Diabetic retinopathy: A review on its pathophysiology and novel treatment modalities

Table 1 Etiological risk factors for diabetic retinopathy

Non-modifiable risk factors	Modifiable risk factors	Newer risk factors
Puberty	Hypertension	Inflammation
Pregnancy	Obesity	Apolipoproteins
	Dyslipidemia	Hormonal influence
	Poor glycemic control	Leptin and adiponectin vitamin D
	Nephropathy	Oxidative stress
		Genetic factors

Table 2 Early treatment of diabetic retinopathy classification of diabetic retinopathy

Category	Features	Follow-up periods
No DR	No findings	12 months
Very mild NPDR	Microaneurysms only	Most of the patients in 12 months
Mild NPDR	Any or all of: Microaneurysms, retinal hemorrhages, exudates, cotton wool spots	6-12 months, depending on the severity of signs, stability, systemic factors, and patient’s personal circumstances
Moderate NPDR	Severe retinal hemorrhages in 1-3 quadrants or mild IRMA; Significant venous beading in no more than one quadrant; Cotton wool spots	Approximately 6 months (PDR in up to 26%, high-risk PDR in up to 8% within a year)
Severe NPDR	The 4-2-1 rule; Severe retinal hemorrhages in all four quadrants; Significant venous beading in ≥ 2 quadrants; Moderate IRMA in > 1 quadrant	4 months (PDR in up to 50%, High-risk PDR in up to 15% within a year)
Very severe NPDR	≥ 2 of the criteria for severe	2-3 months (high-risk PDR in up to 45% within a year)
High-risk PDR	NVD > 1/3rd disc area; Any NVD with vitreous/Pre-retinal hemorrhage; NVE > 1/2 disc area with vitreous/pre-retinal hemorrhage	Laser photocoagulation Intravitreal Anti-VEGF agents Intravitreal Triamcinolone Pars Plana Vitrectomy; Lipid-lowering drugs
Advanced diabetic eye disease	Pre-retinal (retro hyaloid) and/or intragel hemorrhage; Tractional retinal detachment Tractional retinoschisis Rubeosis Iridis (Iris Neovascularization)	Pars plana vitrectomy

NPDR: Non-proliferative diabetic retinopathy; NVD: Neovascularization of the disc; NVE: Neovascularization elsewhere; PDR: Proliferative diabetic retinopathy.

Table 3 Optical coherence tomography classification of diabetic macular edema

Classification features
Large cystoid spaces
Serous detachment of the retina
Tractional detachment of the fovea or vitreomacular traction
Taut posterior hyaloid membrane
Diffuse retinal thickening
Cystoid macular edema with posterior hyaloidal traction serous retinal detachment Tractional retinal detachment

Table 4 International clinical diabetic retinopathy disease severity scale classification of diabetic retinopathy

Disease
Concerning diabetic retinopathy
No apparent retinopathy	No findings
Mild NPDR	Only microaneurysms
Moderate NPDR	More microaneurysms and less than severe disease
Severe NPDR	No signs of PDR; Intraretinal hemorrhages in all four quadrants; Venous beading in ≥ 2 quadrants; Prominent IRMA ≥ 1 quadrant
PDR	Neovascularization; Vitreous or subhyaloid hemorrhage Figure 6 (Fundus picture showing PDR)
Concerning DME
DME apparently absent	No retinal thickening and hard exudates at the posterior
DME apparently present	Apparent retinal thickening and hard exudates present at the posterior pole. Furthermore, it can be classified into three subtypes based on the area of thickening and hard exudates in the center of the Fovea
Mild DME	The retinal thickening or hard exudates are located farther away from the center of the fovea
Moderate DME	Retinal thickening or hard exudates are near the center of the macula but not involving the fovea
Severe DME	Hard exudate and thickening present in the center of the fovea

DME: Diabetic macular edema; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy.