Hormones and Dry Eye Syndrome

An Update on What We Do and Don't Know

Eduardo Melani Roch; Flavio Mantelli, Luis Fernando Nominato; Stefano Bonini


Curr Opin Ophthalmol. 2013;24(4):348-355. 

In This Article

Diabetic Dry Eye

Dry eye syndrome is common in diabetic patients, which makes diabetes mellitus one of the most frequent among the known DES causes.[46–49]

Diabetes mellitus is caused by insulin insufficiency or peripheral tissue resistance to this hormone.[50] Since insulin is a ubiquitous hormone responsible for many events at the cellular level and diabetes mellitus causes complications in various organs and systems that interact with the LG and ocular surface, it is difficult to point to a single underlying mechanism responsible for diabetic DES. Possible mechanisms include decline in insulin hormone expression, LG and ocular surface neuropathy, vascular impairment, and systemic hyperosmotic disturbance (Fig. 3).[51–54]

Figure 3.

Mechanisms of disease related to DES in diabetes mellitus.

In diabetic patients, the frequency of DES varies from 15.4 to 82%. Independently whether they are type I or type II, adult or children, the most frequent reported signs and symptoms are lower TFBUT and tear secretion measured by Schirmer test and conjunctival metaplasia.[55–57] DES may be exacerbated by chronic hyperglycemia, diabetes mellitus duration, and local triggers such as ocular surface trauma or intraocular surgery. This disease seems to be more severe in patients with advanced stages of diabetic retinopathy.[53,54] However, it is not clear whether the severity is just a consequence of the uncontrolled metabolic status and/or side effects of systemic drugs. Other possibilities include multiple surgical manipulation and other interventions to restore or preserve some vision.

Among the aforementioned studies, there are variations among the type and number of parameters used to identify DES in diabetes mellitus. Therefore, better tests are still needed to detect alone diabetic DES, as well as the relationship between ocular and clinical systemic parameters. The reason for this uncertainty is that the patients included in the various studies are heterogeneous in terms of age, disease duration, and clinical control.

Adequate insulin levels are necessary for LG, and ocular surface maintenance and function since in culture this hormone is crucial for acinar LG cell and cornea epithelial cell proliferation.[58,59] Moreover, tear insulin levels are reflective of its systemic levels. Its systemic deprivation in diabetic animal models induces LG size reduction and several histological and molecular changes that are partially reversed by systemic insulin application.[60–62] A clinical study showed that hypoinsulinemia is an independent risk factor for polyneuropathy.[63] These findings may suggest that insulin deprivation or resistance may cause nerve-conduction abnormalities and reduced secretion in association with corneal pain.

Topical insulin application was proposed to treat corneal epithelial defects, not just those related to diabetes mellitus. Its positive effect was observed in rabbits and rats.[46,64–66]

The systemic osmotic imbalance of diabetes mellitus may translate into tear film instability and DES symptoms as recently observed in a clinical study, not specifically addressing diabetes mellitus.[67] In diabetic patients, tear film instability and higher osmolarity may be explained by higher glucose and protein levels in tears and changes in the protein profile.[68] These changes may be influenced by the time length and glucose level control of the diabetes mellitus condition, and also offer a rationale for a diagnostic tool to monitor plasma glycemic levels based on tear glucose levels.[68,69] A recent intent to apply the tear glycemic analysis was unsuccessful.[68]

Diabetic peripheral neuropathic pain is present in 5–42% of individuals with diabetes mellitus. There is a possibility that at some point in the course of this disease (diabetes mellitus) the manifestation of neuropathy in the ocular surface contributes to signs and symptoms of DES.[63,70]

Clinical and experimental evidence indicates that diabetes mellitus causes of DES are multifactorial. The high frequency of diabetes mellitus in the population and DES in diabetic patients indicates that it is relevant to test for diabetes mellitus in DES patients in case of any clinical suspicion. This entails a combined effort among clinicians to periodically determine if these patients' metabolic parameters and ocular health are being controlled. Although the clinical presentation of DES in diabetes mellitus is very heterogeneous and can be already present at an early stage of diabetes mellitus, clinical studies reveal that poorly controlled diabetes mellitus increases the frequency and DES severity in the long term.[53,54]