NCT04116398 - Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema (LOADEX) | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient \> 40 years old * Patients with a significant DME : Macular thickening secondary to DME involving the center of the fovea, as measured by SD-OCT, with Central Subfield Thickness (CST) ≥ 285 μm measured on Spectralis/topcon or ≥ 275 μm, as measured on Cirrus, at screening and VA between 20/32 and 20/320 (between 23 and 78 letters ETDRS) using the ETDRS protocol at the initial testing distance of 4 meters at inclusion * Patient for which a dexamethasone implant is chosen * 100% naive eyes (no history of steroids or anti-VEGF) * Pseudophakic for at least 3 months * HBA1c \< 10% * Blood pressure \< 160/95 * Patient who give voluntary signed informed consent * Patient affiliated with the French universal health care system or similar * Patient able to participated in all visits and medical examinations during the study * If both eyes have to be treated, only one eye will be included : the eye with the lowest visual acuity at the baseline Exclusion Criteria: * Aphatic eye without posterior lens capsule. * Study eye with implant anterior chamber of the eye or intraocular implant with iris fixated or transsclerally or ruptured posterior lens capsule. * Study eye with lens implant ARTISAN® * Ocular or periocular infection active or suspected in the study eye including most viral diseases of the cornea and conjunctiva, epithelial keratitis active Herpes simplex (dendritic keratitis), vaccinia, chickenpox, mycobacterial infections and mycoses * At inclusion, delay after cataract surgery \< 3 months in the study eye * Delay after last session of panretineal Photocoagulation laser \< 1 month in the study eye * Delay after last focal laser session of the posterior pole \< 1 month in the study eye * Vitreomacular traction syndrome, associated ERM in the study eye * History of macular grid laser in the study eye * Focal laser only if the scars are located within 750 microns of the center (1/2 Papillary Diameter) in the study eye * Ischemic maculopathy (increase of more than 2 times the surface of the central avascular zone) * Proliferative diabetic Retinopathy in the study eye * Hypertension or Open Angle Glaucoma (OAG) treated by dual therapy eye drops or more * Patients with a systemic pathology that could interfere in the evolution of the Diabetic Macular Edema and treated by with immunosuppressive drugs, systemic steroids, anti-aldosterone or systemic anti-VEGF. * Patients with systemic treatment with a toxic effect on the lens, retina or optic nerve: deferoxime, chloroquine / hydroxychloroquine, tamoxifen, phenothiazines and ethambutol; in progress or within 6 months of inclusion * Hypersensitivity to the active substance or to any of the excipients and to anesthetic or hypotonizing eye drops * History of any pathology, metabolic disease, or any serious suspicion of disease at clinical or laboratory examination that contraindicates the use of the intra-retinal dexamethasone implant, could affect the interpretation of the results of the study or cause significant risks of complication for the subject * Infectious conjunctivitis and/or active or suspected appendix infection * Any eye condition or condition that the investigator believes may require intraocular surgery within 12 months * Eye contralateral that studied with visual acuity \< 23 letters * Pregnant and breastfeeding woman * Female of reproductive age, sexually active, who does not want to commit to using adequate and highly effective contraception during the study and up to 6 months after the last administration of the study treatment: * Combined hormonal contraception (containing estrogens and progestins) aimed at inhibiting ovulation (oral, intravaginal or transdermal); * Hormonal contraception containing only a progestin intended to inhibit ovulation (oral, injectable or implantable); * Intrauterine device (IUD); * Intrauterine Hormone Release System (IUS); * Ovariectomy with hysterectomy, bilateral tubal obstruction or total hysterectomy for at least 6 weeks before inclusion (for women included) or vasectomy for at least 6 months before inclusion (for partners of a patient included); * Sexual abstinence. A woman will be considered to be of childbearing age from her first period and until the menopause, unless she is sterile or has had an oophorectomy type surgery with hysterectomy, bilateral tubal obstruction or hysterectomy total at least 6 weeks before inclusion. A post-menopausal state is defined as the absence of spontaneous menstruation (that is to say without any other medical treatment, in particular of the hormonal contraceptive type or hormone replacement therapy) for 12 months * Major patient protected under the terms of the law (Public Health Code) * Patient's ongoing participation in another interventional clinical trial (study eye and/or untreated eye) * Follow-up impossible for 24 months, the judgment of the investigator.

Outcomes

Primary Outcomes

Maximum BCVA (Best Corrected Visual Acuity) change (best improvement) from baseline (during one year of treatment)

Best Corrected Visual Acuity (BCVA) is measured on the ETDRS scale at an initial distance of 4 meters.

Time frame: 52 weeks

Secondary Outcomes

The time required to obtain the best BCVA

average, standard deviation, median, minimum and maximum

Time frame: 52 weeks

The number of injections required to obtain the best BCVA

average, standard deviation, median, minimum and maximum

Time frame: 52 weeks

the maximum best corrected visual acuity (BCVA) change (best improvement) measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale

Best Corrected Visual Acuity (BCVA) is measured on the ETDRS scale at an initial distance of 4 meters.

Time frame: between the baseline and 1,5 years and between the baseline and 2 years

values of Visual Acuity (VA) at each visit

Time frame: all visits during 2 years

Area under the curve (AUC) of VA

AUC calculated with the values of VA at each visit

Time frame: between the baseline and 52 weeks and between the baseline and 2 years

Description of Visual acuity (VA)

categorized change of VA (\>=+15 ; +10 -\> +15 ; +5 -\> +10 ; -5 -\> +5 (stable) ; -5 -\> -10 ; -10 -\> -15 ; \> -15)

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

Number of IVI

Time frame: 1 year

Number of IVI

Time frame: 2 years

OCT parameters: Central Subfield Mean Thickness (CSMT)

average, standard deviation, median, minimum and maximum

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters: Central Fovea Thickness

average, standard deviation, median, minimum and maximum

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of interruptions of the ellipsoid line

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of continuous external limiting membrane

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the which obtained the BCVA

OCT parameters : presence of disorganization of the internal retinal layers

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of intraretinal cysts

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of vitreomacular traction

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtain the BCVA

OCT parameters : presence of epiretinal membrane

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of macular exudates

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : persistance of foveolar depression

Time frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA

OCT parameters : presence of intraretinal fluid

Time frame: at each visit

Proportion of patients with macular edema resolution

A macular edema resolution will be defined as absence of intraretinal fluid for at least 6 months after the last

Time frame: at 1 year

Proportion of patients with macular edema resolution

A macular edema resolution will be defined as absence of intraretinal fluid for at least 6 months after the last

Time frame: at 2 years

Retinopathy parameters : presence of intraretinal or subretinal macular hemorrhage

on stereoscopic 7-field color fundus photographs