Clinical Study Of Mesenchymal Stem Cell Therapy Patients With Retinitis Pigmentosa Accompanied By Cystoid Macular Edema

Backgroud and objective:Retinitis pigmentosa(RP) is a set of hereditary retinal degenerative diseases which treat progressive photoreceptor cells and pigment epithelium afunction as a common performance. The clinical features are night blindness, progressive visual field defects and bone cell-like retinal pigmentation, the significant of full-field Electroretinogram(FERG) is abnormality or no waveform. Some patients appear cystoid macular edema(CME), it refers to the macular area of the photosensitive outer plexiform layer of the retina, the presence of liquid accumulated in the extracellular space, and because Henle fiber arranged radially in macular area, so it produces characteristic forms of polycystic edema. When edema serious can spread to the outer plexiform layer adjacent to the structure of several layers of the retina. The incidence of CME in RP patients is 10%- 40%, and usually affects both eyes.This study analyzed clinical phenotype in patients with this disease, to explore the clinical characteristic of patients with RP accompanied by CME. The treatment with RP accompanied by CME is no effective treatment methods. The efficacy of Carbonic anhydrase inhibitor, Vascular endothelial growth factor, Lutein, Laser photocoagulation and vitrectomy is not sure. Triamcinolone acetonide(TA) is the treatment of CME conventional drugs, but the current commonly used way of this drug can cause postoperative high intraocular pressure, pricking the eye, damage to the extraocular muscle. After we set up new post-sclera(post-macula) injection of TA treatment, making the TA on the premise of avoiding complications and better play in the role of the relieve edema, but the half-life of TA is short, and no use to control the progression of RP. Mesenchymal stem cells(MSC) have anti-inflammatory, immune regulation, vascular repair and neurotrophic factor secretion function, clinical application is safe. MSC may be have certain effect on delaying the RP progerss. Therefore this study on the intravenous infusion of MSC curative effect of RP patients with CME, and compared with macular area post-sclera injection of TA.Methods:1. According to the clinical features of RP patients with CME, the establishment of OCT macular edema degree, OCT macular partition, AF highly fluorescent ring diameter grading and FFA leakage rates and other advanced analytical methods. Applying the methods to analysis of clinical phenotypes.2. Twenty patients with RP patients accompanied by CME were recruited, randomized into MSC group and TA group, collecting patients’ history, to take standardized ophthalmologic examination: Best corrected visual acuity(BCVA), intraocular pressure, visual field, Autofluorescence(AF), Fundus fluorescein angiography(FFA), Optical coherence tomography(OCT), Visual electrophysiology(VEP), etc. And analyzed the results.3. MSC patients for randomization generated proceed single intravenous infusion of MSC: 3×106cells/Kg, through the pre-treatment and post-treatment first day, first week, from first to third month, sixth month BCVA, visual field, OCT, FVEP results of the analysis, the efficacy of MSC intravenous infusion were evaluated.4. By Royal College of Surgeons(RCS) retinal degeneration rats were injected TA by post-sclera, prove the safety of post-sclera injection of TA.5. Making a new macular area post-sclera injection device according to the eyeball radian of the patients, using the device to inject TA by macular area post-sclera, to evaluate the efficacy and safety of this technique, and establish a new method of treatment.6. TA patients for randomization generated proceed macular area post-sclera inject TA, through the pre-treatment and post-treatment first day, first week, from first to third month, sixth month BCVA, visual field, OCT, FVEP results of the analysis, the efficacy of macular area post-sclera inject TA.7. MSC patients and TA patients for randomization generated, MSC group were a single intravenous infusion of MSC: 3 × 106 cells / Kg, TA group were macular area post-sclera inject TA 20 mg, through the pre-treatment and post-treatment first day, first week, from first to third month, sixth month BCVA, visual field, OCT, FVEP results of the analysis, curative effect comparison of two groups of patients.Results:1. According to the clinical characteristics of the patients with RP accompanied by ME, first to establish OCT cystoid macular edema degree, OCT macular partition, AF highly fluorescent ring diamter grading and FFA leakage rates and other advanced analytical methods. To the quantitative analysis of ophthalmic imaging examination results, the relationship between the evaluation of each index.2. Using the above methods to analysis concluded that OCT can check out the different levels of CME of 20 patients, but there are eight cases that FFA has no fluorescein leakage, while FFA can be no leakage in those with severe CME, the edema degree of CME and is not associated with leakage degree of FFA(r=0.293,P=0.126); patients with mild CME that the BCVA is still poor, the edema degree of CME and is not associated with BCVA(r=-0.154,P=0.388); the patients whose AF high fluorescence ring diameter smaller can be lighter CME, but these patients have poor BCVA, High fluorescent ring diameter of AF and is not associated with the edema degree of CME(r=0.139,P=0.474), but it was positively correlated with BCVA(r=0.429,P=0.015).3. MSC infusion therapy RP patients with CME can make BCVA remained stable in the six months after treatment, visual field, FVEP indicators improved after treatment in third month, the trend is maintained until the sixth month. OCT macular thickness showed no significant changes within three months after treatment, but improved significantly in the sixth month. It shows that the method improved visual function, and the role of long duration.4. By RCS-P60 rats were injected TA by post-sclera, through the observation of the HE staining of retinal slices that concluded one day group and one week group, injected eyes and control eyes are visible retinal layers intact. Proof of the safety of post-sclera inject TA. And then adopt the method of macular area post-sclera inject TA of 10 RP patients accompanied by CME for treatment.5. Macular area post-sclera inject TA group of patients, can improve the related index of OCT macular thickness of the until post-treatment second month, in the third month when the curative effect of decline. Suggest this method could help alleviate CME, but curative effect only for 3 months.6. MSC group and TA group treated by different methods for comparing curative effect, the thickness of macular foveal 1 zone and average thickness of macular area 1 ~ 9 zones reduced aspect of MSC group are not as good as TA group(P=0.004), however, visual field and FVEP of MSC is better than that of TA, to improve visual function MSC group is better than that of TA group.Conclusion:1. The first establishment of OCT cystoid macular edema degree, OCT macular partition, AF highly fluorescent ring diameter grading and FFA leakage rates is easy to analyze clinical phenotypes of RP accompanied by CME. To the quantitative analysis of ophthalmic imaging examination results. Using the above methods to analysis concluded that OCT can check out the edema degree of CME and is not associated with leakage degree of FFA, the edema degree of CME and is not associated with BCVA, High fluorescent ring diameter of AF and is not associated with the edema degree of CME, but it was positively correlated with BCVA.2. Initial treatment with intravenous infusion MSC in RP patients accompanied by CME, found that therapy helps to improve visual function, the role of a long time, continued until after 6 months of treatment. While relieve CME after 6 months of treatment significantly.3. Established the macular area post-sclera inject of TA method, this method is safe and effective treatment with RP patients accompanied by CME. This method could help relieve CME, but only until 3 months after treatment.4. Compare the curative effect of the two therapeutic method, in terms of BCVA and OCT macular thickness, TA group is better than MSC group; in terms of visual field and F-VEP, MSC group is better than TA group,MSC has curative effect on visual function.