This document discusses familial exudative vitreoretinopathy (FEVR), a hereditary condition caused by defects in genes involved in retinal vascular development. It affects the peripheral retina and can cause retinal detachment. Clinical findings may include avascular areas, abnormal blood vessels, exudates, and retinal detachment. Diagnosis involves family history, examination findings, and imaging like fluorescein angiography. Treatment options depend on the stage and include laser, surgery like scleral buckling, and occasionally anti-VEGF injections. Long-term follow-up is needed as the condition is progressive and asymmetric between eyes. Family screening is also important to identify asymptomatic relatives.

1. Gazi University, Ankara, Turkey
sengulozdek@gmail.com
sozdek@gazi.edu.tr
FEVR

2. FEVR
• Mostly AD inheritance
• Defect in Wnt-NORRIN signal pathway genes:
NDP, FZD4, LRP5, TSPAN12, ZNF408
• Defective retinal angiogenezis: insufficient vascular
differentiation
• Peripheral retinal vascularization is incomplete
• 21- 64% RD: Tractional +/- exudative

3. Clinical Findings
• Peripheral avascular
areas (esp. temporal)
• Straightenning of
vessels, macular
ectopia
• Peripheral vascular
loops abnormal
telangiectatic vessels,
hard exudates, NV
• Fibrovascular
proliferation: Macular
fold
• Exudative and TRD

4. Vitreous
• Disgenic vitreous (FEVR, Norrie, PFV, ROP)
• Vitreo-retinal adhesion is very strong
• Hyaloid membrane is multilaminar like onion rings
• Posterior hyaloid contracts following LPC or Anti-VEGF treatment
• Akito Shimouchi et al. Int Ophthalmol (2013) 33:711–715, Yonekawa Y et al. Ophthalmology
2015;122:2270-2277

5. PENDERGAST-
CLASSIFICATION
• STAGE 1: Peripheral
avascular retina
• STAGE 2: Retinal NVE
• STAGE 3: Macula on RD
(macula ectopic)
• STAGE 4: Macula off RD
(macular fold)
• STAGE 5: Total RD-
Leucocoria

6. Diagnostic tips
• Presence of family history:
• Present in 45% of the cases,
• Asymptomatic family members (Family screening!)
• No Prematurity history
• Bilateral findings: Asymmetry!
• Presence of exudation!
• Life long progressive disease in spite of treatment!

7. Asymptomatic family members
Ultrawidefield FA!

8. 37y old, Father,
No known ocular problems, VA: 1.0/0.7

10. Newborn sibling of 2 days old, term baby

12. • ROP: Classical regular
homogeneous
vascularization pattern
at the ridge
DIFFERENTIAL DIAGNOSIS
FEVR VS ROP
•FEVR: Irregular
vascularization and
sprouting beyond
transition zone
•Vascular prunning
•Pinpoint
hiperfluorescent dots

13. Differential
Diagnosis
• Peripheral avascular retina:
• ROP
• Incontinentia Pigmenti
• Norrie Disease (M)
• Tractional RD: PFV! Toxocara,
Toxoplazma
• Retinal Exudative RD: Coats!
• Neovascularization: IRVAN, Eales

14. Treatment Options
• LASER
• STAGE 1: Peripheral avascular
retina
• STAGE 2: Retinal NVE
• SURGERY
• STAGE 2: Retinal NVE-Vit Hem
• STAGE 3: Macula on RD
(macula ectopic)
• STAGE 4: Macula off RD
(macular fold)
• STAGE 5: Total RD

16. 19y old, M, FEVR, VA: 0.03,
Fellow eye is NVG-Absolute

19. 6y old girl, bilat TRD, VA: 0.05

20. OPTOS
RE: VA: 0.3

21. LE: VA: 0.2

23. VA: 0.2

26. How to follow FEVR cases?
• May be asymmetric!
• Fellow eye should be carefully examined! (FA)
• It is progressive life long!
• May need additional laser treatments even surgery!

28. 34 wk, 1700gr BW, girl baby
1. Microcephaly since 6 mo old
2. 14mo old at presentation
3. RE: Esotropia
4. Mental-Motor Retard (mild-moderate)

33. WHAT TO DO NEXT?

34. DIAGNOSIS?
• ROP?
• FEVR?
• ROPER!
• John VJ, McClintic JI, Hess DJ, Berrocal AM. Ophthalmic
Surg Lasers Imaging Retina. 2016. Retinopathy of
Prematurity Versus Familial Exudative Vitreoretinopathy:
Report on Clinical and Angiographic Findings.

36. LAPPEL Sign
• LAte-Phase
angiographic posterior
and PEripheral vascular
Leakage
• Retinal endothelial cell
inflammation marker
• Capillary dropout
precursor
Thanos A, Todorich B, Trese MT. A Novel Approach to
Understanding Pathogenesis and Treatment of Capillary
Dropout in Retinal Vascular Diseases. Ophthalmic Surg
Lasers Imaging Retina. 2016

37. Anti-VEGFs in FEVR?
The role of intravitreal ranubizumab in the treatment of FEVR of stage
2 or greater. Lu YZ et al. Int J Ophthalmol. 2018
• As primary treatment?
• Tagami M, Kusuhara S, Honda S, Tsukahara Y, Negi A. Rapid regression of
retinal hemorrhage and NV in a case of FEVR treated with IVit bevacizumab.
Graefes Arch Clin Exp Ophthalmol. 2008 (case report)
• As an adjunct to LPC/ VRS?
• Henry CR, Sisk RA, Tzu JH, Albini TA, Davis JL, Murray TG, Berrocal AM.
Long-term follow-up of IVit bevacizumab for the treatment of pediatric retinal
and choroidal diseases. J AAPOS. 2015.
• As a last option in persistent NVE / Exudation?
• Quiram PA, Drenser KA, Lai MM, Capone A, Jr, Trese MT. Treatment of
vascularly active FEVR with Macugen. Retina. 2008

38. Anti-VEGFs in FEVR?
• 13 cases
• 7 eyes with Stage 2/3A: As an adjunct to LPC
• 6 eyes with Stage 3B/4B: as an adjunct to Scleral buckle
and/or PPV
• TRD progressed shortly after IVB in 3 of them and 2
eyes ended up with phytisation!
Henry CR, Sisk RA, Tzu JH, Albini TA, Davis JL, Murray TG, Berrocal AM.
Long-term follow-up of IVit bevacizumab for the treatment of pediatric retinal and
choroidal diseases. J AAPOS. 2015.

39. Steroid injections in FEVR?

40. LSV LV
Gazi University Data
54 eyes, Family history in 33%
0
2
4
6
8
10
12
14
16
SB LPC
TREATMENTS

41. Family history (-)
Screening of 1st degree relatives
Peripheral retnal findings in 37/51 (72.5%) with UWFFA

42. Peripheral loop-shunt-anastomozis (66.6%)

43. Take Home Messages
• Be careful for asymetric disease (fellow eye)
• Family screening for the asymptomatic family members
• Life long follow-up with FA and need for lasers
• VR Surgery and laser saves these eyes.

44. Thank you
sengulozdek@gmail.com
sozdek@gazi.edu.tr