Research paper on diabetic retinopathy - Karan Mody
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Transcript of Research paper on diabetic retinopathy - Karan Mody
DIABETIC RETINOPATHY [This retrospective study was undertaken to see whether there is any correlation between HbA1c sugar levels and duration of diabetes to advancing stages of Diabetic Retinopathy] CATHEDRAL AND JOHN CONNON SCHOOL
KARAN MODY CAID: 12543300
15/08/2014
2
INDEX
1. Acknowledgements………………………………………………………... 3
2. Abstract……………………………………………………………………. 4
3. Introduction……………………………………………………………….. 5
4. Epidemiology……………………………………………………………… 11
5. Pathogenesis……………………………………………………………….. 12
6. Risk Factors……………………………………………………………….. 12
7. Learning Objective………………………………………………………... 12
8. Methodology……………………………………………………………… 12
9. Demographic…………………………………………………………….., 12
10. Study Design……………………………………………………………… 13
11. Results…………………………………………………………………….. 13
12. Discussion………………………………………………………………… 16
13. Conclusion……………………………………………………………….... 19
14. Glossary…………………………………………………………………… 20
15. References………………………………………………………………… 21
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ACKNOWLEDGEMENTS
This research to study the correlation between blood sugar control in patients with diabetes and the
development of various clinical stages of diabetic retinopathy would not have been possible without the
esteemed guidance of my mentor, Dr. Nivedita Patil, Clinical Research Scientist, Krishna Eye Care and
Hon. Consultant, Conwest Jain Clinic, Mumbai. Dr. Patil is one of the volunteering ophthalmologist at
Hasanali Tobaccowala Eye Center, Talwada where she performs eye surgeries for the underserved
populace. I have had the privilege to volunteer in the same eye center and she has been an inspiration with
her knowledge, guidance and support. Dr. Patil has mentored me in this research study at every stage and
has been very cooperative to take out time from her extremely busy schedule to explain the intricacies of
the subject of diabetic retinopathy. The data for the study was collected with her help and the correctness
of its analyses was also double checked. The valuable feedback given by Dr. Patil during the preparation
of this research paper has made these analyses accurate and clinically relevant.
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ABSTRACT Background: Diabetes Mellitus (DM) is a group of diseases characterized by high blood glucose levels and is classed as a metabolism disorder. Diabetic retinopathy (DR) is one of the vascular (blood-vessel related) complications of diabetes mellitus. DR is caused by high blood sugar levels damaging the network of tiny blood vessels that supply blood to the retina. In the initial stages of retinopathy, the damage is limited to tiny bulges (microaneurysms) in the blood vessel walls and in its advanced stages, some of the blood vessels that supply your retina become blocked. New blood vessels start to form which are unstable and prone to bleeding and can cause blurred and patchy vision. Over time, this bleeding can lead to scar tissue forming, which can pull the retina out of position. This is known as retinal detachment, and can lead to a darkening of vision and if left untreated, blindness. DR is a leading cause of vision loss and blindness. Pathogenesis: Increased glucose Increased VEGF Increased capillary permeability/ abnormal vasoproliferation Causing hemorrhages, edema, exudates, ischemia, neo vascularization, fibrosis, traction Objective: To study the co - relation between blood sugar control in patients with diabetes of at least 10 years and the development of various clinical stages of DR. Methodology and Demographic: This retrospective study was done on patients in the age group of 40 to 60 years. A total of 33 patients were studied which included 15 males and 18 females. Patients with hyperlipidemia (high lipids) were excluded from the study. 2 males presented with hyperlipidemia and were excluded and 13 males and 18 females formed the cohort for this study. Design: Patients with atleast 10 years duration of diabetes were included and their past glycemic patient control (HbA1c) records were noted and analyzed. Visual acuity of patients as recorded were noted. The diabetes oral medications or injections were recorded. Patients’ hypertension and hyperlipidemia were recorded. Patients’ fundus images and current stage of DR as recorded were noted. Results: 6 females with HbA1c range 5.50%-6% No signs of DR 6 males and 6 females with HbA1c range 5.40%-8.10% and 5.70%-7.50% respectively Background DR 3 males and 4 females with HbA1c range 6%-9.20% and 6.70%-8.40% respectively Preproliferative DR 2 males and 1 females with HbA1c range 8.70%-10.60% and 10.30% respectively Proliferative DR 2 males and 1 females with HbA1c range 9.10%-12.30% and 9% respectively Diabetic Macular Edema Conclusion: HbA1c data relevant to each patient shows a clear nexus between uncontrolled diabetes and advancing stages of DR. Along with the duration of diabetes its poor management leads to advanced stage of Diabetic Retinopathy, which is a leading cause of vision loss and blindness.
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INTRODUCTION Diabetes Mellitus is a group of diseases characterized by high blood glucose levels. Diabetes results from
defects in the body’s ability to produce or use insulin.
Diabetes (diabetes mellitus) is classed as a metabolism disorder. Metabolism refers to the way our bodies
use digested food for energy and growth. Most of what we eat is broken down into glucose. Glucose is a
form of sugar in the blood - it is the principal source of fuel for our bodies.
When our food is digested, the glucose makes its way into our bloodstream. Our cells use the glucose for
energy and growth. However, glucose cannot enter our cells without insulin being present - insulin makes
it possible for our cells to take in the glucose.
Insulin is a hormone that is produced by the pancreas. After eating, the pancreas automatically releases an
adequate quantity of insulin to move the glucose present in our blood into the cells, as soon as glucose
enters the cells blood-glucose levels drop.
A person with diabetes has a condition in which the quantity of glucose in the blood is too elevated
(hyperglycemia). This is because the body either does not produce enough insulin, produces no insulin, or
has cells that do not respond properly to the insulin the pancreas produces. This results in too much
glucose building up in the blood. This excess blood glucose eventually passes out of the body in urine.
So, even though the blood has plenty of glucose, the cells are not getting it for their essential energy and
growth requirements(1).
Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in
which the pancreas produces little or no insulin, a hormone needed to allow sugar (glucose) to enter cells
to produce energy(2). Only 5% of people with diabetes have this form of the disease(3).
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Type 2 diabetes, once known as adult-onset or noninsulin-dependent diabetes, is a chronic condition that
affects the way your body metabolizes sugar (glucose), your body's important source of fuel. With type 2
diabetes, your body either resists the effects of insulin — a hormone that regulates the movement of sugar
into your cells — or doesn't produce enough insulin to maintain a normal glucose level.
Diabetic retinopathy (DR) is one of the vascular (blood-vessel related) complications of diabetes mellitus.
Diabetic retinopathy is caused by high blood sugar levels damaging the network of tiny blood vessels that
supply blood to your retina(5). The retina is the light-sensitive layer of nerve cells at the back of your eye.
It converts light into electrical signals that are sent to the brain through the optic nerve. The brain
interprets these signals into the images you see. The retina, like all parts of the body, needs a constant
supply of blood, which flows to the retina through a network of tiny blood vessels. Over many years, the
blood vessels can be damaged by high blood sugar (glucose) levels that may be present in people with
poorly controlled diabetes.
During the initial stages of retinopathy, the damage is limited to tiny bulges (microaneurysms) in the
blood vessel walls. Although these can leak blood and fluid, they do not usually affect your vision. If
fluid leaks into the macula, part of the retina which distinguishes colours and focus your eyes for tasks
such as reading and writing, it can cause swelling (macular edema), leading to some loss of vision.
When retinopathy reaches more advanced stages, some of the blood vessels that supply your retina
become blocked. In an attempt to restore the supply of blood, new blood vessels start to form. However,
they are unstable and prone to bleeding, which can cause blurred and patchy vision. Over time, this
bleeding can lead to scar tissue forming, which can pull the retina out of position. This is known as retinal
detachment, and can lead to a darkening of vision and if left untreated, blindness(4). Diabetic retinopathy
usually affects both eyes. Diabetic retinopathy is a leading cause of vision loss and blindness(5).
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Stages of Diabetic Retinopathy(DR) Background Diabetic Retinopathy (BDR)
This is the term used when there is mild damage to the retina from diabetes. The tiny blood vessels in the
retina, the capillaries, become damaged. A doctor or optometrist may see 'dots' and 'blots'. The dots are
some capillaries that have enlarged, that is the tiny blood vessels enlarge to form microaneurysms. As the
damage is mild at this stage, sight will be nearly perfect. However, the condition does progress.
Background retinopathy generally means that the diabetes is not controlled as well as it could be(6).
Fig. 1: Fundus Image showing Background Diabetic Retinopathy
Preproliferative Diabetic Retinopathy (PPDR)
This stage is more extensive than background retinopathy. There are signs of blood flow becoming
restricted, but not yet showing new blood vessels growing(7). This is where there are changes detected in
the retina that do not require treatment but need to be monitored closely as there is a risk that they may
progress and affect the eyesight(8). The condition is called 'pre-proliferative' as it usually progresses to
develop proliferative retinopathy, when 'new vessels' develop(9).
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Fig. 2: Fundus Image showing Preproliferative Diabetic Retinopathy
Proliferative Diabetic Retinopathy (PDR)
Proliferative diabetic retinopathy occurs where fragile new blood vessels form on the surface of the retina
over time. These abnormal vessels can bleed or develop scar tissue causing severe loss of sight(8). This
abnormal growth is called neovascularization. If these abnormal blood vessels grow around your pupil,
glaucoma can result from the increasing pressure within your eye. These new blood vessels have weaker
walls and may break and bleed, or cause scar tissue to grow that can pull the retina away from the back of
your eye, and if left untreated, it can cause severe vision loss, including blindness. Leaking blood can
cloud the vitreous—the clear, jelly-like substance that fills the back of the eye—and block the light
passing through the pupil to the retina, causing blurred and distorted images. In more advanced
proliferative retinopathy, diabetic fibrous or scar tissue can form on the retina(10).
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Fig. 3: Fundus Image showing Proliferative Diabetic Retinopathy
Diabetic Macular Edema (DME)
Macular edema refers to the accumulation of fluid within the retina at the macular area (distinct from the
condition where the fluid accumulates under the retina)(11). Fluid can leak into the center of the macula,
the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, blurring
vision. It can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease
progresses(5). Macular edema occurs in about 10% of patients with diabetic retinopathy and is more
common with severe retinopathy(11). About half of the people with proliferative retinopathy also have
macular edema(5).
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Fig 4: Fundus Image showing Diabetic Macular Edema
Treatment Options In mild cases, treatment for diabetic retinopathy is not necessary. Regular eye exams are critical for
monitoring progression of the disease. Strict control of blood sugar and blood pressure levels can greatly
reduce or prevent diabetic retinopathy. In more advanced cases, treatment is recommended to stop the
damage of diabetic retinopathy, prevent vision loss, and potentially restore vision.
Anti-VEGF therapy (Avastin, Luventis, Eylea)
Vascular endothelial growth factor (VEGF) is a chemical signal produced by cells that stimulates the
growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues when blood
circulation is inadequate. VEGF's normal function is to create new blood vessels during embryonic
development, new blood vessels after injury, and new vessels (collateral circulation) to bypass blocked
vessels. When VEGF is overexpressed, it can contribute to disease. Anti-VEGF therapy involves the
injection of the medication into the back of your eye. The medication is an antibody designed to bind to
and remove the excess VEGF (vascular endothelial growth factor) present in the eye that is causing the
disease state.
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Intraocular steroid injection Intraocular steroid injection is a treatment for diabetic macular edema. This therapy helps reduce the
amount of fluid leaking into your retina, resulting in visual improvement. Due to the chronic nature of
diabetic eye disease, this treatment may need to be repeated or combined with laser therapy to obtain
maximum or lasting effect.
Argon Laser Photocoagulation
Argon Laser is often helpful in treating diabetic retinopathy. To reduce macular edema, a laser is focused
on the damaged retina to seal leaking retinal vessels. For abnormal blood vessel growth
(neovascularization), the laser treatments are delivered over the peripheral retina. The small laser scars
that result will reduce abnormal blood vessel growth and help bond the retina to the back of your eye, thus
preventing retinal detachment. Laser can greatly reduce the chance of severe visual impairment.
Vitrectomy
Vitrectomy may be recommended in advanced proliferative diabetic retinopathy. During this
microsurgical procedure that is performed in the operating room, the blood-filled vitreous is removed and
replaced with a clear solution(10).
Diabetic retinopathy (DR) is a leading cause of vision loss and blindness. The duration of diabetes is the
single most important risk for developing retinopathy.
EPIDEMIOLOGY Prevalence of DR of any severity in the diabetic population is 30% and prevalence of blindness due to DR
is approximately 5%
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PATHOGENESIS Increased glucose
Increased VEGF
Increased capillary permeability/ abnormal vasoproliferation
Causing hemorrhages, edema, exudates, ischemia, neo vascularization, fibrosis, traction RISK FACTORS The following risk factors mainly contribute to the manifestation of DR:
• Poorly-controlled diabetes
• High blood pressure
• Long-term duration of diabetes
• Elevated blood cholesterol levels
• Sleep apnea
• Obesity
LEARNING OBJECTIVE
To study the correlation between blood sugar control in patients with diabetes of at least 10 years and the
development of various clinical stages of DR.
METHODOLOGY Retrospectively looked at and studied the HbA1c values of patients with diabetes and its correlation, if
any, with their current stage of Diabetic Retinopathy.
(laboratory test - Hemoglobin A1c is a measure of the degree of glycemic control over the past 3 months) DEMOGRAPHIC This retrospective study was done on patients in the age group of 40 to 60 years. A total of 33 patients
were studied which included 15 males and 18 females. Patients with hyperlipidemia (high lipids) were
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excluded from the study. 2 males presented with hyperlipidemia and were excluded and 13 males and 18
females formed the cohort for this study.
STUDY DESIGN
• History and presenting complaints of patients were noted
• Visual acuity of patients as recorded was noted
• Patients with atleast 10 years duration of diabetes were included
• Past glycemic patient control (hemoglobin A1c) records of diabetes were noted and analyzed
• Medications for diabetes oral or injections taken by patients were recorded
• History of patients' hypertension (HT) and hyperlipidemia was recorded
• Patients’ dilated fundus examination findings and current stage of DR as recorded were noted
• Patients’ fundus photos, if taken, were looked at
• Treatment Modalities were noted
• Argon laser photocoagulation 1. Focal n grid 2. Pan
• INTRA VITREAL anti VEGF – Bevacizumab, Ranibizumab
• INTRA VITREAL steroids – Triamcinolone acetonide
RESULTS There were 6 patients out of the cohort who presented no signs of DR. All the Patients who did not suffer
from any DR were females and their HbA1c ranged from 5.50% to 6%. 2 out of the 6 females who did
not present signs of DR did suffer from hypertension. The duration of diabetes in these patients ranged
from 10 years to 11.5 years.
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Table 1: Patient details who did not suffer from DR when examined
Table 1 above shows their parameters at the time of examination, including their visual statistics. Table 2: Patient details who presented with signs of BDR on examination
Patient No.
SEX AGE IN YEARS
VISUAL ACUITY START VISIT
VISUAL ACUITY LAST VISIT
DURATION OF DM IN YEARS
AVERAGE OF 20 HBA1C READINGS
HT HYPER LIPIDEMIA
STAGE OF DR
102 F 49 R6/6 L6/6 R6/6p L6/9 10.2 5.70% N N BDR
105 F 60 R6/6L6/9 R6/6p L6/9 10.8 6.50% N N BDR
108 M 59 R6/9 L6/9 R6/9pL6/9 10.6 6.10% N N BDR
110 M 44 R6/6L6/6 R6/6L6/6 10 7% N N BDR
113 F 48 R6/6pL6/6 R6/9pL6/6 10.6 6.60% N N BDR
116 F 42 R6/6L6/6 R6/6L6/6 12 6.20% N N BDR
117 F 52 R6/12pL6/9 R6/6L6/6p 10.6 6.50% N N BDR
119 M 45 R6/9L6/9 R6/6L6/6 11.2 5.90% N N BDR
121 M 49 R6/6L6/6p R6/6L6/6 10.2 7.10% N N BDR
127 F 41 R6/6L6/6 R6/6L6/6p 11.5 7.50% N N BDR
129 M 46 R6/9L6/6 R6/6L6/6 10 5.40% N N BDR
131 M 50 R6/9L6/18p R6/6L6/9 11.6 8.10% N N BDR Out of the cohort of 31 patients, 12 patients showed signs of BDR. There were 6 males and 6 females
with their age ranging from 44 years to 59 years and 41 years to 60 years respectively. The HBA1c for
males ranged from 5.40% to 8.10% and for females from 5.70% to 7.50%. The duration of diabetes form
males ranged from 10 years to 11.6 years. Similar range for females was from 10.2 years to 11.5 years.
None of the patients who presented signs of BDR suffered from HT and their visual parameters were
recorded. These details have been shown in Table 2.
Patient No.
SEX AGE IN YEARS
VISUAL ACUITY START VISIT
VISUAL ACUITY LAST VISIT
DURATION OF DM IN YEARS
AVERAGE OF 20 HbA1C READINGS
HT HYPER LIPIDEMIA
STAGE OF DR
101 F 45 R6/6 L6/6 R6/6 L6/6 11.5 5.50% Y N NO DR
106 F 41 R6/6L6/12p R6/6L6/6 11 5.80% N N NO DR
111 F 59 R6/9 L6/6 R6/6L6/6 10.6 5.60% N N NO DR
120 F 55 R6/6L6/6 R6/6L6/6 10.4 5.70% Y N NO DR
123 F 47 R6/9L6/12 R6/6L6/6p 10 5.60% N N NO DR
126 F 56 R6/9L6/18p R6/6L6/18 11.4 6% N N NO DR
15
Table 3: Patient details who presented with signs of PPDR on examination
Patient No.
SEX AGE IN YEARS
VISUAL ACUITY START VISIT
VISUAL ACUITY LAST VISIT
DURATION OF DM IN YEARS
AVERAGE OF 20 HBA1C READINGS
HT HYPER LIPIDEMIA
STAGE OF DR
103 M 57 R6/9 L6/9 R6/9pL6/9 10 6% N N PPDR
109 F 53 R6/12L6/6 R6/9L6/6 11.6 6.70% N N PPDR
112 M 43 R6/6/L6/6 R6/6pL6/9 10.8 6.90% N N PPDR
114 F 51 R6/12L6/9 R6/12pL6/9 10 8% N N PPDR
122 F 50 R6/9L6/12 R6/6L6/18 11 8.40% N N PPDR
125 M 51 R6/18L6/12 R6/9L6/9 10.8 9.20% N N PPDR
132 F 48 R6/12L6/9 R6/9L6/9 11 7.20% N N PPDR A total of 7 patients from the cohort presented signs of PPDR. The 3 males had age ranging from 43 years
to 57 years. The HBA1c range for the males was 6% to 9.20%, none of them suffered from HT and the
duration for which they were suffering from diabetes was 10 years to 10.8 years. There were 4 females
who showed signs of PPDR and their age range was 48 years to 53 years and the duration of diabetes was
10 years to 11.6 years. The HbA1c range for female patients here was 6.70% to 8.40%. Table 3 also
shows their visual parameters as observed.
Table 4 below shows the list of 3 patients out of the cohort who were suffering from PDR. The 2 males
had ages 53years and 54 years, while the one female patient had an age of 58 years. Their visual
parameters had recorded and are presented in the table below. The males had HbA1c readings of 8.70%
and 10.60% and the female patient had a reading of 10.30%. None of the 3 patients suffered from any HT.
Table 4: Patient details who presented with signs of PDR on examination
Patient No.
SEX AGE IN YEARS
VISUAL ACUITY START VISIT
VISUAL ACUITY LAST VISIT
DURATION OF DM IN YEARS
AVERAGE OF 20 HBA1C READINGS
HT HYPER LIPIDEMIA
STAGE OF DR
118 M 54 R6/36L6/18 R6/24L6/12 10 8.70% N N PDR
124 F 58 R6/12L6/60 R6/12L6/24 10 10.30% N N PDR
128 M 53 R6/36pL6/9 R6/18L6/6 10.7 10.60% N N PDR
16
Table 5: Patient details who presented with signs of DME on examination
Patient No.
SEX AGE IN YEARS
VISUAL ACUITY START VISIT
VISUAL ACUITY LAST VISIT
DURATION OF DM IN YEARS
AVERAGE OF 20 HBA1C READINGS
HT HYPER LIPIDEMIA
STAGE OF DR
107 F 49 R6/24L6/18 R6/18L6/18 11.3 9% N N DME
130 M 60 R6/60L6/60 R6/36L6/24 10.6 12.30% N N DME
133 M 54 R6/12L6/24 R6/12pL6/18 10 9.10% N N DME Table 5 above shows the patients who suffered from advanced DME. There were 2 males and 1 female in
this study who suffered from advanced macular edema. The males were aged 60 years and 54 years, while
the female was 49 years old. The HbA1c diabetes readings for the males were 9.10% and 12.30% and the
female had these readings of 9%. There visual parameters were noted and none of them suffered from
HT.
DISCUSSION The diabetes blood test, also called HbA1c, tells you and your doctor how well diabetes is managed over
time. It measures your average blood sugar in the previous three months to see if it has stayed within a
target range. The target ranges are mentioned below and illustratively shown in Fig. 5:
• Normal HbA1c is 5% or less.
• An HbA1c value above 7% means diabetes is poorly controlled. People with diabetes should aim
for an HbA1c value below 7%.
The illustration in Fig. 6 shows the linear lines for each stage of DR and their corresponding HbA1c
levels for each patient in the cohort. It is a clear finding that the patients who did not suffer from any signs
of DR were the ones who had controlled their diabetes the best. All the patients who did not suffer from
any DR were females and their HbA1c ranged from 5.50% to 6%. Comparing these readings of HbA1c to
the range illustration in fig. 1 as well as in comparison to the other patients who showed different stages
of DR, it is self explanatory that all these patients, irrespective of their sex, had the lowest range of
17
HbA1c, i.e., between 5.50% to 6%. Comparing these ranges to the HbA1c ranges for BDR in males of
5.40% to 8.10% and for females of 5.70% to 7.50%, it is clear that these patients could not control their
diabetes as effectively as the previous group that did not suffer any signs of DR though being diabetic for
more than 10 years.
Fig 5: The HbA1c chart showing indicative ranges for diabetic control
The cumulative range for both the sexes in the group of patients that showed signs of BDR was
5.40% to 8.10%, being higher than the range of HBA1c as shown by the NO DR group.
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Fig. 6: Relation of HBA1c levels and Diabetic Retinopathy
Fig. 6 graphically shows the relation of HbA1c levels to each of the different stages of retinopathy
observed in this study.
Similar is the case with PPDR group having a HbA1c range of 6% to 9.2% for males and 6.70% to 8.40%
for females. The cumulative range being 6% to 8.40%. Here again the preponderance of HbA1c is clear in
the PPDR patients as compared to patients who did not show any retinopathy or patients showing BDR.
The patients suffering from PDR had HbA1c levels which were high as compared to patients who showed
no retinopathy or showed BDR or PPDR. The readings for males in this retinopathy group was 8.7% and
10.60%, while the lone female suffering form PDR in the cohort had HbA1c level of 10.3%. These
HbA1c levels were much higher to the previous groups of patients in this DR and diabetes correlation
study.
The last correlation was made between HbA1c levels in patients suffering from advanced DME as
compared to any other retinopathy. The 3 patients in the cohort who suffered from DME had a HbA1c
level of 10% and 10.6% in both males and 11.3% in the female.
0
2
4
6
8
10
12
14
1 2 3 4 5 6 7 8 9
HbA1c
Levels
Number of Patients
HbA1c levels and DR stages
NO DR
BDR
PPDR
PDR
DME
19
CONCLUSION
The graphical and tabular representation of the HbA1c data relevant to each patient shows a clear nexus
between uncontrolled diabetes and advancing stages of DR. Along with the duration of diabetes its poor
management leads to advanced stage of Diabetic Retinopathy, which is a leading cause of vision loss and
blindness.
20
GLOSSARY 1. Exudates: Exudates are fatty lipids that are left behind after past macular swelling subsides. 2. Ischemia: Blockage that are so dramatic that the involved capillaries cease to function and close off
blood supply to areas of the retina. This is called retinal ischemia or capillary non-perfusion. 3. Neovascularization: The development of new blood vessels, especially in tissues where circulation
has been impaired by trauma or disease. 4. Edema: Edema is a condition of abnormally large fluid volume in the circulatory system or in tissues
between the body's cells (interstitial spaces). In relation to DR it is the fluid within the retina. 5. HbA1c: Hemoglobin A1c is a measure of the degree of glycemic control over the past 3 months
21
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