Diabetic Macular Edema
Conditions
Keywords
Diabetic macular edema, Intravitreal dexamethasone solution, Short term treament
Brief summary
Purpose: To determine the impact of short-term 4mg/ml dexamethasone solution treatment in diabetic macular edema (DME). Design: Phase II, randomized, prospective, parallel, interventional study. Participants: Pseudophakic patients with central-involved DME. Methods: Twenty-seven patients with visual impairment caused by DME were randomized in a 1:1:1 ratio, in order to investigate treatment with 0.01 ml, 0.03 ml and 0.05 ml intravitreous dexamethasone solutions, and followed-up over 28 days Outcome Measures: The primary outcome was macular thickness at three days after intravitreous dexamethasone. The secondary outcomes were macular thickness at 28 days after intravitreous dexamethasone, best-corrected visual acuity (BCVA) and intraocular pressure (IOP) at three and 28 days after intravitreous dexamethasone
Detailed description
This is a prospective, phase II, randomized, interventional, monocentric study. Data of consecutive patients with DME who volunteered to participate in the research at the department of ophthalmology of State University of Campinas (UNICAMP) - Brazil between May 2016 and December 2017 were analysed. At the screening visit, all patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, fluorescein angiography (Visucam NM/ FA Carl Zeiss; Carl Zeiss Meditec, California, USA), SD- OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Central macular thickness was obtained through 7 horizontal lines ( 30° x 5° area), centered on the fovea, with 1536 A scans per line at 240 µm intervals. At the baseline study visit, patients were randomized with a 1:1:1 allocation to receive dexamethasone solution 4 mg/ml: 0,01 ml (40 µg) ; or 0,03 ml (120 µg); or 0,05 ml (200 µg). In follow up visits (1, 3, 7, 14, 21, 28 days after) were performed BCVA, slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, SD- OCT.
Interventions
DRUGIntravitreous Dexamethasone Solution 4mg/ml - vol 0,01 ml
0,01 ml intravitreous dexamethasone solution 4mg/ml injection.
DRUGIntravitreous Dexamethasone Solution 4mg/ml - vol 0,03 ml
0,03 ml intravitreous dexamethasone solution 4mg/ml injection.
DRUGIntravitreous Dexamethasone Solution 4mg/ml - vol 0,05 ml
0,05 ml intravitreous dexamethasone solution 4mg/ml injection.
Sponsors
Universidade Federal de Pernambuco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All the patients were masked. They didn't have acess to the group they belonged. The care provider didn't know the quantity of the drug injected. The outcome assessor was masked as well.
Intervention model description
At the baseline study visit, patients were randomized with a 1:1:1 allocation to receive dexamethasone solution 4 mg/ml: 0,01 ml (40 µg); or 0,03 ml (120 µg); or 0,05 ml (200 µg). In follow up visits (1, 3, 7, 14, 21, 28 days after) were performed BCVA, slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, SD- OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). The randomization schedule was computer generated and stored in a locked cabinet until the study ended. Both patients and the study personnel who collected BCVA, OCT data were masked to the patient study assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* age \> = 18 years; * diagnosis of DM type 2; * pseudophakic patients * presence of clinically significant DME according to ETDRS guidelines; * best correct visual acuity (BCVA) between 20/400 and 20/40; * central macular thickness (CMT) \>= 300 µm measured by spectral domain optical coherence tomography ( Spectralis® Heidelberg). If both eyes of the patient met the elegibility criteria, the eye with worse BCVA at baseline was designated as the study eye.
Exclusion criteria
* any treatment of DME in the previous 4 months; * pan retinal photocoagulation (PRP) in the previous 4 months or antecipated need of PRP for the next 6 months; * any ophthalmologic surgery performed in the previous 4 months; * history of pars plana vitrectomy; * history of open-angle glaucoma or intraocular pressure elevation induced by corticosteroids that required anti-glaucomatous treatment or anti- hypertensive ocular treatment; * intraocular pressure \>= 21 mmHg; * patients with characteristics that meet the inclusion criteria, but refused to sign the written general consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Macular Thickness at 3 Days After Intravitreous Dexamethasone | Three days after intravitreous dexamethasone | Measure macular thickness at 3 days after intravitreous dexamethasone with OCT - unit µm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Macular Thickness at 28 Days After Intravitreous Dexamethasone | 28 days after intravitreous dexamethasone | Measure macular thickness at 28 days after intravitreous dexamethasone with OCT - unit µm |
| Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone | Three days after intravitreous dexamethasone | Measure best corrected visual acuity (BCVA) at 3 days after intravitreous dexamethasone with ETDRS chart |
| Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone | 28 days after intravitreous dexamethasone | Measure best corrected visual acuity (BCVA) at 28 days after intravitreous dexamethasone with ETDRS chart |
| Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone | 3 days after intravitreous dexamethasone | Measure intraocular pressure (IOP) 3 days after intravitreous dexamethasone - unit mmHg |
| Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone | 28 days after intravitreous dexamethasone | Measure intraocular pressure (IOP) 28 days intravitreous dexamethasone - unit mmHg |
Countries
Brazil
Participant flow
Recruitment details
Data from DME diagnosed volunteers was collected and analyzed at the Department of Ophthalmology, State University of Campinas (UNICAMP), Brazil between May 2016 and December 2017
Pre-assignment details
Informed written consent was obtained from all patients, and approved by the ethics committee of the Clinical Hospital of the State University of Campinas
Participants by arm
| Arm | Count |
|---|---|
| 0,01ml Dexamethasone Solution One intravitreous injection of 0,01 ml dexamethasone solution 4 mg/ml.
Intravitreous Dexamethasone Solution 4mg/ml - vol 0,01 ml: 0,01 ml intravitreous dexamethasone solution 4mg/ml injection. | 9 |
| 0,03 ml Dexamethasone Solution One intravitreous injection of 0,03 ml dexamethasone solution 4 mg/ml.
Intravitreous Dexamethasone Solution 4mg/ml - vol 0,03 ml: 0,03 ml intravitreous dexamethasone solution 4mg/ml injection. | 9 |
| 0,05 ml Dexamethasone Solution One intravitreous injection of 0,05 ml dexamethasone solution 4 mg/ml.
Intravitreous Dexamethasone Solution 4mg/ml - vol 0,05 ml: 0,05 ml intravitreous dexamethasone solution 4mg/ml injection. | 9 |
| Total | 27 |
Baseline characteristics
| Characteristic | 0,03 ml Dexamethasone Solution | Total | 0,01ml Dexamethasone Solution | 0,05 ml Dexamethasone Solution |
|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 8.26 | 67.9 years STANDARD_DEVIATION 7.33 | 67 years STANDARD_DEVIATION 5.63 | 71.3 years STANDARD_DEVIATION 7.36 |
| Best corrected visual acuity | 47.2 ETDRS Letters STANDARD_DEVIATION 19.31 | 53.2 ETDRS Letters STANDARD_DEVIATION 16.61 | 52.5 ETDRS Letters STANDARD_DEVIATION 13.98 | 60 ETDRS Letters STANDARD_DEVIATION 15.31 |
| Central macular thickness | 630 µm STANDARD_DEVIATION 254.68 | 537.4 µm STANDARD_DEVIATION 196.94 | 527.6 µm STANDARD_DEVIATION 154.21 | 453.3 µm STANDARD_DEVIATION 140.39 |
| Epirretinal membrane | 3 Participants | 10 Participants | 5 Participants | 2 Participants |
| Eye (Right) | 7 Participants | 15 Participants | 3 Participants | 5 Participants |
| Intraocular pressure | 13.22 mmHg STANDARD_DEVIATION 2.53 | 12.2 mmHg STANDARD_DEVIATION 2.39 | 11.8 mmHg STANDARD_DEVIATION 2.02 | 11.6 mmHg STANDARD_DEVIATION 2.55 |
| Microaneurysms in foveal region | 8 Participants | 25 Participants | 8 Participants | 9 Participants |
| Posterior vitreous detachment | 2 Participants | 9 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 27 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Brazil | 9 participants | 27 participants | 9 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 15 Participants | 6 Participants | 4 Participants |
| Subretinal fluid | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 9 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Macular Thickness at 3 Days After Intravitreous Dexamethasone
Measure macular thickness at 3 days after intravitreous dexamethasone with OCT - unit µm
Time frame: Three days after intravitreous dexamethasone
Population: Macular thickness at 3 days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Macular Thickness at 3 Days After Intravitreous Dexamethasone | 438.44 µm | Standard Deviation 124.55 |
| 0,03 ml Dexamethasone Solution | Macular Thickness at 3 Days After Intravitreous Dexamethasone | 465.22 µm | Standard Deviation 115.25 |
| 0,05 ml Dexamethasone Solution | Macular Thickness at 3 Days After Intravitreous Dexamethasone | 368.22 µm | Standard Deviation 126.92 |
Secondary
Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone
Measure best corrected visual acuity (BCVA) at 28 days after intravitreous dexamethasone with ETDRS chart
Time frame: 28 days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone | 58.33 ETDRS letters | Standard Deviation 15.46 |
| 0,03 ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone | 50.55 ETDRS letters | Standard Deviation 18.51 |
| 0,05 ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone | 64.11 ETDRS letters | Standard Deviation 16.01 |
Secondary
Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone
Measure best corrected visual acuity (BCVA) at 3 days after intravitreous dexamethasone with ETDRS chart
Time frame: Three days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone | 54.22 ETDRS Letters | Standard Deviation 12.77 |
| 0,03 ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone | 52.33 ETDRS Letters | Standard Deviation 16.09 |
| 0,05 ml Dexamethasone Solution | Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone | 60.22 ETDRS Letters | Standard Deviation 17.28 |
Secondary
Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone
Measure intraocular pressure (IOP) 28 days intravitreous dexamethasone - unit mmHg
Time frame: 28 days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone | 12.33 mmHg | Standard Deviation 3.16 |
| 0,03 ml Dexamethasone Solution | Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone | 12.44 mmHg | Standard Deviation 2.74 |
| 0,05 ml Dexamethasone Solution | Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone | 11.88 mmHg | Standard Deviation 2.8 |
Secondary
Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone
Measure intraocular pressure (IOP) 3 days after intravitreous dexamethasone - unit mmHg
Time frame: 3 days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone | 12.33 mmHg | Standard Deviation 3.9 |
| 0,03 ml Dexamethasone Solution | Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone | 13.11 mmHg | Standard Deviation 2.42 |
| 0,05 ml Dexamethasone Solution | Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone | 12.44 mmHg | Standard Deviation 3.97 |
Secondary
Macular Thickness at 28 Days After Intravitreous Dexamethasone
Measure macular thickness at 28 days after intravitreous dexamethasone with OCT - unit µm
Time frame: 28 days after intravitreous dexamethasone
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0,01ml Dexamethasone Solution | Macular Thickness at 28 Days After Intravitreous Dexamethasone | 554.66 µm | Standard Deviation 175.91 |
| 0,03 ml Dexamethasone Solution | Macular Thickness at 28 Days After Intravitreous Dexamethasone | 617.22 µm | Standard Deviation 245.83 |
| 0,05 ml Dexamethasone Solution | Macular Thickness at 28 Days After Intravitreous Dexamethasone | 451.44 µm | Standard Deviation 154.48 |