Characteristics of studies.
Characteristics of included studies
| Audren 2006 | ||
| Methods | Study design: RCT (4 patients with asymmetrical diffuse DME were not randomized). Method of randomization: Randomization sequence was generated from a random number table and was block-randomized into groups of 4. Number randomized: For patients with symmetrical diffuse DME (13 patients, 26 eyes), one eye was randomized to IVTA (13 eyes), and the fellow eye served as a control (13 eyes). Method of allocation concealment: Not reported. Outcome assessor masking: Unclear. Losses to follow up: No losses to follow up at 6 months. Intention-to-treat analysis: Not performed. |
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| Participants | Inclusion criteria: Bilateral diffuse DME which was unresponsive to adequate laser photocoagulation, with no sign of vitreomacular traction on either biomicroscopy or OCT examination; CMT > 380 um on OCT in both eyes; glycated haemoglobin (HbA1c) < 9.5%, systolic blood pressure < 150 mm Hg, and diastolic blood pressure < 90 mmHg. Exclusion criteria: Glaucoma, ocular hypertension and corticosteroid-induced ocular hypertension. Types of DME: diffuse macular edema. Prior laser treatment: Yes. Age: 60.1±9.0 (included four non-randomized patients). Comparability of baseline characteristics: We can not assess the comparability of baseline characteristics because the baseline data presented in the paper consisted of both randomized and non-randomized patients. |
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| Interventions | Test intervention: IVTA (4 mg). Control intervention: No treatment. Repeat IVTA treatment: Not reported. |
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| Outcomes | Primary outcome: Change in CMT at 4, 12 and 24 weeks follow-up. Measurement of primary outcome: CMT was defined by the average thickness of a central macular region 1000 um in diameter, centered on the patient's foveola, and measured using OCT 2 and A5 mapping software. Secondary outcomes: Change in visual acuity relative to pre-injection level; IOP; and cataract progression. Measurement of secondary outcomes: Visual acuity was measured using ETDRS procedure; IOP was measured by Goldmann applanation tonometry; measurement for cataract progression was not reported. |
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| Notes | Data source: Published data. Funding souce: Non-industry funded. Country: France. Others: Data could not be used in meta-analysis because 1) the results reported were not stratified by study design (randomized versus non-randomized eyes); 2) the correlation between paired eyes within a participant was not accounted for. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear | B - Unclear |
| Avitabile 2005 | ||
| Methods | Study design: RCT. Method of randomization: Computer-generated pseudorandom numbers of variable block size was used. Number randomized: 48 DME eyes (17 eyes to IVTA arm, 16 eyes to MLG arm and 15 eyes to IVTA with MLG arm). Method of allocation concealment: Sealed opaque envelopes, each serially numbered, containing the treatment codes were prepared before the study began by an administrative clerk otherwise not involved in the study and guarded in a locked cabinet of the Institute. Outcome assessor masking: Adequately masked. Losses to follow up: No losses to follow up at 6 months; 5/17 (29%) eyes in the IVTA arm and 6/16 (38%) eyes in the MLG arm at 9 months of follow up. Intention-to-treat analysis: Performed. |
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| Participants | Inclusion criteria: Older than 55, ME (DME, CRVO or BRVO) lasting at least 5 months, had VA <= 20/50, refraction below ±3 diopters. Exclusion criteria: Ocular trauma, inflammation, recent surgery, glaucoma or ocular hypertension, poorly controlled diabetes, hypertension, nephropathy, and macular ischemia. Types of DME: CME. Prior laser treatment: None. Age: 64±5 Comparability of baseline characteristics: Baseline visual acuity was comparable in general. Baseline retinal thickness was 535±101 um in IVTA arm and 601±88 um in MLG arm. |
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| Interventions | Test intervention: IVTA (4 mg). Control intervention 1: MLG. Control intervention 2: IVTA with MLG. Repeat IVTA treatment: Allowed. |
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| Outcomes | Primary outcome: Best-corrected VA and CMT at 45 days, 3, 6 and 9 months follow-up. Measurement of primary outcome: VA by ETDRS chart; CMT by OCT. Secondary outcomes: Complication rate, including IOP > 21 mmHg, cataract progression, or injection-related complications. Measurement of secondary outcomes: IOP was measured by applanation tonometer; cataract progression was determined according to Lens Opacities Classification System III grading; patients were monitored for potential injection-related complications (retinal detachment, vitreous hemorrhage, and endophthalmitis). |
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| Notes | Data source: Published data. Funding souce: Non-industry funded. Country: Italy. Others: Only data from DME eyes were used in this review. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Yes | A - Adequate |
| Jonas 2006 | ||
| Methods | Study design: RCT. Method of randomization: Not reported. Number randomized: 40 eyes of 38 patients were randomized at 2:1 ratio into IVTA arm (28 eyes) and shame procedure arm (12 eyes). Method of allocation concealment: Not reported. Outcome assessor masking: Unclear. Losses to follow up: 5/28 (18%) eyes in the IVTA arm and 3/12 (25%) eyes in the shame procedure arm at 6 months of follow up. Intention-to-treat analysis: Not performed. |
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| Participants | Inclusion criteria: Diffuse DME as defined by ETDRS involving the central fovea and persisting for at least 3 months. Laser treatment had been performed, if indicated, according to the ETDRS guidelines at least 3 months prior to inclusion. All patients had refractory macular edema. All patients were observed to have good metabolic control. Exclusion criteria: Uncontrolled glaucoma, loss of vision as result of other causes, systemic treatment with prednisolone, severe systemic disease, or any condition affecting follow-up or documentation. Types of DME: Diffuse DME involving central fovea. Age: IVTA: 65.7±7.5; Placebo: 68.8±9.9. Comparability of baseline characteristics: Baseline VA and IOP were comparable. |
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| Interventions | Test intervention: IVTA (20 mg). Control intervention: Shame procedure (sterile cotton tip placed onto conjunctiva). Repeat IVTA treatment: Not allowed. |
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| Outcomes | Primary outcome: Proportion of improvement of best-corrected logMAR visual acuity by 2 or more lines and 3 or more lines at 6 months follow-up. Measurement of primary outcome: Not reported. Secondary outcomes: Any change in visual acuity compared with the pre-injection level. Measurement of secondary outcomes: Not reported. |
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| Notes | Data source: Published data. Funding souce: Non-industry funded. Country: Germany. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear | B - Unclear |
| Kuppermann 2007 | ||
| Methods | Study design: RCT. Method of randomization: One eye per patient was randomized with a 1:1:1 allocation to observation or treatment with dexamethasone DDS, 350 or 700 ug. Randomization was performed centrally and was stratified by underlying cause of macular edema. Number randomized: 315 eyes were randomized (105 eyes into each arm), among which 172 eyes were diagnosed with DME (58 eyes in dexamethasone DDS 350 ug arm, 57 eyes in the dexamethasone DDS 700 ug arm, and 57 eyes in the observation arm). Method of allocation concealment: Not reported. Outcome assessor masking: Fluorescein angiograms were read by masked graders; not reported for other outcomes. Losses to follow up: 7/105 (6.7%) eyes in the dexamethasone DDS 350 ug arm, 8/105 (7.6%) eyes in the dexamethasone DDS 700 ug arm, and 14/105 (13.3%) eyes in the observation arm lost to follow up at 6 months. Among these losses to follow up, the exact number diagnosed with DME was not reported. Intention-to-treat analysis: Performed. |
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| Participants | Inclusion criteria: Patients were at least 12 years of age; had best corrected VA of 20/40 to 20/200; had persistent macular edema continued for 90 days or more after laser or medical therapy. Exclusion criteria: VA worse than 20/200 in the study eye; history of vitrectomy surgery; use of systemic, periocular or intraocular corticosteroids within 30 days of enrollment; moderate or severe glaucoma; poorly controlled hypertension and diabetes. Types of DME: Not reported. Age: Overall mean age 65.7; range 15–89. Comparability of baseline characteristics: The baseline demographics, duration of macular edema, and VA were comparable between treatment arms. |
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| Interventions | Test intervention 1: Dexamethasone DDS, 350 ug implant. Test intervention 2: Dexamethasone DDS, 700 ug implant. Control intervention: No study treatment or sham procedure. However, any patient who experienced a visual acuity loss of 15 letters or more could be treated with any therapy (including laser photocoagulation) that the investigator deemed appropriate. Repeat treatment: Not allowed. |
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| Outcomes | Primary outcome: Proportion of patients who achieved at least a 10-letter improvement in best corrected VA at the 90 days follow-up. Measurement of primary outcome: Best corrected VA was measured using a standardized ETDRS protocol. Secondary outcomes: Proportion of patients who achieved a 15-letter improvement in best corrected VA; proportion of patients who achieved a 3-grade improvement in fluorescein angiographic leakage (standardized 9-grade scale); change in central retinal thickness; safety parameters. Measurement of secondary outcomes: Macular thickness was measured by OCT (performed at selected sites); fluorescein angiograms were assessed at a central reading center using standardized procedures; the presence of nuclear, cortical, and posterior subcapsular lens opacity was measured during the slitlamp examination using standardized photographs and the clinical lens grading protocol, including the Clinical Lens Grading Protocol slitlamp settings, described in the Age-Related Eye Disease Study reports. |
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| Notes | Data source: Published data. Funding souce: Oculex Pharmaceuticals Inc. Country: The United States. Other notes: The trial participants had different underlying cause of macular edema. We used data for patients with DME whenever possible. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear | B - Unclear |
| Pearson 2002 | ||
| Methods | Study design: RCT. Method of randomization: Not reported. Number randomized: 80 eyes of 80 patients (41 eyes to 0.5 mg FAI arm, 11 eyes to 2 mg FAI arm, and 28 eyes to standard of care (MLG or observation arm). Method of allocation concealment: Not reported. Losses to follow up: Not reported. Outcome assessor masking: Not reported. Intention-to-treat analysis: Not reported, might be used. |
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| Participants | Inclusion criteria: All patients had persistent macular edema despite at least one macular laser procedure at least 3 months prior to randomization and had persistent macular thickening involving the fovea. Best corrected visual acuity was between 20 and 68 letters using an adapted ETDRS protocol (20/400 to 20/50). Exclusion criteria: IOP greater than 25 on two or more medications or a history of uncontrolled pressure in the past 12 months. Types of DME: Persistent, refractory or recurrent DME. Age: 63.8±8.3. Comparability of baseline characteristics: Not reported. |
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| Interventions | Test intervention 1: FAI (0.5 mg). Test intervention 2: FAI (2 mg). Control intervention: Standard of care (MLG or observation). Repeat treatment: Not given. |
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| Outcomes | Primary outcome: Complete resolution of macular edema, change in retinal thickness and visual acuity at 6, 12, and 24 months follow-up. Measurement of primary outcome: Not reported. Secondary outcomes: Not reported. Measurement of secondary outcomes: Not reported. |
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| Notes | Data source: Unpublished data. Funding souce: Bausch&Lomb Inc. Country: The United States. Others: Data from FAI (2 mg) arm were not reported. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear | B - Unclear |
| Pearson 2005 | ||
| Methods | Study design: RCT. Method of randomization: Not reported. Number randomized: 197 eyes of 197 patients were randomized at 2:1 ratio into FAI arm (127 eyes) and standard of care arm (70 eyes). Method of allocation concealment: Not reported. Outcome assessor masking: Not reported. Losses to follow up: Not reported. Intention-to-treat analysis: Not reported, might be used. |
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| Participants | Inclusion criteria: Not reported. Exclusion criteria: Not reported. Types of DME: Not reported. Age: 62.2±10.1. Comparability of baseline characteristics: Not reported. |
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| Interventions | Test intervention: FAI (0.59 mg). Control intervention: Standard of care (MLG or observation). Repeat treatment: Not reported. |
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| Outcomes | Primary outcome: Change in visual acuity, retinal thickness and Diabetic Retinopathy Severity Score, resolution of retinal thickening at 12, 24 and 36 months. Measurement of primary outcome: Not reported. Secondary outcomes: Not reported. Measurement of secondary outcomes: Not reported. |
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| Notes | Data source: Unpublished data. Funding souce: Bausch&Lomb Inc. Country: The United States. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Unclear | B - Unclear |
| Sutter 2004 | ||
| Methods | Study design: RCT. Method of randomization: Computer-generated pseudorandom numbers of variable block size was used. Number randomized: 69 eyes of 43 patients (34 eyes into IVTA arm and 35 eyes into shame treatment arm). Method of allocation concealment: Sealed opaque envelopes, each serially numbered, were prepared by an administrative clerk otherwise not involved in the study and were kept in a locked drawer in the clinic. Outcome assessor masking: Adequately masked. Losses to follow up: 1/34 (3%) eyes in the IVTA arm and 3/35 (9%) eyes in the placebo arm at 3 months of follow up; 3/34 (9%) eyes in the IVTA arm and 6/35 (17%) eyes in the placebo arm at 24 months of follow up. Intention-to-treat analysis: Performed at 24 months report. |
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| Participants | Inclusion criteria: Patients with persistent DME, diffuse or focal, involving the central fovea persisting 3 months or more after adequate laser treatment and best-corrected VA in the affected eye(s) of 6/9 or worse. Exclusion criteria: Uncontrolled glaucoma, loss of vision as a result of other causes, systemic treatment with more than 5mg prednisolone (or equivalent) daily, intercurrent severe systemic disease, or any condition affecting follow-up or documentation. Types of DME: Persistent DME, diffuse or focal, involving central fovea. Age: Mean 64. Comparability of baseline characteristics: Baseline VA, retinal thickness and IOP were comparable between two treatment arms. |
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| Interventions | Test intervention: IVTA (4 mg). Control intervention: Shame treatment (subconjunctival saline injection). Repeat IVTA treatment: Allowed. |
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| Outcomes | Primary outcome: Percentage of eyes in which best-corrected logMAR visual acuity improved by 5 or more letters at 2 years and percentage of eyes with moderate or severe adverse events. Measurement of primary outcome: VA was measured using ETDRS charts with standardized procedures. Secondary outcomes: Change in visual acuity relative to preinjection level; change in macular thickness. Measurement of secondary outcomes: Macular thickness was measured by OCT. |
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| Notes | Data source: Published data. Funding souce: Non-industry funded. Country: Australia. |
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| Risk of bias table | ||
| Item | Authors' judgement | Support for judgement |
| Allocation concealment? | Yes | A - Adequate |
BRVO: branch retinal vein occlusion
CME: cystoid macular edema
CMT: central macular thickness
CRVO: central retinal vein occlusion
DDS: drug delivery system
DME: diabetic macular edema
ETDRS: Early Treatment Diabetic Retinopath Study
FAI: fluocinolone acetonide implant
IOP: intraocular pressure
IVTA: intravitreal triamcinalone acetate injection
MLG: macular laser grid photocoagulation
OCT: optical coherence tomography
RCT: randomized controlled trial
VA: visual acuity