**4. Sugar, and the cornea**

*Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic*

Refractive changes have been noted to occur in diabetic patients. A number of earlier clinical studies had reported an association between sustained hyperglycaemia, and refractive shift towards increased myopia [12, 19, 20]. Myopic shift occurs when a diabetic patient experiences more myopia than the regular refractive error status. This happens due to an increase in the inflow of sugar into the lens through the sorbitol pathway catalysed by the aldose reductase activity [21, 22]. People with diabetes have been observed to have a higher prevalence of myopia compared to those without diabetes [23]. In a study conducted by Jacobsen *et al* [24] it was determined that the prevalence of myopia (spherical equivalent 0.5 D) was 53.3% among 252 type 1 diabetic patient age 16–26 years old. The relative risk of a myopic shift was determined to be 1.7 in patients aged 16–21 years, and 1.6 in patients with HbA1c above 8.8%. Insulin dosage was not related to myopia. Klein et al. [21] showed that persons of similar age with T1D were likely to be more myopic than those with T2D. In general, myopia associated with diabetes reverses when

Although past studies had reported a myopic shift in refractive status following an increase in sugar level, however, recent studies have also noted a hyperopic shift associated with glycaemic control [25, 26]. Hyperopic shift following hyperglycaemia control has been reported to occur when glucose levels fall a few days or weeks after the initiation of glycaemic control [12, 27]. This hyperopia was associated with increased lens thickness, and a decrease in anterior chamber depth [22]. Lin *et al* [12] reported the development of hyperopia in 4 men and 1 woman who was treated with insulin. According to their report, the hyperopia peaked at 11.7 days after initiation of glycaemic control and tapered off at 64.0 days after treatment initiation. From this it can be deduced that institution of treatment in diabetic patients is often followed by two refractive changes; one involving a rapid refractive change towards the direction of hyperopic, and the other is a gradual change to the patient's

In general, both myopic, and hyperopic shifts are transient, and patients' refractive status gradually returns to the baseline values a few days or weeks after sugar stabilizes. Thus, it can be said that both myopic, and hyperopic shift may occur with changes in sugar levels in a hyperglycemic patient [25]. Hence, change in prescription glasses should be approached with caution as glasses prescribed during this

Several studies have reported on biometric changes such as lens thickening, increase in the lens surface curvature and a decrease in the refractive index secondary to diabetes [29]. According to Mathebula, and Makunyane "people with diabetes have accelerated age-related biometric ocular changes compared to people without diabetes" [4]. Elevated sugar levels in pre-presbyopic patients have been associated with a reduction in the amplitude of accommodation. According to Huntjens and O'Donnell, amplitude of accommodation is lower in people living with Type I patients than that of their non-diabetic age-matched, even in the

Amplitude of accommodation is important for maintaining images on the retina while doing near work. A reduction in amplitude of accommodation means that the near point becomes receded, and a patient will have difficulties reading things at near as seen in presbyopic patients. This has unfortunately been found in prepresbyopic diabetic patients who show signs of presbyopia earlier than their age

time will only be durable during the said sugar fluctuations [28].

**3.2 Sugar, and refractive error**

sugar control is instituted.

normal refractive status.

**3.3 Sugar, and accommodation**

absence of non-detectable retinal damage [25].

**24**

The cornea is a superficial organ most affected by high sugar levels [30]. The impact of sugar on the cornea varies with its level and duration, and may underpin specific systemic complications that may be associated with diabetes. At normal glycaemic levels, sugar serves as one of the dissolved nutrients in the tears, and aqueous humour that nourishes the cornea. Sugar is also found in the cornea stroma in the form of polysaccharides (glycosaminoglycan GAG) [31]. GAG reduces the effects of diffraction when light is directed towards the eye. Chondroitin sulphate an element that plays a role in cornea wound healing is also made from polysaccharides.

However, in diabetes, sugar promises to be detrimental to the anatomical and physiological wellbeing of the cornea. Structural components such as the epithelium, the nerves, immune cells, and the endothelium of the cornea are often negatively affected. Sustained hyperglycaemia reduces cornea sensitivity and innervation due to peripheral neuropathy. These nerve alterations occur all over the cornea including at the cornea scleral junction (limbal region) where new epithelial cells are formed [31]. When there is a reduction in corneal sensitivity, affected patients experiences various symptoms, and in most cases become susceptible to further damages to the eye. Reduction in corneal sensitivity has been identified as a predictor for the development of peripheral neuropathy in diabetic patients.

Other cornea complications such as corneal infections, ulcers, and oedema have been reported in diabetic patients with poorly controlled glycaemic levels. Sugar induced cornea swelling increases the fragility of the cornea epithelium and can result in stroma oedema [32]. This for unknown reasons affects the stromal collagen bundles and increases corneal autofluorescence level. The variation between the normal fluorescence level and increased autofluorescence in the corneal may be an indicator of changed corneal metabolism due to impaired corneal mitochondria metabolism. Corneal fluorescence may also be an indicator of a pathological breakdown of the blood-aqueous- barrier as may be seen in patients with proliferative diabetic retinopathy.

Sustained hyperglycaemic levels in the body also increases the chances of corneal erosions, persistent epithelial defects, corneal endothelial damage, and dry eye [6, 22, 32]. With Sustained hyperglycaemia the cornea faces difficulties with wound healing, and most times there is incomplete wound healing, thus small corneal erosions become persistent as wound healing is delayed. Delayed wound healing has been linked to a reduction in cornea epithelium regeneration secondary to a decrease in cornea sensitivity, which occurs as a result of peripheral neuropathy [6]. linked Further, because the ability of the cornea to ward off infections is reduced, infections like fungal keratitis occurs and remains recurrent [33].

### **5. Sugar, and the lids, and conjunctiva**

The lids and conjunctiva are tissues in the body that protects the eye against external invaders. Sustained high blood sugar level increases the susceptibility

of the human system to bacterial infection. In the lid, this susceptibility leads to a recurrent bacterial infection which can lead to the formation of stye, and blepharitis.

High sugar and reduced insulin as is obtainable in diabetes pose damaging consequences to the meibomian gland. Like other sebaceous glands, insulin forms an essential component for the optimal functioning of the sebaceous glands and resistance or reduction in its absorption results in the dysfunction of the Meibomian gland. Similarly, sustained increase in sugar level brings about the lipolysis of adipocytes, this, therefore, means that sustained sugar levels in the Meibomian gland will reduce the quality of the meibum secreted in the eye. Meibum is the secretion responsible for ensuring the liquid part of the tears (aqueous) does not overflow or evaporate, hence reduction in the quality of meibum would allow for tear evaporation, bringing about dry eye effect in diabetic patients.

Similarly, the goblet cells found in the conjunctiva which are responsible for the production of the mucin layer of the tear film are often adversely affected with Hyperglycaemic. Diabetes also affects the conjunctival blood vessels in similar ways as it does to the retinal blood vessels [34]. In the conjunctiva, capillary loss, and microvascular dilatation had similarly been observed as a consequence of sustained hyperglycemia. Similarly, studies have reported on the tortuosity of conjunctival blood vessels.

#### **6. Sugar, and dry eye**

Dry eye is a disorder of the tear film which results in symptoms such as pain, burning, itchiness, stinging, grittiness, foreign body sensation, tearing, and ocular fatigue. Due to the multifactorial nature of dry eye onset, it has been referred to as a disease of the lacrimal function unit (LFU). The lacrimal function unit is made up of the cornea, lid, conjunctiva, Meibomian gland, the sensory, and the motor nerves which all work as a unit to maintain the tear film layer. Dry eye is a common experience in diabetic patients.

The occurrence of dry eye in a diabetic patient may be as a result of the negative effect of hyperglycaemia on any part of the lacrimal function unit. For instance, insufficient production of tears due to reduced cornea sensitivity secondary to autonomic neuropathy has been blamed as part of the reason for dry eye development in diabetic patients [35]. Corneal sensitivity forms part of the neuronal loophole feedback mechanism for reflex tear secretion. Autonomic neuropathy affects the nerves that control the lacrimal gland secretion, bringing about a reduction in tears secretion, due to reduced corneal sensitivity. For instance, damage to the microvasculature of the lacrimal gland accompanied by autonomic neuropathy in diabetic patients often impairs lacrimation, therefore, resulting in dry eye symptoms in such a patient. The reduction in tear secretion accounts for the low Schirmer test result as may be seen in diabetic patients. It is noteworthy that once corneal peripheral neuropathy sets in, corneal sensitivity starts and the magnitude of reflex tear secretion is affected.

Also, dry eye may result due to a reduction in the population density of the goblet cells secondary to the effect of diabetes on the cells on the goblet cell function [22]. The goblet cells are responsible for the secretion of mucin which is the first layer of the tear film. The mucin layer is responsible for maintaining the tear film layer on the cornea to avoid the drying out of the cornea and maintaining its lustre. Therefore, a reduction in the density of the goblet cells will bring about a decrease in the secretion of the mucin layer, resulting in the inability of the tear film to remain stable on the cornea. Also, alongside the reduction in goblet cell density,

**27**

dark rooms.

**8. Sugar, and the vitreous**

*Impact of Sugar on Vision*

patients.

*DOI: http://dx.doi.org/10.5772/intechopen.96325*

glycaemic control, and healthy lifestyle.

with ischaemia secondary to retinal capillary dropout.

**7. Sugar, and the iris**

there is an accompanying reduction in the ability of the mucin layer to "pickup-up' the cytology impression necessary to maintain the tear film spreading, and stability on the cornea. These two factors (goblet cell density, and mucin sensitivity), have been cited to partly be responsible for the reduction in the tear break-up time. Some retinal changes, and procedures have similarly been linked with dry eye in patients with prolonged, and sustained hyperglycaemia. Reduction in total tear secretion has been reported in patients with non-proliferative diabetic retinopathy. This on the other hand is relatively small in people without retinopathy. Also, pan-retinal photocoagulation has been suggested to increase dry eye syndrome in

Dry eye symptoms in diabetic patients are often associated with longer duration of the disease; it may also be associated with glycaemic level (HBA1c) [36]. Further, poorly controlled glycaemic level has been associated with more symptoms of dry eye. The most frequently encountered dry eye disease symptoms in diabetic patients include itching, burning, and foreign body sensation. Detection of dry eye in a diabetic patient can be achieved through conducting a comprehensive eye examination, which among others should measure the volume of tears, and determine the quality of the tears. This can be achieved by running specific diagnostic tests such as the Tear Film Break-Up Time (TFBUT), fluoresce test, Schirmer test, and rose Bengal. Management of dry eye in patients with diabetes strongly revolves around

Hyperglycaemia affects the iris in various ways. Morphologically, changes in the iris structure, vessels, pigment granules, and vacuolation of the pigment. The iris epithelium due to hyperglycaemia can experience depigmentation of the cells which often deposits on the corneal endothelium or is washed by the aqueous flow to the trabecular meshwork where it could block the outflow of aqueous from the meshwork, therefore resulting in the building of ocular tension (increased intraocular pressure). Also, Hyperglycaemic may cause rubeosis iridis (the formation abnormal blood vessels on the epithelial layer of the iris), a response that has been associated

Further, abnormal iris transilluminance has been reported to occur in type 2 diabetes patients. This has been associated with short term retinopathy and is said to be an indicator or marker for rapidly progressive retinopathy in diabetes [37]. Similarly, ultrastructural changes have been reported in the regions of the sphincter, and dilator muscles of the iris, with more of the changes seen in the iris, this may explain why the pupil in diabetic patient's experience miosis while in

In the presence of hyperglycaemia, the vitreous gel and vitreous interface experiences alterations which are often predictors to the development of diabetic retinopathy. Changes in the vitreous gel due to diabetic mellitus may include; increased collagen fibril cross-linking, accumulation of advanced glycation end products, liquidation of the vitreous gels, vitreous haemorrhage and alteration in the concentration of various proteins present in the vitreous [38, 39]. In some cases, there may also be the development of new vessel on the vitreous surface, this can happen in response to retinal ischemia and can result in a structural change in

#### *Impact of Sugar on Vision DOI: http://dx.doi.org/10.5772/intechopen.96325*

*Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic*

tion, bringing about dry eye effect in diabetic patients.

blepharitis.

blood vessels.

**6. Sugar, and dry eye**

ence in diabetic patients.

of reflex tear secretion is affected.

of the human system to bacterial infection. In the lid, this susceptibility leads to a recurrent bacterial infection which can lead to the formation of stye, and

High sugar and reduced insulin as is obtainable in diabetes pose damaging consequences to the meibomian gland. Like other sebaceous glands, insulin forms an essential component for the optimal functioning of the sebaceous glands and resistance or reduction in its absorption results in the dysfunction of the Meibomian gland. Similarly, sustained increase in sugar level brings about the lipolysis of adipocytes, this, therefore, means that sustained sugar levels in the Meibomian gland will reduce the quality of the meibum secreted in the eye. Meibum is the secretion responsible for ensuring the liquid part of the tears (aqueous) does not overflow or evaporate, hence reduction in the quality of meibum would allow for tear evapora-

Similarly, the goblet cells found in the conjunctiva which are responsible for the production of the mucin layer of the tear film are often adversely affected with Hyperglycaemic. Diabetes also affects the conjunctival blood vessels in similar ways as it does to the retinal blood vessels [34]. In the conjunctiva, capillary loss, and microvascular dilatation had similarly been observed as a consequence of sustained hyperglycemia. Similarly, studies have reported on the tortuosity of conjunctival

Dry eye is a disorder of the tear film which results in symptoms such as pain, burning, itchiness, stinging, grittiness, foreign body sensation, tearing, and ocular fatigue. Due to the multifactorial nature of dry eye onset, it has been referred to as a disease of the lacrimal function unit (LFU). The lacrimal function unit is made up of the cornea, lid, conjunctiva, Meibomian gland, the sensory, and the motor nerves which all work as a unit to maintain the tear film layer. Dry eye is a common experi-

The occurrence of dry eye in a diabetic patient may be as a result of the negative effect of hyperglycaemia on any part of the lacrimal function unit. For instance, insufficient production of tears due to reduced cornea sensitivity secondary to autonomic neuropathy has been blamed as part of the reason for dry eye development in diabetic patients [35]. Corneal sensitivity forms part of the neuronal loophole feedback mechanism for reflex tear secretion. Autonomic neuropathy affects the nerves that control the lacrimal gland secretion, bringing about a reduction in tears secretion, due to reduced corneal sensitivity. For instance, damage to the microvasculature of the lacrimal gland accompanied by autonomic neuropathy in diabetic patients often impairs lacrimation, therefore, resulting in dry eye symptoms in such a patient. The reduction in tear secretion accounts for the low Schirmer test result as may be seen in diabetic patients. It is noteworthy that once corneal peripheral neuropathy sets in, corneal sensitivity starts and the magnitude

Also, dry eye may result due to a reduction in the population density of the goblet cells secondary to the effect of diabetes on the cells on the goblet cell function [22]. The goblet cells are responsible for the secretion of mucin which is the first layer of the tear film. The mucin layer is responsible for maintaining the tear film layer on the cornea to avoid the drying out of the cornea and maintaining its lustre. Therefore, a reduction in the density of the goblet cells will bring about a decrease in the secretion of the mucin layer, resulting in the inability of the tear film to remain stable on the cornea. Also, alongside the reduction in goblet cell density,

**26**

there is an accompanying reduction in the ability of the mucin layer to "pickup-up' the cytology impression necessary to maintain the tear film spreading, and stability on the cornea. These two factors (goblet cell density, and mucin sensitivity), have been cited to partly be responsible for the reduction in the tear break-up time.

Some retinal changes, and procedures have similarly been linked with dry eye in patients with prolonged, and sustained hyperglycaemia. Reduction in total tear secretion has been reported in patients with non-proliferative diabetic retinopathy. This on the other hand is relatively small in people without retinopathy. Also, pan-retinal photocoagulation has been suggested to increase dry eye syndrome in patients.

Dry eye symptoms in diabetic patients are often associated with longer duration of the disease; it may also be associated with glycaemic level (HBA1c) [36]. Further, poorly controlled glycaemic level has been associated with more symptoms of dry eye. The most frequently encountered dry eye disease symptoms in diabetic patients include itching, burning, and foreign body sensation. Detection of dry eye in a diabetic patient can be achieved through conducting a comprehensive eye examination, which among others should measure the volume of tears, and determine the quality of the tears. This can be achieved by running specific diagnostic tests such as the Tear Film Break-Up Time (TFBUT), fluoresce test, Schirmer test, and rose Bengal. Management of dry eye in patients with diabetes strongly revolves around glycaemic control, and healthy lifestyle.

### **7. Sugar, and the iris**

Hyperglycaemia affects the iris in various ways. Morphologically, changes in the iris structure, vessels, pigment granules, and vacuolation of the pigment. The iris epithelium due to hyperglycaemia can experience depigmentation of the cells which often deposits on the corneal endothelium or is washed by the aqueous flow to the trabecular meshwork where it could block the outflow of aqueous from the meshwork, therefore resulting in the building of ocular tension (increased intraocular pressure). Also, Hyperglycaemic may cause rubeosis iridis (the formation abnormal blood vessels on the epithelial layer of the iris), a response that has been associated with ischaemia secondary to retinal capillary dropout.

Further, abnormal iris transilluminance has been reported to occur in type 2 diabetes patients. This has been associated with short term retinopathy and is said to be an indicator or marker for rapidly progressive retinopathy in diabetes [37]. Similarly, ultrastructural changes have been reported in the regions of the sphincter, and dilator muscles of the iris, with more of the changes seen in the iris, this may explain why the pupil in diabetic patient's experience miosis while in dark rooms.

#### **8. Sugar, and the vitreous**

In the presence of hyperglycaemia, the vitreous gel and vitreous interface experiences alterations which are often predictors to the development of diabetic retinopathy. Changes in the vitreous gel due to diabetic mellitus may include; increased collagen fibril cross-linking, accumulation of advanced glycation end products, liquidation of the vitreous gels, vitreous haemorrhage and alteration in the concentration of various proteins present in the vitreous [38, 39]. In some cases, there may also be the development of new vessel on the vitreous surface, this can happen in response to retinal ischemia and can result in a structural change in

the vitreous [40, 41]. The presence of severe non-clearing vitreous haemorrhage may be an indicator for the.

#### **9. Sugar, and the retina**

Sugar affects different layers of the retina, and in most cases is very detrimental, and can lead to blindness. Diabetic retinopathy is the most common cause of visual impairment in patients living with diabetes.

#### **9.1 Sugar, and diabetic retinopathy**

Diabetic retinopathy is a microvascular complication of diabetes. It is said to occur to some degree in almost all type 1 diabetic patients and in nearly 77% of people living with type 2 diabetes for more than 2 decades [7]. Its formation has been linked to hyperglycaemic induced electrolyte imbalance secondary to high aldose reductase levels in the retina [39]. The electrolyte imbalance leads to the loss of retinal endothelial cells and loss of vascular pericytes which are responsible for regulating the retinal vascular tone. Loss of endothelial cells results in the breakdown of the blood-retinal-barrier resulting in an increase in the vascular permeability. On the other hand, the loss of the pericytes results in vasodilation and the thickening of the capillary basement membrane all of which leads to microaneurysm (formation of small outpouchings from blood vessel walls) [42], a primary indicator of early retinopathy changes in diabetes [43].

There are different stages of diabetic retinopathy: mild non-proliferative diabetic retinopathy, pre-proliferative diabetic retinopathy, and proliferative diabetic retinopathy. According to the findings of the Wisconsin study, the prevalence of retinopathy in patients with diabetes increases from 2% to 97.5% in people with diabetes less than 2 years, and 15 or more years respectively. Prevalence of proliferative retinopathy was notably at zero but increased with age to 4%, 25%, and 67% among diabetic patients who had lived with diabetes for 10 years, 15 years, and 35 years respectively. Proliferative diabetic retinopathy is the most complicated stage of diabetic retinopathy and is often associated with other complications such as vitreous haemorrhage, tractional retinal detachment, combined tractional rhegmatogenous retinal detachment, and severe fibrovascular proliferation.

Proliferative diabetic retinopathy is said to occur due to prolonged retinal ischemia secondary to Hyperglycaemic. Retinal ischemia leads to the production of angiogenic factors which are produced in an attempt for the retina to revascularize the hypoxic areas of the retina. Thus the release of angiogenic factors is the retinal way of seeking for a secondary means of transporting oxygen to the affected parts of the retina. After the formation of the angiogenic factor, there appears to be an interaction between the angiogenic factors, and the vascular endothelial growth factor (VEGF) thereby inducing the growth of new blood vessels (neovascularization). The new vessels are fragile, and can easily rupture, but they proliferate persistently. The proliferation of the new blood vessels is accompanied by varying degrees of fibrous tissue proliferation. Fibrous tissue proliferation into the vitreoretinal interface brings about the formation of fibrovascular membranes in the vitreoretinal interface.

The fibrovascular tissues attach themselves to the vitreoretinal interface focally (at a point) or broadly (at different points). The point of attachment of the fibrovascular tissue to the vitreoretina exerts tractional forces at these points, therefore, pulling on the retina, and resulting in tractional retinal detachment.

**29**

*Impact of Sugar on Vision*

diabetic retinopathy.

*DOI: http://dx.doi.org/10.5772/intechopen.96325*

activated leukocytes circulating in the retinal blood vessels.

GLP-1 is often activated by SIRT1 an anti-ageing gene.

**10. Sugar and the optic disc, and nerve**

may ensure to proliferative diabetic retinopathy.

The role of angiotensin II in the formation of diabetic retinopathy has been well studied with most studies promoting possible retardation of the proliferation process seen in diabetic retinopathy through the use of drugs that blocks the renin-angiotensin system. This is because angiotensin II which promotes vascular remodelling, and proliferation can cause an increase in the growth of capillaries, and cell permeability, and oxidative stress which is common in the formation of

The role of vasodilators like nitric oxide has rather been inconclusive, and a matter of debate. While some researchers believe that nitric oxide could lead to retinal damage and death, some others believe that nitric oxide enzyme may be protective in the development of diabetic retinopathy. Also, the actions of Glucagon-Like-Peptide-1 (GLP-1) a 30-amino acid, which is a hormone produced in the intestine, and helps in regulating blood glucose has been found to play a protective role on the retinal cells via the reduction of oxidative stress on the retina, which is protective in the development of diabetic retinopathy [11]. The action of

Sustained sugar level affects the optic nerve resulting in nerve abnormalities, for instance, the optic disc often experiences pronounced oxidative stress, ischaemia, and neurodegeneration which eventually results into loss of the retinal nerve fibre layer, and optic atrophy. Optic atrophy may occur due to the inability of the nerves to access nourishment secondary to hyperglycaemia. Optic atrophy secondary to hyperglycaemia is very common in diabetic patients who are in their fourth decade of life. Although this presents no symptoms, it requires constant monitoring as it

Optic nerve atrophy may also occur as a result of damage following photocoagulation treatment. This often shows a characteristics appearance that is abnormal

Although the duration and glycaemic control play a role in the development of retinopathy, genetics, and individual disparity contribute significantly to the development and degree of retinopathy. Diabetic retinopathy has been cited to occur more globally in Latin Americans, and South Asians [5]. Clustering of diabetic retinopathy among people of similar ethnicity suggests that genetics could play a significant role in its development. The role of familial genetics in the development of diabetic retinopathy was demonstrated by Leslie and Pyke who found that 95% of concordant type 2 diabetic twins versus 68% of concordant type 1 diabetic identical twins develop a similar degree of diabetic retinopathy. Also, siblings with diabetes have similar levels of diabetes when compared to other levels of retinopathies seen in nonfamily members. Familial clustering for the risk of developing severe retinopathy to increase among those who have diabetic relatives with positive retinopathy with an odds ratio of 5.4 compared to those whose relatives do not have the retinopathy [44]. Further, the genes responsible for encoding the aldose reductase (ALR), Angiotensin-1-converting enzyme, endothelial nitric oxide synthase (eNOS), a receptor for advanced glycation end products (RAGE), and Vascular Endothelial Growth Factor (VEGF), has been implicated in the development of Diabetic retinopathy [44]. Also, evidence exist which suggest that low-grade inflammatory responses underlies the resultant vascular complications seen in diabetes retinopathy. This, therefore, implies that diabetic retinopathy is an inflammatory disease that results due to elevated systemic cytokines like TNF-a, and IL-1B, and elevated numbers of

#### *Impact of Sugar on Vision DOI: http://dx.doi.org/10.5772/intechopen.96325*

*Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic*

may be an indicator for the.

**9. Sugar, and the retina**

impairment in patients living with diabetes.

indicator of early retinopathy changes in diabetes [43].

ment, and severe fibrovascular proliferation.

**9.1 Sugar, and diabetic retinopathy**

the vitreous [40, 41]. The presence of severe non-clearing vitreous haemorrhage

Sugar affects different layers of the retina, and in most cases is very detrimental, and can lead to blindness. Diabetic retinopathy is the most common cause of visual

Diabetic retinopathy is a microvascular complication of diabetes. It is said to occur to some degree in almost all type 1 diabetic patients and in nearly 77% of people living with type 2 diabetes for more than 2 decades [7]. Its formation has been linked to hyperglycaemic induced electrolyte imbalance secondary to high aldose reductase levels in the retina [39]. The electrolyte imbalance leads to the loss of retinal endothelial cells and loss of vascular pericytes which are responsible for regulating the retinal vascular tone. Loss of endothelial cells results in the breakdown of the blood-retinal-barrier resulting in an increase in the vascular permeability. On the other hand, the loss of the pericytes results in vasodilation and the thickening of the capillary basement membrane all of which leads to microaneurysm (formation of small outpouchings from blood vessel walls) [42], a primary

There are different stages of diabetic retinopathy: mild non-proliferative diabetic retinopathy, pre-proliferative diabetic retinopathy, and proliferative diabetic retinopathy. According to the findings of the Wisconsin study, the prevalence of retinopathy in patients with diabetes increases from 2% to 97.5% in people with diabetes less than 2 years, and 15 or more years respectively. Prevalence of proliferative retinopathy was notably at zero but increased with age to 4%, 25%, and 67% among diabetic patients who had lived with diabetes for 10 years, 15 years, and 35 years respectively. Proliferative diabetic retinopathy is the most complicated stage of diabetic retinopathy and is often associated with other complications such as vitreous haemorrhage, tractional retinal detachment, combined tractional rhegmatogenous retinal detach-

Proliferative diabetic retinopathy is said to occur due to prolonged retinal ischemia secondary to Hyperglycaemic. Retinal ischemia leads to the production of angiogenic factors which are produced in an attempt for the retina to revascularize the hypoxic areas of the retina. Thus the release of angiogenic factors is the retinal way of seeking for a secondary means of transporting oxygen to the affected parts of the retina. After the formation of the angiogenic factor, there appears to be an interaction between the angiogenic factors, and the vascular endothelial growth factor (VEGF) thereby inducing the growth of new blood vessels (neovascularization). The new vessels are fragile, and can easily rupture, but they proliferate persistently. The proliferation of the new blood vessels is accompanied by varying degrees of fibrous tissue proliferation. Fibrous tissue proliferation into the vitreoretinal interface brings about the formation of fibrovascular membranes in the vitreoreti-

The fibrovascular tissues attach themselves to the vitreoretinal interface focally (at a point) or broadly (at different points). The point of attachment of the fibrovascular tissue to the vitreoretina exerts tractional forces at these points, therefore,

pulling on the retina, and resulting in tractional retinal detachment.

**28**

nal interface.

Although the duration and glycaemic control play a role in the development of retinopathy, genetics, and individual disparity contribute significantly to the development and degree of retinopathy. Diabetic retinopathy has been cited to occur more globally in Latin Americans, and South Asians [5]. Clustering of diabetic retinopathy among people of similar ethnicity suggests that genetics could play a significant role in its development. The role of familial genetics in the development of diabetic retinopathy was demonstrated by Leslie and Pyke who found that 95% of concordant type 2 diabetic twins versus 68% of concordant type 1 diabetic identical twins develop a similar degree of diabetic retinopathy. Also, siblings with diabetes have similar levels of diabetes when compared to other levels of retinopathies seen in nonfamily members. Familial clustering for the risk of developing severe retinopathy to increase among those who have diabetic relatives with positive retinopathy with an odds ratio of 5.4 compared to those whose relatives do not have the retinopathy [44].

Further, the genes responsible for encoding the aldose reductase (ALR), Angiotensin-1-converting enzyme, endothelial nitric oxide synthase (eNOS), a receptor for advanced glycation end products (RAGE), and Vascular Endothelial Growth Factor (VEGF), has been implicated in the development of Diabetic retinopathy [44]. Also, evidence exist which suggest that low-grade inflammatory responses underlies the resultant vascular complications seen in diabetes retinopathy. This, therefore, implies that diabetic retinopathy is an inflammatory disease that results due to elevated systemic cytokines like TNF-a, and IL-1B, and elevated numbers of activated leukocytes circulating in the retinal blood vessels.

The role of angiotensin II in the formation of diabetic retinopathy has been well studied with most studies promoting possible retardation of the proliferation process seen in diabetic retinopathy through the use of drugs that blocks the renin-angiotensin system. This is because angiotensin II which promotes vascular remodelling, and proliferation can cause an increase in the growth of capillaries, and cell permeability, and oxidative stress which is common in the formation of diabetic retinopathy.

The role of vasodilators like nitric oxide has rather been inconclusive, and a matter of debate. While some researchers believe that nitric oxide could lead to retinal damage and death, some others believe that nitric oxide enzyme may be protective in the development of diabetic retinopathy. Also, the actions of Glucagon-Like-Peptide-1 (GLP-1) a 30-amino acid, which is a hormone produced in the intestine, and helps in regulating blood glucose has been found to play a protective role on the retinal cells via the reduction of oxidative stress on the retina, which is protective in the development of diabetic retinopathy [11]. The action of GLP-1 is often activated by SIRT1 an anti-ageing gene.

## **10. Sugar and the optic disc, and nerve**

Sustained sugar level affects the optic nerve resulting in nerve abnormalities, for instance, the optic disc often experiences pronounced oxidative stress, ischaemia, and neurodegeneration which eventually results into loss of the retinal nerve fibre layer, and optic atrophy. Optic atrophy may occur due to the inability of the nerves to access nourishment secondary to hyperglycaemia. Optic atrophy secondary to hyperglycaemia is very common in diabetic patients who are in their fourth decade of life. Although this presents no symptoms, it requires constant monitoring as it may ensure to proliferative diabetic retinopathy.

Optic nerve atrophy may also occur as a result of damage following photocoagulation treatment. This often shows a characteristics appearance that is abnormal

which may or may not be similar to glaucomatous damage [45]. This is due to nerve damage that may be associated with the destruction of the axons of the retinal ganglion cells following pan-retinal photocoagulation. Other causes of optic atrophy may include previous diabetic papilopathy, nonarteritic ischemic neuropathy, and multiple nerve fibre layer infarcts.

Neovascularization at the optic disc head may also occur especially in the proliferative stage of diabetes. Although the formation of these vessels are mechanisms by which the eye seems to transport oxygen to areas without nourishment, however, the new vessels formed are both fragile, and vulnerable to rupture, hence presents a danger to the eye.

#### **11. Diabetes induced maculopathy**

Diabetes induced maculopathy is a common occurrence in people with diabetic retinopathy [41]. Its prevalence is often determined by the type of diabetes, the severity of diabetic retinopathy, and duration of the disease. Type 1 diabetic patients are less likely to develop maculopathy, than type 2 diabetic patients [40]. Also, the occurrence of maculopathy in type 1 diabetic patients is highly dependent on the duration of the disease. Most of the patients with type 1 diabetes will rarely develop maculopathy before 8 years of the disease, with about 25–30% developing maculopathy after 20 years of the disease [41, 43]. About 3% of type 2 diabetic patients with non-proliferative retinopathy will have macular oedema, whereas between 40%, and 70% of those with moderate, and proliferative retinopathy respectively would end up developing macular oedema. Among this population, nearly half of them will experience fovea involvement of the macula oedema [43].

#### **12. Pupil involvement in diabetes**

Pupillary involvement is a common occurrence in diabetic patients and has been suggested to be due to autonomic neuropathy secondary to degenerative changes at the nerve terminal. In the pupil, the autonomous nervous system regulates the sphincter, and dilator muscles which controls the pupillary response to light, accommodation, and drugs. Sustained high sugar level often results in autonomic neuropathy which meant that nerves lose their ability to respond or conduct sensations as they ought to. The occurrence of autonomic neuropathy results in partial denervation of mostly the dilator muscle of the pupil. This, therefore, implies different pupillary responses to normal pupillary stimulus diabetic patients will be affected. For instance, diabetic pupils have excessive miotic pupils in dim illumination, also diabetic pupils experience loss of light reflex, non-syphilitic-Argy Robertson pupil has been reported. Further, variations in response to topical mydriatic agents have similarly been noted.

#### **13. Sugar, and glaucoma**

There are still conflicting opinions regarding the relationship between glaucoma and diabetes, however, the mechanism that leads to the autonomic dysfunction in the regulation of intraocular pressure, fluctuation of intraocular pressure, and the increased susceptibility of retinal ganglion cells to cell death can easily be rationalized [46]. According to Negi and Vernon [43], diabetic patients are at high risk

**31**

*Impact of Sugar on Vision*

mellitus.

*DOI: http://dx.doi.org/10.5772/intechopen.96325*

**14. Sugar, and ophthalmoplegia**

**15. Sugar, and low vision**

**15.1 Sugar, and visual acuity**

**15.2 Sugar, and colour vision**

affected patients.

of developing higher intraocular pressures than their non-diabetic counterparts. Proliferative diabetes is one of the leading causes of neovascular glaucoma.

Ophthalmoplegia is a rare adverse effect of diabetes mellitus. It is often associated with multiple cranial nerve palsies affecting nerve III, IV, and VI. Patients with ophthalmoplegia secondary to diabetes often make a full recovery after 12 weeks of the onset of the condition [47]. A study by Kahtani et al. [48] reported ophthalmoplegia to be more common in male than female diabetic patients. Medial squint and Ptosis have also been reported in patients with acute vasculitis due to diabetes

Complications secondary to diabetes mellitus is the leading cause of blindness in developed countries [6, 40]. According to global estimates, 5% of the 37 million cases of blindness occur secondary to diabetic retinopathy [7]. However, not all cases of diabetic retinopathy results in blindness, some others cause low vision in

Low vision as defined by World Health Organization (WHO), is the visual acuity of less than 6/18 in the best-corrected eye of a patient. It can also be defined as the visual field of less than 10 degrees in a patient. There exists a strong relationship between complications resulting from sustained hyperglycaemia as seen in diabetes and low vision. Some of the complications resulting from hyperglycaemia brings about visual changes in sufferers which may eventually lead to low vision. Some visual changes that have been reported by hyperglycaemic patients include changes in Visual acuity, colour vision, contrast sensitivity, reduction in glare tolerance, and

Because visual acuity status is affected by the status of the retina, cornea, lens, and the anterior chamber, visual acuity is one of the visual functions that is heavily affected by hyperglycaemia at different stages of the disease. Visual acuity may be affected by the presence of Diabetic cataract, which reduces the clarity of the lens. Visual acuity may also be affected by the presence of retinopathy which results in irreversible damage in the visual threshold of the patient. Other causes of reduction in visual acuity in a diabetic patients patient may include macular oedema, corneal haze, variations in the refractive status of the eyes due to variations in glycaemic levels, and procedures such as photocoagulation for diabetic macular oedema [49].

Acquired dyschromatopsia has been reported to be common in people living with type 2 diabetes. The Okubo colour study, conducted among type diabetic patients showed that there is an-increased-adjusted-odds (5.89) for the development of colour vision impairment by type 2 diabetic compared with their agematched normal glycaemic peers [2]. Some studies have reported an increase in the incidence of acquired, non-sex-linked blue-yellow colour vision deficit in diabetic patients. According to a study by Melisa et al., the blue-yellow colour deficit is more

visual field all, of which affects a person's quality of life.

*Sugar Intake - Risks and Benefits and the Global Diabetes Epidemic*

multiple nerve fibre layer infarcts.

**11. Diabetes induced maculopathy**

**12. Pupil involvement in diabetes**

mydriatic agents have similarly been noted.

**13. Sugar, and glaucoma**

danger to the eye.

oedema [43].

which may or may not be similar to glaucomatous damage [45]. This is due to nerve damage that may be associated with the destruction of the axons of the retinal ganglion cells following pan-retinal photocoagulation. Other causes of optic atrophy may include previous diabetic papilopathy, nonarteritic ischemic neuropathy, and

Neovascularization at the optic disc head may also occur especially in the proliferative stage of diabetes. Although the formation of these vessels are mechanisms by which the eye seems to transport oxygen to areas without nourishment, however, the new vessels formed are both fragile, and vulnerable to rupture, hence presents a

Diabetes induced maculopathy is a common occurrence in people with diabetic retinopathy [41]. Its prevalence is often determined by the type of diabetes, the severity of diabetic retinopathy, and duration of the disease. Type 1 diabetic patients are less likely to develop maculopathy, than type 2 diabetic patients [40]. Also, the occurrence of maculopathy in type 1 diabetic patients is highly dependent on the duration of the disease. Most of the patients with type 1 diabetes will rarely develop maculopathy before 8 years of the disease, with about 25–30% developing maculopathy after 20 years of the disease [41, 43]. About 3% of type 2 diabetic patients with non-proliferative retinopathy will have macular oedema, whereas between 40%, and 70% of those with moderate, and proliferative retinopathy respectively would end up developing macular oedema. Among this population, nearly half of them will experience fovea involvement of the macula

Pupillary involvement is a common occurrence in diabetic patients and has been suggested to be due to autonomic neuropathy secondary to degenerative changes at the nerve terminal. In the pupil, the autonomous nervous system regulates the sphincter, and dilator muscles which controls the pupillary response to light, accommodation, and drugs. Sustained high sugar level often results in autonomic neuropathy which meant that nerves lose their ability to respond or conduct sensations as they ought to. The occurrence of autonomic neuropathy results in partial denervation of mostly the dilator muscle of the pupil. This, therefore, implies different pupillary responses to normal pupillary stimulus diabetic patients will be affected. For instance, diabetic pupils have excessive miotic pupils in dim illumination, also diabetic pupils experience loss of light reflex, non-syphilitic-Argy Robertson pupil has been reported. Further, variations in response to topical

There are still conflicting opinions regarding the relationship between glaucoma and diabetes, however, the mechanism that leads to the autonomic dysfunction in the regulation of intraocular pressure, fluctuation of intraocular pressure, and the increased susceptibility of retinal ganglion cells to cell death can easily be rationalized [46]. According to Negi and Vernon [43], diabetic patients are at high risk

**30**

of developing higher intraocular pressures than their non-diabetic counterparts. Proliferative diabetes is one of the leading causes of neovascular glaucoma.
