Essay: Glaucoma, Diabetes mellitus and Intra ocular pressure

TITLE: To assess the incidence of glaucoma and Correlation of Diabetes mellitus and Intra ocular pressure in the population of Western India.
ABSTRACT:
The aim of this study was to assess the relationship between Diabetes mellitus and Glaucoma by checking the association between blood sugar levels (BSL) and corresponding intraocular pressure (IOP) in diabetic and non-diabetic patients. Eighty two non-diabetic and Seventy one diabetic subjects were part of the study. The subjects underwent complete ocular examination. IOP using applanation tonometry, at Fasting and Postprandial was recorded. BSL at Fasting and Postprandial was measured by Glucose oxidase/ Peroxidase method. Postprandial IOP was significantly higher than baseline IOP in diabetic (18.01 ± 3.55 versus 15.07 ± 3.23 mmHg; p < 0.001) and non-diabetic patients (14.58 ± 3.31 versus 12.06 ± 2.50 mmHg; p < 0.001). Postprandial BSL were significantly higher than baseline measurements in both diabetic (mean increase of 79.18 mg/dL; p < 0.001) and non-diabetic patients (mean increase of 20.48 mg/dL; p < 0.001). Correlative analysis showed a very statistically significant association between post-prandial BSL and post-prandial IOP in diabetic subjects with Pearson’s coefficient at 0.3728 (p<0.0001). For non-diabetic patients Correlative analysis showed a non-significant correlation with Pearson’s coefficient at 0.1739 (p<0.05). We concluded that there is a significant association between BSL and IOP variation, especially in diabetic patients.
INTRODUCTION:
Primary Open Angle Glaucoma (POAG) is a chronic, progressive optic neuropathy characterised by morphological changes at the optic nerve head and retinal nerve fibre layer in the absence of other ocular disease or congenital anomalies (with / without a raised IOP) [1].
It is the third leading cause of preventable blindness in India [2]. Glaucoma can remain asymptomatic until a severe stage, resulting in a high prevalence of undiagnosed glaucoma worldwide. Asia accounts for 60% of the world’s total glaucoma cases [3]. Although glaucoma is a multifactorial disease, elevated intraocular pressure (IOP) remains its major known risk factor [4,5]. Studies have demonstrated a significant role of IOP in progression of glaucoma [6,7].IOP can be influenced by different systemic factors such as hypertension [8-10], atherosclerotic diseases [8], body mass index [11], and diabetes [8, 12, 13].
Diabetes mellitus is a group of metabolic diseases which is characterized by hyperglycaemia, resulting from defects in insulin secretion, insulin action, or both. Diabetes is one of the world’s greatest health challenges and a leading cause of morbidity worldwide [14]. India is the epicentre of the world’s diabetes epidemic [15]. It is already a world leader, with over 35 million people with diabetes – a number that is predicted to increase to around 80 million by 2030 [16]. Moreover, Asian Indians have an ethnic susceptibility to Type 2 Diabetes [17,18] and a familial aggregation of the disease [19,20].
The chronic hyperglycaemia in diabetes is associated with the long-term damage, dysfunction, and the failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels, causing severe systemic complications such as retinopathy, neuropathy and nephropathy [21]. It is associated with complications which negatively influence both the quality of life and the survival of affected individuals [22]. Diabetic retinopathy (DR) is a common and serious condition associated with diabetes [23]. Diabetes also causes changes in corneal biomechanics.
Many studies have suggested an increase in the relative risk of people with diabetes mellitus to present ocular hypertension during the clinical course of the disease favouring the emergence of open angle glaucoma [13, 24]. However some studies failed to show any significant correlation between diabetes mellitus and intraocular pressure [25,26].
It has not yet been clearly established as to how diabetes affects the intra-ocular pressure. Studies suggest that diabetes may influence risk of Primary Open Angle Glaucoma (POAG) via hyperglycaemia-related vascular constriction leading to elevated intraocular pressure [27,28] and increased susceptibility to glaucomatous optic nerve damage [29]. According to Sato and Roy, high glucose levels in the aqueous humor of patients with diabetes may increase fibronectin synthesis and accumulation in the trabecular meshwork [30].The accelerated depletion of trabecular meshwork cells is a characteristic feature of the outflow system in POAG [30]. Pasquale et al. noted the correlation between glycosylated haemoglobin and increased ocular pressure [24,31,32] and speculated that glycosylation of extracellular matrix proteins in the trabecular meshwork could further reduce outflow facility in patients with type 2 diabetes[31]. Therefore, relative obstruction of the outflow of aqueous humor via the trabecular meshwork may be a primary mechanism by which diabetes affects POAG risk.
Age factor has been given a lesser importance in most studies. However with increase in aging population, the trend of diabetes is expected to increase [33]. This in turn will increase the morbidity of population. Therefore an early intervention would be essential to reduce complications.
Few studies have been conducted to study glucose variation and its impact on glaucoma. In our study we attempted to determine the relationship between glucose level variation and IOP fluctuation in diabetic and non diabetic patients. The correlation would facilitate screening procedures for early detection of glaucoma and in turn reducing morbidity. It can be developed as a tool for monitoring and recording disease progression.
MATERIALS AND METHODOLOGY:
An ethical approval from Institutional Ethics committee was taken before starting the study. Patients attending Medicine and Ophthalmology OPD of our Medical College & General Hospital were prospectively enrolled after applying the inclusion & exclusion criteria. Over a period of 2 months, 153 participants were enrolled in the study. Complete information of study was provided through a Patient Information Sheet and a Written Informed Consent was taken from each participant.
Inclusion criteria:
· Patients of age ≥ 18 years.
· Patients newly diagnosed as glaucoma.
· Patients fulfilling WHO criteria of clinical diagnosis of diabetes
CRITERIA FOR DIAGNOSIS OF DIABETES MELLITUS
Symptoms of diabetes plus random blood glucose concentration ≥ 200mg/dL
Fasting plasma glucose ≥ 126mg/dL
A1C > 6.5%
Two-hour plasma glucose ≥ 200mg/dL during an oral glucose tolerance test
• Healthy individuals were enrolled on basis of a self-reported history of normal glucose level in the past two years.
Exclusion criteria
· Recent ocular surgery done for causes other than glaucoma and cataract within last 6 months
· Secondary glaucoma
· Medications that would affect the Intraocular pressure (Steroids, antidepressants)
· History of endocrinal diseases.
Patients which were Type1 DM were excluded from study because of likely differences in the pathophysiology, risk of associated complications and duration of disease processes between Type1 DM and Type 2 DM.
All diabetic patients included in the study were on medication throughout the study period.
A detailed history followed by ocular examination including visual acuity, central corneal thickness, and visual field using automated perimetry was taken. Intraocular pressure (IOP) using applanation tonometry, at Fasting and post prandial was recorded. Blood sugar level at Fasting and Post prandial was measured by Glucose oxidase/ Peroxidase method (GOD/POD)
Statistical analysis was done using Student’s t test and Pearson’s correlation coefficient.
RESULTS:
A total of 153 patients (82 non-diabetic and 71 diabetic) were included. There were 94 female and 59 male patients in the study. Out of females 35 were diabetic and out of male 36 were diabetic.
Selected characteristics of the study are shown in Table 1. Postprandial IOP was significantly higher than baseline IOP in diabetic (18.01 ± 3.55 versus 15.07 ± 3.23 mmHg; p < 0.001 for right eye and 18.60± 3.72versus 15.79± 3.43 mmHg; p < 0.001 for left eye) and non-diabetic patients (14.58 ± 3.31versus 12.06 ± 2.50 mmHg; p < 0.001 for right eye and 14.98± 3.22 versus 12.69± 2.53mmHg; p < 0.001 for left eye). Postprandial glucose levels were significantly higher than baseline measurements in both diabetic (mean increase of 79.18 mg/dL; p < 0.001) and non-diabetic patients (mean increase of 20.48 mg/dL; p < 0.001).
Correlation between BSL and IOP was done using Pearson’s Test. Correlative analysis showed a very statistically significant association between post-prandial blood sugar levels and post-prandial IOP in diabetic subjects with Pearson’s coefficient at 0.3728 (p<0.0001) for Right Eye and 0.3801 (p<0.0001) for Left Eye. For non-diabetic patients Correlative analysis showed a positive correlation with Pearson’s coefficient at 0.1739 (p<0.05) for the Right Eye and 0.1759 (p<0.05) for the Left Eye. However, it was not as significant as in the case of diabetic patients. This is shown in Table 2 and the scatter diagram is shown in Fig 2.
The correlation between post-prandial BSL and post-prandial IOP were marginally higher in females compared to males. The Pearson’s coefficient between post-prandial blood sugar levels and post-prandial IOP in females was 0.4825 (p<0.0001) for the right eye and 0.4905 (p<0.0001) for the left eye. The Pearson’s coefficient between post-prandial blood sugar levels and post-prandial IOP in males was 0.4658 (p<0.0001) for the right eye and 0.4718 (p<0.0001) for the left eye. This is shown in Table 3 and the scatter diagram in shown in Fig 3.
In our study, of the 71 diabetics evaluated, 2 developed glaucoma.
Table 1: Comparison of variables between Diabetics and Non-diabetics
Table 2: Correlation between BSL and IOP in diabetics and non-diabetics
Table 3: Correlation between BSL and IOP in Females and Males
Fig 1: Gender Distribution in the Study
Fig 2: Scatter Diagram and Correlation between BSL and IOP for Diabetic and Non-Diabetic.
Fig 3: Scatter Diagram and Correlation between BSL and IOP for Females and Males.
DISCUSSION:
Although several risk factors for the development of POAG have been evaluated, this is a field of ongoing investigation [48]. Diabetes has been positively correlated with glaucoma in many previous studies [13,24,33,45,46].
Several hypotheses have been established to explain the association between high glucose levels and IOP. Some researchers believe that genetic factors are associated in family history of diabetes [49]. Other researchers are of opinion that a diabetic person may have an autonomic dysfunction which would lead to an IOP increase [50]. However some authors believe that elevated blood glucose results in the induction of an osmotic gradient which leads to fluid shifts into the intraocular space [13].
Anadhi et al correlated glycosylated haemoglobinA1c (HbA1c) levels and IOP [45]. Their study concluded an increase in IOP in diabetic as compared to controls. Our study results are in agreement with their results. Postprandial IOP was significantly higher than baseline IOP in diabetic (mean IOP 18.01 versus 15.07 mmHg for right eye and 18.60 versus 15.79mmHg for left eye).For ease of measurement in mass population, their study used Schtioz tonometry for IOP measurement. In our study we used applanation tonometry to measure IOP which is a GOLD standard.
Another study by Luis Guilherme et al [46] determined a significant correlation in fasting as well as post prandial variation among diabetics and non diabetics. Our findings are consistent with this study. Their study used peripheral glucose testing to determine blood glucose levels while our study used venous blood sampling. In our study we found a significant positive correlation of glucose variation and IOP in diabetics and non diabetic individuals. The Pearson’s coefficient for fasting blood sugar levels and fasting IOP was 0.3218 (p<0.0001) for Right Eye and 0.3161 (p<0.0001) for Left Eye. The Pearson’s coefficient for post-prandial blood sugar levels and post-prandial IOP was 0.4820 (p<0.0001) for the Right Eye and 0.4659 (p<0.0001) for the Left Eye.
In the Blue Mountain Eye Study[13], the authors attempted to study the relationship between diabetes and open-angle glaucoma and found that glaucoma prevalence was higher in diabetic patients compared to those without diabetes (5.5% versus 2.8%, OR = 2.12). Though our study does not determine the prevalence of glaucoma, it indirectly corroborates the results.
CONCLUSION:
Our study shows a significant positive correlation between blood glucose variation and IOP among diabetics and non diabetics.
The post prandial glucose levels were also found to be significantly higher compared to baseline.
This evaluation demonstrates the need for ophthalmic evaluation in consideration with blood glucose fluctuation, in diabetic individuals.
The study also demonstrates a need for assessment of anti glaucoma medication efficacy in relation with glycemic control of patients.
REFERENCES:
[1] Dr. Devindra Sood, “Advances in the Management of Primary Adult Glaucomas”, All India Ophthalmological Society, CME SERIES (No. 10), 2004, Pg. 4
[2] NPCB Avoidable blindness survey 2006-07
[3] Jacqueline Chua, PhD; Mani Baskaran, MD; Peng Guan Ong, BSc; YingfengZheng, MD, PhD; Tien Yin Wong, FRCS, PhD; Tin Aung, FRCS(Ed), PhD; Ching-Yu Cheng, MD, PhD, “Prevalence, Risk Factors, and Visual Features of Undiagnosed Glaucoma The Singapore Epidemiology of Eye Diseases Study, JAMA Ophthalmology, 2015, vol.133, no.8, pp 938-946.
[4] M. A. Kass, D. K. Heuer, E. J. Higginbotham et al., “The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma, Archives of Ophthalmology, 2002, vol. 120, no. 6, pp. 701-713.
[5] A. Sommer, J. M. Tielsch, J. Katz et al., “Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: the Baltimore eye survey, Archives of Ophthalmology, 1991, vol. 109, no. 8, pp. 1090-1095.
[6] Paul P. Lee, John W. Walt, Lisa C. Rosenblatt on behalf of the glaucoma care study group, “Association between intraocular pressure variation and glaucoma progression: Data from a United States Chart Review, American Journal of Ophthalmology, 2007, vol.144, no.6, pp 901-907
[7] Leslie Hyman, PhD; Anders Heijl, MD, PhD; M. Cristina Leske, MD, MPH; Boel Bengtsson, PhD; Zhongming Yang, PhD, “Natural History of Intraocular Pressure in the Early Manifest Glaucoma Trial” A 6-Year Follow-up for the Early Manifest Glaucoma Trial Group. Archives of Ophthalmology, 2010, vol. 128, no. 5, pp. 601-607.
[8] J. S. Lee, S. H. Lee, B. S. Oum, J. S. Chung, B. M. Cho, and J. W. Hong, “Relationship between intraocular pressure and systemic health parameters in a Korean population, Clinical & Experimental Ophthalmology, 2002, vol. 30, no. 4, pp. 237-241.
[9] C. J¨urgens, R. Grossjohann, and F. H. W. Tost, “Relationship of systemic blood pressure with ocular perfusion pressure and intraocular pressure of glaucoma patients in tele medical home monitoring”, Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2012, vol. 18, no. 11, pp. MT85-MT89.
[10] S. D. McLeod, S. K.West, H. A. Quigley, and J. L. Fozard, “A longitudinal study of the relationship between intraocular and blood pressures”, Investigative Ophthalmology & Visual Science, 1990, vol. 31, no. 11, pp. 2361-2366.
[11] Y. X. Wang, L. Xu, X. H. Zhang, Q. S. You, L. Zhao, and J. B. Jonas, “Five-year change in intraocular pressure associated with changes in arterial blood pressure and body mass index. The Beijing eye study, PLOS ONE, vol. 8, no. 10, Published October 11, 2013, Results section.
[12] F. Memarzadeh, M. Ying-Lai, S. P. Azen, and R. Varma, “Associations with intraocular pressure in Latinos: the Los Angeles Latino Eye Study, American Journal of Ophthalmology, 2008, vol. 146, no. 1, pp.69-76.
[13] Mitchell P, Smith W, Chey T, et al., “Open-angle glaucoma and diabetes: the Blue Mountains eye study, Australia”, Ophthalmology, 1997, vol.104, no.4, pp.712-718.
[14] Zimmet PZ, Diabetes Epidemilogy as a tool to trigger diabetes research and care, Diabetologia, 1999, vol.42, pp.499-518
[15] V Mohan, M Deepa, RM Anjana, H Lanthorn, R Deepa, “Incidence of Diabetes and Pre-diabetes in a Selected Urban South Indian Population (Cups – 19), Journal of Association of Physicians, 2008, vol 56, pp.152-157
[16] Wild S, Roglic G, Green A, Sicree R, King H, “The global prevalence of diabetes: estimates for the year 2000 and projections for the year 2030, Diabetes Care, 2004, vol.27, no.5, pp.1047-1053
[17] Ramchandran et al, “Problems specific to developing countries and effect of Westernization Type 2 Diabetes – Prediction and Prevention, Wiley London, 1999, pp 325-345
[18] Zimmet PZ, “The Epidemiology of Diabetes Mellitus and related conditions associated disorders, The Diabetes Annual No.6, 1991, 1-19.
[19] Mohan V et al, Family histories of Asian Indian and European NIDDM patients, Practical Diabetes, 1986, vol.3, pp.254-256.
[20] Ramchandran et al, “Familial aggregation of Type 2 non-insulin dependent Diabetes mellitus in south India, Diabetic Medicine, March 1996, vol.13 Issue 3, pp.232-237
[21] Marshall SM, Flyvbjerg A., “Prevention and early detection of vascular complications of diabetes, British Medical Journal, 2006,vol.333, pp.475-480.
[22] Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R, “Diabetes and cancer, Endocrine Related Cancer, 2009, no.16, pp.1103-1123.
[23] Mohan Rema, Sundaram Premkumar, Balaji Anitha, Raj Deepa, Rajendra Pradeepa, and Viswanathan Mohan, “Prevalence of Diabetic Retinopathy in Urban India: The Chennai Urban Rural Epidemiology Study (CURES) Eye Study, I”, Investigative Ophthalmology & Visual Science, 2005, Vol. 46, No. 7, pp.2328-2333.
[24] Klein BE, Klein R, Linton KLP, “Intraocular pressure in an American community: The Beaver Dam Eye Study”, Investigative Ophthalmology and Visual Science. 1992; 33:2224–8. [PubMed:1607232]
[25] Simone de Voogd, MD, PhD et al, “Is Diabetes Mellitus a Risk Factor for Open-Angle Glaucoma? The Rotterdam Study”, Ophthalmology 2006;113:1827–1831 the American Academy of Ophthalmology.
[26] Ellis JD, Evans JM, Ruta DA, Baines PS, Leese G, et al (2000), “Glaucoma incidence in an unselected cohort of diabetic patient: is diabetes mellitus a risk factor for glaucoma? DARTS/ MEMO collaboration.Diabetes Audit and Research in Tayside Study. Medicine Monitoring Unit”, Br J Ophthalmology 84: 1217-1224.
[27] Johnson MA, Lutty GA, McLeod DS, Otsuji T, Flower RW, Sandagar G, et al., “Ocular structure and function in an aged monkey with spontaneous diabetes mellitus, Experimental Eye Research, 2005,vol.80, pp.37-42.
[28] Wilson R & Martone J (1996): Epidemiology of chronic open angle glaucoma. In: Ritch R, Shields M & Krupin T (eds). The Glaucomas. Vol 2: 753-768. Mosby
[29] Kanamori A, Nakamura M, Mukuno H, Maeda H, Negi A., Diabetes has an additive effect on neural apoptosis in rat retina with chronically elevated intraocular pressure, Current Eye Research, 2004,vol.28, pp.47-54.
[30] Sato T, Roy S., “Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells”, Investigative Ophthalmology & Visual Science, 2002, vol.43, pp.170-175.
31] Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE., “Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women”, Ophthalmology, 2006, vol.13, pp.1081-1086.
[32] Hennis A, Wu S-Y, Nemesure B, Leske MC, “Hypertension, diabetes, and longitudinal changes in intraocular pressure, Ophthalmology, 2003, vol.110, pp.908-914.
[33] Leske M, Connell A, Schachat A, Hyman L., “The Barbados Eye Study: prevalence of open angle glaucoma”, Archives of Ophthalmology, 1994, vol.112, pp821-829.
[34] Bulletin of the World Health Organization, 1994, vol.72, no.3, pp.323-326
[35] Prevalence of Open-Angle Glaucoma Among Adults in the United States, The Eye Diseases Prevalence Research Group, Archives of Ophthalmology, 2004, vol.122, no.4, pp.532-538.
[36] Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS, Mmbaga BB. Prevalence of glaucoma in a rural East African population, Investigative Ophthalmology & Visual Science, 2000, Vol. 41, pp.40-48.
[37] Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R., “The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER.”, Archives of Ophthalmology, 2001, vol.119, pp.1819-1826.
[38] Wensor MD, McCarty CA, Stanislavsky YL, Livingston PM, Taylor HR., “The prevalence of glaucoma in the Melbourne Visual Impairment Project, Ophthalmology, 1998, vol.105, pp.733-739.
[39] Donald L. Budenz, MD, MPH; Keith Barton, MD, FRCS; Julia Whiteside-de Vos, MD, MPH; et al for the Tema Eye Survey Study Group, “Prevalence of Glaucoma in an Urban West African Population, JAMA Ophthalmology, 2013, vol.131, no.5, pp.651-658.
[40] P.K Nirmalan, J Katz, Thulasiraj RD, J Tielsch, “The Aravind eye survey”, British Journal of Ophthalmology, 2004, vol.88, no.10, pp.1237-1241.
[41] Ramchandran et al., “High prevalence of diabetes and impairedglucose tolerance in India: National Urban Diabetes Survey (INUDS), Diabetologia, 2001, vol.44, pp.1094-1101.
[42] R. W. MORGAN, S. M. DRANCE, “Chronic open-angle glaucoma and ocular hypertension: An epidemiological study”, British Journal of Ophthalmology, 1975, vol.59, pp. 21 1-214.
[43] Chopra V, Varma R, Francis B A., Wu J, Torres M, Stanley P. Azen, “Los Angeles Latino Eye Study Group, Type 2 Diabetes Mellitus and the Risk of Open-angle Glaucoma The Los Angeles Latino Eye Study, Ophthalmology, 2008, vol.115, pp.227-232.
[44] Tan GS, Wong TY, Fong CW, Aung T., “Singapore Malay Eye Study. Diabetes, Metabolic abnormalities and glaucoma”, Archives of Opthalmology, 2009, vol.127, pp.1354-1361.
[45] Anandha Lakshmi S, Petricia H, Saravanan A, Ramachandran C, “Intraocular Pressure in Subjects with Type 2 Diabetes Mellitus”, Journal of Clinical and Diagnostic Research, 2011, vol.5, no.7, pp.1336-1338.
[46] Luis GuilhermeMilesi Pimentel, Carolina P. B. Gracitelli, Leticia Sant’Ana Cardoso da Silva, Aline Katia Siqueira Souza and Tiago Santos Prata, “Association between Glucose Levels and Intraocular Pressure: Pre- and Postprandial Analysis in Diabetic and Nondiabetic Patients, Journal of Ophthalmology, 2015,vol.15, pp.1-5
[47] Thasarat S. et al, “Gender and glaucoma: what we know and what we need to know”, Current Opinion in Ophthalmology, 2010, vol.21, no.2, pp.91-99.
[48] Rivera JL, Bell NP, Feldman RM (2008), “Risk factors for primary open angle glaucoma progression: what we know and what we need to know”, Current Opinion in Ophthalmology, vol.19, 102-106.
[49] C. V. Clark and R. Mapstone, “The prevalence of diabetes mellitus in the family history of patients with primary glaucoma”, Documenta Ophthalmologica, 1986, vol. 62, no. 2, pp. 161-163,
[50] R. Mapstone and C. V. Clark, “Prevalence of diabetes in glaucoma”, British Medical Journal, 1985, vol. 291, no. 6488, pp. 93-95.