Cover Image

Inflammatory Choroidal Neovascular Membranes in Patients With Noninfectious Uveitis: The Place Of Intravitreal Anti-VEGF Therapy

Omer Karti, Sefik Can İpek, Yesim Ates, Ali Osman Saatci


Inflammatory choroidal neovascularization (iCNV) is an infrequent but an important cause of visual morbidity in patients with non-infectious uveitis and mostly occurs in intermediate or posterior uveitis. Punctate inner choroiditis, Vogt-Koyanagi-Harada disease and multifocal choroiditis are among the leading causes of uveitis entities resulting in iCNVs. The diagnosis and management of iCNVs still remain a challenge. Use of multimodal imaging techniques such as fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT) and OCT-angiography may be necessary for the diagnosis of iCNVs. The treatment algorithm is not straightforward for iCNV. While control of the active inflammation with steroids and/or immunosuppressive agents is a key to success, various adjunctive treatment modalities such as thermal laser photocoagulation, photodynamic therapy and surgical membrane removal were also coadministered previously. Nowadays, vascular endothelial growth factor (VEGF) inhibitors has become the most commonly administered adjunctive treatment option as they provide better anatomical and functional outcome and the recurrence rate of CNV is relatively low. We hereby reviewed important clinical studies and case series on anti-VEGF administration in iCNVs and briefly overviewed their results.


Mansour AM, Mackensen F, Arevalo JF, Ziemssen F, Mahendradas P, Mehio-Sibai A, et al. Intravitreal bevacizumab in inflammatory ocular neovascularization. Am J Ophthalmol. 2008;146(3):410-6. doi: 10.1016/j.ajo.2008.05.024 pmid: 18619571

Neri P, Lettieri M, Fortuna C, Manoni M, Giovannini A. Inflammatory choroidal neovascularization. Middle East Afr J Ophthalmol. 2009;16(4):245-51.

Invernizzi A, Pichi F, Symes R, Zagora S, Agarwal AK, Nguyen P, et al. Twenty-four-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens. Br J Ophthalmol. 2019. doi: 10.1136/bjophthalmol-2019-315257 pmid: 31744798

D'Ambrosio E, Tortorella P, Iannetti L. Management of uveitis-related choroidal neovascularization: from the pathogenesis to the therapy. J Ophthalmol. 2014;2014:450428. doi: 10.1155/2014/450428 pmid: 24868454

Baxter SL, Pistilli M, Pujari SS, Liesegang TL, Suhler EB, Thorne JE, et al. Risk of choroidal neovascularization among the uveitides. Am J Ophthalmol. 2013;156(3):468-77 e2. doi: 10.1016/j.ajo.2013.04.040 pmid: 23795984

Agarwal A, Invernizzi A, Singh RB, Foulsham W, Aggarwal K, Handa S, et al. An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management. J Ophthalmic Inflamm Infect. 2018;8(1):13. doi: 10.1186/s12348-018-0155-6 pmid: 30209691

Dreyer RF, Gass DJ. Multifocal choroiditis and panuveitis. A syndrome that mimics ocular histoplasmosis. Arch Ophthalmol. 1984;102(12):1776-84. doi: 10.1001/archopht.1984.01040031440019 pmid: 6508619

Morgan CM, Schatz H. Recurrent Multifocal Choroiditis. Ophthalmology. 1986;93(9):1138-47. doi: 10.1016/s0161-6420(86)33611-x

Brown J, Jr., Folk JC, Reddy CV, Kimura AE. Visual prognosis of multifocal choroiditis, punctate inner choroidopathy, and the diffuse subretinal fibrosis syndrome. Ophthalmology. 1996;103(7):1100-5. doi: 10.1016/s0161-6420(96)30561-7 pmid: 8684800

Watzke RC, Packer AJ, Folk JC, Benson WE, Burgess D, Ober RR. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98(5):572-84. doi: 10.1016/0002-9394(84)90243-5 pmid: 6208783

Reddy CV, Brown J, Jr., Folk JC, Kimura AE, Gupta S, Walker J. Enlarged blind spots in chorioretinal inflammatory disorders. Ophthalmology. 1996;103(4):606-17. doi: 10.1016/s0161-6420(96)30645-3 pmid: 8618760

Kuo IC, Cunningham ET, Jr. Ocular neovascularization in patients with uveitis. Int Ophthalmol Clin. 2000;40(2):111-26. doi: 10.1097/00004397-200004000-00009 pmid: 10791260

Jampol LM, Orth D, Daily MJ, Rabb MF. Subretinal neovascularization with geographic (serpiginous) choroiditis. Am J Ophthalmol. 1979;88(4):683-9. doi: 10.1016/0002-9394(79)90665-2 pmid: 92200

Laatikainen L, Erkkila H. Subretinal and disc neovascularisation in serpiginous choroiditis. Br J Ophthalmol. 1982;66(5):326-31. doi: 10.1136/bjo.66.5.326 pmid: 6176258

Blumenkranz MS, Gass JD, Clarkson JG. Atypical serpiginous choroiditis. Arch Ophthalmol. 1982;100(11):1773-5. doi: 10.1001/archopht.1982.01030040753008 pmid: 6182866

Saatci AO, Ayhan Z, Engin Durmaz C, Takes O. Simultaneous Single Dexamethasone Implant and Ranibizumab Injection in a Case with Active Serpiginous Choroiditis and Choroidal Neovascular Membrane. Case Rep Ophthalmol. 2015;6(3):408-14. doi: 10.1159/000442346 pmid: 26955341

Rao NA, Gupta A, Dustin L, Chee SP, Okada AA, Khairallah M, et al. Frequency of distinguishing clinical features in Vogt-Koyanagi-Harada disease. Ophthalmology. 2010;117(3):591-9, 9 e1. doi: 10.1016/j.ophtha.2009.08.030 pmid: 20036008

Yang P, Ren Y, Li B, Fang W, Meng Q, Kijlstra A. Clinical characteristics of Vogt-Koyanagi-Harada syndrome in Chinese patients. Ophthalmology. 2007;114(3):606-14. doi: 10.1016/j.ophtha.2006.07.040 pmid: 17123618

Ipek S, Ayhan Z, Emre S, Saatci A. Favorable clinical outcome with intravitreal aflibercept treatment in a case with bilateral choroidal neovascular membrane and quiescent Vogt-Koyanagi-Harada syndrome. GMS Ophthalmology Cases. Forthcoming 2020.

Mehta S, Hariharan L, Ho AC, Kempen JH. Peripapillary choroidal neovascularization in pars planitis. J Ophthalmic Inflamm Infect. 2013;3(1):13. doi: 10.1186/1869-5760-3-13 pmid: 23514324

Pagliarini S, Piguet B, Ffytche TJ, Bird AC. Foveal involvement and lack of visual recovery in APMPPE associated with uncommon features. Eye (Lond). 1995;9 ( Pt 1):42-7. doi: 10.1038/eye.1995.6 pmid: 7713249

Saatci AO, Ayhan Z, Ipek SC, Soylev Bajin M. Intravitreal Aflibercept as an Adjunct to Systemic Therapy in a Case of Choroidal Neovascular Membrane Associated with Sympathetic Ophthalmia. Turk J Ophthalmol. 2018;48(4):209-11. doi: 10.4274/tjo.09076 pmid: 30202619

Inagaki M, Harada T, Kiribuchi T, Ohashi T, Majima J. Subfoveal choroidal neovascularization in uveitis. Ophthalmologica. 1996;210(4):229-33. doi: 10.1159/000310714 pmid: 8841071

Rouvas AA, Ladas ID, Papakostas TD, Moschos MM, Vergados I. Intravitreal ranibizumab in a patient with choroidal neovascularization secondary to multiple evanescent white dot syndrome. Eur J Ophthalmol. 2007;17(6):996-9. doi: 10.1177/112067210701700623 pmid: 18050132

Brucker AJ, Deglin EA, Bene C, Hoffman ME. Subretinal Choroidal Neovascularization in Birdshot Retinochoroidopathy. American Journal of Ophthalmology. 1985;99(1):40-4. doi: 10.1016/s0002-9394(14)75864-7

Grossniklaus H, Gass JD. Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. American Journal of Ophthalmology. 1998;126(1):59-69. doi: 10.1016/s0002-9394(98)00145-7

Dhingra N, Kelly S, Majid MA, Bailey CB, Dick AD. Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and treatment. Indian J Ophthalmol. 2010;58(1):3-10. doi: 10.4103/0301-4738.58467 pmid: 20029141

Ganesh S, Ahmed A, Biswas J. Analysis of the Clinical Profile and Management of Inflammatory Choriodal Neovascular Membranes in Uveitic Eyes: A Study from a Tertiary Referral Center. Ocul Immunol Inflamm. 2019;27(3):424-34. doi: 10.1080/09273948.2017.1375119 pmid: 29040008

Bischoff PM, Flower RW. Ten years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue? Doc Ophthalmol. 1985;60(3):235-91. doi: 10.1007/bf00157827 pmid: 2414083

Agrawal RV, Biswas J, Gunasekaran D. Indocyanine green angiography in posterior uveitis. Indian J Ophthalmol. 2013;61(4):148-59. doi: 10.4103/0301-4738.112159 pmid: 23685486

Atmaca LS, Batioglu F, Atmaca P. Evaluation of choroidal neovascularization in age-related macular degeneration with fluorescein and indocyanine green videoangiography. Ophthalmologica. 1996;210(3):148-51. doi: 10.1159/000310695 pmid: 8738457

Kotsolis AI, Killian FA, Ladas ID, Yannuzzi LA. Fluorescein angiography and optical coherence tomography concordance for choroidal neovascularisation in multifocal choroidtis. Br J Ophthalmol. 2010;94(11):1506-8. doi: 10.1136/bjo.2009.159913 pmid: 20472744

Karti O, Saatci AO. Optical Coherence Tomography Angiography in Eyes with Non-infectious Posterior Uveitis; Some Practical Aspects. Med Hypothesis Discov Innov Ophthalmol. 2019;8(4):312-22. pmid: 31788494

Astroz P, Miere A, Mrejen S, Sekfali R, Souied EH, Jung C, et al. Optical Coherence Tomography Angiography to Distinguish Choroidal Neovascularization from Macular Inflammatory Lesions in Multifocal Choroiditis. Retina. 2018;38(2):299-309. doi: 10.1097/IAE.0000000000001617 pmid: 28368976

Yeo JH, Chung H, Kim JT. Swept-Source Optical Coherence Tomography Angiography According to the Type of Choroidal Neovascularization. J Clin Med. 2019;8(9). doi: 10.3390/jcm8091272 pmid: 31443399

Nussenblatt RB, Coleman H, Jirawuthiworavong G, Davuluri G, Potapova N, Dahr SS, et al. The treatment of multifocal choroiditis associated choroidal neovascularization with sirolimus (rapamycin). Acta Ophthalmol Scand. 2007;85(2):230-1. doi: 10.1111/j.1600-0420.2006.00858.x pmid: 17305748

Mateo-Montoya A, Baglivo E, de Smet MD. Intravitreal methotrexate for the treatment of choroidal neovascularization in multifocal choroiditis. Eye (Lond). 2013;27(2):277-8. doi: 10.1038/eye.2012.262 pmid: 23222567

Karti O, Saatci AO. Intravitreal Dexamethasone Implant in the Treatment of Non-Infectious Uveitic Macular Edema. Med Hypothesis Discov Innov Ophthalmol. 2018;7(4):169-75. pmid: 30505868

Thomas AS. Biologics for the treatment of noninfectious uveitis: current concepts and emerging therapeutics. Curr Opin Ophthalmol. 2019;30(3):138-50. doi: 10.1097/ICU.0000000000000562 pmid: 30844945

Parodi MB, Iacono P, Spasse S, Ravalico G. Photodynamic therapy for juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Am J Ophthalmol. 2006;141(1):123-8. doi: 10.1016/j.ajo.2005.07.045 pmid: 16386985

Coco RM, de Souza CF, Sanabria MR. Photodynamic therapy for subfoveal and juxtafoveal choroidal neovascularization associated with punctate inner choroidopathy. Ocul Immunol Inflamm. 2007;15(1):27-9. doi: 10.1080/09273940601174020 pmid: 17365803

Nowilaty SR, Bouhaimed M, Photodynamic Therapy Study G. Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease. Br J Ophthalmol. 2006;90(8):982-6. doi: 10.1136/bjo.2006.091538 pmid: 16687455

Rogers AH, Martidis A, Greenberg PB, Puliafito CA. Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization. American Journal of Ophthalmology. 2002;134(4):566-76. doi: 10.1016/s0002-9394(02)01566-0

Avery RL, Castellarin AA, Steinle NC, Dhoot DS, Pieramici DJ, See R, et al. Systemic Pharmacokinetics and Pharmacodynamics of Intravitreal Aflibercept, Bevacizumab, and Ranibizumab. Retina. 2017;37(10):1847-58. doi: 10.1097/IAE.0000000000001493 pmid: 28106709

Barth T, Zeman F, Helbig H, Gamulescu MA. Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to punctate inner choroidopathy. Int Ophthalmol. 2018;38(3):923-31. doi: 10.1007/s10792-017-0536-0 pmid: 28424992

Fine HF, Zhitomirsky I, Freund KB, Barile GR, Shirkey BL, Samson CM, et al. Bevacizumab (avastin) and ranibizumab (lucentis) for choroidal neovascularization in multifocal choroiditis. Retina. 2009;29(1):8-12. doi: 10.1097/IAE.0b013e318187aff9 pmid: 18784620

Doctor PP, Bhat P, Sayed R, Foster CS. Intravitreal bevacizumab for uveitic choroidal neovascularization. Ocul Immunol Inflamm. 2009;17(2):118-26. doi: 10.1080/09273940802650406 pmid: 19412874

Cornish KS, Williams GJ, Gavin MP, Imrie FR. Visual and optical coherence tomography outcomes of intravitreal bevacizumab and ranibizumab in inflammatory choroidal neovascularization secondary to punctate inner choroidopathy. Eur J Ophthalmol. 2011;21(4):440-5. doi: 10.5301/EJO.2010.6117 pmid: 21188681

Parodi MB, Iacono P, La Spina C, Knutsson KA, Mansour A, Arevalo JF, et al. Intravitreal bevacizumab for choroidal neovascularisation in serpiginous choroiditis. Br J Ophthalmol. 2014;98(4):519-22. doi: 10.1136/bjophthalmol-2013-304237 pmid: 24414400

Menezo V, Cuthbertson F, Downes SM. Positive response to intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to punctate inner choroidopathy. Retina. 2010;30(9):1400-4. doi: 10.1097/IAE.0b013e3181d374dc pmid: 20224465

Tran TH, Fardeau C, Terrada C, Ducos De Lahitte G, Bodaghi B, Lehoang P. Intravitreal bevacizumab for refractory choroidal neovascularization (CNV) secondary to uveitis. Graefes Arch Clin Exp Ophthalmol. 2008;246(12):1685-92. doi: 10.1007/s00417-008-0906-4 pmid: 18682970

Carreno E, Moutray T, Fotis K, Lee RW, Dick AD, Ross AH, et al. Phase IIb clinical trial of ranibizumab for the treatment of uveitic and idiopathic choroidal neovascular membranes. Br J Ophthalmol. 2016;100(9):1221-6. doi: 10.1136/bjophthalmol-2015-307806 pmid: 26674776

Lai TYY, Staurenghi G, Lanzetta P, Holz FG, Melissa Liew SH, Desset-Brethes S, et al. Efficacy and Safety of Ranibizumab for The Treatment of Choroidal Neovascularization Due to Uncommon Cause: Twelve-Month Results of The Minerva Study. Retina. 2018;38(8):1464-77. doi: 10.1097/IAE.0000000000001744 pmid: 28704254

Kramer M, Axer-Siegel R, Jaouni T, Reich E, Hemo I, Priel E, et al. Bevacizumab for choroidal neovascularization related to inflammatory diseases. Retina. 2010;30(6):938-44. doi: 10.1097/IAE.0b013e3181c96a00 pmid: 20168273

Arevalo JF, Adan A, Berrocal MH, Espinoza JV, Maia M, Wu L, et al. Intravitreal bevacizumab for inflammatory choroidal neovascularization: results from the Pan-American Collaborative Retina Study Group at 24 months. Retina. 2011;31(2):353-63. doi: 10.1097/IAE.0b013e3181ed8cec pmid: 20890239

Rouvas A, Petrou P, Douvali M, Ntouraki A, Vergados I, Georgalas I, et al. Intravitreal ranibizumab for the treatment of inflammatory choroidal neovascularization. Retina. 2011;31(5):871-9. doi: 10.1097/IAE.0b013e3182003ca8 pmid: 21358461

Hernandez-Martinez P, Dolz-Marco R, Alonso-Plasencia M, Abreu-Gonzalez R. Aflibercept for inflammatory choroidal neovascularization with persistent fluid on intravitreal ranibizumab therapy. Graefes Arch Clin Exp Ophthalmol. 2014;252(8):1337-9. doi: 10.1007/s00417-014-2634-2 pmid: 24789465

Garcia CA, Segundo Pde S, Garcia Filho CA, Garcia AC. Intermediate uveitis complicated by choroidal granuloma following subretinal neovascular membrane: case reports. Arq Bras Oftalmol. 2008;71(6):890-3. doi: 10.1590/s0004-27492008000600026 pmid: 19169529

Wu W, Li S, Xu H, Liu Y, Wang Y, Lai TYY, et al. Treatment of Punctate Inner Choroidopathy with Choroidal Neovascularization Using Corticosteroid and Intravitreal Ranibizumab. Biomed Res Int. 2018;2018:1585803. doi: 10.1155/2018/1585803 pmid: 30302336

Pai SA, Hebri SP, Lootah AM. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate. Indian J Ophthalmol. 2012;60(6):551-2. doi: 10.4103/0301-4738.103795 pmid: 23202396

Tsaousis KT, Nassr M, Kapoor B, Konidaris VE, Tyradellis S, Empeslidis T. Long-term results of intravitreal bevacizumab and dexamethasone for the treatment of punctate inner choroidopathy associated with choroidal neovascularization: A case series. SAGE Open Med Case Rep. 2018;6:2050313X18772478. doi: 10.1177/2050313X18772478 pmid: 29760922

Full Text: Full Text PDF

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.