Macular edema (ME) is an important issue in retinal pathology as it damages macula, eventually affecting the central visual acuity (VA). This has significant impact on quality of life of the patients [1, 2]. ME occurs due to fluid accumulation in the retinal layers surrounding the fovea, leading to an increase in retinal thickness (edema). The vision loss associated with ME results due to the alteration of the functional cell relationship in the retina and activation of the inflammatory responses [2]. It can either be intracellular or extracellular. In intracellular ME, the blood-retinal barrier (BRB) remains intact with swollen retinal cells causing excessive accumulation of neurotransmitters. In extracellular ME, BRB is damaged and the tissue volume increases due to an increase in the retinal extracellular space [2].
ME occurs in various ocular complications, including vascular retinopathies, diabetic retinopathy, macular degeneration, uveitis, trauma, and intraocular surgery [3]. Diabetic retinopathy (DR) and ME are common diabetes-related microvascular complications that cause deterioration of central VA and acquired blindness, in mostly working-age adults worldwide [4-6]. In diabetic patients, high blood glucose level impairs the small capillaries supplying blood to the retina and this causes leakage of blood and its solutes from capillaries in the extracellular space beneath the macula causing fluid accumulation, and this is referred to as diabetic macular edema (DME) [7]. Moreover, in diabetic patients, cataract surgery can lead to higher risk of complications with poor visual outcome compared to non-diabetics [3, 8, 9]. This occurs due to some histological changes in the retina that activates the inflammatory mediators and triggers endothelial cell death, causing damage of BRB, leakage, and accumulation of fluid and serum in the outer plexiform layer leading to DME [3].
Pathogenesis of DME is complex and multifactorial, including angiogenic, inflammatory and hypoxic processes, and vitreomacular traction [5, 10]. Inflammation is the main cause since the disruption of the BRB releases wide range of inflammatory mediators, such as vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1, and leukostasis [7, 11, 12].
Traditionally, DME was treated with focal/grid laser photocoagulation and by controlling diabetes medically in past decades [11]. However, in recent years, the therapeutic landscape of DME had a remarkable change [13] with the emergence of new intravitreal pharmacological therapies, such as anti-VEGF agents and corticosteroids. These therapies are known to prevent visual loss and improve anatomic outcomes efficiently [6]. Three anti-VEGFs, aflibercept (Eylea®), ranibizumab (Lucentis®), and bevacizumab (Avastin®) are the widely used intravitreal VEGF inhibitors; among which aflibercept and ranibizumab received approval from the United States Food and Drug Administration (USFDA) and European Marketing Authorization (EMA) for the treatment of DME [4, 6, 13]. A significant proportion of eyes had failed to achieve reduction of central retinal thickness (CRT) and <10-letter improvement in best corrected VA (BCVA) after one or two years of treatment [14, 15]. The partial responders or non-responders then require additional or alternative treatments [16].
Corticosteroids are considered to be effective in treating eyes with DME and vision loss [16]. Intravitreal corticosteroids exert influence on multiple signal transduction pathways and prevent the action of VEGFs, prostaglandins, and pro-inflammatory cytokines and thus inhibit leukostasis [7, 17, 18]. Consequently, they decrease the damage of the BRB and retinal thickening [16]. Among different corticosteroids (e.g. dexamethasone, triamcinolone, and fluocinolone), dexamethasone seems to be the most effective to treat DME, both, from the functional and anatomical viewpoints [19, 20].
Dexamethasone intravitreal implant (Ozurdex®, Allergen, Inc, Irvine, CA, USA), a biodegradable device, is used to release dexamethasone slowly into the vitreal cavity. The chief advantage of this sustained release dexamethasone implant is that the anti-inflammatory action of dexamethasone remains for a period of about four to six months with the peak level of activity during the first two months [18, 21]. A study by Pacella et al (2016) reported a significant reduction of CRT after one (T1), three (T3) (p < 0.001) , and four months (T4) (p< 0.05) from implants, while at six months (T6), CMT values were not statistically different from baseline demonstrating that the greatest efficacy of dexamethasone is obtained within the first three months [22]. USFDA had approved the use of dexamethasone intravitreal implant, releasing dexamethasone at a rate of 0.7 mg, for the treatment of DME and noninfectious uveitis affecting the posterior segment of the eye [13, 23, 24].
Ozurdex is effective for phakic and pseudophakic eyes showing inadequate response to anti-VEGF therapy, patients with severe edema, as well as for those who have undergone vitrectomy. Additionally, DME patients with glaucoma can receive corticosteroid treatment; however, intraocular pressure (IOP) needs to be controlled by one or two medications [25]. In addition to retinal thickness assessment, optical coherence tomography (OCT) helps to evaluate potential biomarkers related to other retinal abnormalities, for eg. integrity of outer retinal bands (the ellipsoid zone and external limiting membrane), disorganization of the retinal inner layers (DRIL), presence of hyper-reflective spots and subretinal fluid, that act as predictors of better visual outcome in DME patients administered with dexamethasone implant [26]. Even though dexamethasone intravitreal implant is considered as an effective treatment for DME, there is a scarcity of real-world data regarding the efficacy of this implant in DME patients. The objective of this study was to evaluate efficacy and safety of intravitreal dexamethasone implant (Ozurdex) in management of ME with varied etiology, particularly DME, in real-world clinical practice.