Korean J Ophthalmol.  2013 Dec;27(6):425-432. 10.3341/kjo.2013.27.6.425.

Anti-VEGF-refractory Exudative Age-related Macular Degeneration: Differential Response According to Features on Optical Coherence Tomography

• Shin JY
• Woo SJ
• Ahn J
• Park KH

• KMID: 1792078
• DOI: http://doi.org/10.3341/kjo.2013.27.6.425

Abstract

PURPOSE
To describe optical coherence tomography (OCT) characteristics of neovascular age-related macular degeneration (AMD) patients refractory to intravitreal anti-vascular endothelial growth factor (VEGF) injections (ranibizumab, bevacizumab) and their responses to alternative anti-VEGF agents or photodynamic therapy (PDT).
METHODS
A retrospective review of 267 neovascular AMD patients treated with intravitreal anti-VEGF injections.
RESULTS
Twenty patients (7.5%) were refractory to anti-VEGF injections (stationary or increased retinal exudation despite three or more monthly injections). They were grouped into either the extensive intraretinal fluid group (IRF group, 9 patients) or the subretinal fluid only group (SRF group, 11 patients) according to OCT findings. In the IRF group, response rates to subsequent treatment were 0% (0 / 7) for bevacizumab, 50% (3 / 6) for ranibizumab and 50% (3 / 6) for PDT +/- anti-VEGF. Three out of four bevacizumab-refractory patients showed response to ranibizumab as a secondary treatment. In the SRF group, response rates were lower with 0% (0 / 7) for bevacizumab, 22.2% (2 / 9) for ranibizumab and 28.6% (2 / 7) for PDT +/- anti-VEGF. One out of four bevacizumab-refractory patients responded to ranibizumab. The visual outcome was worse in the IRF group (median 20 / 1,000) than in the SRF group (median 20 / 100).
CONCLUSIONS
In anti-VEGF-refractory neovascular AMD, patients with extensive IRF refractory to bevacizumab can be responsive to ranibizumab while patients with SRF may be refractory to both, suggesting a different pathophysiology and intraocular pharmacokinetics.

Keyword

Bevacizumab; Drug resistance; Macular degeneration; Optical coherence tomography; Ranibizumab

MeSH Terms

Aged
Aged, 80 and over
Angiogenesis Inhibitors/administration & dosage
Antibodies, Monoclonal, Humanized/*administration & dosage
Female
Fluorescein Angiography
Follow-Up Studies
Fundus Oculi
Humans
Intravitreal Injections
Male
Middle Aged
Retrospective Studies
Tomography, Optical Coherence/*methods
Treatment Outcome
Vascular Endothelial Growth Factor A/*antagonists & inhibitors
Visual Acuity
Wet Macular Degeneration/*drug therapy/metabolism/pathology
Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Case 7. A 65-year-old male diagnosed with polypoidal choroidal vasculopathy (A, fundus photography; B, fluorescein angiography). His initial visual acuity was 20 / 500, and findings compatible with polypoidal choroidal vasculopathy were observed on indocyanine green angiography (C). Optical coherence tomography (D) showed extensive intraretinal fluid. He was refractory to six sequential bevacizumab injections and was treated with combined photodynamic therapy and bevacizumab injections twice without success (E, optical coherence tomography). The patient received ranibizumab injections monthly, effectively decreasing the intraretinal fluid (F, optical coherence tomography), although his visual acuity was limited to 20 / 1,000.

• 

  Fig. 2 Case 11. A 76-year-old male diagnosed with occult choroidal neovascularization (A, fundus photography; B, fluorescein angiography). His visual acuity was 20 / 50, and he showed no evidence of polypoidal choroidal vasculopathy on indocyanine green angiography (C). Optical coherence tomography (D) revealed subretinal fluid only. The patient was refractory to three sequential ranibizumab injections and received combined photodynamic therapy and ranibizumab injections, which also had no effect (E, optical coherence tomography). He was prescribed additional ranibizumab injections, but the SRF still remained (F, optical coherence tomography). At the last follow-up visit, his visual acuity was 20 / 100.

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  Fig. 3 A 78-year-old female diagnosed with occult choroidal neovascularization with extensive exudation (A, fundus photography; B, optical coherence tomography). In six years, the exudation progressed to involve a larger area, encompassing more than half of the retina (C, fundus photography).

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