This document presents a case of a 76-year-old male patient with neovascular age-related macular degeneration (AMD) in the right eye who developed a retinal pigment epithelium (RPE) tear in the left eye following ranibizumab injection. The right eye showed a good response to ranibizumab injections over time with stabilization of vision. The left eye initially had a serous pigment epithelial detachment (PED) near the fovea, which increased in size after the first ranibizumab injection, leading to an RPE tear from the second injection. The RPE tear progressed to involve the fovea. The patient's vision improved in the left eye over time despite

1. Presented By:
Dr. MAB
Dr. ABJ
Dr. KSD
Case presentation

2. A male patient, 76 years old
DOV in the right eye since 1 year back .
OU Cataract surgery done
VA: OD: 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 1st injection
OD:
- SF I/R Fluid
- Schitic Spaces
- Retinal Thickening,
- SF Scarring CNVM
- PED
OS:
Normal Foveal DIP
Drusenoid PEDs Close to
Fovea
FT:
OD: 473 MICRONS
OS: 200 MICRONS

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

7. •OD Post 5th injection
OD Post 4th Inj. & Before 5th Inj.
•OD Post 6th injection

8. 28.08.2014
01.01.2015
09.10.2014
16.03.2015
14.05.2015
OS: Sequential OCT’s
09.07.2015

9. •OD: Ranibizumab injection under TA
Right eye showed good response to Ranibizumab
OD: 6 Ranibizumab injection under TA last one on
22.May.2015

10. On 9.July.2015
The patient came for regular follow up
VA:
OD: 6/18,N24
OS: 6/6,N6
IOP:
OD:15 mmHg
OS:16 mmHg
Anterior segment was WNL
OU: Pseudophakia

11. Fundus:
.
OD: Stable
OS: SRF at the fovea with increase in
PED size

12. OCT:
383µ
2539µ

13. AF:

14. FFA
OS: Speckled
fluorescence with
single area of
increased
hyperfluorescence
ST to the fovea

15. •OS: Ranibizumab injection under TA on 14.July.2015
•OS: 1st Day post injection Fundus showed RPE Tear + (small
sparing fovea)

16. •OS: 3rd Day post injection
Fundus showed RPE Tear + (progressed to involve fovea)

17. On 30.July.2015

18. On 31.August.2015
Vision in left had improved, though patient still c/o
metamorphopsia in left eye
Right eye stable
VA:
OD: 6/18,N18
OS: 6/9, N6
IOP:
OD: 14 mmHg
OS:14 mmHg
Anterior segment was WNL
OU Pseudophakia

19. Fundus :

21. OCT:

22. RPE TEAR
Associated conditions, incidences and Clinical features
Investigations
How does RPE Tear occur?
Grading of RPE tear
Risk factors
What to be done if we have significant risk factors?
Why it is more common in AMD compared to PCV?
Fate of RPE tear
Should we continue Anti VEGF Rx in patients with RPE tear?
Prognostic indicators

23. RPE tear- Associated conditions,
incidences and Clinical features

24. •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.

25. •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.

26. 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
•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.

27. Clinical features
•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.

28. FFA,ICG and OCT
•FFA- Hyperfluorescence in area of bare choroid and
hypofluorescence 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 hyperfluorescence in area of retracted RPE
•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.

29. OCT
•Interruption of hyperreflective RPE layer with elevated or
scrolled edge of torn RPE flap
•Three configurations of retracted RPE-
Dome shaped
Pleated
Tented
•Increased reflectivity in area of bare choroid
•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.

30. How does RPE Tear occur

31. Theories proposed
•Increased intra PED
hydrostatic pressure due to
enlargement
•Tangential forces on
posterior surface of detached
RPE
Gass JD (1984) Pathogenesis of tears of the retinal pigment epithelium. Br J Ophthalmol 68:513–519

32. Grading of RPE tear

33. •RPE tears grading based on the greatest length in the
vector direction of the tear and involvement of the fovea
using FA analysis
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.

34. Risk factors

35. •Fibrovascular PED > Serosanguinous PED> Serous
•Height of PED
•Greatest linear dimension of PED
•A 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%
•Hyperreflective linear lines on Near Infrared Imaging
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.

36. Clemens CR, Bastian N, Alten F, et al. Prediction of retinal pigment epithelial tear in serous vascularized pigment
epithelium detachment. Acta Ophthalmol 2014;92:e50–56.

37. What to be done if we have
significant risk factors

38. PED height >400 µm
Presence of hyperreflective lines in NIR images
Pause anti- VEGF therapy
Re-evaluate the lesion in 1–2 weeks
Look for contraction of CNV membrane that has
relaxed to some extent and to re-inject again.
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.
Clemens CR, Bastian N, Alten F, et al. Prediction of retinal pigment epithelial tear in serous vascularized pigment
epithelium detachment. Acta Ophthalmol 2014;92:e50–56.

39. Why it is more common in AMD
compared to PCV?

40. 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.

41. Does Anti-VEGF predisposes to
RPE tear

42. RPE tear post anti VEGF injections
•Bevacizumab, Ranibizumab, Pegabtinib, Aflibercept
•Overall incidence 5-19.7%
•Average number of injections before RPE tear 1.3
•Duration of appearance
•Earliest 1st 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

43. •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.

44. FATE OF RPE TEAR

45. Repair mechanism
•Within 24 hours, the area where the RPE is absent
becomes covered by hypopigmented RPE cells
•Persistent SRF after an RPE tear may lead to
subsequent repair with thickened proliferative tissue at
the area where the RPE was lost
•Early resolution of the SRF after the RPE tear, the
•outer retina appeared to be directly attached to Bruch
membrane.

46. •Persistent SRF and active CNV may result in the horizontal
proliferation of the CNV membranes along Bruch membrane
within the SRF at the area where the RPE was lost.
•Weak leakage from inactive CNV may result in a rapid
resolution of the SRF. In addition, inactive CNV may not cause
any pooling of the SRF or cause any growth horizontally at the
area where the RPE disappeared. As a result, this may lead to the
attachment of the outer retina to Bruch membrane
•An ingrowth of a faintly opaque tissue layer into the area of the
tear, which gave the appearance of blunting of the edges of the
tear.

47. Mukai R, Sato T, Kishi S. Repair mechanism of retinal pigment epithelial tears in
Age-related macular degeneration. Retina 35:473–480, 2015

48. Mukai R, Sato T, Kishi S. Repair mechanism of retinal pigment epithelial tears in
Age-related macular degeneration. Retina 35:473–480, 2015

49. Should we continue Anti VEGF Rx in
patients with RPE tear?

52. •Chan et al reported continued improvement in visual acuity in
67% eyes treated with bevacizumab/ranibizumab after developing
RPE tear
•Gamulescu et al reported mean BCVA to be stable at 12 months
in eyes that received additional anti VEGF treatment
•Continuing anti VEGF Rx may reduce possible fibrotic ingrowth
replacing RPE tear
•Chan CK, Meyer CH, Gross JG, et al. Retinal pigment epithelial tears after intravitreal bevacizumab injection for
neovascular age-related macular degeneration. Retina 2007;27:541–551.
•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: 1037–1040.
Sarraf D, Reddy S, Chiang A, et al. A new grading system for retinal pigment epithelial tears. Retina 2010;30:1039–1045.

53. Prognostic indicators

54. 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
•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.

55. Prognostic indicators
•Additional prognostic factor-Fibrovascular scarring and
atrophy in RPE free area
•Fibrovascular-poorer prognosis
•Grading of RPE tear: Grade 4 is associated with poor
visual prognosis
•Treatment modality: Continued Anti VEGF therapy is
associated with stabilisation of visual acuity and even
improvement
•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.

56. Take home message
• RPE tear are more common in patients with FVPED
• Increased incidence in anti VEGF era
• Baseline OCT measurements of height & GLD of FVPED
for subsequent follow ups-explain visual prognosis
• Look for hyperreflective lines on NIR imaging-If present,
wait for 2 weeks before injecting anti VEGF
• If RPE tear develops, have early follow ups to look for
progression
• Explain further course of the disease to the patient
• If persistent exudative changes noted with RPE tear, do
not hesitate to inject further anti VEGF injections