The abnormal hemodynamics and the destruction of the blood-retina barrier in CRVO patients lead to retinal edema due to fluid leakage, and the macular is more prone to fluid accumulation due to its loose tissue structure. With the expansion of the non-perfusion area, the release of VEGF increases, and the vascular permeability increases subsquently, macular edema represented. Long time edema can cause permanent damage, such as the loss of photoreceptor cells, the disorder of ellipsoid zone arrangement, the delay of P1 peak, and the decrease of amplitude, which are still irreversible after anti-VEGF treatment, which is related to the apoptosis caused by severe ischemia and hypoxia. With the application of optical coherence tomography angiography (OCTA) technology, the research on RVO-ME in recent years mainly focuses on the improvement of the macular structure and the re-perfusion of macular after anti-VEGF.[5–7] The purpose of this study is to explore the functional change of foveal and the correlation after structure improvement.
The circulation of inner and middle layers is disturbed in CRVO patients.While mf-ERG originates from inner retinal cells and ON and OFF- bipolar cells. Tomoharu Nishimura confirmed that the accumulation of fluid will inhibit its function, subretinal fluid will also cause abnormal light transmission, and the sensitivity of cones to light will decrease, which will directly affect the transmission of synaptic signals between cones and bipolars.After intravitreal conbercept, the fluid will gradually decrease to absorption, and the function of cells will be partially restored,  the implicit time and amplitude will gradually become normal, and mf-ERG will be significantly improved.However, after severe ischemic, axons of ganglion cells are broken and muller cells are irreversibly damaged.Even after absorption of fluid after anti-VEGF treatment, their electrical activity has not been improved, suggesting that macular function is permanently damaged.Nishijima et al reported that VEGF, as a vascular factor, not only plays an important role in regulating the generation of vascular endothelial cells but also has a protective effect on the central nervous system and retinal ganglion cells. Animal experiments show that the decrease of intracellular VEGF concentration will significantly reduce ganglion cells.Under the condition of mild ischemia caused by CRVO, the 30-Hz flicker response of full-field ERG will slightly increase.  And the activity of cones is the main source of flicker response, the combination of VEGF and its receptors will activate inner retinal cells and cones, and the decreased level of VEGF in cells directly reduce the amplitude.The integrity of photoreceptor cells will be destroyed in macular edema. After anti-VEGF treatment for 3 months, the integrity of photoreceptor cells in some patients tends to be normal, and the visual recovery is positively correlated with the morphology of baseline photoreceptor cells.  U MIT U Beyt I ˙ Nan  studied the ultrastructure of photoreceptors in the fovea of CRVO animal model by scanning an electron microscope. After intravitreal injection of bevacizumab, a series of changes occurred in mitochondria of photoreceptor inner segment cells, such as swelling, disordered arrangement, decreased density, loss of cristae, increase of amorphous corpuscles rich in phospholipids, and then apoptosis started.
Mitzy E.T.  reported that the functions of retinal ganglion cells and cone cells did not change in a short time after bevacizumab was used in AMD, high myopia CNV, PDR, and RVO.Rohit Shetty came to a different conclusion, research showed that mf-ERG increased slightly to moderately in a short time after intravitreal injection of bevacizumab, but it was not directly related to the best corrected visual acuity and the improvement of retinal thickness in fovea maculae.Compared with monoclonal antibody drugs such as ranibizumab.Conbercept, however as a fusion protein, can bind to the extracellular domain 2 of VEGF receptor 1 and the extracellular domains 3 and 4 of VEGF receptor 2.  This study showed that conbercept had the same or even better effect in RVO-ME patients. The conclusion of this study was consistent with Rohit Shetty's, after treatment, the macular function was significantly improved at one week and two months compared with the baseline, which confirmed that conbercept had no toxic effect on cones and inner retinal cells in a short time.The first and second rings of mf-ERG reflects the fovea and inner retinal function within 10°. The improvement of amplitude density and implicit time of P1 wave and N1 wave indicated that anti-VEGF could alleviate the ischemia and hypoxia condition of inner retina in a short time and break the positive feedback process of VEGF production.In this study, most patients suffered from photoreceptor cell loss and ellipsoid zone disorder before the treatment, and some patients had obvious changes in cell integrity and distribution two months after treatment, and the BCVA also improved significantly.
This study showed that the morphology and function of the macular of CRVO-ME patients improved significantly in a short time after anti-VEGF treatment and did not show the cytotoxic effect of anti-VEGF drugs, which was consistent with previous reports, but there was no correlation between them. There were several reasons for this: 1. The subretinal fluid of the foveal was decreased after anti-VEGF treatment, and the central visual acuity was improved. Considering economic factors and the patient's ischemic state is not very serious, the intensity of anti-VEGF treatment was not enough, which made the functions of cones and inner retinal cells not fully recovered, so there was no correlation between the improvement of macular function and structure.2. Whether some patients had changed to ischemic central retinal vein occlusion within two months of follow-up; Also, because some patients are older, whether there were degenerative changes in macula during treatment and follow-up.3. Choriocaphillaris is the main source of blood supply to the macula, and its endothelial cells have loose junction, so oxygen is easy to diffuse to the inner layer cells. Whether conbercept would affect the permeability of its endothelial cells and reduce the intercellular space, thus reducing the fovea blood supply, have been rarely reported in the past.4. Because of the small number of samples, short follow-up time, and the lack of preoperative evaluation of choroidal blood supply, the size, and the location of retinal capillary non-perfusion area, etc, whether these factors will affect the experimental results remains to be demonstrated in the next step.Full-field ERG reflects the electrical activity of the whole retinal cells. The non-perfusion area of CRVO patients starts from the peripheral retina where a large number of rods are located. Whether its response to ischemic state is more sensitive than that of macular area, whether it has been damaged before the macular changes, whether the amacrine cells change reversibly after improvement of ischemia, whether circulation changes of the peripheral retinal synchronize with the macular area, and whether their changes are consistent and related, which need to be clarified by full-field ERG examination. We will focus on it in the follow-up study.
To sum up, the BCVA, the structure, and the function of the macular were greatly improved after intravitreal conbercept for central retinal vein occlusion induced macular edema; therefore there was no significant correlation between the improvement of the function of macular with the structure of macular and vision.