Clinical trial NCT04387604: Effect of the Vitreous in Response to Intravitreal Injections of Ranibizumab for the Treatment of Diabetic Macular Edema
Official title: Effect of the Vitreous in Response to Intravitreal (IV) Injections of Ranibizumab (0.5mg/0.05ml) for the Treatment of Diabetic Macular Edema
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Macular Edema
Lead sponsor: Centro Hospitalar do Porto
Sponsor class: OTHER
First posted: 2020-05-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with DME followed on the ocular diabetes consultation of Centro Hospitalar e Universitário do Porto, Portugal, or Hospital Santa Maria Maior de Barcelos, Portugal, either non vitrectomized or vitrectomized.

Brief summary: PURPOSE: To evaluate the effect of the vitreous in response to intravitreal (IV) injections of ranibizumab 0.5 mg/0.05ml (Lucentis; Genentech, South San Francisco, CA) for the treatment of diabetic macular edema (DME).

METHODS: Prospective, observational, multicenter study, conducted at Centro Hospitalar e Universitário do Porto, Portugal. Best-corrected visual acuity and central foveal thickness will be evaluated at baseline and every month until the end of follow-up. OCT biomarkers such as retinal layers thickness will also be analyzed.

A p value of 0.05 or less will be considered to be statistically significant. HYPOTHESIS: Vitrectomized patients will improve less than non-vitrectomized patients.

Detailed description: Patients will be included in two different groups according to the vitreous status: group 1 - non vitrectomized eyes; group 2 - vitrectomized eyes. Patients will be followed-up according to the standard of care and a final analysis of the results will be performed at 12+/-1 months of follow-up, which is the minimum follow-up period required for each patient. In group 1 the effect of VMA existence and PVD status will also be analyzed. The recruitment period will be of 6 months.

Treatment All patients will be treated with IV ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen. The injections will be performed in the operating room following the standard intravitreal injections protocol. When required, adjunct treatment, with macular and/or peripheral LASER (rescue LASER), will be also admitted at or after 24 weeks if persistent DME not improving after at least 2 injections.

Treatment Schedule Repeat injections at every 4-week visit if eye "improves" or "worsens" (defined as ≥5 letter change from last injection or ≥10% CST change on OCT from last injection or CSF\>300 μm at any timepoint).

Defer injections if either BCVA of 85 letters and OCT CSF "normal" (CSF≤300 μm and non-existent intra- or sub-retinal fluid); or OCT CSF "normal" (CSF≤300 μm) and stable BCVA (defined as \< 5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CSF "normal" and stable BCVA).

Resume injections if BCVA or OCT worsens.

Eligibility criteria: Inclusion Criteria:

* at least 18 years of age with either type 1 or type 2 diabetes mellitus;
* maximal central subfield foveal thickness (CSF) of at least 300μm (according to SD-OCT images - Spectral Domain Optical Coherence Tomography);
* BCVA of 20 to 80 letters, using ETDRS letters chart;
* ability to provide written informed consent.

Exclusion Criteria:

* Pregnant or lactating;
* Epiretinal membrane (ERM) existence in the study eye;
* persistent posterior hyaloid adherence after vitrectomy for group 2;
* previous vitrectomy for group 1;
* history of other retinal vascular diseases in the study eye;
* LASER photocoagulation or intravitreal injections (IV) of anti-VEGF or systemic anti-VEGF or pro-anti-VEGF treatment and cataract surgery in the 6 months previously to the study eye inclusion;
* IV or peribulbar corticosteroid injections in the 6 months previously to study eye inclusion;
* history of IV of implant of fluocinolone acetonide in the study eye;
* vitreous hemorrhage or opacification in the study eye;
* active proliferative diabetic retinopathy in the study eye;
* active ocular inflammation or infection in either eye;
* aphakia in the study eye;
* other causes for macular edema, for example, after cataract surgery in the study eye;
* other causes of visual loss in the study eye;
* other diseases that may affect the course of macular edema in the study eye;
* uncontrolled glaucoma in either eye (intraocular pressure \> 24 mmHg with treatment);
* history of arterial thrombotic event in the previous 6 months;
* uncontrolled arterial hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg);
* ward of the state.

Primary outcomes:
measure: assess the number of IV injections needed to control DME between groups
timeFrame: 18 months
Secondary outcomes:
measure: compare the functional changes at the end of follow-up between groups
timeFrame: 18 months
measure: compare the anatomical changes at the end of follow-up between groups
timeFrame: 18 months
measure: compare the percentage of type of responder during the follow-up period between groups
timeFrame: 18 months
measure: access the percentage, in group 2, of focal VMA and PVD status and type of response
timeFrame: 18 months
measure: assess retinal layers thickness as prognostic and pathophysiological biomarkers of DME treatment response
timeFrame: 18 months
Other outcomes:
Locations:
city: Porto
country: Portugal
facility: Hospital de Santo António
Study officials:
affiliation: Centro Hospitalar e Universitário do Porto
name: Bernardete Pessoa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pessoa B, Leite J, Heitor J, Coelho J, Monteiro S, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers. Sci Rep. 2021 Nov 29;11(1):23055. doi: 10.1038/s41598-021-02532-4.
citation: Pessoa B, Marques JH, Leite J, Silva N, Jose D, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Choroidal Blood Flow After Intravitreal Ranibizumab in Vitrectomized and Non-Vitrectomized Eyes with Diabetic Macular Edema. Clin Ophthalmol. 2021 Oct 9;15:4081-4090. doi: 10.2147/OPTH.S325037. eCollection 2021.