Study On The Effectiveness,Safety And Feasibility Of Vitrectomy Combined With Tumor Resection In The Treatment Of Retinal Vasoproliferative Tumors

Part 1: Comparison of two vitreous surgical outcomes of RVPTObjective: To summarize the clinical features of RVPT patients undergoing vitrectomy and to discuss the efficacy and safety of combined vitrectomy with tumor excision in the treatment of RVPT.Methods: This is an ambispective cohort study.Retrospective cohort: Thirteen eyes of 11 patients with RVPT from January 2011 to July 2017 in Wenzhou branch of Zhejiang Eye Hospital,Wenzhou Medical University.Prospective cohort: Five eyes of 5 patients with RVPT from 2014 to July 2017 in Hangzhou branch were treated consecutively.A total of 16 patients with 18 eyes accounted for 1.2% of vitrectomy over the same period.Detailed records of patients with preoperative clinical data and features of the tumor were used to summarize the clinical features of patients who undergoing vitreous surgery.Seventeen eyes of 15 patients who had a postoperative follow-up of no less than 6 months were analyzed.Eight eyes with tumor resected were included in the resectional treatment group(group R)and the remaining nine were included in the conservative treatment group(group C).The postoperative follow-up duration,best corrected visual acuity at 6 months after surgery,best corrected visual acuity at the last follow-up,intraoperative complication,postoperative complication at the first month and last follow-up,re-treatment method and tumor activity were collected.Results: Women(69%)were more common.The mean age was 50 years with81% older than 40.The youngest was 28 years old and the oldest was 69 years old.The left eye(59%)was slightly more common than the right eye(41%).Fifteen patients were monocular disease and only one was bilateral incidence.The most common symptom was decreased visual acuity(89%),followed floaters(39%),visual distortion(19%),visual field defect(6%),photopsia(6%).The duration of symptoms ranged from 0.25 months to 36 months,with an average of 7.88 months.The preoperative best corrected visual acuity ranged from 1.0 to hand movement with an average of 0.82 LogMAR.The intraocular pressure was normal before operation.Patients were all not high myopia,their axial length ranged from 21.61 mm to 24.67 with an average of 23.27 mm.Eleven(65%)of them were primary RVPT and six(35%)of them were secondary which were associated with uveitis.Of the retinal diseases,the epiretinal membrane(67%)was the most common followed by vitreous hemorrhage(39%),uveitis(39%),subretinal fluid(28%),retinal exudate(23%),traction retinal detachment(18%)and macular holes(6%).Preoperative physical examination revealed tumor in 12 eyes,ultrasound detected tumor in 3 eyes.All tumors were isolated,focal lumps.The tumor located commonly inferiorly(70%)and temporally(72%),of which 53% was inferior temporal.Gender was the only baseline characteristic that differed between two groups.The group R was significantly more effective than the group C at 6 months of follow-up and the last visit on best corrected visual acuity(P = 0.006 and P = 0.033).The best corrected visual acuity improved 0.2LogMAR or above in six months was 2 eyes in the group C,and 7eyes in the group R.Eyes with vision reduced was 2 in the group C and 1 in the group R.Eight of the tumors in the group R were completely resected,while three in the group C(33.3%)had definite activity.No intraoperative complications occurred in the two groups.The common postoperative complications were transient intraocular pressure elevation and small intraocular hemorrhage.One eye in the group R occurred lens dislocation.Persistent uveitis is common in postoperative follow-up with one eye in the group C and four in the group R,but were dimished compared with preoperative.Epiretinal membrane hyperplasia was less common consisted 3eyes in the group C and 1 eye in the group R.In the conservative treatment group,submacular exudation and macular neovascularization occurred in 2 eyes.Conclusion: RVPT was more likely to occur in non-high myopia patients.Epiretinal membrane and vitreous hemorrhage were the main causes for vitreous surgery in RVPT patients.Compared with conservative treatment,surgical resection of the tumor is more benefitial to patients on visual acuity recovery and preventing long-term postoperative complications.It is a safe and effective way to treat RVPT.Part 2: Pathology of RVPTObjective: To evaluate the possible pathological process of RVPT byinvestigating the natural pathological features of 5 untreated tumors.Methods: Five patients in the prospective cohort who had not undergone conservative treatment were enrolled in this study.Paraffin-embedded and HE staining were performed to test the GFAP,S100,SOX10,CD31,Olig2,VEGF and Ki67 by immunohistochemistry.The slices were analyzed by two senior pathologist.Results: The histopathology showed that all the cases showed small blood vessel with hyaline degeneration,fibrinous exudation with different degrees of inflammatory cell infiltration and hemorrhage.In the tumors,2 cases were mainly composed of hyaline degenerative blood vessels,of which 1 case accompanied by significant fibrinous exudation and inflammatory cell infiltration and the other 3 cases mainly consisted of astrocytosis.Lesions were limited to the nerve fiber layer,ganglion cell layer and the inner plexiform layer.Few several broke through the inner nuclear layer.The tumor and the retinal layers staggered without clear boundary.Two samples with visible hyaline degeneration were sent for examination.The results of immunohistochemistry showed that the vascular endothelial cells expressed CD31 and VEGF,and the proliferative glial GFAP and VEGF were positive.Expression of VEGF varied in different cases.It also differed between glial cells and vascular endothelial cells in the same case.Proliferative glial cells showed no heteromorphism and Ki67 staining showed a low proliferation index.Conclusion: RVPT has a kind of pathological morphology which is completely based on vascular with hyaline degeneration.Vascular hyaline degeneration is the most characteristic and repetitive pathological features of RVPT,the degree of astrocytosis in the different tumors vary greatly.Others such as fibrinous exudation,hemorrhage,inflammatory cells and Rosenthal fibers are also common pathological changes.Due to the significant difference in the proportion of vascular and glial cells in different tumors,we speculate that the natural pathological process of RVPT may start from proliferation of abnormal blood vessels.Repair of astrocytosis then occur due to some conditions and gradually evolve into the main component of the tumor.RVPT induced epiretinal membrane included blood vessels with hyaline degeneration.VEGF may play an critical role in the development of RVPT.Part 3: Design of RVPT related VitrectomyObjective: To discuss the vitreous surgery proposal based on the clinical features and pathology of RVPT.Methods: The subjects were 17 eyes of 15 patients from the group C and R.The operation time,intraoperative management of the tumor,retinal around the tumor,lens,internal limiting membrane and the use of electrocoagulation,tamponade and triamcinolone acetonide,intraoperative and 1 month postoperative complications were recorded.The detailed surgical procedure of 3 patients were evaluated.Results: The mean operation time of the resection group was 90 minutes.Tumor in 3 eyes were directly excised and the mean time was 83 minutes.The tumor was extracted in 5 eyes with an average time of 94 minutes.In the conservative treatment group,the mean operation time was 59 minutes.The operation time was significant different between the two groups(t =-3.582,P = 0.003).In the group C,8 eyes(88.9%)were treated with simple cryocoagulation therapy and 1(11.1%)was treated with photocoagulation.The final follow-up confirmed the presence of tumor activity in 3 eyes(33.3%).Retina around the tumor in the group C was treated by cryocoagulation in 4 cases the remaining patients were treated with intraoperative laser treatment.Patients with lens extraction were all over 50 years old,5 eyes in the group C and 1 eye in the group R.Both 6 eyes in two groups underwent internal limiting membrane stripping.In the group C,5 eyes were filled with BSS solution,3 eyes with long-acting gas and 1 eye with air.In the group R,6 eyes was filled with silicone oil,2 eyes with long-acting gases and 1 eye with air.Adjuvant intravitreal injection of triamcinolone acetonide was used in 7 eyes in the group C and 1 eye in the group R intraoperatively.No intraoperative complications occurred in both groups.One month after surgery,the intraocular pressure elevated transiently and there was small amount of hemorrhage.One patient in the group R occurred plume like posterior capsular opacities shortly after surgery..Conclusion: Vitrectomy combined with tumor resection can achieve the purpose of complete removal of the tumor.Rational surgical design can avoid serious intraoperative and postoperative complications.It is a feasible treatment for RVPT.