Effectiveness of Periocular Drug Injection in CATaract Surgery

Phase 3TerminatedNCT05158699

Luigi Rondas628 enrolled

Overview

Cystoid macular edema (CME) is a major cause of suboptimal postoperative visual acuity after cataract surgery. Topical steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs) are used to prevent CME. However, noncompliance with eye drops may compromise the effectiveness of treatment. Dropless periocular drug delivery during cataract surgery may improve the outcomes and cost-effectiveness of cataract surgery, and may alleviate the burden on homecare organizations.

In a recent European multicentre study (PREvention of Macular EDema after cataract surgery; PREMED), it was demonstrated that the combination of topical corticosteroids and NSAIDs results in the lowest risk of developing CME after cataract surgery. However, noncompliance with eye drops may compromise the effectiveness of treatment. Noncompliance is often unintentional and related to forgetfulness or incorrect instillation, particularly in the elderly cataract surgery population. The objective of this study is to evaluate the effectiveness of different treatments to prevent CME after cataract surgery, using either topical drugs (control group) or intra-/periocular injections (intervention groups). The hypothesis of this study is that intra-/periocular anti-inflammatory drug delivery during cataract surgery is effective in preventing CME, with better health-related quality of life and improved cost-effectiveness compared to standard topical drug delivery. The primary outcome measure is the change in central subfield mean macular thickness (CSMT) at 6 weeks postoperatively as compared to baseline. Secondary outcome measures are the incidence of CME; the incidence of clinically significant macular edema (CSME); mean corrected distance visual acuity (CDVA); para- and perifoveal thickness and total macular volume (TMV); intraocular pressure (IOP); anterior chamber inflammation; vision-related quality of life; and cost-effectiveness. The design of this study is a European randomised controlled multicenter trial. The study population will consist of 808 patients aged 21 years or older who require cataract surgery in at least one eye. Patients with a foreseen increased risk of developing CME or ophthalmic disorders other than cataract will be excluded. Follow-up duration is 12 weeks. The study will be conducted over a period of 36 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

BromfenacDRUG

Bromfenac topical eye drops (Yellox)

DexamethasoneDRUG

Dexamethasone topical eye drops

Triamcinolone AcetonideDRUG

0.25ml of 40mg/ml (10mg) triamcinolone acetonide (Triesence/Vistrec) will be injected subconjunctivally

Ketorolac-Phenylephrine Ophthalmic 0.3%-1% Intraocular SolutionDRUG

Omidria is added to the irrigation fluid used during cataract surgery. At the end of surgery, the anterior chamber will be filled with the ketorolac solution.

Eligibility

Sex: ALLMin age: 21 Years

Medical Language ↔ Plain English

Inclusion Criteria: * who are undergoing routine phacoemulsification (one eye per patient); * who are 21 years or older; * who should be able to communicate properly and understand instructions. * willing and/or able to comply with the scheduled visits and other study procedures. Exclusion Criteria: * patients who already participated with their contralateral eye; * combined surgery (e.g. combined phacoemulsification and trabeculectomy); * patients with an increased risk of developing cystoid macular edema (CME) in the study eye (e.g. diabetes mellitus, previous retinal venous occlusion, or a history of uveitis, macular edema, epiretinal membrane, or previous retinal surgery); * patients who developed CME after cataract surgery in the contralateral eye; * patients with cystoid macular changes in the study eye at baseline; * patients with an increased risk of developing perioperative complications (e.g. Fuchs' endothelial dystrophy); * patients with permanent moderate visual impairment in the contralateral eye (decimal visual acuity less than 0.3); * patients with a history of steroid induced IOP rise or glaucomatous visual field loss; * patients using drugs that reduce or increase the risk of macular edema (e.g., periocular or intraocular corticosteroid, NSAID, or antivascular endothelial growth factor (VEGF) injection; topical corticosteroid or NSAID use; systemic corticosteroids (\>= 20mg prednisolon), methotrexate, biologicals, or acetazolamide), or in the previous 4 months; * patients with a contraindication for any of the investigated drugs; * patients who are cardiovascular unstable; * patients who have a history of hyperthyroidism.

Locations (10)

Hospital of the Brothers of Saint John of God

Vienna, Austria

Vienna Institute for Research in Ocular Surgery, Hanusch Krankenhaus

Vienna, Austria

Goethe University

Frankfurt am Main, Germany

Amphia

Breda, Netherlands

Deventer Ziekenhuis

Deventer, Netherlands

Zuyderland Medisch Centrum

Heerlen, Netherlands

University Eye Clinic Maastricht UMC+

Maastricht, Netherlands

Canisius Wilhelmina Ziekenhuis Nijmegen

Nijmegen, Netherlands

Elisabeth-Twee Steden Ziekenhuis, locatie Elisabeth

Tilburg, Netherlands

University Hospital Coimbra

Coimbra, Portugal

Outcomes

Primary Outcomes

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, measured using Optical Coherence Tomography (OCT)

Time frame: Baseline, 6 weeks postoperatively

Secondary Outcomes

Change in central subfield mean macular thickness as a measurement of efficacy

Measured using OCT

Time frame: Baseline, 12 weeks postoperatively

No. of subjects developing clinically significant macular edema as a measurement of efficacy

The occurrence of postoperative clinically significant macular edema (CSME) within 12 weeks postoperatively

Time frame: Until 12 weeks postoperatively

Change in parafoveal retinal thickness in the central inner circle (1.0 - 3.0mm) as a measurement of efficacy

Measured using OCT

Time frame: Baseline, 6 weeks and 12 weeks postoperatively

Change in perifoveal retinal thickness in the central outer circle (3.0 - 6.0mm) as a measurement of efficacy

Measured using OCT

Time frame: Baseline, 6 weeks and 12 weeks postoperatively

Change in macular volume in the central 6.0mm area as a measurement of efficacy

Measured using OCT

Time frame: Baseline, 6 weeks and 12 weeks postoperatively

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)

Time frame: Baseline, 1 week, 6 weeks, and 12 weeks postoperatively

Change in Intraocular pressure (IOP) as a measurement of safety

IOP (in mmHg) will be measured by Goldmann applanation tonometry (preferred), Non-Contact Tonometry, or iCare tonometry

Time frame: Baseline, 1 week, 6 weeks, and 12 weeks postoperatively

Anterior chamber inflammation as a measurement of safety

Grading will be performed using the classification of the "Standardization of Uveitis Nomenclature" (SUN) working group using a 2mm long and 1mm wide slit beam: 1. grading aqueous cells between grade 0 \[\<1cell, best outcome\] up to grade +4 \[\>50 cells, worse outcome\] 2. grading aqueous flare between grade 0 \[none detectable\] up to +4 \[intense aqeous flare or fibrinous exudate\] Higher grade scores mean a worse outcome.

Time frame: Baseline, 1 week , 6 weeks, and 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; abnormal sensation in the eye, pain or irritation, conjunctival hyperaemia, inflammation and corneal edema after intracameral injection with phenylephrine/ketorolac.

Time frame: Until 12 weeks postoperatively

Patient reported outcome measures (PROMs): NEI VFQ-25

Patient satisfaction and vision-specific quality of life as measured by National Eye Institute Visual Function Questionnaire (NEI VFQ-25). From 25 questions, the original numeric values given (1-10) are converted to a 0 to 100 scale, so that the scores are set between 0 points (worst outcome) and 100 points (best outcome).

Time frame: Baseline and 12 weeks postoperatively

Patient reported outcome measures (PROMs): Catquest-9SF

Patient satisfaction and vision-specific quality of life as measured by the Catquest-9SF questionnaire. The possible range in Catquest scores are -3.94 (no difficulties) to +3.52 (great difficulties).

Time frame: Baseline and 12 weeks postoperatively

Patient reported outcome measures (PROMs): HUI3

Health-related quality of life as measured by HUI3 (Health Utility Index Mark 3) questionnaire. The HUI3 questionnaire consists of 8 attributes, including vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. For each attribute, the HUI3 questionnaire provides utility (preference) scores on a generic scale where dead = 0.00 and perfect health = 1.00.

Time frame: Baseline and 12 weeks postoperatively

Patient reported outcome measures (PROMs): EQ-5D-5L

Health-related quality of life as measured by the 5-level EQ-5D version (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). 1. The EQ-5D descriptive system results in a number between 1 (best) and 5 (worse) that expresses the level selected for that dimension. 2. The EQ VAS indicates the general health status with 0 indicating the worst and 100 indicating the best health status.

Time frame: Baseline and 12 weeks postoperatively

Quality Adjusted Life Years (QALYs)

Calculated based on generic health-related quality of life, using the EQ-5D-5L and HUI-3 questionnaires