Relationship between morphological changes in the foveal avascular zone of the epiretinal membrane and postoperative visual function

Introduction

Epiretinal membrane (ERM) is a common macular disease that causes fibro cellular proliferation of the internal limiting membrane (ILM), leading to macular morphological disturbance, metamorphopsia and loss of vision. The incidence of ERM is 12.1% among Asians, and the risk increases with age and long axial length.1 Treatment involves vitrectomy to reduce traction on the retinal surface caused by ERM and to improve macular morphology and restore visual function.2 3 The ILM is peeled during surgery to prevent the recurrence of ERM.4 Since the 1990s, optical coherence tomography (OCT) has been indicated for the diagnosis of macular diseases.5 OCT enables detailed observation of the retinal structures and correlation of visual acuity with impairment of the outer retinal layer; for example, the morphologies of the ellipsoid zone and interdigitation zone in the central fovea were first reported as prognostic factors for ERM.6–10 Furthermore, OCT has been used to show the correlation between structural changes and metamorphopsia such as the appearance and thickening of an ectopic inner retinal layer in the fovea due to ERM traction,11–15 and changes in the inner retinal layer affecting the pathway of blood vessels in this layer.12 16 Although the relationship between the ERM-associated visual function of the outer and inner layers has been reported using OCT, there is no consensus on the severity of ERM and optimal timing of surgery.14 Recently, OCT angiography (OCTA) has emerged as a minimally invasive method that enables detailed observation of the retinal blood vessels. It is widely used to evaluate diseases characterised by damage to the retinal blood vessels, such as branch retinal vein occlusion and diabetic retinopathy. It also helps assess the morphology of the foveal avascular zone (FAZ), a circular non-vascular area found in the macula in such diseases.17 18 Although the FAZ enlarges after ERM surgery,19 the differences between preoperative and postoperative FAZ morphology and visual function are unclear. Therefore, in this study, we retrospectively investigated the changes that occurred in the FAZ after vitrectomy for ERM and evaluated their relationship with visual function and macular morphology.

Materials and methods

FAZ area ratio of the FAZ

The FAZ in both eyes of healthy adults is of the same size.21 Using the fellow eye as control, we defined the FAZ area ratio as the ratio of the FAZ area of the preoperative ERM and control eyes.

FAZ area ratio=preoperative FAZ of the ERM eye/FAZ of the control eye (figure 1).

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Figure 1

Representative images from OCTA and swept-source OCTA. Representative images from a woman in her early 60s with ERM stage 3. Images of the FAZ (yellow area on images) and measurement range (purple dotted line, the internal limiting membrane to the inner plexiform layer) of (A) the control eye, where the preoperative FAZ was 0.20 mm²; (B) the eye with ERM, where the preoperative FAZ was 0.03 mm², and the FAZ area ratio was 0.15; and (C) the eye with ERM 6 months postoperatively, when the postoperative FAZ was 0.06 mm². (D) Preoperative macular morphology indicated ERM stage 3. (E) Postoperative macular morphology. ERM, epiretinal membrane; FAZ, foveal avascular zone; OCTA, optical coherence tomography angiography.

SS-OCT evaluation

We analysed the morphology of macular using the SS-OCT scanner (DRI OCT one Topcon, Tokyo, Japan). We evaluated the preoperative ERM stage based on the 12 mm radial scan mode images using the criteria suggested by Govetto et al14 (figure 2).

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Figure 2

Representative images from different epiretinal membrane stages. (A) Stage 1 shows the presence of the foveal pit and well-defined retinal layers, (B) stage 2 shows a loss of the foveal pit but with well-defined retinal layers, (C) stage 3 has the features of stage 2 with ectopic inner foveal layers and (D) stage 4 shows loss of the foveal pit with ectopic inner foveal layers and disrupted retinal layers.

Results

We enrolled 36 participants in this study. Table 1 shows the baseline clinical characteristics and visual acuity in patients with ERM.

Discussion

Vitrectomy with ILM peeling for ERM can improve visual acuity and horizontal and vertical metamorphopsia. Furthermore, FAZ was significantly enlarged postoperatively in this cohort. These findings stand in contrast to those of a Japanese study by Okawa et al, involving 20 patients, wherein no significant postoperative enlargement of the FAZ was reported.22 The lack of FAZ enlargement was believed to be due to the contraction of the retina after surgery due to ILM peeling. Compared with our present findings, the mean preoperative visual acuity in their study22 was better, suggesting mild FAZ contraction, which could explain the lack of its enlargement. In this study, most eyes with no postoperative FAZ enlargement were ERM stage 2 or below, suggesting that the postoperative FAZ enlargement depended on the preoperative severity of ERM. The preoperative FAZ area was smaller in all ERM eyes compared with the corresponding control eyes. However, 6 months postoperatively, the FAZ area was significantly enlarged, yet remained contracted compared with the control eyes. The negative correlation between the FAZ area ratio and ERM stage (table 3) suggests that the morphology of the retina changes both vertically and horizontally due to the force of afferent contraction caused by ERM. Vertical morphological changes involve changes in the structure of the retinal layer, including the appearance of the ectopic inner retinal layers in the fovea or disruption of the retinal layers, as ERM progresses. Horizontal changes are a result of contraction of the retinal surface and include contraction of the FAZ or retinal folds. Govetto et al reported a significant correlation between the ERM stage and preoperative and postoperative visual acuity, attributed to the development of an ectopic inner foveal layer as ERM progressed, which caused damage to the photoreceptor cells and outer retinal layers.14 23 However, we found that the FAZ area ratio showed a significant negative correlation with preoperative visual acuity, but not with postoperative visual acuity. Overall, we found that the mean postoperative visual acuity was good, which could explain the lack of its correlation with the FAZ area ratio. Further evaluation of cases with greater variation in ERM stages is necessary and warranted to confirm our findings.

We identified a significant negative correlation between the FAZ area ratio and degree of improvement in visual acuity after surgery (table 3). The FAZ area ratio also correlated with the degree of improvement in visual acuity for the entire ERM stage. Although an association between the ERM stage and visual outcomes has been reported,14 23 in our study, a higher preoperative FAZ contraction rate, that is, a lower FAZ area ratio was associated with a more significant improvement in visual acuity. Thus, we propose that the FAZ area ratio may be an indicator of visual prognosis and may help determine the patients’ readiness for surgery. ERM may disrupt the ellipsoid zone and affect the prognosis of visual acuity.8 In this study, we detected the disruption of the ellipsoid zone in one patient with ERM stage 4. The risk of the ellipsoid zone disruption increases as the ERM stage progresses,14 and a smaller FAZ area ratio (more contracted FAZ) is associated with increased mechanical stress on the outer layer of the retina. Therefore, the removal of this stress by surgery may have significantly improved the patients’ visual acuity in this study. This suggests that in cases where the ERM is only associated with FAZ contraction but has not yet progressed to ellipsoid disruption, surgery can significantly improve the visual acuity.

ERM causes afferent contractions in the macula and structural changes in the inner retinal layer11–15; the latter believed to be due to polarisation of Muller cells, which affects the position of the photoreceptor cells and leads to visual dysfunction such as metamorphopsia and aniseikonia.13 Several studies have reported correlations between the intraretinal granular layer thickening and preoperative and postoperative metamorphopsia.11 13 15 Vessels in the superficial retina are located in the ganglion cells and nerve fibre layers, whereas those in the deeper layers are located in the inner nuclear layer.14 This would suggest that metamorphopsia involves changes in retinal vascularisation; however, we did not observe a correlation between the change in the FAZ and metamorphopsia or between the FAZ area ratio and postoperative M-CHARTS score. Kitagawa et al reported a lack of correlation between the area of the superficial-layer and deep-layer FAZ and postoperative metamorphopsia and minimal postoperative FAZ enlargement.19 Detailed segmentation of the layer structure is difficult using the Cirrus HD-OCT 5000 scanner; therefore, we analysed only the superficial-layer vascular network of the retina (ILM-IPL) and not the deep-layer vascular network. This may be why we did not observe a correlation between the change in the FAZ and metamorphopsia. On the other hand, it has been reported that aniseikonia, which is the main symptom of ERM as well as metamorphosia, correlated with FAZ area ratio.24 Future studies with a larger number of patients and using equipment with the ability to analyse the deep retinal vascular network in detail, particularly in cases that exhibit large enlargements of the FAZ, are needed to clarify this point. Chen et al reported that afferent traction of the macula due to ERM impairs visual function by creating an imbalance in which the density of vessels is increased in the inner retinal layer of the fovea and decreased in the parafovea. Surgical release of traction was reported to correct the imbalance and improve visual acuity.25 The relationship of vascular density/imbalance with visual function warrants further investigation in the future.

This study has some limitations that should be acknowledged. First, this was a retrospective study with a small number of cases and a short follow-up period. Second, because ERM involves disruption of the retina’s layered structure, blurred images are removed, but segmentation errors may have occurred during the FAZ analysis. In the future, more cases should be analysed using OCTA, which enables more precise segmentation of the structures, including the deep retinal vessels.

Conclusion

The FAZ gradually reduced as ERM progressed and enlarged significantly after vitrectomy. The FAZ area ratio based on the preoperative FAZ is an indicator of postoperative visual acuity.