When to laser, when to watch: a difficult, but fateful question? Diabetic retinopathy (DR) is a leading cause of blindness and visual disability worldwide. If left untreated, chronic retinal ischemia can lead to increased capillary permeability, microvascular occlusions, and neovascularization – increasing risk for eventual retinal detachments. The diabetic retinopathy study (DRS) was a multi-center, randomized control trial designed to determine whether intervention with panretinal photocoagulation (PRP) could help prevent severe vision loss (VA <5/200) in patients with advanced DR.
The DRS was one of the early landmark studies in ophthalmology that is still quite relevant today. The DRS established firm evidence for the benefits of PRP and identified important prognostic indicators of severe vision loss in DR.
Victory for the vitrectomy! In this 1990 trial, three distinct sub-investigations sought to:
Overall, the DRVS is a landmark study because it highlighted how early vitrectomy can result in significantly better visual outcomes both immediately and long term for patients with Type 1 Diabetes, monocular patients, and those with advanced diabetic eye disease. Beyond removing hemorrhaged blood, vitrectomies relieve traction on the retina and eliminate the scaffolding that promotes new vessel proliferation.
Ever wonder where those famous “EDTRS letters” come from?The Early Treatment Diabetic Retinopathy Study (ETDRS) explored the role of focal laser coagulation, panretinal photocoagulation (PRP), and aspirin use for the treatment of non-proliferative diabetic retinopathy (NPDR) and early proliferative diabetic retinopathy (PDR). A total of 3,711 patients were included in ETDRS and randomized into two cohorts according to aspirin use (aspirin, 650 mg/day, n = 1,856; placebo, n = 1855). For each patient, each eye was assigned to early or deferred photocoagulation. The cohort of early photocoagulation eyes was further subdivided according to timing of focal and panretinal/scatter photocoagulation. Photocoagulation in deferred eyes was initiated upon detection of high-risk PDR.
Overall, the ETDRS demonstrated that early focal photocoagulation can avert vision loss related to diabetic macular edema. PRP is beneficial for patients with PDR or severe NPDR, but the risks outweigh the benefits for patients with mild or moderate NPDR. This study further laid the groundwork for many future Diabetic Retinopathy and other retina studies.
Is putting off the sweets worth the reward? The DCCT sought to understand whether tighter glycemic control would lead to better outcomes in diabetic retinopathy (DR). Prior to this study, there were limited cutoffs and guidance as to what Hemoglobin A1c levels and what type of insulin regimens were best for managing patients with Type 1 Diabetes. The DCCT randomized 1441 patients with Type 1 Diabetes to “intensive” versus “conventional” glucose control, and measured both the rate of retinopathy development (cohort 1) and retinopathy progression (cohort 2).
The DCCT (and the similar themed UKPDS for Type 2 Diabetes) illustrated across large sample sizes and randomized controlled trials the importance of tight glycemic control. Together, these two studies created a target goal for Hgb A1c < 7.0% for patients to avoid long-term ophthalmic complications from diabetes.
This UKPDS sought to answer a variety of questions related to the natural history and impact of hyperglycemia control for patients with Type II Diabetes. Such questions included what risk factors dictate the incidence and progression of diabetic retinopathy, in addition to what impact intensive glycemic control would yield on incidence and progression.
Overall, the UKPDS is a landmark study because it highlighted the important risk factors of high blood pressure and hyperglycemia in promoting the onset or progression of retinopathy in patients with Type II (non-insulin-dependent) diabetes mellitus. Furthermore, along with the DCCT (which studied Type I Diabetics), these studies helped to identify a new target for blood glucose control in Diabetic patients.
Trick or treat? While eyeball injections and lasers give off haunted house vibes, patients may be in for a treat! The DRCR I evaluated the safety and efficacy of intravitreal ranibizumab with prompt or deferred laser and intravitreal triamcinolone with laser as compared to laser alone for the treatment of diabetic macular edema over 1 year.
DRCR I demonstrated that treating patients with intravitreal ranibizumab + prompt or deferred laser is a safe and efficacious option to improve visual acuity and decrease central subfield thickness in patients with diabetic macular edema. This study introduced anti-VEGF agents as a leading option for the treatment of diabetic macular edema.
Can ranibizumab pull its weight? How does the monoclonal antibody compare to PRP?
In the 2015 DRCR S study, patients with proliferative diabetic retinopathy were randomized to treatment with PRP (n = 191 eyes) and ranibizumab (n = 203 eyes) to determine if anti-VEGF therapy was a reasonable alternative to PRP.
Overall, the DRCR S study is a landmark study because it showed that ranibizumab was theoretically non-inferior to PRP for the treatment of PDR. In fact, the study showed that it might have superior visual outcomes (visual acuity and visual field measurements at 2 years). It is important to note that a key concern for long-term anti-VEGF therapy instead of PRP is that it requires high patient compliance and repeated interventions. As such, while the clinical study showed non-inferiority, clinicians must be wary about how these factors would impact the care of their patients and cost of care.
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