Comment on “Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography”

Dear Editor,

We enjoy reading the retrospectively study by Deng et al^[1] which investigated microvascular changes in eyes with macular edema resulting from central retinal vein occlusion (CRVO) before and after intravitreal conbercept (Lumintin; Chengdu Kanghong Biotech Co, Ltd., China) injection and evaluated correlations between these changes, best-corrected visual acuity (BCVA), and retinal thickness. The authors concluded that optical coherence tomography angiography (OCTA) enables the non-invasive, layer-specific and quantitative assessment of microvasacular changes, and can be used to obtain quantitative data and more detailed information regarding the vascular network of the superficial capillary plexus (SCP) and deep retinal capillary plexus (DCP), outer retina (photoreceptor), and choriocapillaris (choroid) in eyes with CRVO. We would like to address several issues, which make interpretation of these results challenging.

There was a selection bias attributable to inclusion in the study and pooled analysis of patients with 2 forms of CRVOs (ischemic and nonischemic occlusions) having definitely different pathogenesis, clinical features, prognoses, and management. Likewise, 2 completely different etiologic subgroups of patients have been encompassed and lumped together, namely, patients older than 50y who usually have common systemic conditions such as hypertension, diabetes, and patients younger than 50y, in whom other mechanisms, such as the hyperviscosity syndrome or inflammatory condition should be specifically considered and accounted for. Taken together, these findings may have confounded the results.

The ischemic type of CRVO was defined when the non-perfused area was larger than 10 disc areas on fluorescein angiogram. However, nothing was stated referring to the criteria used for the diagnosis of the ischemic type of CRVO when marked and extensive intraretinal hemorrhages prevented a clear angiographic evaluation of retinal capillary nonperfusion zones. Accordingly, we suggested the presence of at least of 4 of the 5 following criteria: the BCVA score ≤20/400 Snellen equivalent; the ability to see ≤V/4e isopter with the Goldmann perimeter; the presence of the relative afferent pupillary defect in patients having a normal fellow eye; the extensive ocular fundus changes [more striking amount of hemorrhages, venous tortuosity, cotton wool spots (>5), disc and macular edema]; and an intraocular pressure reduction in the occluded eye of ≥4 mm Hg compared with the congener eye^[2].

The disorganization of retinal inner layers (DRIL) extent, its severity and correlation with the BCVA were not analysed at presentation and at the end of the study. Accordingly, the DRIL can be divided into 3 groups, namely, the mild DRIL [the boundary between the ganglion cell-inner plexiform layer complex (GCIPL) and inner nuclear layer (INL) cannot be distinguished and is irregular]; the severe DRIL (both the boundaries between the GCIPL and INL and between the INL and outer plexiform layer cannot be delineated and are irregular); and the severe DRIL with damaged ellipsoid zone (EZ).

The latest foveal avascular zone (FAZ) relevant parameters including the FAZ area, the FAZ perimeter (PERIM), the acircularity index (AI), the vessels density within a 300-µm width ring surrounding the FAZ (FD-300) as well as the blood flow area in choriocapillaris were thoroughly quantified on a retina slab in CRVO eyes both before and after conbercept injection. Noting was stated referring to the FAZ diameter whose enlargement would be defined more precisely the macular ischemia (e.g., FAZ enlargement >1000 µm in at least one diameter) than did the criteria employed in this series. In addition, the role of FAZ area in predicting BCVA outcomes in the context of DRIL was not assessed.

The epiretinal membrane was an exclusion criterion for the patients of this study. Noting was stated if the eyes with the other 4 optical coherence tomography patterns of the vitreoretinal interface abnormalities (e.g., vitreomacular adhesiontraction, full-thickness macular hole, and lamellar macular hole) were included or not in this study.

The following relevant data are missing from the study: the age stratification (0<age≤50y) the optical coherence tomography patterns of the macular edema (diffuse, subretinal fluid, cystic changes, and mixed type) and the location of the intraretinal cystoid fluid (inner or outer nuclear layers or ganglion cell layer); the qualitative status of the outer nuclear layer, the external limiting membrane band, the EZ, the interdigitation zone, and the retinal pigment epithelial band-Bruch's membrane complex; the proportion of patients with fibrotic and nonfibrotic scars, the macular atrophy, and the extramacular geographic atrophy; the proportion of patients with subretinal hyperreflective material and its composition (e.g., fibrosis, exudation, blood, fibrin, and choroidal neovascularization): and the subfoveal choroidal thickness^[3].

Altogether, the authors of this study revealed 2 significant correlations with regard to the baseline OCTA relevant parameters-detected microvasculature changes in CRVO eyes, namely, the blood flow area in the choriocapillaris negatively correlated with the full foveal and parafoveal retinal thickness and the duration time after onset of CRVO positively correlated with the PAZ parameters. However, the validation, extrapolation, and generalizability of the authors' conclusions can be made only by statistical analyses including all the missing baseline potential predictive factors mentioned by us in addition to the baseline characteristics already evaluated in this study, serving to identify the quantitative OCTA predictive metrics influencing functional and anatomic improvements.