In Table 1 the P values of the comparisons are reported. They suggest that RPE cells may play an important role in the development of CNV, the SDF1/CXCR4 axis is present in human, and there is a statistically significant association between detectable SDF1 and the neovascularization marker VEGFR-2.įurthermore we performed an adjunctive statistical analysis on the dataset reported by Guerin: using Mann-Whitney test (in R environment ) we tested if immunohistochemical staining grading of the three main tissues (RPE, vascular network, and fibroblasts) for SDF1, CXCR4, and VEGFR-2 differs between inflammatory CNV and ARMD. There were some unavoidable biases in the study: for example, only advanced and partially fibrous membranes were collected, often unresponsive to the previous therapy. performed a detailed study on CNV of various etiologies, testing some of the most known hypothesis on this subject. CXCR4 can also be expressed by some leukocytes that are involved in the membrane formation. The only known receptor for SDF1 is CXCR4 that is expressed on the EPC and is responsible for their chemotaxis toward the damaged tissue. The endothelial progenitor cells (EPCs) are attracted by the stromal cell derived factor 1-alpha (SDF1) that is known to be secreted by hypoxic or damaged retinal pigment epithelium (RPE) or retina. The cytokines promote secretion of matrix metalloproteinases that cut and activate the VEGF-165 and possibly degrade the extracellular meshwork allowing heavier form to be released and then activated after a plasmin dependent cleavage. Four major VEGF isoforms exist: 2 diffusive forms for intercellular signaling (VEGF-121 and VEGF-165) and 2 heparin binding heavier forms (VEGF-189 and VEGF-206). The major signal to the production of these cytokines seems to be the hypoxia via the activation of hypoxia induced factor (HIF) pathways. VEGF is produced by endothelial cells, pericytes, Müller cells, Ganglion cells, photoreceptors, and RPE cells that can produce the growth factor in a polarized way towards Brüch's membrane and choriocapillaris. In CNV a key role of vascular endothelial growth factor (VEGF) in the new blood vessels development has been widely demonstrated. Given the low incidence of inflammatory CNV and the difficulty in obtaining a reliable experimental model, most of our knowledge about this disease is mutated from the histopathological studies on ARMD-related CNV, supposing that similar clinical features correspond to common biological pathways. time domain OCT was used mostly theoretically using the spectral domain OCT this discrepancy is unlikely to be observed, even though a definitive study still lacks. showed that FA has a greater capability to detect the membrane features compared to OCT. Nowadays a growing role is played by optical coherence tomography (OCT), a fast, noninvasive instrument able to assess the presence and the activity of the disease. Indocyanine green angiography (ICG) is useful for highlighting the feeder vessel or occult membranes the new Heidelberg SLO video ICG enhances the diagnostic potentialities of this procedure. Fluorescein angiography (FA) has been for long time the principal way to assess the presence and the activity of a CNV in uveitic patients, showing early hyperfluorescence in the choroidal phase and late leakage, associated sometimes with screen effect in presence of blood or pigment. In this case the role of the diagnostic imaging is crucial. A membrane can manifest only with macular edema or serous retinal detachment however, macular edema and serous retinal detachment also can represent signs of inflammation found in course of intermediate/posterior uveitis, leading sometimes to a misdiagnosis or imprecise evaluation of the activity of the underlying disease. Often a bigger CNV can have a mixed pattern, bearing active foci in a globally fibrous plaque. However, opthalmoscopically subretinal membrane could be missed because of very few levels of exudation the only indirect sign could be a small intraretinal hemorrhagic lesion. In uveitis the classic membrane strongly shows the main type it has a grayish appearance with an evidence of exudative or hemorrhagic foci surrounding the lesion. As in ARMD, the microscopical features define type 1 or type 2 membrane, if it invades or not the subretinal space.
Otherwise, an extrafoveal membrane may be asymptomatic and can be found only at a follow-up examination or in case of posterior pole acute hemorrhage. The first is often early recognized by the patient himself complaining of metamorphopsia or central scotoma and can lead to the diagnosis of a subclinical posterior or intermediate uveitis. Inflammatory CNV can develop close to chorioretinal scar or choroidal granuloma and is classified topographically as foveal, juxtafoveal, or extrafoveal.