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Sustained and expedited resolution of diabetic papillopathy with combined PRP and bevacizumab

      Diabetic papillopathy (DP) is a rare condition that occurs in 1.4% of patients with type I and II diabetes.
      • Bayraktar Z.
      • Alacali N.
      • Bayraktar S.
      Diabetic papillopathy in type II diabetic patients.
      It is unilateral in 50% of cases and associated with diabetic retinopathy progression.
      • Bayraktar Z.
      • Alacali N.
      • Bayraktar S.
      Diabetic papillopathy in type II diabetic patients.
      Although it is traditionally a self-limited disease with spontaneous resolution within 3 to 4 months,
      • Ostri C.
      • Lund-Andersen H.
      • Sander B.
      • Hvidt-Nielsen D.
      • Larsen M.
      Bilateral diabetic papillopathy and metabolic control.
      • Vaphiades M.S.
      The disk edema dilemma.
      it may precede the development of nonarteritic anterior ischemic optic neuropathy, which can result in permanent vision loss. It is controversial whether DP is actually a mild reversible form of nonarteritic anterior ischemic optic neuropathy.
      • Hayreh S.S.
      • Zimmerman B.
      Nonarteritic anterior ischemic optic neuropathy: clinical characteristics in diabetic patients versus nondiabetic patients.
      The cause of DP is poorly understood and there is no validated treatment. Success with intravitreal or periocular corticosteroids
      • Mansour A.M.
      • El-Dairi M.A.
      • Shehab M.A.
      • Shahin H.K.
      • Shaaban J.A.
      • Antonios S.R.
      Periocular corticosteroids in diabetic papillopathy.
      • Al-Haddad C.E.
      • Jurdi F.A.
      • Bashshur Z.F.
      Intravitreal triamcinolone acetonide for the management of diabetic papillopathy.
      and anti–vascular endothelial growth factors
      • Ornek K.
      • Oğurel T.
      Intravitreal bevacizumab for diabetic papillopathy.
      • Al-Dhibi H.
      • Khan A.O.
      Response of diabetic papillopathy to intravitreal bevacizumab.
      • Feng J.
      • Qu J.F.
      • Jiang Y.R.
      Resolution of diabetic papillopathy with a single intravitreal injection of bevacizumab combined with triamcinolone acetonide.
      have been reported. We report a case of DP that was treated with combination panretinal photocoagulation (PRP) laser and intravitreal bevacizumab, which provided sustained and rapid resolution of DP.
      A 22-year-old female with poorly controlled diabetes mellitus type I since the age of 2 years presented with blurry vision and transient visual obscurations in both eyes. Her hemoglobin A1C was 12.2%, and she was recently an inpatient for diabetic ketoacidosis. She denied any headaches, her baseline weight was around 130 pounds, and she had no other systemic diseases. Her vision at presentation was 20/100 OD and 20/25 OS. Intraocular pressure was normal OU. Slit-lamp examination was unremarkable OU. Dilated examination revealed profound disc edema OD and mild disc edema OS (Fig. 1A, 1B). The patient had severe nonproliferative diabetic retinopathy (NPDR) OU. There was no clinically significant diabetic macular edema OU. Fluorescein angiography revealed profound hyperfluorescence at the optic nerve OD > OS, with multiple patchy areas of intraretinal microvascular abnormalities and peripheral capillary nonperfusion (Fig. 2). Optical coherence tomography (OCT) of the optic nerve quantified the degree of retinal nerve fibre layer thickening (OD 359 μm, OS 157 μm). OCT of the macula showed a sliver of subfoveal fluid and marked fluid emanating from the nerve to within a disc diameter of the fovea centre OD. There was optic nerve edema OS, but no subfoveal fluid or cystoid macular edema.
      Figure thumbnail gr1
      Fig. 1Montage colour fundus photograph of both eyes, demonstrating diabetic papillopathy (DP) OD > OS, severe nonproliferative diabetic retinopathy (NPDR) OU (A, B). At 2-month follow-up, there was rapid resolution of the disc swelling and intraretinal microvascular abnormalities OD after 2 intravitreal bevacizumab injections and staged panretinal photocoagulation (C). The left eye had high-risk severe NPDR with persistent but mild disc edema as compared with 2 months prior (D). At 6-month follow-up, there was sustained regression of the DP and NPDR OD, and persistent trace disc edema OS that was confirmed with OCT of the nerve (not shown) (E, F).
      Figure thumbnail gr2
      Fig. 2Fluorescein angiography in early and late frames demonstrating profound disc leakage OD > OS and scattered hyperfluorescence throughout the peripapillary and macular region at initial presentation. There were scattered areas of peripheral capillary nonperfusion OU.
      The patient was treated with combined intravitreal bevacizumab and staged PRP OD. At 1-month follow-up, her vision improved to 20/25 OD with complete resolution of her disc edema and subretinal fluid between the fovea and optic nerve. She received another injection of bevacizumab and fill-in PRP OD. At 2-month follow-up, there was no recurrence of her disc edema and the telangiectatic leaking papillary vessels were extinguished (Fig. 1C, 1D). Meanwhile, the left eye continued to have mild disc edema and severe NPDR. The patient elected for observation at that time. At 6-month follow-up, the patient’s vision remained excellent with no signs of recurrent DP or proliferative disease (Fig. 1E, 1F). The OCT of the optic nerve showed an average retinal nerve fibre layer thickness of OD 98 μm and OS 133 μm.
      The patient’s DP regressed very rapidly with combined treatment using scatter PRP and intravitreal bevacizumab. Although visual prognosis without treatment is often favourable in these cases, it generally takes a prolonged period to improve.
      • Regillo C.D.
      • Brown G.C.
      • Savino P.J.
      • et al.
      Diabetic papillopathy: patient characteristics and fundus findings.
      PRP has never been described as a treatment option for DP, and it may also have utility in preventing the complications arising from severe NPDR such as vitreous hemorrhage, subsequent vitrectomy, and visual impairment.
      • Lövestam-Adrian M.
      • Agardh C.D.
      • Torffvit O.
      • Agardh E.
      Type 1 diabetes patients with severe non-proliferative retinopathy may benefit from panretinal photocoagulation.
      The mechanism of action of bevacizumab in DP is not well understood; however, the accelerated response to bevacizumab combined with scattered laser suggests that vascular endothelial growth factors play an important role in the pathogenesis of this condition. Prior reports of accelerating improvement of DP with intravitreal and periocular corticosteroids suggest that an inflammatory component could also be involved in the pathogenesis of this disorder.
      • Mansour A.M.
      • El-Dairi M.A.
      • Shehab M.A.
      • Shahin H.K.
      • Shaaban J.A.
      • Antonios S.R.
      Periocular corticosteroids in diabetic papillopathy.
      • Al-Haddad C.E.
      • Jurdi F.A.
      • Bashshur Z.F.
      Intravitreal triamcinolone acetonide for the management of diabetic papillopathy.
      The patient’s untreated left eye serves as a surrogate control for persistent papillopathy and high-risk retinopathy; however, additional studies are needed to determine the exact efficacy and safety of this combined treatment.

      Acknowledgements

      The authors thank Dr. Randy H. Kardon for his review of this manuscript.

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