Clinical trial NCT01774474: PRevention of Macular EDema After Cataract Surgery
Official title: PRevention of Macular EDema After Cataract Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystoid Macular Edema
Cataract
Diabetes Mellitus
Keywords: Prevention
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: European Society of Cataract and Refractive Surgeons
First posted: 2013-01-24
Enrollment: 1127
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cystoid macular edema (CME) is a common cause of vision loss after cataract surgery. In the last few years, several new treatments have been tried to address the problem of CME after cataract surgery in diabetic and non-diabetic patients. The investigators will perform a large RCT with the aim to provide more definite evidence-based recommendations for clinical guidelines to prevent the occurrence of CME after cataract surgery in patients with and without diabetes mellitus (DM).

Detailed description: The objective of this study is to evaluate the effect of different preventive strategies on the occurrence of CME after cataract surgery in non-diabetic and diabetic patients. The design of the study is a multicentre randomised controlled clinical trial. The study population will consist of 926 non-diabetic patients and 209 patients with diabetes mellitus (DM) who require cataract surgery in at least one eye. All patients will receive a phacoemulsification for cataract and placement of a posterior chamber intraocular lens (IOL).

In the non-diabetic population, the patients will receive either bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperative, dexamethasone 0.1% eye drops four times daily starting two days before surgery and continuing four times daily during the first postoperative week and one drop less per day every following week or a combination of both drugs.

In the diabetic population patients will receive either:

* Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose;
* Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose and a subconjunctival injection of 40 mg triamcinolone acetonide;
* Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose and an intravitreal injection of 1.25 mg bevacizumab;
* Topical bromfenac 0.09% and dexamethasone 0.1% in the aforementioned dose, a subconjunctival injection of 40 mg triamcinolone acetonide and an intravitreal injection of 1.25 mg bevacizumab.

The primary endpoint is the change in central subfield mean macular thickness in the 1 mm area (central subfield macular thickness, CSMT) as compared to baseline within the first 6 weeks postoperative.

The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively. Other study endpoints are mean CDVA in logMAR at 6 weeks and 12 weeks postoperatively; OCT measured average retinal thickness in the central inner circle (3mm), the outer circle (6mm), and the macular volume at 6 weeks and 12 weeks postoperatively; intraocular pressure at 6 weeks and 12 weeks postoperatively.

In case of clinically significant macular edema, treatment will be initiated and its effect will be part of the evaluation at 12 weeks. Medical data of all patients who develop macular edema during this study will be checked at least 6 months after surgery.

Eligibility criteria: Inclusion Criteria:

* All patients undergoing routine phacoemulsification (one eye per patient)
* willing and/or able to comply with the scheduled visits and other study procedures.
* able to communicate properly and understand instructions.
* accepting possible off-label use of intravitreal bevacizumab and/or subconjunctival preservative-free TA.

Exclusion criteria will be different for non-diabetic and diabetic patients. All ophthalmic exclusion criteria are applicable to the study eye only, unless stated otherwise.

General exclusion criteria for participation in this study are:

1. age below 21 years old;
2. participation in another clinical study;
3. post-traumatic cataract;
4. combined surgery;
5. functional monoculus;
6. previous ocular surgery;
7. progressive glaucoma with severe visual field defects, use of anti-glaucomatous medication or steroid-induced IOP elevation that required IOP-lowering treatment;
8. IOP ≥ 25 mmHg;
9. history of any intraocular inflammation or uveitis;
10. history of pseudoexfoliation syndrome, which is expected to cause peroperative complications;
11. history of Fuchs' endothelial dystrophy or cornea guttata 3+;
12. history of retinal vein occlusion;
13. any macular pathology that might influence VA, other than DME;
14. use of intravitreal bevacizumab or ranibizumab in the previous 6 weeks or intravitreal aflibercept in the previous 10 weeks;
15. use of intra- or periocular corticosteroid injection in the previous 4 months;
16. current use of topical NSAIDs or corticosteroids;
17. use of systemic corticosteroids (≥ 20 mg prednisolone or equivalence);
18. history of relevant adverse events, including serious adverse events (SAE), occurring after administration of NSAIDs, acetylsalicylic acid, sodium sulphite, corticosteroids or bevacizumab;
19. contraindications for use of topical NSAIDs, topical or subconjunctival corticosteroids or intravitreal bevacizumab or related drugs;

Non-diabetic patients with a history of CME will be excluded from participation in the study.

Additionally, diabetic patients will be excluded from participation in case of:

1. macular edema with a CSMT ≥450 µm;
2. very severe NPDR or proliferative DR requiring panretinal photocoagulation or vitrectomy;
3. vitreous haemorrhage present during preoperative visit(s);
4. cerebrovascular accident (CVA), myocardial infarction (MI) or other thromboembolic events in the previous 3 months;
5. a history of recurrent thromboembolic events;
6. a history of severe systemic bleeding in the previous 3 months;
7. major surgery in the previous 3 months;
8. history of glaucoma;

Primary outcomes:
measure: Change in central subfield mean macular thickness as a measurement of efficacy
timeFrame: 6 weeks postoperatively
Secondary outcomes:
measure: No. of subjects developing clinically significant macular edema as a measurement of efficacy
timeFrame: 12 weeks postoperatively
Other outcomes:
measure: Change in corrected distance visual acuity (CDVA) as a measurement of efficacy
timeFrame: 6 postoperatively
measure: Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy
timeFrame: 6 weeks postoperatively
measure: Intraocular pressure (IOP) as a measurement of safety
timeFrame: 6 postoperatively
measure: Health-related quality of life as a measurement of efficacy and tolerability
timeFrame: 12 weeks postoperatively
measure: No. of subjects with Adverse Events as a measurement of safety and tolerability
timeFrame: 6 weeks postoperatively
measure: Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy
timeFrame: 6 weeks postoperatively
measure: Change in macular volume as a measurement of efficacy
timeFrame: 6 postoperatively
measure: Vision-related quality of life as a measurement of efficacy and tolerability
timeFrame: 12 weeks postoperatively
measure: Cost-effectiveness
timeFrame: 12 weeks postoperatively
measure: Change in corrected distance visual acuity (CDVA) as a measurement of efficacy
timeFrame: 12 weeks postoperatively
measure: Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy
timeFrame: 12 weeks postoperatively
measure: Intraocular pressure (IOP) as a measurement of safety
timeFrame: 12 weeks postoperatively
measure: No. of subjects with Adverse Events as a measurement of safety and tolerability
timeFrame: 12 weeks postoperatively
measure: Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy
timeFrame: 12 weeks postoperatively
measure: Change in macular volume as a measurement of efficacy
timeFrame: 12 weeks postoperatively
measure: Change in central subfield mean macular thickness as a measurement of efficacy
timeFrame: 12 weeks postoperatively
Locations:
city: Vienna
country: Austria
facility: Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus
city: Vienna
country: Austria
facility: Hospital of the Brothers of Saint John of God
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Frankfurt am Main
country: Germany
facility: Goethe University
city: Budapest
country: Hungary
facility: Semmelweis University
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Breda
country: Netherlands
facility: Amphia Hospital Breda
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Center
city: Hilversum
country: Netherlands
facility: Eye Hospital Zonnestraal
city: Maastricht
country: Netherlands
facility: University Eye Clinic Maastricht UMC+
city: the Hague
country: Netherlands
facility: Medical Centre Haaglanden
city: Tilburg
country: Netherlands
facility: St. Elisabeth Hospital
city: Veldhoven
country: Netherlands
facility: Máxima Medical Center Veldhoven
city: Coimbra
country: Portugal
facility: University Hospital Coimbra
city: Barcelona
country: Spain
facility: Instituto Microcirurgia Ocular
Study officials:
affiliation: University Eye Clinic Maastricht, University Hospital Maastricht
name: prof. Rudy MM Nuijts, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simons RWP, Wielders LHP, Nuijts RMMA, Veldhuizen CA, van den Biggelaar FJHM, Winkens B, Schouten JSAG, Dirksen CD; ESCRS PREMED Study Group. Economic evaluation of prevention of cystoid macular edema after cataract surgery in diabetic patients: ESCRS PREMED study report 6. J Cataract Refract Surg. 2022 May 1;48(5):555-563. doi: 10.1097/j.jcrs.0000000000000785.
citation: Simons RWP, Wielders LHP, Dirksen CD, Veldhuizen CA, van den Biggelaar FJHM, Winkens B, Schouten JSAG, Nuijts RMMA; ESCRS PREMED Study Group. Economic evaluation of prevention of cystoid macular edema after cataract surgery in patients without diabetes: ESCRS PREMED study report 4. J Cataract Refract Surg. 2021 Mar 1;47(3):331-339. doi: 10.1097/j.jcrs.0000000000000449.