Proliferative Diabetic Retinopathy

Proliferative diabetic retinopathy (PDR) is the sight threatening stage in which retinal ischaemia drives release of VEGF and growth of new vessels on the optic disc (neovascularisation of the disc, NVD), elsewhere on the retina (NVE), or the iris and angle (NVI).

• Occurs in about 5 to 7 percent of people with diabetes; more frequent in type 1 diabetes (up to 50 percent after 20 years) and in poor control.
• High risk characteristics: NVD greater than one third to one quarter of the disc area, any NVD with vitreous or preretinal haemorrhage, or NVE of at least half a disc area with haemorrhage.
• Complications: vitreous haemorrhage, fibrovascular proliferation and tractional retinal detachment, neovascular glaucoma, macular oedema and ischaemia.
• Without treatment, severe visual loss occurs in about 50 percent over 5 years in high risk eyes.

• May be asymptomatic until sudden floaters, a curtain or dark cloud in vision (vitreous haemorrhage), or gradual loss from macular oedema or traction.
• NVD: fine network of vessels on or within 1 disc diameter of the disc; NVE: vessels beyond 1 disc diameter from the disc, along the vascular arcades and at the border of non-perfused retina.
• Preretinal and vitreous haemorrhage, fibrovascular membranes with contraction, traction folds, tractional detachment (central macular involvement when taut).
• Rubeosis iridis and neovascular glaucoma if untreated.
• Background changes of severe NPDR in the rest of the retina.

• Dilated fundus examination including the retinal periphery; undilated examination of the iris and gonioscopy for rubeosis.
• Widefield fluorescein angiography: leakage from new vessels (the disc and retina), peripheral non-perfusion.
• Optical coherence tomography (macular oedema, vitreoretinal traction); B-scan ultrasound if haemorrhage obscures the fundus.
• Check HbA1c, blood pressure, renal function and lipids.

• Control systemic factors: glucose, blood pressure, lipids, smoking, and renal disease.
• Panretinal photocoagulation (PRP): the standard treatment for high risk PDR; 1200 to 1600 burns (more for severe disease) of 200 to 500 micrometres, 0.1 seconds, placed 1 spot width apart, applied in 2 to 3 sessions over 2 to 4 weeks; reduces severe visual loss by about 50 percent. Adverse effects: reduced night vision, peripheral field loss, transient macular oedema (treat the macula first or concurrently), accommodation loss.
• Intravitreal anti-VEGF as an alternative or adjunct to PRP: aflibercept 2 mg, ranibizumab 0.5 mg or bevacizumab 1.25 mg monthly then as needed; regresses new vessels within weeks and preserves peripheral field; requires reliable follow up because losing the patient to follow up leads to rebound and haemorrhage. Also helps when there is concurrent macular oedema.
• Vitreous haemorrhage: observe for 4 to 12 weeks with the head elevated (clearing is common), PRP or anti-VEGF when the view allows.
• Vitrectomy: for non-clearing vitreous haemorrhage (over 1 to 3 months, earlier in type 1 diabetes and when rubeosis is present), tractional detachment threatening or involving the macula, combined tractional and rhegmatogenous detachment, and dense premacular haemorrhage. Intravitreal bevacizumab 1.25 mg 3 to 7 days before surgery reduces intraoperative bleeding.
• Neovascular glaucoma (rubeosis): PRP, anti-VEGF, pressure lowering (timolol 0.5 percent twice daily, dorzolamide 2 percent three times daily) and a drainage device.
• Cataract surgery under cover of anti-VEGF or PRP when needed.
• Follow every 1 to 3 months until stable, then 3 to 6 months.