Clinical Studies:
DRCR PROTOCOL AA
Citation: Aiello LP, Odia I, Glassman AR, et al. Comparison of Early Treatment Diabetic Retinopathy Study standard 7-field imaging with ultrawide-field imaging for determining severity of diabetic retinopathy. JAMA Ophthalmol. 2019;137(1):65–73. doi:10.1001/jamaophthalmol.2018.4982
Key Points
- Evaluate the role of ultra-widefield (UWF) imaging in assessing diabetic retinopathy (DR) and predicting its progression compared to the 7 standard ETDRS fields.
- Rationale: Improved prediction of DR progression through peripheral lesions could enhance patient management and follow up, provide insights into retinal pathology mechanisms, and reduce imaging time for greater patient comfort.
- Total of 350 adults (175 predominantly with peripheral lesions and 175 without predominant peripheral lesions).
- Baseline UWF fluorescein angiography (FA) predominantly peripheral lesions (PPLs) were associated with a significantly greater risk of DR progression. Eyes with baseline PPLs had a 70% greater risk of DR worsening compared to those without PPLs over four years.
Objective
Primary: Assess use of UWF images to evaluate the retinal far periphery to assess DR and predict rates of DR worsening over time compared to the area within the 7 standard ETDRS fields.
Secondary: Determine quality of UWF photos compared to DRCR modified 7-field photos; evaluate whether the extent and location of non-perfusion on UWF FA is predictive for worsening of DR over time; using peripheral lesions to redefine the DR severity grading; determine if renal and cardiovascular complications are associated with retinal vascular characteristics.
Study Design
Prospective observational longitudinal study at 38 sites in US and Canada. Duration: 4 years.
Study Subjects
- Inclusion Criteria:
- Age ≥18 years
- Type 1 or 2 DM
- Ability to cooperate with imaging procedures
- Primary intraocular pathology is diabetic retinopathy with no substantial non-diabetic intraocular pathology including age-related macular degeneration or other conditions leading to ocular neovascularization
- At least one eye meeting all of the below:
- NPDR on clinical examination (Confirmed on 7-field photos without UWF imaging level 35-53)
- No CI-DME on exam or OCT
- No history of PRP or vitrectomy, and PRP not anticipated for next 6 months
- No intravitreal treatment over prior 12 months and not anticipated for next 6 months
- No history of major ocular surgery
- Exclusion Criteria:
- History of chronic renal failure requiring dialysis or kidney transplant
- Inability to comply with the follow up regimen
- Initiation of intensive insulin treatment (pump or multiple daily injections) within 4 months prior to enrollment or plans to do so in the next 4 months
- Participation in investigational trial within 30 days of enrollment involving treatment with any systemic drug or if drug affects the eyes
- Systemic Anti-VEGF or pro VEGF treatment within 4 months prior to study
- Participants expecting to move to an area not covered by a clinical site during the 2 years
- History of ARMD or other substantial ocular pathology
Study Procedure
- Comprehensive eye exam with refraction by E-ETDRS VA testing (Baseline, year 1-4)
- OCT OU (Mac and choroidal thickness) Baseline and Year 1-4
- BP, Blood and urine testing and medical conditions assessments (Baseline and Year 1-4)
- ETDRS protocol 7 modified-field fundus photography OU (Baseline)
- UWF images (Baseline and Year 1-4)
- UWF FA (Baseline, Year 1 and 4)
Key Findings
- Baseline UWF fluorescein angiography (FA) predominantly peripheral lesions (PPLs) were associated with a significantly greater risk of DR progression. Eyes with baseline PPLs had a 70% greater risk of DR worsening compared to those without PPLs over four years.
- The presence of PPLs on UWF FA imaging was a stronger predictor of DR progression than the presence of PPLs on UWF color imaging.
- The study highlighted the importance of assessing the retinal periphery in DR evaluation and suggested that UWF imaging could enhance the prediction of DR worsening.
Implications for Clinical Practice
- Protocol AA suggests that incorporating UWF imaging into routine clinical practice will improve the grading of DR severity and enhance the prediction of disease progression, especially with the use of UWF-FA.
- By identifying peripheral lesions that may not be captured with the standard ETDRS 7 images, there can be better stratification of patients' risks and tailored treatment strategies accordingly.