Foveal Eversion is Associated with High Persistence of Macular Edema and Visual Acuity Deterioration in Retinal Vein Occlusion

Abstract

Introduction: Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO).

Methods: This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up.

Results: The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up.

Conclusions: FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

Keywords: BRVO; CRVO; Foveal eversion; Macular edema; OCT; Retinal vein occlusion.

Fig. 1

Foveal eversion (FE) patterns in retinal vein occlusion. Starting from the definition of FE as a complete eversion of the foveal profile, FE pattern 1a (A) is characterized by the presence of thick intraretinal vertical columns, with at least one column with a thickness > 100 µm. FE pattern 1b (B) shows thinner intraretinal vertical columns than pattern 1a, whereas FE pattern 2 (C) has no sign of columns in the context of intraretinal macular edema. RVO eyes with macular edema, showing a sign of foveal depression, are classified as no FE eyes (D). RVO retinal vein occlusion

Fig. 2

A case of CRVO without FE. Baseline structural OCT (A) shows the combined presence of intraretinal and subretinal fluid (LogMAR BCVA 0.5). After the loading dose of anti-VEGF injections, the regression of intraretinal edema is seen, with persistence of subretinal fluid (B). After 6 months of treatment, also subretinal fluid was almost reabsorbed (C). One- and 2-year follow-ups confirm the positive effect of the treat-and-extend regimen in preserving retinal integrity, with final LogMAR BCVA of 0.0 (D, E). CRVO central retinal vein occlusion, FE foveal eversion, OCT optical coherence tomography, BCVA best corrected visual acuity, anti-VEGF anti-vascular endothelial growth factor

Fig. 3

A case of BRVO with FE pattern 1b. Baseline structural OCT (A) shows the presence of a completely everted foveal profile with multiple thin intraretinal vertical columns (LogMAR BCVA 0.8). Macular edema was already reabsorbed after the loading dose of anti-VEGF injections (B), and 6-month, 1-year and 2-year follow-ups confirmed the stability of the clinical picture and the positive outcome with a final LogMAR BCVA of 0.2 (C–E). BRVO branch retinal vein occlusion, FE foveal eversion, OCT optical coherence tomography, BCVA best corrected visual acuity, anti-VEGF anti-vascular endothelial growth factor

Fig. 4

A case of BRVO with FE pattern 2. Baseline structural OCT (A) shows the presence of a completely everted foveal profile without central vertical columns (LogMAR BCVA 0.8). Despite the intensive anti-VEGF treatment regimen and switching to corticosteroid implants during the follow-up, this eye was always characterized by macular edema persistence over the entire follow-up window [after loading dose (B); 6-month follow-up (C); 1-year follow-up (D); 2-year follow-up (E)]. Final LogMAR BCVA was 0.5. BRVO branch retinal vein occlusion, FE foveal eversion, OCT optical coherence tomography, BCVA best corrected visual acuity, anti-VEGF anti-vascular endothelial growth factor

Fig. 5

The possible evolution of foveal eversion in RVO. Baseline image shows a BRVO complicated by macular edema with complete eversion of the foveal profile and multiple thin vertical columns, classified as FE pattern 1b (A). After 6 months (B), we can observe a dry retina with the presence of a central vertical hyperreflective line, which can be interpreted as a gliotic reaction of the Müller cells. Nine-month follow-up (C) examination shows the recurrence of macular edema, with a marked thinning of the vertical intraretinal columns and degenerative signs of inner retinal layers, which are further evident at 1-year follow-up (D). Eighteen-month follow-up (E) is characterized by almost complete response to intravitreal treatments, although it is possible to observe the central disruption of retinal layers. Thirty-month follow-up (F) is characterized by recurrent behavior of macular edema. Interestingly, at 40-month follow-up (G), it is possible to observe the presence of a mixed reflectivity material in the context of the intraretinal macular edema, highlighting the passage through FE pattern 2. From this point, macular edema assumes a persistent course, as confirmed by 5-year follow-up examination (H). BRVO branch retinal vein occlusion, FE foveal eversion