comparator: Placebo
Group 3 will receive topical placebo (artificial tears substitute) 2x daily before the surgery
Procedure: Phacoemulsification surgery (PHACO)
About 0.1-0.2 mL of aqueous humor will be collected at the beginning of the cataract surgery (PHACO) through paracentesis, aqueous will then be transported in dry ice with a dedicated box to the laboratory and stored at -80C until the analysis. IL6 concentration will be analyzed with Human IL6 Quantikine Elisa kit (R&D System).
Drug: Placebo
topical placebo (artificial tears substitute) 2x daily before the surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Interleukin 6 concentration
Time Frame: up to 12 weeks
IL6 concentration in aqueous humor will be analyzed with Human IL6 Quantikine Elisa kit R&D System
up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central foveal subfield thickness (CFT) measured by optical coherence tomography (OCT)
Time Frame: 7 days before the surgery, on the day of the surgery, on 1, 7, 30 and 90 postoperative day
Macular thickness will be reported according to the EDTRS thickness map. Central foveal subfield thickness (CFT) corresponds to the mean macular thickness in the central 1.0 mm area measured by optical coherence tomography (OCT).
7 days before the surgery, on the day of the surgery, on 1, 7, 30 and 90 postoperative day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Klinički Bolnički Centar Zagreb

Collaborators

University of Zagreb

Investigators

  • Principal Investigator: Andjela Jukic, MD, FEBO, Klinički bolnički centar Zagreb
  • Study Director: Miro Kalauz, MD, PHD, Klinički bolnički centar Zagreb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2021

Primary Completion (Actual)

October 1, 2021

Study Completion (Actual)

January 1, 2022

Study Registration Dates

First Submitted

June 14, 2021

First Submitted That Met QC Criteria

June 17, 2021

First Posted (Actual)

June 25, 2021

Study Record Updates

Last Update Posted (Actual)

May 20, 2022

Last Update Submitted That Met QC Criteria

May 15, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR ZAG 02/21 AG 8.1-16/183-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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