PCME Prevention in Patients With NPDR

NCT ID: NCT04940338

Last Updated: 2022-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-01

Study Completion Date

2022-01-01

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Cystoid Macular Edema Following Cataract Surgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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Bromfenac

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

Group Type EXPERIMENTAL

Bromfenac Ophthalmic 0.09% Ophthalmic Solution

Intervention Type DRUG

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

Phacoemulsification surgery (PHACO)

Intervention Type 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).

Dexamethasone

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

Group Type EXPERIMENTAL

Dexamethasone Ophthalmic

Intervention Type DRUG

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

Phacoemulsification surgery (PHACO)

Intervention Type 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).

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Phacoemulsification surgery (PHACO)

Intervention Type 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).

Interventions

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Bromfenac Ophthalmic 0.09% Ophthalmic Solution

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

Intervention Type DRUG

Dexamethasone Ophthalmic

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

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).

Intervention Type PROCEDURE

Other Intervention Names

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Bromfenac Dexamethasone

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Zagreb

OTHER

Sponsor Role collaborator

Klinički Bolnički Centar Zagreb

OTHER

Sponsor Role lead

Responsible Party

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Andjela Jukic

MD, ophthalmologist, FEBO

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andjela Jukic, MD, FEBO

Role: PRINCIPAL_INVESTIGATOR

Klinički Bolnički Centar Zagreb

Miro Kalauz, MD, PHD

Role: STUDY_DIRECTOR

Klinički Bolnički Centar Zagreb

Locations

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KBCZagreb

Zagreb, City of Zagreb, Croatia

Site Status

Countries

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Croatia

References

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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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Eriksson U, Alm A, Bjarnhall G, Granstam E, Matsson AW. Macular edema and visual outcome following cataract surgery in patients with diabetic retinopathy and controls. Graefes Arch Clin Exp Ophthalmol. 2011 Mar;249(3):349-59. doi: 10.1007/s00417-010-1484-9. Epub 2010 Sep 9.

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Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M; Acular LS for Cystoid Macular Edema (ACME) Study Group. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol. 2008 Oct;146(4):554-560. doi: 10.1016/j.ajo.2008.04.036. Epub 2008 Jul 2.

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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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Sarfraz MH, Haq RI, Mehboob MA. Effect of topical nepafenac in prevention of macular edema after cataract surgery in patients with non-proliferative diabetic retinopathy. Pak J Med Sci. 2017 Jan-Feb;33(1):210-214. doi: 10.12669/pjms.331.11644.

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Other Identifiers

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CR ZAG 02/21 AG 8.1-16/183-2

Identifier Type: -

Identifier Source: org_study_id

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