PCME Prevention in Patients With NPDR

NCT04940338 | Completed Phase 4

• 1 other identifier: CR ZAG 02/21 AG 8.1-16/183-2
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Cystoid Macular Edema Following Cataract Surgery

Keywords

Pseudophakic cystoid macular edema (PCME); Interleukin-6 (IL6); Central foveal subfield thickness (CFT); Spectral domain Optical coherence tomography (SD-OCT)

Outcome Measures

Primary Outcomes (1)

• Interleukin 6 concentration

  IL6 concentration in aqueous humor will be analyzed with Human IL6 Quantikine Elisa kit R\&D System

  up to 12 weeks

Secondary Outcomes (1)

• Central foveal subfield thickness (CFT) 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

Study Arms (3)

Bromfenac

EXPERIMENTAL

Group 1 will receive topical bromfenac (0.9 mg/mL) 2x daily, 7 days before the surgery

Drug: Bromfenac Ophthalmic 0.09% Ophthalmic Solution; Procedure: Phacoemulsification surgery (PHACO)

Dexamethasone

EXPERIMENTAL

Group 2 will receive topical dexamethasone (1mg/mL) 2x daily before the surgery

Drug: Dexamethasone Ophthalmic; Procedure: Phacoemulsification surgery (PHACO)

Placebo

PLACEBO COMPARATOR

Group 3 will receive topical placebo (artificial tears substitute) 2x daily before the surgery

Drug: Placebo; Procedure: Phacoemulsification surgery (PHACO)

Interventions

Bromfenac Ophthalmic 0.09% Ophthalmic Solution DRUG

topical bromfenac (0.9 mg/mL) 2x daily 7 days before the surgery

Also known as: Bromfenac

Bromfenac

Dexamethasone Ophthalmic DRUG

topical dexamethasone (1 mg/mL) 2x daily 7 days before the surgery

Also known as: Dexamethasone

Dexamethasone

Placebo DRUG

topical placebo (artificial tears substitute) 2x daily before the surgery

Placebo

Phacoemulsification surgery (PHACO) PROCEDURE

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).

Bromfenac; Dexamethasone; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Klinički Bolnički Centar Zagreb: lead
• University of Zagreb: collaborator

Study Sites (1)

KBCZagreb

Zagreb, City of Zagreb, 10000, Croatia

Location

Related Publications (21)

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• Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556-64. doi: 10.2337/dc11-1909. Epub 2012 Feb 1.

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  PMID: 30644770 BACKGROUND

• Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol. 2002 Jan;133(1):70-7. doi: 10.1016/s0002-9394(01)01269-7.

  PMID: 11755841 BACKGROUND

• Malecaze F, Chollet P, Cavrois E, Vita N, Arne JL, Ferrara P. Role of interleukin 6 in the inflammatory response after cataract surgery. An experimental and clinical study. Arch Ophthalmol. 1991 Dec;109(12):1681-3. doi: 10.1001/archopht.1991.01080120065027.

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• Wielders LHP, Schouten JSAG, Winkens B, van den Biggelaar FJHM, Veldhuizen CA, Murta JCN, Goslings WRO, Kohnen T, Tassignon MJ, Joosse MV, Henry YP, Nagy ZZ, Rulo AHF, Findl O, Amon M, Nuijts RMMA; ESCRS PREMED study group. Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2. J Cataract Refract Surg. 2018 Jul;44(7):836-847. doi: 10.1016/j.jcrs.2018.05.015.

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MeSH Terms

Interventions

Ophthalmic Solutions; bromfenac; Dexamethasone

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Andjela Jukic, MD, FEBO

  Klinički Bolnički Centar Zagreb

  PRINCIPAL INVESTIGATOR

• Miro Kalauz, MD, PHD

  Klinički Bolnički Centar Zagreb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The drug pipettes will be covered with tape by hospital pharmacy and put into marked envelopes. The blinding will be uncovered after analyzing the data.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, ophthalmologist, FEBO

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 25, 2021
• Study Start: May 1, 2021
• Primary Completion: October 1, 2021
• Study Completion: January 1, 2022
• Last Updated: May 20, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)