{"id":99652,"date":"2024-10-14T14:07:45","date_gmt":"2024-10-14T13:07:45","guid":{"rendered":"https:\/\/touchendocrinology.com\/?p=99652"},"modified":"2024-11-01T16:45:36","modified_gmt":"2024-11-01T16:45:36","slug":"dry-eye-in-diabetes-the-indian-diabetic-and-endocrine-eye-diseases-indeed-review","status":"publish","type":"post","link":"https:\/\/touchendocrinology.com\/diabetes\/journal-articles\/dry-eye-in-diabetes-the-indian-diabetic-and-endocrine-eye-diseases-indeed-review\/","title":{"rendered":"Dry Eye in Diabetes: The Indian Diabetic and Endocrine Eye Diseases (INDEED) Review"},"content":{"rendered":"

Dry eye disease (DED) is known as dry eye syndrome (DES) or keratoconjunctivitis sicca. According to the Tear Film and Ocular Surface Society\u2019s Dry Eye Workshop II (TFOS DEWS II), it constitutes a multifactorial disease of the ocular surface, characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms.1,2<\/sup><\/span>\u00a0It may cause ocular discomfort and\/or visual symptoms and inflammatory disease of the ocular surface. DED, similar to other ocular conditions such as diabetic retinopathy (DR), papillopathy, cataract and glaucoma, is associated with high morbidity. It negatively affects the quality of life, results in difficulties in performing daily activities and also reduces productivity at work.3\u20135<\/sup><\/span><\/p>\n

DED is an important clinical condition, found in a large proportion of people with diabetes; it is reported in 18\u201354% of patients with\u00a0d<\/span>iabetes across India.6<\/sup><\/span>\u00a0India is home to 101 million patients with\u00a0d<\/span>iabetes, nearly 67% of whom suffer from poor glycaemic control.7,8<\/sup><\/span>\u00a0DED is an inadequately addressed condition in the diabetes management process, and the awareness among physicians regarding it is low. DED may impact self-care in patients with diabetes \u2013 it may interfere with self-confidence, physical activity and self-administration of injectable glucose-lowering drugs.9<\/sup><\/span>\u00a0Therefore, it was found imperative to address DED in patients with diabetes.5<\/sup><\/span><\/p>\n

This review aims to obtain insights into the correlation between\u00a0dry eye and d<\/span>iabetes, with a focus on data published in the Indian population. The aim was to address major aspects commonly associated with DED and diabetes and make specific suggestions for the management of DED in this population so that this review could be an invaluable resource for doctors managing patients with both conditions. A comprehensive literature review was performed using\u00a0MEDLINE<\/span>\u00a0and Google Scholar, along with an internet\u2010based search of publicly available information and peer\u2010reviewed publications that may not have been indexed in these databases. The recommendations from several important societies for patients with DED have also been reviewed.<\/p>\n

Prevalence,\u00a0risk factors and pathogenesis<\/span>\u00a0of dry eye disease in\u00a0diabet<\/span>es<\/h1>\n

The worldwide prevalence studies have reported a range of 15.0%\u201354.3% DED in people with diabetes.10,11 <\/sup><\/span>Symptomatic or asymptomatic DED is present in at least half of the people with diabetes mellitus (DM) globally, which is nearly fivefold higher than the number of patients with DED and no DM.12<\/sup><\/span>\u00a0The proportion of patients with symptomatic DED is also twice as high in those with diabetes.13<\/sup><\/span>\u00a0Several studies from India have reported a significantly higher prevalence of DED in people with diabetes than those without.14\u201316<\/sup><\/span>\u00a0The eyes are exposed organs and therefore influenced by climatic and environmental factors.17<\/sup><\/span>\u00a0Previous studies have found that climatic and environmental changes have differential adverse impacts on dry eyes and likely occur in tropical countries where sunlight and wind exposure are immense.18<\/sup><\/span><\/p>\n

The prevalence of DED in patients with\u00a0type 2 d<\/span>iabetes (T2D) has been reported to be between 15 and 33% in people older than 65 years, and 20% in those aged 43\u201386 years.19<\/sup><\/span>\u00a0Among children and adolescents with type 1 diabetes, the 3-year incidence rate was 22.5%.20<\/sup><\/span>\u00a0In a study from India, the age-adjusted prevalence of DED in patients with T2D was 18.4% and 23.3% in males and females, respectively.21<\/sup><\/span><\/p>\n

Population-based studies have shown that poor glycaemic control has also been associated with severe DED symptoms.22,23<\/sup><\/span>\u00a0<\/sup>A significant correlation between the severity of DED and the duration of diabetes has also been reported.24<\/sup><\/span>\u00a0The prevalence of mild DED was\u00a0<\/span>~12% in those with 5\u201310 years, 37\u201339% in 11\u201320 years and\u00a0<\/span>~43% in >20 years of T2D diagnosis.24<\/sup><\/span> However, it has been argued that the symptoms of DED are less severe in patients with prolonged disease due to reduced corneal sensitivity associated with diabetic peripheral corneal neuropathy.25 <\/sup><\/span>The presence of retinopathy or macular oedema doubles the odds of DED.26,27<\/sup><\/span>\u00a0Ocular surgeries for cataract and retinopathy are also associated with DED.28<\/sup><\/span><\/p>\n

A meta-analysis of four studies including the data from more than two million persons confirmed a significant association between DM and the risk of DED.29<\/sup><\/span>\u00a0Risk factors for DED in the general population also apply to people with diabetes and may increase the cumulative risk (Table 1<\/em><\/span>).27,30<\/sup><\/span><\/em><\/p>\n

\n

Table 1: <\/span>Risk factors for dry eye disease in\u00a0d<\/span>iabetes27<\/sup><\/span><\/p>\n

\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Intrinsic factors<\/p>\n<\/td>\n

\n

Extrinsic factors<\/p>\n<\/td>\n<\/tr>\n<\/thead>\n

\n

Female gender (including post-menopausal status)<\/p>\n<\/td>\n

\n

Environmental factors, such as poor humidity, high temperatures, pollution, and excessive screen time for reading<\/p>\n<\/td>\n<\/tr>\n

\n

Advancing age<\/p>\n<\/td>\n

\n

Psychological factors, such as depression and stress<\/p>\n<\/td>\n<\/tr>\n

\n

Duration of diabetes<\/p>\n<\/td>\n<\/tr>\n

\n

Poor glycaemic control<\/p>\n<\/td>\n<\/tr>\n

\n

Diabetic retinopathy and interventions to treat it<\/p>\n<\/td>\n<\/tr>\n

\n

Pre-existing comorbidities, such as chronic viral infections and Parkinson’s disease<\/p>\n<\/td>\n<\/tr>\n

\n

Concomitant use of anticholinergic medications, beta-blockers, oestrogen, interferons and chemotherapy<\/p>\n<\/td>\n<\/tr>\n

\n

Ocular surgeries<\/p>\n<\/td>\n<\/tr>\n

\n

Blepharitis<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n

<\/div>\n<\/div>\n

Insulin deficiency and consequent hyperglycaemia lead to histological abnormalities in the various ocular components that increase the risk of DED.30,31<\/sup><\/span>\u00a0Insulin resistance or deficiency and chronic hyperglycaemia may reduce the meibomian gland epithelial cells and goblet cells, leading to a deficient tear film.6<\/sup><\/span>\u00a0Moreover,\u00a0<\/span>T2D leads to structural anomalies in the corneal nerve fibres, which may also result in decreased sensitivity.6<\/sup><\/span>\u00a0Recent evidence from a cross-sectional study has demonstrated impaired\u00a0m<\/span>eibomian gland and tear function in patients with T2D, which deteriorated with moderate or long diabetic duration and a high glycated haemoglobin (HbA1c) level. The values of meibomian gland parameters and the corneal fluorescein staining score were significantly lower in patients with T2D without DED than those with T2D with DED. Thus, asymptomatic\u00a0Meibomian gland dysfunction<\/span>\u00a0(MGD) may occur before the ocular discomfort, and DED develops in patients with T2D<\/sup>\u00a0(Figure 1<\/span><\/span>).31,32<\/sup><\/span><\/p>\n

\n

Figure 1: <\/span>Pathogenesis of\u00a0dry eye disease<\/span>\u00a0in patients with d<\/span>iabetes32<\/sup><\/span><\/p>\n

\"\"<\/p>\n

Chronic hyperglycaemia leads to histological abnormalities in the lacrimal glands and corneal epithelium and interferes with the regulation of expression of certain mediators causing dysfunction of the lacrimal functional unit, resulting in dry eye disease.<\/em><\/p>\n

AGEs = advanced glycation end-products; ALS2CL =\u00a0ALS2 C-Terminal Like<\/span>; APC = antigen-presenting cells; Apo = apolipoprotein<\/span>;\u00a0ARHGEF19<\/span>\u00a0=\u00a0Rho Guanine Nucleotide Exchange Factor 19; CAMs = cell adhesion molecules;<\/span>\u00a0CD = cluster of differentiation;\u00a0IFN = interferon;\u00a0IL = interleukin<\/span>; KIAA1109 =\u00a0FSA (fragile site-associated) protein;<\/span>\u00a0LFU = lacrimal functional units; MMP = matrix metalloproteinase; NF = neuronal<\/span>\u00a0fibres; PLXNA1 = Plexin A1; POLG =\u00a0DNA polymerase subunit gamma<\/span>; SIRT = sirtuin; TH = T-helper cells; WIPI1 =\u00a0WD repeat domain, phosphoinositide interacting 1<\/span>; ZMIZ2 =\u00a0Zinc Finger MIZ-Type Containing 2<\/span>.<\/span><\/em><\/p>\n<\/div>\n

Clinical\u00a0m<\/span>anifestations of dry eye disease in\u00a0d<\/span>iabetes<\/h1>\n

Patients with DED often display signs and symptoms of ocular discomfort, such as burning sensation, photopsia, foreign body sensation, soreness, itchiness, redness and blurred vision.13<\/sup><\/span>\u00a0It may cause severe irritation to the ocular surface, predominantly the cornea, causing corneal complications.13<\/sup><\/span>\u00a0Studies have demonstrated a direct association between a higher grade of DED in those with DM compared with those without and more severe signs and symptoms in those with poor glycaemic control (high A1c) versus those with normoglycaemia.14<\/sup><\/span>\u00a0Thus, DM and DED increase the risk of corneal infection, scarring, perforation and irreparable tissue injury.32<\/sup><\/span><\/p>\n

In both Caucasians and Asians, the degree of DED severity scores was found to be higher, and corneal sensitivity poorer, in patients with\u00a0d<\/span>iabetes than those without.33<\/sup><\/span>\u00a0A recently published study from India also demonstrated that corneal nerve sensitivity was reduced more in patients with diabetes and moderate DED.6<\/sup><\/span>\u00a0Histological evaluation showed a greater extent of ocular tissue abnormalities in patients with\u00a0d<\/span>iabetes and DED than in those with DED alone.33,34<\/sup><\/span>\u00a0Prospective, controlled studies comparing age- and gender-matched patients have found approximately twofold higher frequency of DED symptoms in patients with diabetes than those without.33,35<\/sup><\/span>\u00a0A recent meta-analysis including more than 3,500 participants from 59 studies across the globe indicated worse tear function scores among patients with DM than those without.36<\/sup><\/span>\u00a0These differences were maintained regardless of the type of diabetes and ethnicity.36,37<\/sup><\/span>\u00a0Thus, unlike in patients without DM, these data suggest that in patients with DM, decreased tear production and poor corneal sensitivity due to persistent hyperglycaemia-induced injury to the corneal receptors result in a more severe dry eye vicious cycle. This is corroborated by the results of this meta-analysis, which found no significant difference in tear function between patients with DM having good glycaemic control and participants without DM.36<\/sup><\/span><\/p>\n

Screening of dry eye disease in\u00a0p<\/span><\/span>atients with\u00a0d<\/span>iabetes<\/h1>\n

Nearly 60% of patients with diabetes have one or more of the ocular complications, which progressively increase after 5 years of a diabetes diagnosis.38<\/sup><\/span>\u00a0However, as DED is a multifactorial disease, the presence of multiple risk factors (environmental factors such as digital screens, intrinsic factors such as hypertension and concomitant therapies increasing the DED risk) in addition to diabetes may prepone the occurrence.<\/p>\n

A dry eye examination, as described in detail in the TFOS DEWS II Diagnostic Methodology report, should be added to the routine monitoring of patients with DM, at least in those at high risk.2,39<\/sup><\/span><\/p>\n