Evaluation of vision-related quality of life with autologous internal limiting membrane transplantation for refractory macular hole.

Background: To evaluate the vision-related quality of life of vitrectomy combined with autologous internal limiting membrane(ILM) transplantation for refractory macular hole Methods: A prospective and nonrandomized clinical study was carried out. There were fourty eyes with refractory macular hole included and all eyes received 23G vitrectomy and ILM peeling with autologous ILM transplantation. Preoperative and postoperative basic conditions were recorded, including best corrected visual acuity (BCVA), intraocular pressure, central retinal thickness (CRT) measurement by Optical coherence tomography (OCT) examination, macular hole index (MHI) and operative complications. The Chinese version of visual-related quality of life scale -25 (CVRQoL-25) was used to evaluate the visual related quality of life of patients after operation. The correlation between the quality of life and the postoperative visual acuity and the size of the macular hole before operation was tested by Spearman rank correlation test. Results: All patients were followed up for three months after surgery, and 38 patients achieved anatomical closure. The mean postoperative logMAR BCVA was 1.09±0.33, which has significantly improved than that before operation (P=0.000). The vision-related quality of life of patients after surgery was closely related to the macular hole index (r=0.375, P=0.017), but was negatively correlated with the best corrected visual acuity before and after surgery (r=-0.495, P=0.001; r=-0.760P=0.000). It was also found that the vision-related quality of life of patients positively correlated with the postoperative CRT ( r=0.414P=0.008). Conclusions: The anatomical structure of refractory macular hole patients with ILM peeling combined with autologous ILM transplantation was largely reduced, and the visual acuity of the patients improved significantly. Meanwhile, the vision-related quality of life was significantly improved after surgery. Trial Registration: ChiCTR-INR-16008660, date of registration: 2016/06/17

3 Background Macular hole refers to the continuous interruption of the retinal neuroepithelial layer in the macula zone, which causes metamorphopsia and decreased vision. Presently, macular hole is generally treated with vitrectomy combined with internal limiting membrane (ILM) peeling [1]. However, for patients with complex traumatic macular holes, large macular holes (diameter > 600um), high myopia macular holes with retinal detachment and other refractory macular holes, simple ILM peeling may be difficult to achieve stage I rupture closure and the postoperative visual function improvement is limited [2]. In view of the above refractory macular holes, some studies have found that the methods of ILM tamponade, inverted ILM flap and autologous ILM transplantation have relatively better effect on hole closure [3]. In this study, patients with refractory macular hole including macular hole with large diameter, high-myopia macular hole and secondary macular hole All the patients were conducted with 23G vitrectomy with ILM peeling combined with autologous ILM transplantation successfully. The surgical method was as follows: three channels through pars plana corporis ciliaris were established, and the vitreous body was excised. Indocyanine green staining was performed for 15 seconds. Afterwards, intraocular forceps were used to tear the inner limiting membrane within the range of 1 papillary diameter (PD) in the macular area. The inner limiting membrane was retained according to the size of the macular hole, which was slightly larger than the diameter of the hole. CVRQoL-25 questionnaire was composed of 12 dimensions and in total of 26 items [4]. The 12 dimensions as follows: "holistic health conditions", "general vision", "ophthalmodynia", "close-range activity", "remote activity", "drive", "surrounding vision", "colour vision", "limitation of social role", "degree of dependence", "social function" and "mental health conditions". There are six grades of A, B, C, D, E and F for each dimension, and the first five are scoring 100, 75, 50, 25 and 0 respectively, while F is deemed as '"no response'".
The higher the score, the better the survival quality of the project. No corresponding situation was regarded as deficiency, and was not counted into the final score statistics.
For example, if the colour perception dimension is missing, the general score is conducted with the average value of other dimensions except from color vision dimension. SPSS 17.0 statistical software was used for statistical analysis. The measurement data was expressed as mean ±standard deviation and the counting data were expressed as rate (%). Descriptive statistics and independent-sample t-test were used to compare measurement data and Spearman rank correlation analysis was used to compare the correlations between parameters. P<0.05 was used for statistically significance.

Results
After 3 months follow-up, 38 eyes with macular hole were anatomically closed and the hole closure rate was 95.0%. The 2 unclosed eyes had significantly MHI improved. The preoperative logMAR BCVA was 1.52 ± 0.29 and MHI was 0.51 ± 0.18. After three months of surgery the logMAR BCVA was 1.09 ± 0.33 and the CRT was 160.05 ± 14.88μm. The overall average value of CVRQoL-25 before surgery and 3 months after surgery were 57.28 6 ± 6.63 and 71.50 ± 8.81, respectively ( Table 1). The t test results showed that postoperative visual acuity was significantly improved (t=6.234, p=0.000). The general average score of CVRQoL-25 was also increased (t=-8.162 p=0.000).

Discussion
The ILM peeling combined with autologous ILM transplantation is a new option to treat refractory macular hole. In recent years, several researches have indicated that this method can significantly increase the closure rate of macular hole [5]. However, only clinical anatomical reduction of macular hole cannot completely reflect the visual functional recovery of patients. Therefore, the improvement of visual acuity and patients' subjective sensation of life quality after surgery are also the key factors to evaluate the success of surgery. In this research, CVRQoL-25 scores and recovery status of macular holes were assessed, which to evaluate the efficacy of ILM peeling combined with transplantation on refractory macular hole, and to provide a new direction for the prognosis assessment of such diseases.
We found that CVRQoL-25 was negatively correlated with pre-and post-operative logMAR BCVA, and the postoperative logMAR BCVA was also significantly improved. Anatomical Macular hole index is commonly used to assess deformation degree of macular hole. The larger of the macular hole index, the smaller preoperative deformation of macular hole is, of which suggesting that postoperative visual recovery could be better. Kusuhara et al. [8] showed that MHI was closely related to postoperative BCVA. The visual prognosis of MHI>0.5 group was significantly better than that of MHI<0.5 group. In this study, we  [9]. Some other researches suggesting that the closure of macular hole is due to the removal of traction from photoreceptor cells by surgery, so that the cells can be repositoned to achieve the purpose of closing the macular hole [10]. In this study, the ILM was implanted as a scaffold above the macular hole, and the photoreceptors were repositioned by the proliferation of glial cells to promote the repairment of the retinal neuroepithelial layer, thus promoting macular hole healing. In addition, some studies suggest that the transplanted ILM can reconstruct the lacuna between the retinal neuroepithelial layer and the pigment epithelial layer, which improve the pump function of the pigment epithelial cells, and promote the healing of the macular hole [11].

Consent for publication
We obtained written informed consent for publication from the patients related to details and images.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.   Figure 1 The correlation between postoperative CVRQoL-25 and preoperative logMAR BCVA.

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