Diabetic Macular Edema
Conditions
Keywords
diabetic, macular, edema, intravitreal, triamcinolone, laser, photocoagulation, DME
Brief summary
The study involves the enrollment of patients over 18 years of age with diabetic macular edema(DME). Patients with one study eye will be randomly assigned (stratified by visual acuity and prior laser) with equal probability to one of the three treatment groups: 1. Laser photocoagulation 2. 1mg intravitreal triamcinolone acetonide injection 3. 4mg intravitreal triamcinolone acetonide injection For patients with two study eyes (both eyes eligible at the time of randomization), the right eye (stratified by visual acuity and prior laser) will be randomly assigned with equal probabilities to one of the three treatment groups listed above. The left eye will be assigned to the alternative treatment (laser or triamcinolone). If the left eye is assigned to triamcinolone, then the dose (1mg or 4 mg) will be randomly assigned to the left eye with equal probability (stratified by visual acuity and prior laser). The study drug, triamcinolone acetonide, has been manufactured as a sterile intravitreal injectable by Allergan. Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg. There is no indication of which treatment regimen will be better. Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment. In addition, standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection.
Detailed description
Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin. In a review of three early studies concerning the natural history of diabetic macular edema, Ferris and Patz found that 53% of 135 eyes with diabetic macular edema, presumably all involving the center of the macula, lost two or more lines of visual acuity over a two year period. In the Early Treatment Diabetic Retinopathy Study (ETDRS), 33% of 221 untreated eyes available for follow-up at the 3-year visit, all with edema involving the center of the macula at baseline, had experienced a 15 or more letter decrease in visual acuity score (equivalent to a doubling of the visual angle, e.g., 20/25 to 20/50, and termed moderate visual acuity loss). In the ETDRS, focal/grid photocoagulation of eyes with clinically significant macular edema (CSME) reduced the risk of moderate visual loss by approximately 50% (from 24% to 12%, three years after initiation of treatment). Therefore, 12% of treated eyes developed moderate visual loss in spite of treatment. Furthermore, approximately 40% of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months, as did 25% of treated eyes at 36 months. Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, as demonstrated by the ETDRS, and intensive glycemic control, as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS). In the DCCT, intensive glucose control reduced the risk of onset of diabetic macular edema by 23% compared with conventional treatment. Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control, with a 58% risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study. The frequency of an unsatisfactory outcome following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. These studies suggest that vitreomacular traction, or the vitreous itself, may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema. It also requires a complex surgical intervention with its inherent risks, recovery time, and expense. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and antibodies targeted at vascular endothelial growth factor (VEGF) are under investigation. The use of intravitreal corticosteroids is another treatment modality that has generated recent interest. The optimal dose of corticosteroid to maximize efficacy with minimum side effects is not known. A 4mg dose of Kenalog is principally being used in clinical practice. However, this dose has been used based on feasibility rather than scientific principles. There is also experience using Kenalog doses of 1mg and 2mg. These doses anecdotally have been reported to reduce the macular edema. There is a rationale for using a dose lower than 4mg. Glucocorticoids bind to glucocorticoid receptors in the cell cytoplasm, and the steroid-receptor complex moves to the nucleus where it regulates gene expression. The steroid-receptor binding occurs with high affinity (low dissociation constant (Kd) which is on the order of 5 to 9 nanomolar). Complete saturation of all the receptors occurs about 20-fold higher levels, i.e., about 100-200 nanomolar. A 4mg dose of triamcinolone yields a final concentration of 7.5 millimolar, or nearly 10,000-fold more than the saturation dose. Thus, the effect of a 1mg dose may be equivalent to that of a 4mg dose, because compared to the 10,000-fold saturation, a 4-fold difference in dose is inconsequential. It is also possible that higher doses of corticosteroid could be less effective than lower doses due to down-regulation of the receptor. The steroid implant studies provide additional justification for evaluating a lower dose, a 0.5mg device which delivers only 0.5 micrograms per day has been observed to have a rapid effect in reducing macular edema. There has been limited experience using doses greater than 4mg. Jonas' case series reported results using a 25mg dose. However, others have not been able to replicate this dose using the preparation procedure described by Jonas. In the trial, 4mg and 1mg doses will be evaluated. The former will be used because it is the dose that is currently most commonly used in clinical practice and the latter because there is reasonable evidence for efficacy and the potential for lower risk. Although there is good reason to believe that a 1mg dose will reduce the macular edema, it is possible that the retreatment rate will be higher with this dose compared with 4mg since the latter will remain active in the eye for a longer duration than the former. Insufficient data are available to warrant evaluating a dose higher than 4mg at this time.
Interventions
PROCEDUREStandard of Care Group
Standard of care group: conventional treatment consisting of focal/grid photocoagulation.
DRUG1mg triamcinolone acetonide
Intravitreal injection of 1mg of triamcinolone acetonide at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.
DRUG4mg triamcinolone acetonide
4mg intravitreal triamcinolone acetonide injection at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.
Sponsors
National Eye Institute (NEI)
Allergan
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible, the following inclusion criteria must be met: 1. Age ≥18 years 2. Diagnosis of diabetes mellitus (type 1 or type 2) 3. Able and willing to provide informed consent. 4. Patient understands that (1) if both eyes are eligible at the time of randomization, one eye will receive intravitreal triamcinolone acetonide and one eye will receive laser, and (2) if only one eye is eligible at the time of randomization and the fellow eye develops DME later, then the fellow eye will not receive intravitreal triamcinolone acetonide if the study eye received intravitreal triamcinolone acetonide (however, if the study eye was assigned to the laser group, then the fellow eye may be treated with the 4mg dose of the study intravitreal triamcinolone acetonide formulation, provided the eye assigned to laser has not received an intravitreal injection; such an eye will not be a study eye but since it is receiving study drug, it will be followed for adverse effects).
Exclusion criteria
A patient is not eligible if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. | Baseline to 2 Years | Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0. |
| Median Change in Visual Acuity Baseline to 2 Years | Baseline to 2 Years | Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. |
| Distribution of Change in Visual Acuity Baseline to 2 Years | baseline to 2 years | Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years | Baseline to 2 Years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. |
| Central Subfield Thickness < 250 Microns at 2 Years | 2 Years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. |
| Change in Visual Acuity From Baseline to 3 Years | Baseline to 3 year | Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. |
| Central Subfield Thickness at 2 Years | 2 Years | Median central subfield thickness at two-years. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. |
| Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years | 3 years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. |
| Change in Central Subfield Thickness on OCT Baseline to 3 Years | Baseline to 3 years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement. |
| Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years | Baseline to 3 years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement. |
| Distribution of Visual Acuity Change Baseline to 3 Years | Baseline to 3 years | Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale=97, worst=0 |
| Mean Change in Central Subfield Thickness Baseline to 2 Years | Baseline to 2 years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes and improvement. |
| Median Change in Central Subfield Thickness Baseline to 2 Years | Baseline to 2 Years | Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement. |
Countries
United States
Participant flow
Recruitment details
Eighty-eight academic and community based sites across the United States recruited 693 subjects from May 2004 to July 2006.
Participants by arm
| Arm | Count |
|---|---|
| Focal/Grid Laser Photocoagulation Standard of care group: conventional treatment consisting of focal/grid photocoagulation. | 330 |
| 1mg Intravitreal Triamcinolone Intravitreal injection of 1mg of triamcinolone acetonide | 256 |
| 4 mg Intravitreal Triamcinolone Intravitreal injection of 4mg of triamcinolone acetonide | 254 |
| Total | 840 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 2 Years | Death | 20 | 12 | 12 |
| 2 Years | Dropped | 34 | 19 | 33 |
| 2 Years | Missed visit | 4 | 5 | 4 |
Baseline characteristics
| Characteristic | Focal/Grid Laser Photocoagulation | 1mg Intravitreal Triamcinolone | 4 mg Intravitreal Triamcinolone | Total |
|---|---|---|---|---|
| Age, Continuous | 63 years | 63 years | 63 years | 63 years |
| Central subfield thickness on OCT | 398 Microns | 405 Microns | 396 Microns | 400 Microns |
| Diabetes Type Type 1 | 14 Participants | 12 Participants | 12 Participants | 38 Participants |
| Diabetes Type Type 2 | 316 Participants | 244 Participants | 242 Participants | 802 Participants |
| Duration of Diabetes | 15 Years | 15 Years | 16 Years | 15 Years |
| e-ETDRS visual acuity | 62 Letter Score | 62 Letter Score | 62 Letter Score | 62 Letter Score |
| HbA1c | 7.5 Percentage | 7.5 Percentage | 7.6 Percentage | 7.5 Percentage |
| History of ocular hypertension No Ocular Hypertension | 327 Eyes | 248 Eyes | 250 Eyes | 825 Eyes |
| History of ocular hypertension Ocular Hypertension | 3 Eyes | 8 Eyes | 4 Eyes | 15 Eyes |
| Intraocular pressure | 16 microns | 16 microns | 16 microns | 16 microns |
| Lens status phakic (clinical examination) Phakic | 262 Eyes | 203 Eyes | 197 Eyes | 662 Eyes |
| Lens status phakic (clinical examination) Pseudophakic | 68 Eyes | 53 Eyes | 57 Eyes | 178 Eyes |
| OCT cystoid abnormality (questionable or definite) Missing/can not grade | 3 Eyes | 4 Eyes | 2 Eyes | 9 Eyes |
| OCT cystoid abnormality (questionable or definite) No Evidence | 12 Eyes | 9 Eyes | 6 Eyes | 27 Eyes |
| OCT cystoid abnormality (questionable or definite) OCT cystoid abnormality (questionable or definite) | 315 Eyes | 243 Eyes | 246 Eyes | 804 Eyes |
| OCT subretinal fluid present (questionable or definite Missing (or ungradeable) | 1 Eyes | 4 Eyes | 1 Eyes | 6 Eyes |
| OCT subretinal fluid present (questionable or definite No OCT subretinal fluid present | 235 Eyes | 188 Eyes | 192 Eyes | 615 Eyes |
| OCT subretinal fluid present (questionable or definite OCT subretinal fluid present | 94 Eyes | 64 Eyes | 61 Eyes | 219 Eyes |
| Prior Panretinal scatter photocoagulation No Prior Panretinal scatter photocoagulation | 277 Eyes | 216 Eyes | 212 Eyes | 705 Eyes |
| Prior Panretinal scatter photocoagulation Prior Panretinal scatter photocoagulation | 53 Eyes | 40 Eyes | 42 Eyes | 135 Eyes |
| Prior photocoagulation for diabetic macular edema No Prior photocoagulation for DME | 132 Eyes | 102 Eyes | 96 Eyes | 330 Eyes |
| Prior photocoagulation for diabetic macular edema Prior photocoagulation for DME | 198 Eyes | 154 Eyes | 158 Eyes | 510 Eyes |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 2 participants | 2 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Asian | 7 participants | 8 participants | 5 participants | 20 participants |
| Race/Ethnicity, Customized Black | 31 participants | 22 participants | 26 participants | 79 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 39 participants | 34 participants | 33 participants | 106 participants |
| Race/Ethnicity, Customized More than 1 race | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Unknown/not reported | 6 participants | 3 participants | 4 participants | 13 participants |
| Race/Ethnicity, Customized White | 243 participants | 186 participants | 183 participants | 612 participants |
| Retinal volume on OCT | 9.2 cubic millimetre | 8.9 cubic millimetre | 8.9 cubic millimetre | 9.0 cubic millimetre |
| Retinopathy severity (ETDRS severity scale) High-risk proliferative | 9 Eyes | 8 Eyes | 6 Eyes | 23 Eyes |
| Retinopathy severity (ETDRS severity scale) Microaneurysms only | 1 Eyes | 1 Eyes | 0 Eyes | 2 Eyes |
| Retinopathy severity (ETDRS severity scale) Mild-moderately severe nonproliferative | 186 Eyes | 156 Eyes | 151 Eyes | 493 Eyes |
| Retinopathy severity (ETDRS severity scale) Mild to moderate proliferative | 79 Eyes | 56 Eyes | 62 Eyes | 197 Eyes |
| Retinopathy severity (ETDRS severity scale) Missing (ungradeable) | 12 Eyes | 8 Eyes | 10 Eyes | 30 Eyes |
| Retinopathy severity (ETDRS severity scale) Severe nonproliferative | 43 Eyes | 27 Eyes | 25 Eyes | 95 Eyes |
| Sex: Female, Male Female | 166 Participants | 120 Participants | 125 Participants | 411 Participants |
| Sex: Female, Male Male | 164 Participants | 136 Participants | 129 Participants | 429 Participants |
| Visual Acuity Categorized by Randomization Strata 35-24 (20/200-20/320) | 12 Eyes | 13 Eyes | 13 Eyes | 38 Eyes |
| Visual Acuity Categorized by Randomization Strata 59-36 (<20/631-20/200) | 129 Eyes | 94 Eyes | 92 Eyes | 315 Eyes |
| Visual Acuity Categorized by Randomization Strata 73-60 (20/32-2-20/62) | 189 Eyes | 149 Eyes | 149 Eyes | 487 Eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 69 / 330 | 98 / 256 | 163 / 254 |
| serious Total, serious adverse events | 135 / 330 | 69 / 256 | 54 / 254 |
Outcome results
Primary
Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years.
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Time frame: Baseline to 2 Years
Population: The primary analysis included all randomized eyes and followed the intent-to-treat principle.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. | 1 Letter score | Standard Deviation 17 |
| 1mg Intravitreal Triamcinolone | Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. | -2 Letter score | Standard Deviation 18 |
| 4 mg Intravitreal Triamcinolone | Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. | -3 Letter score | Standard Deviation 22 |
Comparison: P values for two group comparisons for difference in mean change.p-value: 0.02ANCOVA
Comparison: P Values for 2 group comparisons of difference in mean changep-value: 0.002ANCOVA
Comparison: P Values for 2 group comparisons of difference in mean changep-value: 0.49ANCOVA
Primary
Distribution of Change in Visual Acuity Baseline to 2 Years
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.
Time frame: baseline to 2 years
Population: The primary analysis included all randomized eyes and followed the intent-to-treat principle
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | 14 to 10 letter improvement | 13 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | 5-9 letters worse | 10 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | same +- 4 letters | 24 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | >= 15 letter improvement | 18 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | >=15 letters worse | 14 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | 10-14 letters worse | 5 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Change in Visual Acuity Baseline to 2 Years | 9 to 5 letter improvement | 16 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | same +- 4 letters | 27 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | >= 15 letter improvement | 14 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 14 to 10 letter improvement | 11 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 9 to 5 letter improvement | 14 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 5-9 letters worse | 9 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 10-14 letters worse | 6 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | >=15 letters worse | 20 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 5-9 letters worse | 6 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 14 to 10 letter improvement | 11 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | >=15 letters worse | 20 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 10-14 letters worse | 8 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | same +- 4 letters | 23 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | 9 to 5 letter improvement | 15 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Change in Visual Acuity Baseline to 2 Years | >= 15 letter improvement | 17 Percentage of Eyes |
Comparison: Proportion with 15-letter or more worseningp-value: 0.03GEE Repeated Measures
Comparison: Proportion with 15-letter or more worseningp-value: 0.01GEE Repeated Measures
Comparison: Proportion with 15-letter or more worseningp-value: 0.82GEE Repeated Measures
Primary
Median Change in Visual Acuity Baseline to 2 Years
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement.
Time frame: Baseline to 2 Years
Population: The primary analysis included all randomized eyes and followed the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Median Change in Visual Acuity Baseline to 2 Years | 4 Letter score |
| 1mg Intravitreal Triamcinolone | Median Change in Visual Acuity Baseline to 2 Years | 1 Letter score |
| 4 mg Intravitreal Triamcinolone | Median Change in Visual Acuity Baseline to 2 Years | 2 Letter score |
Secondary
Central Subfield Thickness < 250 Microns at 2 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.
Time frame: 2 Years
Population: Only subjects with available OCTs at baseline and 2 years are included in the OCT analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Central Subfield Thickness < 250 Microns at 2 Years | 53 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Central Subfield Thickness < 250 Microns at 2 Years | 34 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Central Subfield Thickness < 250 Microns at 2 Years | 38 Percentage of Eyes |
Comparison: P Values not adjusted for multiple comparisonsp-value: <0.001GEE Repeated Measures
Comparison: P Value not adjusted for statistical analysisp-value: <0.001GEE Repeated Measures
Comparison: P Value not adjusted for statistical analysisp-value: 0.55GEE Repeated Measures
Secondary
Central Subfield Thickness at 2 Years
Median central subfield thickness at two-years. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.
Time frame: 2 Years
Population: Only subjects with an available Optical coherence tomography (OCT) at baseline and 2 years are included in the OCT analysis.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Central Subfield Thickness at 2 Years | 243 Microns | Inter-Quartile Range 148 |
| 1mg Intravitreal Triamcinolone | Central Subfield Thickness at 2 Years | 305 Microns | Inter-Quartile Range 167 |
| 4 mg Intravitreal Triamcinolone | Central Subfield Thickness at 2 Years | 279 Microns | Inter-Quartile Range 160 |
Secondary
Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.
Time frame: 3 years
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years | 211 Microns |
| 1mg Intravitreal Triamcinolone | Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years | 269 Microns |
| 4 mg Intravitreal Triamcinolone | Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years | 248 Microns |
Secondary
Change in Central Subfield Thickness on OCT Baseline to 3 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.
Time frame: baseline to 3 years
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -158 Microns |
| 1mg Intravitreal Triamcinolone | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -103 Microns |
| 4 mg Intravitreal Triamcinolone | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -114 Microns |
Secondary
Change in Central Subfield Thickness on OCT Baseline to 3 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.
Time frame: Baseline to 3 years
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -175 Microns | Standard Deviation 149 |
| 1mg Intravitreal Triamcinolone | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -124 Microns | Standard Deviation 184 |
| 4 mg Intravitreal Triamcinolone | Change in Central Subfield Thickness on OCT Baseline to 3 Years | -126 Microns | Standard Deviation 159 |
Secondary
Change in Visual Acuity From Baseline to 3 Years
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement.
Time frame: Baseline to 3 year
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Change in Visual Acuity From Baseline to 3 Years | 5 Letter Score | Standard Deviation 17 |
| 1mg Intravitreal Triamcinolone | Change in Visual Acuity From Baseline to 3 Years | 0 Letter Score | Standard Deviation 16 |
| 4 mg Intravitreal Triamcinolone | Change in Visual Acuity From Baseline to 3 Years | 0 Letter Score | Standard Deviation 21 |
Secondary
Change in Visual Acuity From Baseline to 3 Years
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best Value on the scale=97, Worst Value=0
Time frame: Baseline to 3 year
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Change in Visual Acuity From Baseline to 3 Years | 8 Letter Score |
| 1mg Intravitreal Triamcinolone | Change in Visual Acuity From Baseline to 3 Years | 2 Letter Score |
| 4 mg Intravitreal Triamcinolone | Change in Visual Acuity From Baseline to 3 Years | 4 Letter Score |
Secondary
Distribution of Visual Acuity Change Baseline to 3 Years
Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale=97, worst=0
Time frame: Baseline to 3 years
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters better | 18 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters worse | 4 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | no change, + - 4 letters | 21 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | >= 15 letters better | 26 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | >=15 letters worse | 8 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters worse | 4 Percentage of Eyes |
| Focal/Grid Laser Photocoagulation | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters better | 18 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | no change, + - 4 letters | 23 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | >= 15 letters better | 20 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters better | 4 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters better | 17 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters worse | 10 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters worse | 9 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | >=15 letters worse | 17 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters worse | 6 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters better | 16 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | >=15 letters worse | 16 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 10-14 letters worse | 6 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | no change, + - 4 letters | 24 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | 5-9 letters better | 9 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Distribution of Visual Acuity Change Baseline to 3 Years | >= 15 letters better | 21 Percentage of Eyes |
Secondary
Mean Change in Central Subfield Thickness Baseline to 2 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes and improvement.
Time frame: Baseline to 2 years
Population: Only subjects with available OCTs at baseline and 2 years are included in the OCT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Focal/Grid Laser Photocoagulation | Mean Change in Central Subfield Thickness Baseline to 2 Years | -139 Microns | Standard Deviation 148 |
| 1mg Intravitreal Triamcinolone | Mean Change in Central Subfield Thickness Baseline to 2 Years | -86 Microns | Standard Deviation 167 |
| 4 mg Intravitreal Triamcinolone | Mean Change in Central Subfield Thickness Baseline to 2 Years | -77 Microns | Standard Deviation 160 |
Comparison: P value not adjusted for multiple comparisonsp-value: <0.001ANCOVA
Comparison: P Value not adjusted for multiple comparisonsp-value: <0.001ANCOVA
Comparison: P Values not adjusted for multiple comparisonsp-value: 0.91ANCOVA
Secondary
Median Change in Central Subfield Thickness Baseline to 2 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.
Time frame: Baseline to 2 Years
Population: Only subjects with an available OCT's at baseline and 2 years are included in the OCT analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Median Change in Central Subfield Thickness Baseline to 2 Years | -131 Microns |
| 1mg Intravitreal Triamcinolone | Median Change in Central Subfield Thickness Baseline to 2 Years | -74 Microns |
| 4 mg Intravitreal Triamcinolone | Median Change in Central Subfield Thickness Baseline to 2 Years | -76 Microns |
Secondary
Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.
Time frame: Baseline to 2 Years
Population: Only subjects with available OCTs at baseline and 2 years are included in the OCT analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years | 67 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years | 46 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years | 48 Percentage of Eyes |
Comparison: P Values not adjusted for multiple comparisonsp-value: <0.001GEE Repeated Measures
Comparison: P Values not adjusted for multiple comparisonsp-value: <0.001GEE Repeated Measures
Comparison: P Value not adjusted for multiple comparisonsp-value: 0.6GEE Repeated Measures
Secondary
Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years
Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.
Time frame: Baseline to 3 years
Population: The study discontinued early. Only subjects with 3 years data are included in 3 year analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Focal/Grid Laser Photocoagulation | Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years | 68 Percentage of Eyes |
| 1mg Intravitreal Triamcinolone | Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years | 43 Percentage of Eyes |
| 4 mg Intravitreal Triamcinolone | Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years | 51 Percentage of Eyes |