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Effects of Intravitreal Pegaptanib or Bevacizumab and Laser in Treatment of Threshold Retinopathy of Prematurity in Zone I and Posterior Zone II – Four Years Results


Authors: R. Autrata 1;  K. Šenková 1;  M. Holoušová 1;  I. Krejčířová 1;  Z. Doležel 2;  I. Borek 3
Authors place of work: Dětská oční klinika LF MU a FN, Brno, přednosta prof. MUDr. Rudolf Autrata, CSc. MBA 1;  Pediatrická klinika LF MU a FN, Brno, přednosta prof. MUDr. Zdeněk Doležel, CSc. 2;  Neonatologické oddělení, Fakultní nemocnice, Brno, primářp MUDr. Ivo Borek 3
Published in the journal: Čes. a slov. Oftal., 68, 2012, No. 1, p. 29-36
Category: Original Article

Summary

Purpose:
To evaluate efficacy and safety of intravitreal injection of pegaptanib or bevacizumab and laser photocoagulation for treatment of threshold stage 3+ retinopathy of prematurity (ROP) affecting zone I and posterior zone II, and to compare the results in terms of regression, development of peripheral retinal vessels with conventional laser photocoagulation or combined with cryotherapy.

Methods:
In this prospective comparative study, 174 eyes of 87 premature babies, from January 2008 to December 2011, were included. All infantns were diagnosed with stage 3+ ROP for zone I or posterior II. Patients were randomly assigned to receive intravitreal pegaptanib (0.3 mg) or bevacizumab (0.625 mg/0.025 ml of solution) with conventional diode laser photocoagulation (Group A, 92 eyes of 46 infants) or laser therapy combined with cryotherapy (Group B, 82 eyes of 41 infants), bilaterally.

The main evaluated outcomes include time of regression and decrease of plus signs and development of peripheral retinal vessels after treatment, final strucutral-anatomic outcomes compared in the both groups of patients. Risk factors and other characteristics of infnats include birth weight, gestational age, Apgar score, duration of intubation and hospitalizations, postmenstrual age at treatment, sepsis, surgery for necrotizing enterocolitis, intraventricular hemorrhage.

Primary outcome of treatment success was defined as absence of recurrence of stage 3+ ROP in one or both eyes ( reccurrence rate = 0) by 55 weeks’ postmenstrual age. Treatment failure was defined as the recurrence of neovascularization (reccurrence rate = 1 or 2) in one or both eyes requiring retreatment.

The mean follow-up after treatment was 23.5 months (range 4 - 45 months) in the Group A, and 25.2 months in the Group B ( range 3 - 48 months).

Results:
Final favorable anatomic outcome and stable regression of ROP at last control examination have 90.2 % of eyes after adjuvant intavitral pagaptanbib or bevacizumab in the Group A, and 62 % of eyes after only conventional treatment in the Group B (P = 0.0214).

Regression of plus disease and peripheral retinal vessels development appeared significantly more rapidly in Group A patients who received intravitreal VEGF inhibitors and laser.

An absence of recurrence of neovascularization (stage 3+ ROP) was identified at 87 % of patients in the Group A, and 53 % of patients in the Group B. This difference between the both groups was statistically significant (P = 0.0183). ROP reccured in 7 from 92 eyes (7.6 %) in the Group A, and 23 from 82 eyes (28 %) in the group B (P = 0.0276). Significantly better treatment effect was found for adjuvant intravitreal pagaptanib or bevacizumab with laser compared with conventional therapy of ROP 3+ in zone I and posterior zone II.

Perioperative retinal haemorrhages after laser photocoagulation occured in 8 % of eyes in the Group A, and 11 % of eyes in the group B (P = 0.358), in all eyes with spontaneous resorption. No systemic or significant ocular complications of intravitreal anti-VEGF injections, such as endophthalmitis or retinal detachment were found during follow-up period after operation.

Conclusions:
A combination of intravitreal pegaptanib or bevacizumab injection and laser photocoagulation showed to be a safe, well tolerated and effective therapy in patients with stage 3+ ROP in zone I and posterior zone II.

Adjuvant intravitreal antiVEGF injection, as compared with conventional laser or cryotherapy, showed significant benefit in terms of better final anatomic outcome, induction of prompt regression, rapid development of peripheral retinal vascularization and decrease of recurrence rate of neovascularization. Results of this study support the administration of pegaptanib and bevacizumab as an alternative usefull therapy in the management of stage 3+ ROP.

Key words:
retinopathy of prematurity, stage 3+, zone I, posterior zone II, anti–vascular endothelial growth factor therapy, pegaptanib (Macugen), bevacizumab (Avastin), intravitreal injections, RetCam photography


Zdroje

1. Aiello, L.P., Pierce, E.A., Foley, E.D., et al.: Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 1995; 92: 10457–10461.

2. Alon, T., Hemo, I., Itin, A., Peter, J., Stone, J., Keshet, E.: Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1995; 1: 1024–1028.

3. Altinsoy, H.I., Mutlu, F.M., Güngör, R., Sarici, S.U.: Combination of laser photocoagulation and intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging 2010; 27: 345–349.

4. Apte, R.S., Modi, M., Masonson, H., et al.: Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration. Ophthalmology 2007; 114: 1702–12.

5. Arevalo, J.F., Garcia-Amaris, R.A.: Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev 2009; 5: 39–46.

6. Avery, R.L., Pearlman, J., Pieramici, D.J. et al.: Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology, 2006; 113: 1695–1705.

7. Axer-Siegel, R., Snir, M., Cotlear, D., et al.: Diode laser treatment of posterior retinopathyof prematurity. Br J Ophthalmol 2000; 84: 1383–6.

8. Axer-Siegel, R., Snir, M., Cotlear, D, et al.: Diode laser treatment of posterior retinopathy of prematurity. Br J Ophthalmol 2000; 84: 1383–1386.

9. Bakri, S.J., Cameron, J.D., McCannel, C.A., Pulido, J.S., Marler, R.J.: Absence of histologic retinal toxicity of intravitreal bevacizumab in a rabbit model. Am J Ophthalmol, 2006; 142: 162–164.

10. Beer, P.M., Wong, S.J., Hammad, A.M., Falk, N.S., O’Malley, M.R., Khan, S.: Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients. Retina 2006, 26: 871–876.

11. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Arch Ophthalmol 1988; 106: 471–9.

12. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trial of cryotherapy for retinopathy of prematurity. Three-month outcome. Arch Ophthalmol 1990; 108:195–204.

13. Dorta, P., Kychenthal, A. Treatment of type 1 retinopathy of prematurity with intravitreal bevacizumab (Avastin). Retina 2010; 30: Suppl: S24–S31.

14. Drenser, K.A., Tresem M.T., Capone, A. Jr.: Aggressive posterior retinopathy of prematurity. Retina 2010; 30: Suppl: S37–S40.

15. Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the Early Treatment for Retinopathy of Prematurity randomized trial. Arch Ophthalmol 2003; 121: 1684–94.

16. Flynn, J.T., Chan-Ling, T.: Retinopathy of prematurity: Two distinct mechanisms that underlie zone 1 and zone 2 disease. Am J Ophthalmol, 2006, 142: 46–59.

17. Fung, A.E., Rosenfeld, P.J., Reichel, E.: The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol,2006, 90:1344–1349.

18. Gilbert, C.: Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implication for control. Early Hum Dev 2008; 84: 77–82.

19. Honda, S., Hirabayashi, H., Tsukahara, Y., Negi, A.: Acute contraction of the proliferative membrane after intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2008; 246: 1061–3.

20. Chan-Ling, T., Gock, B., Stone, J.: The effect of oxygen on vasoformative cell division. Evidence that ‘physiological hypoxia’ is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci 1995; 36: 1201–1214.

21. Chen, J., Smith, L.E.: Retinopathy of prematurity. Angiogenesis 2007; 10: 133–140.

22. Chung, E.J., Kim, J.H., Ahn, H.S., Koh, H.J.: Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2007; 245: 1727–30.

23. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123: 991–9. (Erratum, Arch Ophthalmol 2006; 124: 1669–70.)

24. Ishida, S.,, Usui, T., Yamashiro, K., et al.: VEGF 164-mediated inflammation is required for pathological, but not physiological, ishcemia-reduced retinal neovascularization. J Exp Med 2003, 198: 483–489.

25. Katz, X., Kychenthal, A., Dorta, P.: Zone Iretinopathy of prematurity. J AAPOS 2000; 4: 373–6.

26. Kusaka, S., Shima, C., Wada, K., et al.: Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study. Br J Ophthalmol 2008; 92: 1450–5.

27. Kychenthal, A., Dorta, P., Katz, X.: Zone I retinopathy of prematurity: clinical characteristics and treatment outcomes. Retina 2006; 26: Suppl: S11–S15.

28. Lalwani, G.A., Berrocal, A.M., Murray, T.G., et al.: Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina 2008; 28: Suppl: S13–S18. (Erratum, Retina 2009; 29: 127.)

29. Law, J.C., Recchia, F.M., Morrison, D.G., Donahue, S.P., Estes, R.L.: Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity. J AAPOS 2010;14: 6-10.

30. Lee, J.Y., Chae, J.B., Yang, S.J, Yoon, Y.H., Kim, J.G.: Effects of intravitreal bevacizumab and laser in retinopathy of prematurity therapy on the development of peripheral retinal vessels. Graefes Arch Clin Exp Ophthalmol 2010; 248: 1257–62.

31. Lynch, S.S., Cheng, C.M.: Bevacizumab for neovascular ocular diseases. Ann Pharmacother 2007, 41: 614–625.

32. Manzano, R.P., Peyman, G.A., Khan, P., Kivilcim, M.: Testing intravitreal toxicity of bevacizumab (Avastin). Retina, 2006, 26: 257–261.

33. Marcus, D.M.: VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Four-year safety of pegaptanib sodium in neovascular age-related macular degeneration (AMD): results of the V.I.S.I.O.N. trial. Invest Ophthalmol Vis Sci 2008; 49: E-abstract 5069.

34. Mintz-Hittner, H.A., Kennedy, K.A., and Chuang, A.Z.: Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity N Engl J Med 2011, 364;7: 603–615.

35. Mintz-Hittner, H.A., Kuffel, R.R. Jr.: Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina 2008; 28: 831–8. (Erratum, Retina 2008; 28: 1374.)

36. Naug, H., Browning, J., Gole, G., Gobe, G.: Vitreal macrophages express VEGF165 in oxygen-induced retinopathy. Clin Exp Optom, 2000, 28: 48–52.

37. Nazari, H., Modarres, M., Parvaresh, M.M., Falavarjani, K.G.: Intravitreal bevacizumab in combination with laser therapy for the treatment of severe retinopathy of prematurity (ROP) associated with vitreous or retinal hemorrhage. Graefes Arch Clin Exp Ophthalmol 2010; 248: 1713–8.

38. O’Keefe, M., Lanigan, B., Long, VW.: Outcomes of zone I retinopathy of prematurity.Acta Ophthalmol Scand 2003; 81: 614–6.

39. Récsán, Z., Vámos, R., Salacz, G.: Laser treatment of zone I prethreshold andstage 3 threshold retinopathy of prematurity. J Pediatr Ophthalmol Strabismus 2003;40: 204–7.

40. Repka, M.X., Tung, B., Good, W.V., et al.: Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP). Arch Ophthalmol 2006; 124: 24–30.

41. Robinson, G.S., Pierce, E.A., Rook, S.L., Foley, E., Webb, R., Smith, L.E.: Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci U S A 1996; 93: 4851–4856.

42. Roohipoor, R., Ghassemi, H., Ghassemi, F., Karkhanech, R. et al.: Intravitreal bevacizumab in retinopathy of prematurity: an intervetional case series Graefes Arch Clin Exp Ophthalmol 2011; 2489: 1295–1301

43. Shah, P.K., Narendran, V., Tawansy, K.A., Raghuram, A., Narendran, K.: Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol, 2007, 55: 75–76.

44. Shahar, J., Avery, R.L., Heilweil, G. et al.: Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina, 2006, 26: 262–269.

45. Schouten, J.S., La Heij, E.C., Webers, C.A., Lundqvist, I.J., Hendrikse, F.: A systematic review on the effect of bevacizumab in exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2009; 247: 1–11.

46. Singerman, L.J., Masonson, H., Patel, M., et al.: Pegaptanib sodium for neovascularage-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial. Br J Ophthalmol 2008; 92: 1606–11.

47. Smith, L.E.H.: Through the eyes of achild: understanding retinopathy throughROP: the Friedenwald lecture. Invest Ophthalmol Vis Sci 2008; 49: 5177–82.

48. Smith, L.E., Wesolowski, E., McLellan, A., et al.: Oxygen induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 1994; 35: 101–111.

49. Spencer, R.: Long-term visual outcomes in extremely low-birth-weight children (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc 2006;104: 493-516.

50. Stenkuller, P.G., Du, L., Gilbert, C et al.: Childhood blindness. J AAPOS 1999, 3: 26–32.

51. Storkebaum, E., Carmeliet, P.: VEGF: critical player in neurodegeneration. J.CLin Invest., 2004, 113: p. 14-18.

52. Travassos, A., Teixeir, S., Ferreira, P., et al.: Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging 2007; 38: 233–7.

53. Quinn, G.E., Dobson, V., Barr, C.C., et al.: Visual acuity of eyes after vitrectomy forretinopathy of prematurity: follow-up at5 1/2 years. Ophthalmology 1996; 103: 595–600.

54. Quiroz-Mercado, H., Martinez-Castellanos, M.A., Hernandez-Rojas, M.L, Salazar- Teran, N, Chan, R.V.: Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity. Retina 2008; 28: Suppl: S19–S25.

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