60. Proliferative Diabetic Retinopathy

60.1 Definitions Proliferative diabetic retinopathy (PDR) Neovascularization (NV) 60.2 Symptoms Decreased vision, floaters 60.3 Signs Vitreous hemorrhage, preretinal hemorrhage, tractional retinal detachment (TRD) NV is characterized by location: neovascularization of the disk (NVD) or neovascularization elsewhere (NVE). Patients with neovascularization of the iris (NVI) or angle (NVA) are at high risk of developing neovascular glaucoma (NVG). 60.4 Epidemiology The prevalence of PDR in the United States has been reported as 1.5 % in diabetics over the age of 40 years. Type I diabetics have a higher prevalence of PDR. The Wisconsin Epidemiologic Study of Diabetic Retinopathy reported a 25-year progression to PDR of 42 % in type 1 diabetics. 60.5 Risk Factors Hyperglycemia Duration since diagnosis of diabetes Pregnancy (PDR typically progresses more rapidly in pregnancy) Smoking Cardiovascular risk factors Renal disease 60.6 Differential Diagnosis The patient’s history and features of NPDR on exam will help distinguish PDR from other causes of proliferative retinopathy (Table 60.1). Table 60.1 Differential diagnosis of proliferative retinopathy Neovascularization secondary to CRAO, CRVO, or BRVO Ocular ischemic syndrome Sickle cell retinopathy Occlusive retinal vascular disease (e.g., Eales disease, Behcet’s disease) Other inflammatory eye diseases (e.g., sarcoid, systemic lupus erythematous, pars planitis) Radiation retinopathy Hypercoagulability 60.7 Etiology VEGF and other angiogenic factors are produced by ischemic retina, resulting in new vessel formation. The new vessels are initially intraretinal (intraretinal microvascular abnormalities) and subsequently penetrate through the ILM. The new vessels will proliferate and may be associated with fibrous tissue. The fine and delicate new vessels are prone to rupture with either contraction of fibrovascular tissue or posterior vitreous detachment, resulting in vitreous or preretinal hemorrhage. 60.8 Workup/Testing Anterior segment slit examination and gonioscopy are recommended prior to dilation for evaluation of NVI and NVA. Dilated fundus exam with careful attention to the disk and posterior pole, which are the most common sites for NV (Fig. 60.1). Fig. 60.1 Neovascularization of the disk × Fluorescein angiography (FA) may be used to evaluate areas of retinal ischemia and NV. FA combined with wide field imaging is especially beneficial in the assessment of peripheral NV. Consider performing an OCT to determine the presence of coexistent cystoid macular edema (CME), as well as to detect changes in the vitreo-macula interface (such as VMT or VMA). If dense vitreous hemorrhage is present, B-scan ultrasound is necessary to rule out a TRD. Check most recent glycated hemoglobin (a1c). 60.9 Prognosis and Management Panretinal photocoagulation (PRP) is indicated if any of the high-risk features of PDR are present (Table 60.2). However, some specialists will perform PRP for any degree of PDR, especially in poorly compliant patients or type 1 diabetics, who usually progress more rapidly. PRP induces regression of NV and reduces further neovascular tissue formation (Table 60.3). Peripheral ischemic retina is destroyed, thereby lowering the VEGF drive from ischemic retina. Furthermore, decreased oxygen consumption and increased choroidal perfusion of oxygen in areas of PRP scars both serve to increase the overall oxygen tension of the retina (Figs. 60.2 and 60.3). Table 60.2 Diagnostic features of high-risk PDR (as defined by the Diabetic Retinopathy Study) 1 of the following: Preretinal hemorrhage or vitreous hemorrhage and NVE >0.5DD Preretinal hemorrhage or vitreous hemorrhage and NVD NVD >0.25DD Table 60.3 Laser parameters for PRP Laser: Argon green. Kryton red or diode laser can be used in media opacity Widefield lens ~ ×2.0 magnification Spot size – 500 μm Separation – half a spot size Duration – 0.05–0.2 s Power – 130 mW, titrate until white-gray burn 1200 spots or more Location: burns should extend from the arcades to the equator. Start nasally >500 μm from optic disk. Start temporally >2.5DD from fovea Fig. 60.2 Late-phase fluorescein angiography showing staining of PRP scars Fig. 60.3 Fundus photo showing regressed NVD and dense PRP laser scars in the periphery and dense focal laser scars in the macula × × Complications from resultant fibrovascular tissue contraction include vitreous hemorrhage, TRD, and combined tractional-rhegmatogenous detachment. Involvement of the long ciliary nerves can disrupt accommodation and pupillary function and impair corneal sensation. Other adverse effects from PRP include decreased visual acuity, reduced peripheral vision, nyctalopia, worsening macula edema, decreased color vision, reduced contrast sensitivity, choroidal detachment, and serous retinal detachment. Anti-VEGF drugs may be used as a temporizing measure to decrease vessel leakage and induce regression of NV (both anterior segment and retinal). Due to its short-term effect, anti-VEGF therapy is beneficial as an adjunct to laser photocoagulation, either to cause regression of vessels prior to vitrectomy (Table 60.4), in treatment refractory PDR, or to expedite resolution of NVA. However, anti-VEGF in this setting carries the risk of retinal tears and combined tractional-rhegmatogenous retinal detachment from sudden fibrovascular tissue contraction, as well as potentially worsening macula ischemia. Non-clearing vitreous hemorrhage or TRD requires vitrectomy (Table 60.4). Table 60.4 Indications for vitrectomy in PDR Dense non-clearing vitreous hemorrhage or dense pre-macula hemorrhage Macula involving TRD Tractional-rhegmatogenous RD Severe fibrovascular proliferation refractory to PRP Diabetic CME refractory to treatment or CME associated with significant traction of the posterior hyaloid Ghost cell glaucoma NVI or NVA with vitreous hemorrhage precluding PRP 60.10 Follow-Up Dilated fundus exam is recommended every 2–3 months for PDR not classified as high risk. More frequent follow-up is needed for high-risk PDR. Pregnant women with PDR should have dilated exams monthly.

Medicine Matters Diabetes

60. Proliferative Diabetic Retinopathy

Abstract

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