DIABETES MELLITUS AND GLAUCOMA

 INTRODUCTION:

A number of studies have analyzed the association of diabetes mellitus with glaucoma. It is assumed that low ocular blood flow and other pathophysiological abnormalities such as damaged microvasculature and reduced nutritional supply to the retinal ganglion cells (RGC), seen in diabetics, would contribute to the development of glaucoma. Others have suggested that increased surveillance of diabetics in hospitals leads to higher chances of such individuals being detected with glaucoma. Since the prevalence rates of glaucoma increase with age, therefore increased healthcare contact could be responsible for the diagnosis of such co-morbidities. However, no clear association between the two conditions has been found based on experimental, clinical and population-based studies.

This post debates the various studies in favor and against such a relationship. 

STUDIES SHOWING POSITIVE ASSOCIATION:

A number of questions arise with respect to the possible association of diabetes and glaucoma. Do patients with diabetes have a greater risk of developing glaucoma? Is glaucoma progression faster and more severe in patients with diabetic glaucoma? If diabetes increases risk for glaucoma, what is the etiology of this increased risk?

Let us take a look at some studies showing evidence of such a relationship.

Experimental studies in the streptozotocin-induced diabetic mouse and rat model have demonstrated RGC loss as well as abnormal morphology and increased numbers of dendritic terminals in the surviving ganglion cells after 3 months. Also, large and medium-type RGCs show reduced retrograde axoplasmic flow suggestive a positive link between increased blood glucose and glaucoma. Elisaf et al studied metabolic abnormalities amongst patients with known POAG and showed that elevated glucose as well as uric acid levels were significantly higher as compared to a matched control group.

Oh et al have reported insulin resistance in patients with the metabolic syndrome was associated with elevated IOP, and that mean IOP increased linearly with the presence of increasing numbers of components for the metabolic syndrome.

Optic disc hemorrhages are frequently seen in primary open angle glaucoma (POAG), with a hazard ratio of 4.4 as compared to nondiabetics.

The prevalence of POAG appears to be higher in the diabetic population by a factor of about 2 in the majority of population-based surveys. (Shields)

In the Latino cohort of the Los Angeles Latino Eye Study, presence of type 2 diabetes and a longer duration of diabetes were independently associated with an increased risk for POAG. The study also reported that those with type 2 diabetes mellitus, defined as having diabetes after the age of 30, the prevalence of glaucoma was 40% higher than those without type 2 diabetes.

In another recent prospective analysis of a cohort of women over 40 years of age from the Nurses’ Health Study observed between 1980 and 2000, Pasquale et al found that type 2 diabetes mellitus was positively associated with development of POAG as confirmed by record review with a relative rate ratio of 1.82.

The Ocular Hypertension Treatment Study (OHTS) initially showed that having diabetes, in fact, was surprisingly protective of the development of glaucoma. However, a follow-up study determined that a history of diabetes mellitus was not statistically significantly predictive for the development of POAG and failed to support the original conclusion that diabetes was protective of glaucoma in patients with ocular hypertension.

A smaller cohort of ocular hypertensives from the Diagnostic Innovations in Glaucoma Study yielded similar hazard ratios as in the OHTS analysis for all reported risk factors for progression, except that diabetics who progressed to glaucoma had an increased hazard ratio as compared to those that did not progress.

In a study conducted in Wisconsin, USA, a predominantly Caucasian population with diabetes was compared to a smaller group of nondiabetics and was found to have a tendency toward a greater mean IOP than nondiabetics and higher rates of a positive history of glaucoma than in diabetic participants.

The Early Manifest Glaucoma Trial (EMGT), Blue Mountain Eye Study, and the Baltimore Eye Study found persons with diabetes appear to have a slightly higher IOP and have been reported to have a higher prevalence of ocular hypertension and incidence of IOP elevation, compared with persons who do not have diabetes.

Finally, some systematic reviews and meta-analysis throw some more light on the issue. In a meta-analysis by Zhao et al, diabetes, fasting glucose and the risk of glaucoma were studied and found to have a positive association. Similarly, Zhou et al, in their meta-analysis of diabetes mellitus as a risk factor for POAG, found it to be a significant risk factor. Recently, Zhao and Chen in their meta-analysis of seven prospective cohort studies found a pooled risk ratio (RR) of 1.36, implying significant association between diabetes and POAG.

STUDIES SHOWING NEGATIVE ASSOCIATION:

In the European Glaucoma Prevention Study (EGPS) only 4.7% of 1,077 randomized participants with ocular hypertension reported diabetes, a number too small to determine prospectively the effect of diabetes on progression to glaucoma.

Vijaya et al did not find diabetes to be associated with glaucoma in a South Indian population in Chennai, India.

The Baltimore Eye Survey, a predominantly African-American population, failed to show that diabetes was associated in the development of glaucoma. The Rotterdam Study also negated such an association.

Ellis et al in their study of a population in Scotland, UK, (based on the Diabetes Audit Research in Tayside Study [DARTS]), reported the incidence of POAG in diabetes of 1.1/1000 patient years compared to 0.7/1000 patient years in non-diabetics showing a non-significant increase.

In a population-based study in 3280 Malay adults aged 40 to 80 years, diabetes and metabolic abnormalities were associated with a small increase in IOP but were not significant risk factors for glaucomatous optic neuropathy.

Certain old studies such as those by Waite and Beetham (1935), Palomar-Palomar (1956), Armaly and Baloglou (1967), Bankes (1967), as well as Bouzas et al (1971), had refuted a link between diabetes and glaucoma.

CONCLUSION:

The relationship between diabetes and glaucoma is not well established and currently remains the subject of much controversy.  While at least three meta-analyses have shown an association of glaucoma with diabetes, yet, there remain a number of confounding factors regarding this relationship. One study showed that changes in the biomechanical properties of the cornea due to increased glycosylated hemoglobin may artificially influence intraocular pressure measurements leading to a false-positive association between diabetes and elevated intraocular pressure.

Krueger and Ramos-Esteban proposed that corneal stiffening due to glucose-mediated collagen cross-linking may account for higher intraocular pressure readings in diabetics.

On the other hand, some authors have suggested that the diabetes related increase in the thickness of the lens could be responsible for the shallowing of anterior chamber and increased risk of angle-closure glaucoma.