Tear production and corneal sensitivity in diabetes

doi:10.1016/j.jdiacomp.2006.05.008

Journal of Diabetes and its Complications

Volume 21, Issue 6, November–December 2007, Pages 371-373

https://doi.org/10.1016/j.jdiacomp.2006.05.008 Get rights and content

Aim

Diabetic patients are at significant risk of developing corneal lesions such as superficial punctate keratitis, recurrent corneal erosions, persistent epithelial defects, and microbial keratitis. The aim of this study was to investigate whether diabetes mellitus is correlated with both reduced corneal sensation and reduced tear production.

Methods

In 25 type II diabetic patients with a history of retinopathy only and in 25 nondiabetic control subjects (age and sex matched), we performed noncontact corneal aesthesiometry and assessed basal tear production using Schirmer's test with topical anesthesia. The noncontact corneal aesthesiometer (NCCA) is a new noninvasive device for quantifying threshold corneal sensitivity.

Results

The diabetic patients demonstrated a significantly reduced Schirmer's test result (P<.001) and significantly reduced corneal sensitivity (P<.01).

Conclusion

Our study supports previous reports of reduced basal tear production, lending more support to the theory of a peripheral neuropathy affecting lacrimal gland function in diabetes. We also confirmed reduced threshold corneal sensitivity in diabetic patients using the NCCA.

Introduction

Diabetes mellitus is a systemic disease characterized by chronic hyperglycemia. Ocular complications such as retinopathy, cataract, and glaucoma are well documented. Diabetic patients are also at significant risk of developing corneal lesions such as superficial punctate keratitis, recurrent corneal erosions, and persistent epithelial defects (Inoue et al., 2001, Rehany et al., 2000). Susceptibility to local and systemic infections is also increased in patients with diabetes and is manifest with an increased incidence of microbial keratitis. More recently, interest has therefore been directed toward corneal changes in this group of patients.

Studies have shown changes within every layer of the cornea, including decreased number of epithelial cells and basement membrane alterations, affecting epithelial adherence and epithelialization, and altered epithelial barrier function. Further changes have been described, including alteration of stromal hydration, wrinkling of Descemet's membrane, endothelial cell polymegethism, decreased pleomorphism, and differences in cell area (Sanchez-Thorin, 1998). The ocular surface disease in diabetes has been reported to be characterized by reduced corneal sensitivity and by alteration in tear quantity and quality (Inoue et al., 2001). We therefore sought to compare tear production and corneal sensitivity between diabetic patients and nondiabetic subjects.

Section snippets

Materials and methods

Patients were recruited from the Princess Alexandra Eye Pavilion ophthalmology outpatient diabetic and cataract clinics. Diabetic patients meeting the following inclusion criteria were selected: with type II diabetes mellitus; with a history of retinopathy only; with no significant maculopathy with 6/24 vision or better; and with English spoken as a first language. Exclusion criteria included involvement in other research studies, history of corneal disease, glaucoma, contact lens wear, current

Results

The data are summarized in Table 1. Twenty-five diabetic patients and 25 control subjects were recruited into the study. Patients were sex matched, and statistical analysis revealed no significant age difference between the diabetic and control groups. The mean age of the diabetic patients was 61.84 years (S.D., 9.24 years), whereas that of the control subjects was 62.28 years (S.D., 10.8 years). Seventy-six percent of the patients in both groups were male.

The mean Schirmer's test result of the

Discussion

Diabetic patients are at significant risk of developing corneal lesions (Inoue et al., 2001). Diabetes mellitus affects every structure of the cornea. Abnormal glucose metabolism in the corneal epithelium and basement membrane has been shown to lead to enlargement of the epithelial basement membrane, deterioration of basal cell adhesion, and breakdown of barrier function (Rehany et al., 2000). Rehany et al. (2000) examined the ultrastructural changes found in diabetic corneas. In addition to

Acknowledgments

We thank Dr. Sudi Patel for giving permission to use the NCCA. We also thank Dr. Peter Aspinall and Dr Adrian Hill for their help with statistical analysis of the data.

References (9)

M. Dogru et al.
Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus
Ophthalmology
(2001, Mar)
P.J. Murphy et al.
Reliability of the non-contact corneal aesthesiometer & its comparison with the Cochet–Bonnet aesthesiometer
Ophthalmic and Physiological Optics
(1998, Nov)
K. Inoue et al.
Ocular and systemic factors relevant to diabetic keratoepitheliopathy
Cornea
(2001, Nov)
A. Loy et al.
Diabetes and the myo-inositol paradox
Diabetes
(1990, Oct)

There are more references available in the full text version of this article.

Cited by (111)

Effects of hypoxia in the diabetic corneal stroma microenvironment
2024, Experimental Eye Research
Corneal dysfunctions associated with Diabetes Mellitus (DM), termed diabetic keratopathy (DK), can cause impaired vision and/or blindness. Hypoxia affects both Type 1 (T1DM) and Type 2 (T2DM) surprisingly, the role of hypoxia in DK is unexplored. The aim of this study was to examine the impact of hypoxia in vitro on primary human corneal stromal cells derived from Healthy (HCFs), and diabetic (T1DMs and T2DMs) subjects, by exposing them to normoxic (21% O₂) or hypoxic (2% O₂) conditions through 2D and 3D in vitro models. Our data revealed that hypoxia affected T2DMs by slowing their wound healing capacity, leading to significant alterations in oxidative stress-related markers, mitochondrial health, cellular homeostasis, and endoplasmic reticulum health (ER) along with fibrotic development. In T1DMs, hypoxia significantly modulated markers related to membrane permeabilization, oxidative stress via apoptotic marker (BAX), and protein degradation. Hypoxic environment induced oxidative stress (NOQ1 mediated reduction of superoxide in T1DMs and Nrf2 mediated oxidative stress in T2DMs), modulation in mitochondrial health (Heat shock protein 27 (HSP27), and dysregulation of cellular homeostasis (HSP90) in both T1DMs and T2DMs. This data underscores the significant impact of hypoxia on the diabetic cornea. Further studies are warranted to delineate the complex interactions.
TFOS Lifestyle: Impact of nutrition on the ocular surface: TFOS Lifestyle Workshop: Nutrition report
2023, Ocular Surface
Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.
The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas
2022, Progress in Retinal and Eye Research
Citation Excerpt :
Likewise, Misra et al. found that higher severity of neuropathy in T1DM patients was correlated with significantly poorer tear film quality - namely, reduced stability, thickness, and quantity (Misra et al., 2014). Tear secretions in diabetic patients were usually significantly lower than in the normal population (Cousen et al., 2007), and the osmolality of the tear film was significantly increased (Beckman, 2014). The lacrimal gland has also been found to be susceptible to AGE-mediated damage and disordered autonomic control secondary to DM (Nakata et al., 2014; Zhang et al., 2016).
Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, with several underlying pathophysiological mechanisms, some of which are still uncertain. The cornea is an avascular tissue and sensitive to hyperglycemia, resulting in several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity, and tear film changes. The manifestation of DPN in the cornea is referred to as diabetic neurotrophic keratopathy (DNK). Recent studies have revealed that disturbed epithelial-neural-immune cell interactions are a major cause of DNK. The epithelium is supplied by a dense network of sensory nerve endings and dendritic cell processes, and it secretes growth/neurotrophic factors and cytokines to nourish these neighboring cells. In turn, sensory nerve endings release neuropeptides to suppress inflammation and promote epithelial wound healing, while resident immune cells provide neurotrophic and growth factors to support neuronal and epithelial cells, respectively. Diabetes greatly perturbs these interdependencies, resulting in suppressed epithelial proliferation, sensory neuropathy, and a decreased density of dendritic cells. Clinically, this results in a markedly delayed wound healing and impaired sensory nerve regeneration in response to insult and injury. Current treatments for DPN and DNK largely focus on managing the severe complications of the disease. Cell-based therapies hold promise for providing more effective treatment for diabetic keratopathy and corneal ulcers.
Insulin facilitates corneal wound healing in the diabetic environment through the RTK-PI3K/Akt/mTOR axis in vitro
2022, Molecular and Cellular Endocrinology
Diabetic patients can develop degenerative corneal changes, termed diabetic keratopathy, during the course of their disease. Topical insulin has been shown to reduce corneal wound area and restore sensitivity in diabetic rats, and both the insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) stimulate cell signaling of the PI3K-Akt pathway. The purpose of this study was to assess a mechanism by which improved wound healing occurs by characterizing expression within the PI3K-Akt pathway in corneal epithelial and stromal cells. In vitro scratch tests were used to evaluate wound healing outcomes under variable glucose conditions in the presence or absence of insulin. Protein expression of intracellular kinases in the PI3K pathway, stromal cell markers, and GLUT-1 was evaluated by immunoblotting.TGF-β1 expression was evaluated by ELISA. Insulin promoted in vitro wound healing in all cell types. In human corneal epithelial cells, insulin did not induce PI3K-Akt signaling; however, in all other cell types evaluated, insulin increased expression of PI3K-Akt signaling proteins compared to vehicle control. Fibroblasts variably expressed α-SMA under all treatment conditions, with significant increases in α-SMA and TGF-β1 occurring in a dose-dependent manner with glucose concentration. These results indicate that insulin can promote corneal cellular migration and proliferation by inducing Akt signaling. Exogenous insulin therapy may serve as a novel target of therapeutic intervention for diabetic keratopathy.
Systemic diseases and the cornea
2021, Experimental Eye Research
There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.
Diabetic corneal neuropathy and its relation to the severity of retinopathy in patients with type 2 diabetes mellitus: an in vivo confocal microscopy study
2024, International Ophthalmology

View all citing articles on Scopus

View full text

Original articleTear production and corneal sensitivity in diabetes

Aim

Methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgments

Ophthalmology

Ophthalmic and Physiological Optics

Ocular and systemic factors relevant to diabetic keratoepitheliopathy

Cornea

Diabetes and the myo-inositol paradox

Diabetes

Original article
Tear production and corneal sensitivity in diabetes