J Korean Ophthalmol Soc.  2016 Jan;57(1):71-79. 10.3341/jkos.2016.57.1.71.

Intravitreal Anti-Vascular Endothelial Growth Factor for Retinal Pigment Epithelial Tear in Retinal Angiomatous Proliferation

• Hwang HJ
• Chang YS
• Kim JW
• Lee TG
• Kim CG
• Cho SW
• Lee DW
• Han JI
• Kim JH

• KMID: 2213843
• DOI: http://doi.org/10.3341/jkos.2016.57.1.71

Abstract

PURPOSE
To evaluate the treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) therapy for retinal pigment epithelial (RPE) tear in retinal angiomatous proliferation (RAP).
METHODS
In the present study we retrospectively analyzed the medical records of 14 patients (14 eyes) diagnosed with RPE tear secondary to RAP treated with intravitreal anti-VEGF. Best-corrected visual acuity (BCVA) when the RPE tear developed was compared with BCVA at 6 months and at the final follow-up.
RESULTS
The mean age of the study patients was 75.1 +/- 7.0 years and the mean follow-up period was 23.7 +/- 13.7 months. During the follow-up period, patients were treated with a mean of 2.8 +/- 1.3 intravitreal anti-VEGF injections. The mean logarithm of minimal angle of resolution BCVA when the RPE tear developed, at 6 months and at the final follow-up was 1.25 +/- 0.44, 1.44 +/- 0.56, and 1.65 +/- 0.39, respectively. The BCVA at 6 months was not different from the baseline value (p = 0.258), whereas the BCVA at the final follow-up was significantly worse than the baseline value (p = 0.002).
CONCLUSIONS
The prognosis of RPE tear in RAP is poor despite anti-VEGF therapy. This result suggests further investigations regarding the prevention of RPE tear or more effective treatment method for this condition are necessary.

Keyword

Age-related macular degeneration; Anti-vascular endothelial growth factor; Retinal angiomatous proliferation; Retinal pigment epithelial tear

MeSH Terms

Endothelial Growth Factors*
Follow-Up Studies
Humans
Macular Degeneration
Medical Records
Prognosis
Retinaldehyde*
Retrospective Studies
Tears*
Visual Acuity
Endothelial Growth Factors
Retinaldehyde

Figure

• 

  Figure 1. Fundus photography, fluorescein angiography, indicyanine-green angiography, and optical coherence tomography find-ings in a 72-year-old patient with retinal angiomatous proliferation. In this patient, retinal pigment epithelial tear was noted at diag-nosis (A, B, C, D) and the best-corrected visual acuity at diagnosis was 0.1. The patient was treated with 3 intravitreal ranibizumab injections during the 6 months follow-up period. At 6 months (E, F), the best-corrected visual acuity was decreased to 0.05 despite resolution of fluid. Arrow in figure A and E indicates optical coherence tomography line (figure D and figure F, respectively). Arrowheads in figure A indicate the extent of RPE tear. RPE = retinal pigment epithelial.

• 

  Figure 2. Fundus photography, fluorescein angiography, indicyanine-green angiography, and optical coherence tomography find-ings in a 71-year-old patient with retinal angiomatous proliferation. In this patient, retinal pigment epithelial tear was developed 1 month (A, B, C, D) following 3 monthly ranibizumab injections (E, F, G). The best-corrected visual acuity (BCVA) 1 month before the retinal pigment epithelial tear was 0.1. The BCVA decreased to 0.02 when retinal pigment epithelial tear was developed. The patient was treated with 2 additional intravitreal bevacizumab injections. At 45 months (H, I), the BCVA was measured as counting finger. Arrow in figure F and H indicates optical coherence tomography line (figure G and I, respectively). Arrowheads in figure E indicate the extent of RPE tear. RPE = retinal pigment epithelial.

• 

  Figure 3. Changes in BCVA in eyes with RPE tear secondary to RAP. (A) Changes in all 14 included patients. (B) Changes in 9 patients who experienced development of RPE tear during the treatment course of RAP. ‘RPE tear’ means when the RPE tear was developed, ‘Before tear’ means 1.9 ± 1.3 months be-fore the development of RPE tear, and ‘Final visit’ means 23.7 ± 13.7 months (A) and 23.4 ± 15.3 months (B) after the de-velopment of RPE tear; Statistical analysis: (A) Repeated measures analysis of variances with Bonferroni’s correction, (B) Wilcoxon signed ranks test. BCVA = best-corrected visu-al acuity; RPE = retinal pigment epithelial; RAP = retinal an-giomatous proliferation; M = months.

Reference

References

1. Bressler SB, Bressler NM, Fine SL. . Natural course of choroi-dal neovascular membranes within the foveal avascular zone in se-nile macular degeneration. Am J Ophthalmol. 1982; 93:157–63.

2. Rosenfeld PJ, Brown DM, Heier JS. . Ranibizumab for neo-vascular age-related macular degeneration. N Engl J Med. 2006; 355:1419–31.

3. Kim YH, Kim ES, Yu SY, Kwak HW. Long-term effect of intra-vitreal bevacizumab for CNV secondary to age-related macular degeneration. J Korean Ophthalmol Soc. 2008; 49:1935–40.

4. Rofagha S, Bhisitkul RB, Boyer DS. . Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013; 120:2292–9.

5. Yannuzzi LA, Negrão S, Iida T. . Retinal angiomatous pro-liferation in age-related macular degeneration. Retina. 2001; 21:416–34.

6. Freund KB, Ho IV, Barbazetto IA. . Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina. 2008; 28:201–11.

7. Park KH, Song SJ, Lee WK. . The results of nation-wide regis-try of age-related macular degeneration in Korea. J Korean Ophthalmol Soc. 2010; 51:516–23.

8. Kim JH, Kim JR, Kang SW. . Thinner choroid and greater dru-sen extent in retinal angiomatous proliferation than in typical exu-dative age-related macular degeneration. Am J Ophthalmol. 2013; 155:743–9. 749.e1-2.

9. Cohen SY, Dubois L, Tadayoni R. . Prevalence of reticular pseudodrusen in age-related macular degeneration with newly di-agnosed choroidal neovascularisation. Br J Ophthalmol. 2007; 91:354–9.

10. Shin JY, Yu HG. Optical coherence tomography-based ranibizu-mab monotherapy for retinal angiomatous proliferation in Korean patients. Retina. 2014; 34:2359–66.

11. Kim DB, Kim JH, Jeong SH. . Twelve-month outcomes of in-travitreal anti-vascular endothelial growth factor therapy for retinal angiomatous proliferation. J Korean Ophthalmol Soc. 2013; 54:1700–7.

12. Cho HJ, Yoo SG, Kim HS. . Risk factors for geographic atro-phy after intravitreal ranibizumab injections for retinal angioma-tous proliferation. Am J Ophthalmol. 2015; 159:285–92.e1.

13. Chan CK, Meyer CH, Gross JG. . Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration. Retina. 2007; 27:541–51.

14. Park JH, Choae WS, Yoon HS. Long-term observation of retinal pigment epithelial tear after anti-VEGF treatment for age-related macular degeneration. J Korean Ophthalmol Soc. 2014; 55:1340–6.

15. Gutfleisch M, Heimes B, Schumacher M. . Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD. Eye (Lond). 2011; 25:1181–6.

16. Forooghian F, Cukras C, Chew EY. Retinal angiomatous pro-liferation complicated by pigment epithelial tear following intra-vitreal bevacizumab treatment. Can J Ophthalmol. 2008; 43:246–8.

17. Riusala AM, Immonen IJ. Predictors of structural findings in old disciform lesions. Am J Ophthalmol. 2004; 138:245–53.

18. Sarraf D, Reddy S, Chiang A. . A new grading system for reti-nal pigment epithelial tears. Retina. 2010; 30:1039–45.

19. Holladay JT. Visual acuity measurements. J Cataract Refract Surg. 2004; 30:287–90.

20. Shin JY, Choi M, Chung B, Byeon SH. Pigment epithelial tears af-ter ranibizumab injection in polypoidal choroidal vasculopathy and typical age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2015; 253:2151–60.

21. Casswell AG, Kohen D, Bird AC. Retinal pigment epithelial de-tachments in the elderly: classification and outcome. Br J Ophthalmol. 1985; 69:397–403.

22. Pauleikhoff D, Löffert D, Spital G. . Pigment epithelial detach-ment in the elderly. Clinical differentiation, natural course and pathogenetic implications. Graefes Arch Clin Exp Ophthalmol. 2002; 240:533–8.

23. Doguizi S, Ozdek S. Pigment epithelial tears associated with an-ti-VEGF therapy: incidence, long-term visual outcome, and rela-tionship with pigment epithelial detachment in age-related macular degeneration. Retina. 2014; 34:1156–62.

24. Sarraf D, Joseph A, Rahimy E. Retinal pigment epithelial tears in the era of intravitreal pharmacotherapy: risk factors, pathogenesis, prognosis and treatment (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2014; 112:142–59.

25. Mullins RF, Johnson MN, Faidley EA. . Choriocapillaris vas-cular dropout related to density of drusen in human eyes with early age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011; 52:1606–12.

26. Berenberg TL, Metelitsina TI, Madow B. . The association be-tween drusen extent and foveolar choroidal blood flow in age-re-lated macular degeneration. Retina. 2012; 32:25–31.

27. Alten F, Heiduschka P, Clemens CR, Eter N. Multifocal electro-retinography in eyes with reticular pseudodrusen. Invest Ophthalmol Vis Sci. 2012; 53:6263–70.

28. Ooto S, Ellabban AA, Ueda-Arakawa N. . Reduction of retinal sensitivity in eyes with reticular pseudodrusen. Am J Ophthalmol. 2013; 156:1184–91.e2.

29. Yamazaki T, Koizumi H, Yamagishi T, Kinoshita S. Subfoveal cho-roidal thickness in retinal angiomatous proliferation. Retina. 2014; 34:1316–22.

30. Koizumi H, Iida T, Saito M. . Choroidal circulatory disturbances associated with retinal angiomatous proliferation on in-docyanine green angiography. Graefes Arch Clin Exp Ophthalmol. 2008; 246:515–20.

31. Fung AE, Lalwani GA, Rosenfeld PJ. . An optical coherence tomography-guided, variable dosing regimen with intravitreal rani-bizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007; 143:566–83.