Ocular Complications of Diabetes and Therapeutic Approaches

Abstract

Diabetes mellitus (DM) is a metabolic disease defined by elevated blood glucose (BG). DM is a global epidemic and the prevalence is anticipated to continue to increase. The ocular complications of DM negatively impact the quality of life and carry an extremely high economic burden. While systemic control of BG can slow the ocular complications they cannot stop them, especially if clinical symptoms are already present. With the advances in biodegradable polymers, implantable ocular devices can slowly release medication to stop, and in some cases reverse, diabetic complications in the eye. In this review we discuss the ocular complications associated with DM, the treatments available with a focus on localized treatments, and what promising treatments are on the horizon.

Diabetic complications in the cornea

“…Clinically observed corneal diabetic alterations include increased corneal thickness, epithelial defects, epithelial fragility and recurrent erosions, ulcers, edema, superficial punctate keratitis, delayed and incomplete wound repair, endothelial changes, and neuropathy exemplified by reduced corneal sensitivity (Herse, 1988; Cavallerano, 1992; Saini and Khandalavla, 1995; Sánchez-Thorin, 1998; Malik et al, 2003; Negi and Vernon, 2003; Saito et al, 2003; Gekka et al, 2004; Wylegała et al, 2006; Su et al, 2008; Módis et al, 2010; Bikbova et al, 2012; Vieira-Potter et al, 2016; Shih et al, 2017). Diabetic corneal neuropathy, corneal autofluorescence [possibly due to the accumulation of advanced glycation end products (AGEs)], and epithelial fragility are all augmented in patients with DR (Chang et al, 1995; Janiec et al, 1995; Saini and Mittal, 1996a; Van Schaik et al, 1999; Bikbova et al, 2012; DeMill et al, 2016; Calvo-Maroto et al, 2016).…”

“…Signs of diabetic keratopathy include epithelial fragility, defects and recurrent erosions, non-healing ulcers, corneal edema due to altered epithelial barrier function, superficial punctate keratitis, abnormally slow and often incomplete wound healing, lower cell density especially in the basal layer, and increased susceptibility to injury (Ben Osman et al, 1995; Saini and Khandalavla, 1995; Ohashi, 1997; Sánchez-Thorin, 1997; Inoue et al, 2001; Cavallerano, 2002; Gekka et al, 2004; Quadrado et al, 2006; Wylegała et al, 2006; Szalai et al, 2016; Vieira-Potter et al, 2016). The data on the prevalence of diabetic keratopathy depending on the type of diabetes remain inconsistent and need to be revisited (Schultz et al, 1981; Didenko et al, 1999).…”

“…At the same time, other parts of the eye (e.g., iris, lens, optic nerve) also suffer from diabetic complications, although they are encountered in less than 30% of diabetic patients (Ducrey, 1996; Nakamura et al, 2005; Blum et al, 2007; Helbig, 2007; Murtha and Cavallerano, 2007). Corneal problems seem to be more frequent in diabetics affecting up to 70% of examined diabetic patients (Schultz et al, 1981; Didenko et al, 1999; Abdelkader et al, 2011; Vieira-Potter et al, 2016). However, these changes are rarely diagnosed (Herse, 1988; Wylegała et al, 2006).…”

“…Earlier reviews on diabetic corneal disease focused primarily on clinical problems (Sánchez-Thorin, 1998; Cisarik-Fredenburg, 2001; Kaji, 2005). More recently, appropriate attention was given to mechanisms of disease and available therapies (Bikbova et al, 2012; Calvo-Maroto et al, 2014; Misra et al, 2016; Vieira-Potter et al, 2016; Shih et al, 2017). This review provides recent updates in this rapidly developing field and analyzes in more detail the latest therapeutic candidates.…”

Corneal thickness and endothelial cell density in diabetic and non- diabetic patients: a hospital based comparative study

“…Although the most common, DR is not the only ocular complication of diabetes; others include corneal dysfunction, cataract, glaucoma, neuropathy, ischemic optic neuropathy, and diabetic macular edema. 5,6 Corneal diseases being one of the complications of DM, are difficult to manage like diabetic retinopathy. Functional abnormalities may induce increased corneal autofluorescence as measured by fluorophotometry as well as increased corneal endothelial permeability, although some researchers have reported that corneal endothelial permeability is not increased.…”