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| Name | Class |
|---|---|
| European Society of Cataract and Refractive Surgeons | OTHER |
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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).
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non diabetics: bromfenac | Active Comparator | bromfenac 0.09% eye drops twice daily starting two days before surgery and continuing 2 weeks postoperatively |
|
| Non diabetics: dexamethasone | Active Comparator | 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 |
|
| Non diabetics: bromfenac & dexamethasone | Active Comparator | 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 |
|
| Diabetics: eye drops | Active Comparator | 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 |
|
| Diabetics: eye drops & TA |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bromfenac | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in central subfield mean macular thickness as a measurement of efficacy | 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 postoperatively. | 6 weeks postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| No. of subjects developing clinically significant macular edema as a measurement of efficacy | The secondary endpoint is the occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively. | 12 weeks postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| Change in corrected distance visual acuity (CDVA) as a measurement of efficacy | CDVA measurements will be taken using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts (logMAR). | 6 postoperatively |
| Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy |
Inclusion Criteria:
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| prof. Rudy MM Nuijts, MD, PhD | University Eye Clinic Maastricht, University Hospital Maastricht | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus | Vienna | A-1140 | Austria | |||
| Hospital of the Brothers of Saint John of God |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34417781 | Derived | 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. | |
| 33009281 |
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| Active Comparator |
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 & a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA, Triesence/Vistrec) |
|
| Diabetics: eye drops & bevacizumab | Active Comparator | 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 & a peroperative intravitreal injection of 1.25 mg bevacizumab (Avastin) |
|
| Diabetics: eye drops, TA & bevacizumab | Active Comparator | 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 & a peroperative subconjunctival injection of 40 mg triamcinolone acetonide (TA) & a peroperative intravitreal injection of 1.25 mg bevacizumab |
|
|
| Dexamethasone | Drug |
|
|
| Bevacizumab | Drug |
|
|
| Triamcinolone Acetonide | Drug |
|
|
Measured using Optical Coherence Tomography (OCT) |
| 6 weeks postoperatively |
| Intraocular pressure (IOP) as a measurement of safety | IOP (in mmHg) will be measured by Goldmann applanation tonometry | 6 postoperatively |
| Health-related quality of life as a measurement of efficacy and tolerability | Using the Health Utility Index mark 3 (HUI-3) | 12 weeks postoperatively |
| No. of subjects with Adverse Events as a measurement of safety and tolerability | An adverse event (AE) is defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the investigational product. All adverse events reported spontaneously by the subject or observed by the principal investigator or his staff will be recorded. Most frequently reported adverse events which might occur while using the study medication: abnormal sensation in the eye, pain or irritation, redness or headache while using eye drops; increased IOP and masking of infections while using corticosteroids; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab. | 6 weeks postoperatively |
| Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy | Using OCT | 6 weeks postoperatively |
| Change in macular volume as a measurement of efficacy | Using OCT | 6 postoperatively |
| Vision-related quality of life as a measurement of efficacy and tolerability | Using the National Eye Institute Visual Functioning Questionnaire 25 (NEI-VFQ 25) | 12 weeks postoperatively |
| Cost-effectiveness | Incremental cost-effectiveness ratios of the costs per quality-adjusted life year (QALY) and costs per improved patient on the NEI VFQ-25 and HUI-3. | 12 weeks postoperatively |
| Change in corrected distance visual acuity (CDVA) as a measurement of efficacy | CDVA measurements will be taken using ETDRS visual acuity testing charts (logMAR). | 12 weeks postoperatively |
| Change in retinal thickness in the central inner circle (3mm) as a measurement of efficacy | Measured using Optical Coherence Tomography (OCT) | 12 weeks postoperatively |
| Intraocular pressure (IOP) as a measurement of safety | IOP (in mmHg) will be measured by Goldmann applanation tonometry | 12 weeks postoperatively |
| No. of subjects with Adverse Events as a measurement of safety and tolerability | An adverse event (AE) is defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the investigational product. All adverse events reported spontaneously by the subject or observed by the principal investigator or his staff will be recorded. Most frequently reported adverse events which might occur while using the study medication: abnormal sensation in the eye, pain or irritation, redness or headache while using eye drops; increased IOP and masking of infections while using corticosteroids; retinal detachment, thrombo-embolic events, endophthalmitis and anterior chamber reactions after intravitreal injections of bevacizumab. | 12 weeks postoperatively |
| Change in retinal thickness in the central outer circle (6mm) as a measurement of efficacy | Using OCT | 12 weeks postoperatively |
| Change in macular volume as a measurement of efficacy | Using OCT | 12 weeks postoperatively |
| Change in central subfield mean macular thickness as a measurement of efficacy | Using OCT | 12 weeks postoperatively |
| Vienna |
| Austria |
| University Hospital Antwerp | Edegem | B-2650 | Belgium |
| Goethe University | Frankfurt am Main | 60590 | Germany |
| Semmelweis University | Budapest | H-1085 | Hungary |
| VU University Medical Center | Amsterdam | 1081 HZ | Netherlands |
| Academic Medical Center | Amsterdam | Netherlands |
| Amphia Hospital Breda | Breda | Netherlands |
| Zuyderland Medical Center | Heerlen | 6419 PC | Netherlands |
| Eye Hospital Zonnestraal | Hilversum | Netherlands |
| University Eye Clinic Maastricht UMC+ | Maastricht | 6202 AZ | Netherlands |
| Medical Centre Haaglanden | The Hague | Netherlands |
| St. Elisabeth Hospital | Tilburg | Netherlands |
| Máxima Medical Center Veldhoven | Veldhoven | Netherlands |
| University Hospital Coimbra | Coimbra | 3000-075 | Portugal |
| Instituto Microcirurgia Ocular | Barcelona | 08035 | Spain |
| 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. |
| ID | Term |
|---|---|
| D008269 | Macular Edema |
| D002386 | Cataract |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D007905 | Lens Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C053083 | bromfenac |
| D003907 | Dexamethasone |
| D000068258 | Bevacizumab |
| D014222 | Triamcinolone Acetonide |
| D014221 | Triamcinolone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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