ILM peeling has been considered as a useful technique in surgeries for vitreomacular interface diseases. It has been reported that the macular hole closure rate was 90-100% when treated with vitrectomy and ILM peeling, while it was only 60–90% without ILM peeling [15-18]. However, potential damages to retinal function caused by ILM peeling was considered as a side effect of this technique.
The findings of previous studies about influence of ILM peeling on retinal function were controversial. Some studies evaluated a dissociated optic nerve fiber layer (DONFL) in ILM-peeling area and found the retinal function in this area did not changed after surgery. Yasuki et al.  compared the retinal sensitivity of DONFL area and non-DONFL area in twenty ILM-peeled eyes with MH more than 4 months after the vitrectomy by scanning laser ophthalmoscopy (SLO) microperimetry. Yoshinori et al.  performed static microperimetry-1 in 31 eyes with MH and receiving vitrectomy to explore the possible relationship between the DONFL appearance and retinal function. Hiroki et al.  investigated the effects of DONFL on retinal sensitivity in 17 eyes with an idiopathic macular hole that underwent vitrectomy and internal limiting membrane (ILM) peeling. They all found DONFL associated with ILM peeling does not alter retinal function in the area of the DONFL. While all these studies focused on the changes of retinal structure (DONFL) followed by ILM peeling, the results can only prove that the function of DONFL area, instead of ILM peeling area, had not been injured. In the current study, the DONFL was observed in 3 patients, which was only 7.1% of all cases. Therefore, the existence of DONFL can not be the main reason to interfere the retinal function in the current case series. In this study, we mainly discussed the retinal function in ILM-peeling area instead of the DONFL area. The detection method was also different with previous studies. So, the changes of retinal function in DONFL area can not be evaluated in this article.
Other studies supported that retinal function decreased after ILM-peeling. Terasaki et al.  analyzed recordings of focal macular electroretinograms (FMERGs), observing retinal physiology in the macular region of subjects undergoing ILM removal. The results demonstrated a limited and delayed recovery of the b-wave amplitude 6 months after surgery. Lim et al.  also assessed it by ERG and found that implicit time (time- to-peak of the b-wave) was prolonged, indicating subtle macular dysfunction after ILM peeling. Ramin et al.  compared retinal sensitivity and frequency of microscotomas found by SD-OCT combined with SLO microperimetry after idiopathic macular hole closure, in eyes that underwent internal limiting membrane (ILM) peeling and eyes that did not. They found mean retinal sensitivity was lower after ILM peeling and postoperative microscotomas were significantly more frequent. However, one limitation of these studies was inclusion of the macular hole area into analysis when comparing the pre- and post-operation retinal function. It may confound the results. The other limitation of these studies was failure to compare the pre- and post-operative retinal function in a point-to-point pattern due to the inherent limitation of MP-1 and MP-2.
In our study, we assessed the functional changes of the normal retina surrounding the MH after ILM peeling using MP-3. In order to ensure the result gives a strong indication for the effect of ILM peeling on the normal retinawe only choose points in the outer two rings which corresponded to the normal retina surrounding the macular hole, and the area within MH was excluded. There were 28 points in the outer two rings, which occupied 60% of the whole 45 points, but covered more than 75% area of the 8° retina. These points were located from 4° to 8°. The diameter of 8° visual field was 2500um (about 1.6 PD). During the operation, the ILM we peeled off was at least 2 PD, which means the 8° area was completely contained in the ILM peeling area. In the current study, the diameter of the largest MH is 876 μm, which corresponded to approximately central 3.5° in visual field. To further excluding the confounding effect of MH on functional analysis for ILM peeling, the points with a distance from the margin of MH less than 0.5 PD were also excluded.
Patients with severe cataract, which may interfere with the MP-3 measurements (the opacities of all patients’ lens under LOCSIII NO3C2P1 grade), were excluded. Phacoemulsification and IOL implantation were performed in 35 eyes. MRS increased in both groups. The increasing extent of MRS had no difference between the patients with phacoemulsification and those without, suggesting that opacity of lens was not severe in patients with phacoemulsification and this extra procedure did not influence the results.
In the current study, retinal sensitivity in ILM peeling area increased at both 1 and 4 months postoperatively. The reason for this unexpected result in our research might be as following. Firstly, this was a short-term study. We only observed the changes in retinal function for 4 months after surgery. The ILM peeling procedure itself could be an injury to motivate retinal neural protection and lead to the release of neural protective factors [20,21]. These factors might improve retinal function in a short-term. If the retinal function was observed for a longer time (such as more than 6 months), the result might be different. Secondly, in the current study, retinal function was evaluated by MP-3. Compared with MP-1 and MP-2, MP-3 has auto tracking and auto aligment, fixation test, wider measurement range, higher resolution non-mydriatic fundus camera and a better system to accomplish the images for pre- and post-treatment comparison. These techniques enable us to do more accurate assessment of macular function. At last, there are often retinal cysts around the margin of macular holes. These cysts can decrease retinal sensitivity. It has been proved that the elimination of retinal cysts followed by MHs healing can increase retinal sensitivity of corresponding area . Although we chose the outer rings to avoid the influence of the function change around the hole as much as possible, it still may cover some areas of the retinal cysts, which may affect the results of normal function measurement.
The post-operative MRS in the selected area increased in 37 patients and deceased in 7 patients. Patients with decreased MRS were significantly older than other patients. We think the reason may be related with retinal recovery ability. Patients with younger age may have a better recovery ability in RS than aged patients. If the sample enlarged, the result might be different.
The pre-operative MRS had no difference between superior and inferior retina or between nasal and temporal retina pre-operation. While the increasing extent of retinal sensitivity in superior retina was significantly higher than that in inferior retina. When performing ILM peeling, the surgeon used to start from superior retinal area. The initiation of ILM peeling may bring more mechanical injury to the superior retina. It may be the reason of this phenomenon. We also found the increasing extent of retinal sensitivity in temporal retina was significantly lower than that in nasal retina. Takayuki et al.  had the similar result. They performed vitrectomy and ILM peeling on 39 eyes with MH, and found the retinal sensitivity was significantly lower in the temporal area than in the other areas 3 and 6 months after surgery. The reason for this restricted change to the temporal retina might be as following. Firstly, the removal of the ILM started from the temporal superior retina to the fovea. Secondly, the nerve fiber layer has been reported to be thinnest in temporal quadrant around fovea . Thirdly, the density of ganglion cells at the temporal retina is less than that at the nasal retina within 2 mm from fovea .
The limitations of the current study included lack of a control group. A prospective randomized control study is indicated in the future to draw more definitive conclusion.
In conclusion, ILM peeling in normal retina did not decrease the retinal function in a short-term after surgery, except in some patients with older age. During the surgery, we didn’t use any dye, whose retinal toxicity still needs further study. ILM peeling alone is a safe and useful technique in surgeries for closing macular hole.