Prevalence of type 1 (T1DM) and type 2 (T2DM) diabetes have reached a state of epidemic highs with the incidence of diabetes increasing at an alarming pace.1–4 Worldwide, diabetes is estimated to affect 463 million people and future estimates suggest an increase to 578 million by the year 2030.1 Diabetes can cause serious sight threatening complications like diabetic retinopathy (DR) and diabetic macular edema (DME).5 Within the first 10 years of living with diabetes, retinopathy can be diagnosed in nearly all T1DM patients and in over 60% of those with T2DM.6 A meta-analysis of pooled incidence of diabetic eye disease among individuals with diabetes in Europe shows a 25.7% and 3.7% prevalence of DR and DME, respectively. A meta-regression shows a higher prevalence of DR in persons with T1DM compared to persons with T2DM (54.4% vs. 25%). In Europe, it is estimated that persons with diabetes affected by any diabetic eye disease will increase from 6.4 to 8.6 million by 2050, of whom 30% will require close monitoring and/or treatment.7
DME is a severe ocular complication of diabetes which affects best-corrected visual acuity (BCVA) and can lead to blindness if left untreated.8 The pathophysiology of DME is complex, involving oxidative stress, mitochondrial dysfunction, elevated concentrations of vascular endothelial growth factor (VEGF) and a breakdown of the inner blood-retinal barrier, resulting in the extracellular fluid accumulation in the macula and decreased vision.9 DME is characterized by cystic thickening of the retina and/or lipid deposition The long-term prognosis for DME is poor, and treatment is recommended immediately, once a patient is diagnosed.10 However, patients are typically not started on treatment before visual impairment is present.11 Evidence from randomized, controlled trials indicates that early intervention in DME is imperative for optimal improvement in vision outcomes.12–14 Improvement in the pathological underpinnings of the disease at earlier stages prior to significant visual impairment is of interest.
Until recently, the standard ophthalmic treatment for patients with visual impairment due to DME was non-pharmacological interventions including laser photocoagulation, which provides vision stabilization. The use of intravitreal treatments (IVT) of agents that inhibit vascular endothelial growth hormone (anti-VEGF) has replaced laser photocoagulation as first-line therapy based on several multi-center clinical trial data demonstrating superiority over laser treatment.15 However, treatments with anti-VEGF agents are invasive, requiring multiple repeated injections into the eye, are expensive, and are only partially effective in some patients. Intravitreal injections also have potential severe sight-threatening complications such as endophthalmitis or retinal detachment.15 The development, testing and application of novel treatment strategies is critical for reducing the impending clinical and socioeconomic burden of diabetic eye disease state and will provide quantifiable benefits to a patient population that demonstrates a significant need for clinical aid.
Photobiomodulation (PBM) involves the use of visible light to near infrared light (NIR) (500–1000 nm) produced by a laser or a non-coherent light source applied to the surface of the body to produce beneficial effects in a wide range of disease states.16–19 The mechanism of PBM at the cellular level has been ascribed to the activation of mitochondrial respiratory chain components resulting in stabilization of metabolic function and initiation of signaling cascades, which promote cellular proliferation and cytoprotection.20–23 A growing body of evidence suggests that Cytochrome c Oxidase (CcO) is a key photoacceptor of light in the far red to NIR spectral range and the primary mode for mechanistic underpinnings.20–23 The utility of PBM in ocular indications has been explored both preclinically and clinically and shows promising results in both clinical, anatomical and quality of life (QoL) endpoints.24–26
Several independent studies show potential benefit of PBM in patients with DME.27–29 Oxidative stress and local inflammatory changes are believed to contribute to progression of DME. PBM shows inhibitory effects on both oxidative stress and inflammatory processes and therefore may be of benefit in DME.27 This series of case studies aimed to investigate through a post-hoc analysis the potential impact of multiwavelength PBM on clinical, anatomical, and QoL parameters in early-stage DME patients with good vision.
