Surgical management and ultrastructural study of choroidal neovascularization in punctate inner choroidopathy after bevacizumab

Abstract

PurposeThis study aims to describe surgical management results and the pathologic features of choroidal neovascularization (CNV) secondary to punctate inner choroidopathy (PIC) following anti-vascular endothelial growth factor treatment.DesignThis study is a case report on the surgical management and ultrastructural study of choroidal neovascularization.MethodsClinicopathologic and ultrastructural report of CNV membranes excised from both eyes of one patient was presented.ResultsThe right eye responded to bevacizumab, and recurrence 17 months later did not; the left eye never responded. Excision of the active CNVs was performed 3 months after the last injection. In the right eye, there was no recurrence 23 months after surgery. In the left eye, CNV recurred after 6 months, with no response to bevacizumab. Electron microscopy revealed subretinal neovascular tissue and, additionally, Bruch's membrane and inner choroid in the left. In the right eye, lumens of many neovascular channels were occluded by microfibrils and pericytes were infrequent. In the left eye, patent CNV units with pericytes were present. There were scattered macrophages but no lymphocytes in either membrane. An inner focal choroidal lymphocytic infiltrate was discovered.ConclusionsSubmacular surgery did not cause complications following treatment with bevacizumab. Mostly nonfunctional capillaries in the right membrane failed to display pericytes. The left membrane, which was unresponsive to bevacizumab, displayed well-formed neovascular units consistently exhibiting pericytes. A focus of inner choroidal lymphocytic infiltration was found in the left eye despite the absence of overt clinical intraocular inflammation. This is the first pathological study employing human tissue that points to pericytes as a potential critical therapeutic target with the aggravating influence of inner choroidal chronic inflammation in PIC.

A new kind of labyrinth-like capillary is responsible for leakage from human choroidal neovascular endothelium, as investigated by high-resolution electron microscopy

“…Another study described neovascular channels that were occluded by microfibrils (Fig. 4b of that study) in a patient suffering from punctuate inner choroidopathy treated with bevacizumab [23]. Such vessels were also seen in this study in all CNVs, but we think that the endothelium of this vessel type has degenerated and the former vessel lumen, indicated by the remaining basement membrane, is filled by the extracellular matrix.…”

Prospective PED-study of intravitreal aflibercept for refractory vascularized pigment epithelium detachment due to age-related macular degeneration: morphologic characteristics of non-responders in optical coherence tomography

“…In the course of a continuative anti-VEGF therapy, fluid in the sub-RPE space resorbs, and the CNV remodels and eventually reaches a higher level of vascular maturity. Such inactive mature vessels are non-leaking, un-fenestrated, and covered by pericytes and may act as a diffusion barrier counteracting the resorption of subretinal fluid [14,15]. At this stage, intravitreal anti-VEGF can hardly induce resorption of subretinal fluid as these vessels are only poorly accessible to antibodies.…”

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to punctate inner choroidopathy

“…Before the anti-VEGF era, this severe complication of PIC was treated either by observation only, or by steroids, immunosuppressants, laser, PDT [1,10,11,14,15] or even submacular surgery [30]. Although older reports recommended watchful observation [15], nowadays there is consensus that especially subfoveal lesions should receive immediate ophthalmic treatment [1].…”