Diabetic keratopathy: Insights and challenges

Abstract

Ocular complications from diabetes mellitus are common. Diabetic keratopathy, the most frequent clinical condition affecting the human cornea, is a potentially sight-threatening condition caused mostly by epithelial disturbances that are of clinical and research attention because of their severity. Diabetic keratopathy exhibits several clinical manifestations, including persistent corneal epithelial erosion, superficial punctate keratopathy, delayed epithelial regeneration, and decreased corneal sensitivity, that may lead to compromised visual acuity or permanent vision loss. The limited amount of clinical studies makes it difficult to fully understand the pathobiology of diabetic keratopathy. Effective therapeutic approaches are elusive. We summarize the clinical manifestations of diabetic keratopathy and discuss available treatments and up-to-date research studies in an attempt to provide a thorough overview of the disorder.

Introduction

Diabetes mellitus (DM) is one of the most common deadly metabolic disease worldwide. The incidence rate of DM has risen over the years and is expected to double by the year 2030.¹⁴⁷ The steep increase of the diabetic population is thought to be mainly due to the changes in lifestyle that results in elevated calorie intake and obesity. Increase in the diabetic population has led to significant financial and clinical burdens and spurs demands for effective clinical treatments.¹⁴⁷

DM develops when the pancreas fails to synthesize enough insulin or the body becomes resistant to insulin, or both, leading to high levels of blood glucose. The three main types are type 1 diabetes mellitus (type 1DM), type 2DM, and gestational DM (characterized in Table 1). DM is correlated with a number of complications accounting for increased disability, morbidity, and mortality.²⁰⁹ Acute metabolic complications associated with a high mortality rate and abnormally high blood glucose concentrations (hyperglycemia) include ketoacidosis. On the other hand, extremely low blood glucose concentrations (hypoglycemia) can lead to coma. Chronic uncontrolled DM may lead to devastating consequences in the form of long-term vascular complications.⁹⁷ The hyperglycemic condition during DM has various implications on various tissues, and the most common complications witnessed during such conditions are retinopathy, nephropathy, neuropathy, and keratopathy.^11,169,171

DM is known to cause structural and functional alterations to the human cornea. The cornea is a clear, highly organized, external layer of the eye responsible for letting in and focusing light. It has three distinct layers separated by acellular membranes. The outermost layer is the epithelium (Fig. 1), responsible for protecting the eye against various foreign particles and providing protection to the other internal structures of the eye. Below the epithelium is a tough condensed layer known as the Bowman layer (Fig. 1). The Bowman layer is acellular and composed of collagen fibers difficult to penetrate, protecting the cornea from any deeper injury. The next and the thickest layer of the cornea is the stroma (Fig. 1), which provides the cornea its structure and elastic form and is also responsible for the corneal transparency. The fourth layer lying below the stroma is the Descemet membrane (Fig. 1), a thin elastic layer of the cornea that protects the cornea against various infections. The fifth and the most posterior layer of the cornea is the neuroepithelial layer, commonly referred to as the endothelium (Fig. 1), responsible for keeping the cornea clear by controlling the hydration of the cornea. The endothelium is a single layer of hexagonal cells approximately 5 micrometers in thickness.³⁷ All the different layers of the cornea have their own unique functions and together support the normal functioning of the eye.