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Diabetic Retinopathy – An Overview

“There is currently an epidemic of diabetes in the world, principally type 2 diabetes that is linked to changing lifestyle, obesity, and increasing age of the population. Latest estimates from the International Diabetes Federation (IDF) forecasts a rise from 366 million people worldwide to 552 million by 2030. Type 1 diabetes is more common in the Northern hemisphere with the highest rates in Finland and there is evidence of a rise in some central European countries, particularly in the younger children under 5 years of age. Modifiable risk factors for progression of diabetic retinopathy (DR) are blood glucose, blood pressure, serum lipids, and smoking. Nonmodifiable risk factors are duration, age, genetic predisposition, and ethnicity. Other risk factors are pregnancy, microaneurysm count in an eye, microaneurysm formation rate, and the presence of any DR in the second eye. DR, macular edema (ME), and proliferative DR (PDR) develop with increased duration of diabetes and the rates are dependent on the above risk factors.”1

Diabetes Type 1 & Type 2 can lead to the microvasculature of the eye becoming damaged and causing intra-retinal leakage that causes permanent blindness and other complications. The weakening of the vasculature of the eye is made possible by the presence of high glucose levels so naturally, diabetic retinopathy is a complication of high importance in the management of any diabetes type.

“Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia along with dyslipidemia, hypoinsulinemia and hypertension. Increasing evidence points to inflammation as one key player in diabetes-associated retinal perturbations, however, the exact underlying molecular mechanisms are not yet fully understood. Interlinked molecular pathways, such as oxidative stress, formation of advanced glycation end-products and increased expression of vascular endothelial growth factor have received a lot of attention as they all contribute to the inflammatory response.”2

Unfortunately, symptoms do not arise until some loss of vision has already taken place. Blurriness or partial blindness is a grievance that does not arrive with a warning. This is why important steps and precautions should be taken when suffering from diabetes; simply because dealing with complications can compound the disease entirely and affect its outlook sharply. The obvious prophylactic measure to practice is a yearly eye examination (with dilation) so as to catch unwelcome developments early on.

“Diabetic retinopathy (DR) is the primary cause of visual impairment in the working-age population of the Western world. Among microvascular complications related to diabetes mellitus such as nephropathy and neuropathy, DR is the most common. The prevalence rate for DR for all adults with diabetes aged 40 and older is 28.5% in the United States (4.2 million people) while estimated at 34.6% worldwide (93 million people). With the prevalence of diabetes expected to continue to rise, the prevalence of DR in the United States by year 2020 is expected to be 6 million persons with 1.34 million persons having vision-threatening disease. The substantial worldwide public health burden of DR highlights the importance of continuously searching for new approaches beyond current standards of diabetes care.”3 

A more accurate type of test, called an angiography, uses a special dye that is injected into your bloodstream. This dye has a radioactive isotope for detection and visualization of retinal damage and can be viewed by an x-ray machine or a CT scan as it makes its way through the vasculature. Once the dye reaches the eye blood vessels, the blood vessel damage can be witnessed as it circulates.

 

Clinical features of diabetic retinopathy and causative pro-inflammatory chemokines
“Clinical features of diabetic retinopathy and causative pro-inflammatory chemokines. (A) A fundus photograph shows the right eye of a 57-year-old man with 20/80 visual acuity and signs of severe non-proliferative diabetic retinopathy with non-significant macular edema (the region of macular edema is indicated by the bracket). Vascular pathologies are depicted in blue, whereas neurodegenerative features are black. Notable features include dot blot hemorrhages, DH; hard exudates, HE; cotton-wool spots, CWS. Each are associated with the upregulation of certain chemokines; (B) Optical coherence tomography with a horizontal scan through the central fovea reveals moderate thickening and edema of the macula with cysts; (C) Ang: Angiopoietin; IL: interleukin; TNF: Tumor Necrosis Factor; NO: nitric oxide; MCP: Monocyte Chemoattractant Protein.”4

 

“Numerous risk factors have been associated with diabetic retinopathy, including duration of diabetes, high HbA1c levels (chronic hyperglycemia), hypertension, and ethnicity. Potential risk factors such as dyslipidemia and body mass index (or obesity) have been less consistently linked with diabetic retinopathy; some studies have reported these as risk factors, while others have not.”5

“Hyperglycemia’s harmful effects are directly related to the structural damage inflicted on small retinal blood vessels and are governed by the systemic and local ocular factors. Although there are genetic factors also at play, but individuals with elevated blood glucose levels have severe retinopathy than those with strict blood glucose control. HbA1c measures overall glucose level in blood over a period of 3 months. HbA1c levels less than 7.0% are generally recommended to minimize the risk of vascular complications, including DR (diabetic retinopathy). On the other hand, increased levels of blood lipids may also impart some role in the progression of DR as lipid-lowering compounds such as fenofibrate offers benefits in preventing the progression of DR. The complete details of the mechanism(s) underlying this protection are not well understood. Moreover, the genetics and epigenetics of an individual can influence susceptibility to DR and response to the treatment. However, the exact number and nature of the genes involved or the epigenomics elements that are involved remain elusive. Other demographic risk factors for DR include Hispanic or African American ethnicity, systemic hypertension, duration of disease, and pregnancy. DME (Diabetic macular edema) is one of the most common complications and the cause of vision loss in diabetics. The early stage of DR is called non-proliferative diabetic retinopathy (NPDR) and is characterized by the presence of intra-retinal hemorrhages, microaneurysms, intra-retinal microvascular abnormalities, and cotton wool spots (fluffy white patches in the retina caused by focal swelling in the retinal nerve fiber layer). Development of retinal NV (new blood vessels) is called PDR (proliferative diabetic retinopathy), an advanced form of DR that carries a risk of other structural complications. Retinal changes occur after approximately a decade of living with T1D (diabetes type 1).”6

Luckily, Diabetic Retinopathy can be treated if caught in its early stages. An amazing laser technique is available where the laser used is so precise and accurate that it can target the “leakage” problem zones and seal off the vessels’ weakness. However, the length of time in which Diabetic Retinopathy has already been present is a contributing factor in the efficacy of laser treatment. As should be expected, the drawbacks and benefits should be weighed and determined with the assistance of your eye professional.

“An important cause of blindness, diabetic retinopathy has few visual or ophthalmic symptoms until visual loss develops. At present, laser photocoagulation for diabetic retinopathy is effective at slowing the progression of retinopathy and reducing visual loss, but the treatment usually does not restore lost vision. Because these treatments are aimed at preventing vision loss and retinopathy can be asymptomatic, it is important to identify and treat patients early in the disease. To achieve this goal, patients with diabetes should be routinely evaluated to detect treatable disease.7

The prophylaxis of Diabetic Retinopathy goes hand in hand with the proper management of any diabetes type, namely, keeping blood sugar at respectable levels. Controlling the reigns when it comes to blood glucose is the common denominator of success and is logically considered to be the crucial biochemical and dietary aspect for treatment among all of diabetes and its accompanying complications. Hence, a winning strategic combination would be yearly eye exams along appropriate maintenance of blood sugar levels.

“Management of DR (diabetic retinopathy) starts with screening patients for the signs of retinopathy and then treating them if vision-threatening lesions are identified. Typically, DME (Diabetic macular edema) is treated with intravitreal administration of anti-VEGF (vascular endothelial growth factor) based biologics or small organic molecules such as steroids. Recent clinical trials have established that PDR can also be treated with repeated anti-VEGF injections, though it is still unclear how long a patient be treated if one opts for the injection strategy. Other drugs that are currently being tried are the potential agonists for peroxisome proliferator activated receptors (PPARs), plant extracts such as forskolin (it binds to glucose receptor, specifically GLUT1), minocycline (it serves as an anti-inflammatory agent), celecoxib, another COX-2, and angiopoietin 2 antagonists. Anti-VEGF agents have been shown to have a disease-modifying effect. However, such an approach carries a significant treatment burden. Thus, there remains a considerable unmet medical need for the development of effective strategy (ies) to prevent DR or at least slow its progression. Critical aspects of this endeavor are to ensure that the anticipated intervention is safe, well tolerated, and less burdensome than the currently available options. Some investigations have implicated inflammation and pyroptosis as a possible cell-molecular mechanism in DR biology.”8

“Novel drug delivery methods to the posterior segment of the eye could prove promising for the treatment of diabetic retinopathy. Encapsulated cell technology (ECT) allows a genetically modified group of cell lines expressing the gene of interest to be encapsulated in synthetic semi-permeable capsules, which allows diffusion of nutrients to these cells while protecting them from the host’s defense mechanisms. These capsules can be surgically implanted in target areas including the posterior segment of the eye. This technology has already been tested in a number of neurodegenerative diseases. Proof-of-concept and phase I/II studies are currently underway to evaluate the efficacy of capsules with anti-VEGF (vascular endothelial growth factor) activity.”9

 

References

(1) Epidemiological Issues in Diabetic Retinopathy. Scanlon, P.H., Aldington, S.J. &  Stratton, I.M. Middle East African Journal of Ophthalmology. 2013. http://www.meajo.org/article.asp?issn=0974-9233;year=2013;volume=20;issue=4;spage=293;epage=300;aulast=Scanlon

(2, 3, 4) Role of Inflammation in Diabetic Retinopathy. Rübsam, A., Parikh, S. & Fort, P.E. International Journal of Molecular Sciences. 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979417/

(5, 9) New Therapeutic Approaches in Diabetic Retinopathy. Vaziri, K., Schwartz, S.G., Relhan, N., Kishor, K.S. & Flynn Jr, H.W. The Review of Diabetes Studies. 2015. http://www.soc-bdr.org/content/e4/e887/volRdsVolumes17003/issRdsIssues17109/chpRdsChapters17181/strRdsArticles17193/?preview=preview&showfulltext=1

(6, 8) Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis. Homme, R.P., Singh, M., Majumder, A., George, A.K., Nair, K., Sandhu, H.S., Tyagi, N., Lominadze, D. & Tyagi S.C. Frontiers in Physiology. 2018. https://www.frontiersin.org/articles/10.3389/fphys.2018.01268/full

(7) Retinopathy in Diabetes. Fong, D.S., Aiello, L., Gardner, T.W., King, G.L., Blankenship, G., Cavallerano, J.D., Ferris III, F.L. & Klein, R. Diabetes Care. 2004. http://care.diabetesjournals.org/content/27/suppl_1/s84.full

 

María Laura Márquez
13 October, 2018

Written by

María Laura Márquez, general doctor graduated from The University of Oriente in 2018, Venezuela. My interests in the world of medicine and science, is focused on surgery and its greatest advances. Nowadays I practice my...read more:

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