1. Presented By: Dr. MAB Dr. ABJ Dr. KSD CASE PRESENTATION

2.  A male patient, 76 years old  Main complaints : DOV in the right eye since 1 year back. Past Ocular History: OU Cataract surgery done VA: OD  3/60,N36  6/24 with PH OS  6/9,N6 IOP: OD: 18 mmHg OS: 20 mmHg Anterior segment was WNL OU:Pseudophakia

3. FUNDUS:

4. FFA: a large feeder net with temporal leakage s/o mature vessels

5. OCT Before 1 st injection

6. Action Plan : OD: Ranibizumab injection under TA OD: 6 Ranibizumab injection under TA last one on 22.05.2015 The Right eye show good response for the injection and doing well now The following OCT tests done during follow up between injections and show good response for injection:

7. OD Post 1 st injectionOD Post 2 nd injection OD Post 3 rd injection OD Post 4 th injection

8. Action Plan: To be watch OD Post 5 th injection OD Post 4 th Inj. & Before 5 th Inj. OD Post 6 th injection

9. ON 9.7.2015 The patient came for regular follow up without any ocular complaints VA: OD  6/18,N24 OS  6/6,N6 IOP: OD:15 mmHg OS:16 mmHg Anterior segment was WNL OU: Psuedophakia

10. FUNDUS:. OD: Stable OS: Has SRF at the fovea with increase in PED size

11. OCT:

12. OS: Speckled fluorscence with a single area of increased hyperfluorescence ST to the fovea AF:

13. FFA: OS: Speckled fluorscence with a single area of increased hyperfluorescence ST to the fovea

14. Action Plan : OS: Ranibizumab injection under TA OS: Ranibizumab injection under TA monotherapy given on 14.07.2015 On 15.07.2015 OS: 1 st Day post injection Accentrix Fundus Show RPE RIP + (small sparing fovea) On 18.07.2015 OS: 3 rd Day post injection Accentrix Fundus Show RPE RIP + progressing

16. ON 30.07.2015

17. ON 2015-08-31 The patient felt Vision dropped since three months C/O metamorphopsia in left eye Right eye stable VA: OD  6/18,N18 OS  6/9,N8  BCVA 6/9, N6 IOP: OD: 14 mmHg OS:14 mmHg Anterior segment was WNL

18. FUNDUS :

20. OCT:

22. RPE TEAR: IN ERA OF ANTI VEGF AGENTS

23. First described by Hoskin et al Varied etiologies Trauma, CSC, Angioid streak, Myopia AMD PCV RAP Hoskin A, Bird AC, Sehmi K. Tears of detached retinal pigment epithelium. Br J Ophthalmol 1981;65(6):417-422.

24. Most commonly associated with neovascular AMD Can be spontaneous or associated with treatment Anti VEGF, PDT, Laser photocogaulation Incidence spontaneous tear rate 10-12 % Bilateral incidence 53% Chuang EL, Bird AC. The pathogenesis of tears of the retinal pigment epithelium. Am J Ophthalmol 1988;105:285–290.

25. THEORIES PROPOSED Increased intra PED hydrostatic pressure due to enlargement Tangential forces on posterior surface of detached RPE Stretched RPE- blow out tear Goldstein BG, Pavan PR. Blow-outs in the retinal pigment epithelium. Br J Ophthalmol 1987;71:676–681

26. RPE TEAR POST ANTI VEGF INJECTIONS Bevacizumab, Ranibizumab, Pegaptinib,Afliberept Overall incidence 5-19.7% Average number of injections before RPE tear 1.3 Duration of appearance Earliest 1 st day postoperative in our patient (Unpublished data) Literature 11 days after initial injection (Range 11 days to 46.3 weeks) Chang LK, Sarraf D. Tears of the retinal pigment epithelium: an old problem in a new era. Retina 2007;27:523-534 M Gutfleisch et al. Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD. Eye 2011;25:1181–86

27. IOP shifts post anti VEGF injection Interruption of tight junction maintenance post anti VEGF Vitreomacular traction CTGF VEGF imbalance post anti VEGF Nagiel A, Freund KB, Spaide RF, Munch IC, Larsen M, Sarraf D. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography. Am J Ophthalmol 2013;156(5):981-988.e982.

28. CLINICAL FEATURES Abrupt sudden onset loss of vision Clinically, a well demarcated area of bare choroid visible adjacent to hyperpigmented area, which is retracted, redundant retina Temporal edge of PED most commonly affected Often accompanied by subretinal hemorrhages,exudation or break through vitreous hemorrhage Initial course, good prognosis Long term follow up- progressive visual loss Depends of foveal involvement Foveal involvement incidence range 23-75% Chang LK, Sarraf D. Tears of the retinal pigment epithelium: an old problem in a new era. Retina 2007;27(5):523-534. Gamulescu MA, Framme C, Sachs H. RPE-rip after intravitreal bevacizumab (Avastin) treatment for vascularised PED secondary to AMD. Graefes Arch Clin Exp Ophthalmol 2007; 245:1037–40.

29. RPE tears graded based on the greatest length in the vector direction of the tear and involvement of the fovea using FA analysis, a measurement of greatest linear diameter [millimeter] was obtained Sarraf D, Reddy S, Chiang A, Yu F, Jain A. A new grading system for retinal pigment epithelial tears. Retina 2010;30(7):1039-1045.

30. Prospective study Incidence of RPE tear -14% RPE tear + PED height >550μ-31% RPE tear + PED height > 550μ + ring sign on FFA/Grade 1 tear- 67% Sarraf D, Chan C, Rahimy E, Abraham P. Prospective evaluation of the incidence and risk factors for the development of RPE tears after high- and low-dose ranibizumab therapy. Retina 2013;33(8):1551-1557.

31. AMD V/S PCV More common in AMD – 3.5 % v/s 0.62% in PCV Pathogenesis differs Element of FVPED in AMD Anti VEGF causes fibrotic contraction ripping overlying RPE Large serosanguinous PED in PCV Vascular complexes in PCV may not contract enough AntiVEGF reduces leakage, but shrinkage of polypoidal dilatations hardly affected. Adhesions of PCV components to RPE might be weak Micro rips (7.1%) at margin of PED reduces intra PED pressure and thereby frank RPE tear Shin et al. Pigment epithelial tears after ranibizumab injection in polypoidal choroidal vasculopathy and typical age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-015-2977-3 Musashi K, Tsujikawa A, Hirami Y, et al. Microrips of the retinal pigment epithelium in polypoidal choroidal vasculopathy. Am J Ophthalmol 2007;143(5):883-885.

32. FFA,ICG AND OCT FFA-Hyperfluoresecence in area of bare choroid and hypofluoresence in area of retracted and elevated RPE flap No leak in area of bare choroid-Atrophy of choriocapillaris ICG- Normal choroidal fluorescence in area of bare choroid and varying degrees of hyperfluoresence in area of retracted RPE OCT- Interrruption of hyperreflective RPE layer with elevated or scrolled edege of torned RPE flap Three configurations of retracted RPE-Dome shaped, pleated, tent like Increased reflectivity in area of bare choroid Arroyo JG, Schatz H, McDonald R, Johnson RN. Indocyanine green videoangiography after acute retinal pigment epithelial tears in age- related macular degeneration. Am J Ophthalmol 1997;123:377–385. Giovannini A, Amato G, Mariotti C, Scassellati-Sforzolini B. Optical coherence tomography in the assessment of retinal pigment epithelial tear. Retina 2000;20:37–40.

33. PROGNOSTIC INDICATORS Pre injection PED height >400 μ PED height predicts RPE tear risk with 85% sensitivity and 92% specificity GLD of PED- 5 mm PED duration <4.5 months- Predicts RPE tear risk with 77% sensitivity and 98% specificity Additional prognostic factor-Fibrovascular scarring and atrophy in RPE free area Fibrovascular-poorer prognosis Chan et al. Optical coherence tomography–measured pigment epithelial detachment height as a predictor for retinal pigment epithelial tears associated with intravitreal bevacizumab injections. Retina 2010;30:203–11. Doguizi and Ozdek. Pigment epithelial tears associated with anti-VEGF therapy. Incidence, long-term visual outcome, and relationship with pigment epithelial detachment in age-related macular degeneration. Retina 2014 ;34:1156–62. Sarraf D, Chan C, Rahimy E, Abraham P. Prospective evaluation of the incidence and risk factors for the development of RPE tears after high- and low-dose ranibizumab therapy. Retina 2013;33(8):1551-1557.

34. Does anti VEGF cause RPE tear? Why it is more common in AMD? What are the risk factors? Height and GLD What is the prognosis? What is the further course of treatment?