This study investigated the clinical importance of EIFL grading (mild to severe) in a cohort of 138 eyes diagnosed with iERMs and exposed to PPV (solely ERM peeling); and a significant relationship was detected between higher baseline thickness of EIFL and high recurrence rate, lower baseline and final BCVA over long-term follow-ups (p < 0.05).
There is not any common consensus on the timing of surgery on eyes with iERMs. Determining the severity of ERM and assessment of the prognosis by surgical removal may be difficult [15]. The characterization of reliable prognostic biomarkers is thereby crucial among surgeons who predict postoperative functional and anatomical results in eyes with iERMs. It has been shown in various studies that ILM peeling with ERM does not provide an anatomical and visual benefit compared to ERM peeling alone in iERM patients. The rate of recurrent ERM and the need for repetition of ERM surgery were found to be lower in eyes that peeled up with ILM and ERM [18–20]. Although similar rates were observed in our study, we found a positive correlation between ERM recurrence and EIFL thickness. This study may contribute to the hypothesis of visual and anatomical disruption of Müller cells in the development of EIFLs.
Up to date, there is numerous number of OCT studies which analyse the prognostic role of inner retinal changes on decrement of BCVA in iERMs. In fact, recent studies suggest that impairment of external retinal layers may be inadequate in order to explain vision deterioration precisely in ERM formation. However, the integrity of the photoreceptor and the outer retinal layer had an important prognostic value in final visual acuity during long-term follow-ups [10–14, 15]. In this context, we have classified the presence of EIFL in a subset of iERMs and associated this incidence of anatomical findings with poor initial BCVA.
Govetto et al. evaluated the effect of EIFL on anatomical and functional outcomes on 111 eyes of 107 patients with iERMs that both ERM and ILM were peeled up in a retrospective study for 12 months. The presence of EIFL had a respectable impact on the initial and final BCVA; and it was observed that the higher the EIFL correlated with lower the initial BCVA. The EIFLs were detected in 56 of 111 eyes (50.4%) before ERM and ILM peeling surgery. EIFL continued to exist on 51 (91%) of 56 eyes after the surgery due to the diagnosis of stage 3 and 4 iERMs. Although thickness of the EIFL manifested a decrease after the surgery (p < 0.001), the reduction of EIFL in postoperative period did not cause to any change in final BCVA. They suggested that presence of EIFL may be a negative prognostic factor for postoperative anatomical and visual recovery [21]. Predicting prognostic efficacy of inner retinal changes on visual function may cause bias for assessment of such analysis due to the strong correlation between inner retinal thickness and CMT. Previous studies have demonstrated independent relationships among the inner retinal thickness and visual acuity in iERMs; however, the automated software may usually take analyses corresponding to the incorrect retinal layer rather than inner retinal parameters [13, 22]. In our study, EIFL was present at baseline in 98/138 (71%) of patients in our study and decreased in 72/138 (52%) post-surgery but did not disappear completely. In current study, we may suppose that excess amount of EIFL had a negative prognostic effect in terms of ERM recurrence rate, visual acuity improvement, and recovery of foveal anatomy.
In a recent study by Mavi Yıldız et al., both ERM and ILM were peeled up in 112 eyes of 112 patients, and less visual and anatomical gains were achieved in advanced stages (stage 3 and 4) [23]. In our study, after solely performing ERM peeling, both the number of recurrences were higher and the visual and anatomical gains were less for advanced stage (stage 3 and 4).
Ectopic inner foveal layer thickness decreased during postoperative follow ups [24]. This decrement was evident up to 6 months, and minimum between 6 months and 12 months following ERM surgery in our study. However, it showed that postoperative EIFL thinning did not directly affect alterations of postoperative visual acuity. This fact could be raised new questions about EIFL-associated visual deterioration and limited functional and anatomical recovery following ERM surgery. In fact, recent studies suggested that the more the thickness of the EIFL, the lower the final BCVA [22, 25]. It may be considered that ectopic retinal tissue can act as a physical barrier effect on image formation by being located between afferent light and photoreceptors, which obstructs or distorts the visual image projected onto the foveal cones. The severity of this image distortion may be directly proportional to the increase in EIFL thickness [25].
In the presence of EIFL, various changes may develop in retinal microstructures. Chronic inner foveal displacement may lead to damage and disruption on photoreceptors and other retinal cells resulting with disturbances in normal neural conduction, visual deterioration, and metamorphosia on eyes with iERM [15, 22, 26, 27]. This fact may be particularly associated with stage 4 ERMs which are involved by complete foveal irregularity and lower postoperative visual achievements. As stated in the study of Matthews et al., complete recovery of foveal depression in the long follow-up periods after surgery gradually decreased with increment of ERM grade [28]. Persistence of EIFL following ERM surgery in most eyes with stage 3 and 4 ERM may clarify the low postoperative anatomical gain and lower visual outcomes in these groups. Ellipsoid zone disruption and outer retinal layers changes in stage 4 might have affected final visual acuity in present study.
The presence of EIFL in the absence of traction suggests that it may result in mechanical displacement of the inner retinal tissue, possibly as a result of other molecular reactions caused by Müller cells [15]. Müller cell activation may be responsible for inner retinal reorganization on fovea in postoperative period in eyes with stage 2 ERM, and symbolize a reparative reaction following ERM surgery. Therefore, internal limiting membrane peeling has negligible effect on visual results following ERM surgery. ERM recurrences are minimized by peeling of the ILM, nevertheless most recurrences are clinically insignificant [19, 20]. In a study by Ahn et al., better outcomes were found in terms of anatomical and functional recovery in patients with iERM whose ILM was not peeled in the 1st month. They declared that in line with visual outcome and photoreceptor integrity, supplementary ILM peeling may not be an obligatory procedure [29]. Recently, the development of myrocystic macular edema without vascular leakage in fluorescein angiography with ganglion cell loss and thickening of the inner nuclear layer has been termed retrograde maculopathy. This condition is common seen in patients with iERMs who had undergone both ERM and ILM peeled up [30]. In our study, none of the patients developed retrograde maculopathy and did not affect functional gains notably.
To the best of our knowledge, this is the first study to evaluate EIFL, recurrence rate, anatomical and visual outcomes according to the SD-OCT-based ERM staging scheme before and after ERM peeling alone.
The limitations of current study include the retrospective design and absence of high-density macular scanning for all cases. Despite the use of high-intensity SD-OCT imaging in most of involved eyes, the central fovea might have been overlooked by a standard macular raster or single high-definition horizontal B-scan, resulting in mismatch and overlooked classification of some iERMs.
Strengths of our study include convenient follow-ups and sample size, two blinded independent evaluators and the usage of SD-OCT eye tracking systems that enable definitive analysis of postoperative anatomical alterations in all cases. Although longer follow-up periods represent the strength of our study, it was reported that both visual acuity and SD-OCT parameters return to normal within approximately 2 years after surgery, which may support that long-term follow-up provides greater opportunities for evaluation of postoperative anatomical and visual outcomes [31].
In this study, the prognostic value of the ERM classification was investigated by SD-OCT which was convenient and accessible tool to predict functional and anatomical postoperative outcomes. The existence of EIFL should not be the main factor in the surgical decision-making process when ERM grading was assessed. However, according to this study, we may suggest that the surgical timing which may be preferred in terms of visual improvement, postoperative anatomical gain and lower recurrence rate is stage 2 and below. Moreover, we may discuss that it is an early grades of EIFL (stage 1 and 2), the outer retinal layers are not affected, and the foveal cavity formation is higher in the postoperative period. Also, ILM peeling may not be an indispensable surgical procedure in the early grades of iERMs (stage 1 and 2). The thickness of the EIFL correlates with both baseline and final BCVAs. Furthermore, postoperative EIFL thinning and severity indirectly affect postoperative BCVA alterations. Therefore, formation of EIFL may cause irreversible retinal damage; and the existence of EIFL may reflect a negative prognostic ingredient for postoperative anatomical and visual recovery.
However, prospective studies involving large patient groups are needed to confirm our results and to evaluate the prognostic effect of the ERM staging scheme more accurately. Over and above, supplementary clinicopathological studies are needed to determine the pathophysiology of EIFL development better before performing surgical procedures. Finally, automated segmentation of inner retinal layers and further imaging methods would be crucial to advance the ability to identify and quantify of EIFL. We hope outcomes of current study would spur the design of future studies that will evolve the surgical management of these lesions.