Retinopathy is the emerging disease in Pakistan over the age of 30 in diabetic patients. In diabetic patients this disease causes blindness, visual loss, and hazy eyesight. Several suggested metabolic mechanisms that connect micro vascular problems to hyperglycemia. Activation of protein kinase C (PKC), oxidative stress, polyol buildup, and the production of advanced glycation end products (AGEs) are a few of these. The anti-VEGF drugs, laser, eye surgery is the treatment of Retinopathy. The patient HBA1C lab test below than 6.5% will be preferred for surgery. The Diabetic patient should control their blood glucose level to reduce the complexicity of the disease.

Retinopathy is a disease that can cause blindness and vision loss in aged peoples. It mostly occurs in diabetic patients so it called Diabetic Retinopathy (Shah 2008). Worldwide, the number of people with diabetes is more than 135 million. Over 18.2 million Americans, or 6.3% of the population, have diabetes, and 800,000 new instances of type 2 diabetes are diagnosed in the country each year (Jonnalagadda 2004). It affects the blood vessels in the light sensitive layer of tissues of the retina. In early stages of this disease have no symptoms. But some people face problems in reading and seeing faraway objects. In the later stage of disease, the bleeding from blood vessels of retina in the form of gel like fluid. If this happens you see dark, floating spots like cobwebs. If the treatment on time it will benefit the patient but after time without time it become worse (Sayres, Taly et al. 2019). Diabetic Macular Edema (DME) Approximately 1 in 15 diabetics will eventually develop DME. DME occurs when fluid leaks from retinal blood vessels into the macula, a region of the retina required for crisp, centre vision. This results in hazy eyesight (Holekamp 2016).

Figure 1: Diabetic Macular Edema

Neo vascular glaucoma

Unusual blood vessels that emerge from the retina as a result of diabetic retinopathy may obstruct the flow of fluid out of the eye. 

One kind of glaucoma, which is a collection of eye conditions that can result in blindness and visual loss, is brought on by this (Hu, Zangalli et al.2014).

Figure 2: Neo vascular glaucoma

Glaucoma: A class of eye conditions known as glaucoma can result in blindness and visual loss by harming the optic nerve, a nerve located at the back of the eye. You might not notice the symptoms at first since they might appear so slowly (Bhowmik, Kumar et al. 2012). A thorough dilated eye exam is the only method to determine if you have glaucoma. While there is no known cure for glaucoma, 

vision protection and damage may frequently be stopped with early intervention.

Retinal detachment

The back of your eye may develop scars as a result of diabetic retinopathy. Tractional retinal detachment refers to the condition when your retina pulls away from the back of your eye due to scarring (Peate 2022).
 

Figure 3: Retinal detachment

Pathophysiology:

There are several suggested metabolic mechanisms that connect micro vascular problems to hyperglycemia. Activation of protein kinase C (PKC), oxidative stress, polyol buildup, and the production of advanced glycation end products (AGEs) are a few of these. Through their influence on cellular metabolism, signaling, and growth factors, these mechanisms are hypothesized to modify the disease process (González, Lozano et al. 2023).

Polyol accumulation of polyol occurs in experimental hyperglycemia, which in rats and dogs is associated with the development of basement thickening, pericyte loss, and micro aneurysm formation (G Obrosova and F Kador 2011). High concentrations of glucose increase flux through the polyol pathway with the enzymatic activity of aldosereductase, leading to an elevation of intracellular sorbitol concentrations. This rise in intracellular sorbitol accumulation has been hypothesized to cause osmotic damage to vascular cells (Garg and Gupta2022). Aldose reductase inhibitors (ARIs) have been evaluated for the prevention of retinal and neural damage in diabetes. However, three clinical trials of ARIs in humans have not shown efficacy in preventing the incidence or progression of retinopathy. The efficacy of new, more potent ARIs remains to be evaluated in clinical trials (Mara and Oates 2008). AGEs another well-characterized pathway is damage resulting from accumulation of AGEs. High serumglucose can lead to nonenzymatic binding of glucose to protein side chains, resulting in the formation of compounds termed AGEs. After 26 weeks of induced hyperglycemia, the retinal capillaries of diabetic rats have marked accumulation of AGEs as well as a loss of pericytes (Smitand Lutgers 2004). Furthermore, diabetic rats treated with amino guanidine (AGE formation inhibitor) have reduced AGE accumulation and reduced histological changes, including micro aneurysm formation and pericyte loss. An ongoing clinical trial is investigating the effect of amino guanidine in humans. Preliminary results suggest that amino guanidine reduces the progression of retinopathy but is associated with anemia

Figure 4: advanced glycation end products mechanism in eye Polyol accumulation

In rats and dogs, experimental hyperglycemia leads to the accumulation of polyol and is linked to the development of micro aneurysm formation, pericyte loss, and basement thickening. 

Elevated intracellular sorbitol concentrations result from high glucose concentrations increasing flow via the polyol pathway with the enzymatic activity of aldose reductase (G Obrosova and F Kador2011). It has been proposed that vascular cells may sustain osmotic injury as a result of this increase in intracellular sorbitol buildup. Aldosereductase inhibitors (ARIs) have been studied in relation to preventing diabetic nerve and retinal damage. Nonetheless, according to three human clinical trials, ARIs are ineffective at stopping the onset or development of retinopathy. Clinical studies need to be conducted to determine the effectiveness of new, more powerful ARIs (Zhu2013).

AGEs Damage brought on by a buildup of AGEs is another well-established route. Elevated blood glucose levels have the potential to cause non enzymatic glucose binding to side chains of proteins, which can lead to the creation of substances known as AGEs. (Chilelli, Burlina et al.2013) Following 26 weeks of induced hyperglycemia, diabetic rats' retinal capillaries show a significant buildup of AGEs and a pericyte loss. Additionally, diabetic rats given amino guanidine, an inhibitor of AGE synthesis, showed decreased buildup of AGE and decreased histological alterations, such as the development of micro aneurysms and the loss of pericytes (Luo, Fan et al. 2012). The effects of amino guanidine in humans are being studied in a clinical study that is now underway. According to preliminary findings, amino guanidine slows the development of retinopathy but is linked to anaemia.

In Pakistan, over the age of 30 the retinopathy become leading disease in diabetic patient. Several mechanisms like PKC, AGES   play role in this disease. In the patient the diseases cause color 

blindness, overall blindness, hazy eyesight, and visual loss. The doctor suggests the patient towards surgery and maintain hemoglobin A1C tests below than 6.5. The Laser and VEGF are alternative treatment against surgery in this disease. After surgery patient have care from sunlight exposure.

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I am grateful to all of those with whom I have had the pleasure to work during this and other related projects.