Due to the serious shortage of corneal donor, the development of penetrating keratoplasty and corneal endothelial transplantation is severely restricted in clinical practice.The root cause is the limited proliferation capacity of healthy corneal endothelial cells.With the continuous development of tissue engineering technology and cell engineering technology, the research of tissue-engineered cornea has made some progress. In vitro culture of corneal endothelial cells with high density and healthy endothelial function for transplantation is a hot topic in current tissue engineering research.The keys of tissue-engineered corneal endothelial technology include seed cells, vector materials and the strategy of cell transplantation.At present, many research teams domestic and abroad have reported that the source of seed cells includes human corneal endothelial cells, stem cells, vascular endothelial cells and human amniotic epithelial cells.Vector materials include amniotic membrane, acellular corneal stroma, posterior elastic layer, anterior capsular membrane and various biomaterials.The cultured cells are transplanted by penetrating keratoplasty, corneal endothelial transplantation or anterior chamber injection.This review summarized the latest progress in the research on the source of corneal endothelial seed cells, the selection of vectors and the methods of corneal endothelial transplantation, and summed up the problems faced in the current research and looked forward to its prospects.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Objective:To assess the changes in corneal endothelial cell density (CD) and morphology in patients with different stages of keratoconus.Methods:A cross-sectional study was conducted.One hundred and nineteen patients (199 eyes) with keratoconus who were treated in the Eye Hospital of Shandong First Medical University were included from March 2018 to October 2021.The 199 eyes were classified into stage Ⅰ (111 eyes of 58 cases), stage Ⅱ (41 eyes of 30 cases), stage Ⅲ (47 eyes of 31 cases) keratoconus groups according to the Amsler-Krumeich classification.In the same period, 25 age- and sex-matched healthy subjects (50 eyes) were enrolled as a normal control group.Corneal topography and anterior segment parameters such as keratometry (K), central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior chamber depth (ACD), corneal diameter and corneal volume were obtained by Pentacam 3-dimensional anterior segment imaging and analysis system.The corneal endothelial CD, percentage of hexagonal cells (6A), average cell area (AVE), maximum cell area (MAX), minimum cell area (MIN), cell area standard deviation (SD) and cell area coefficient of variation (CV) in the central area were evaluated by non-contact specular microscopy.The correlation between corneal endothelial CD, morphological parameters and corneal topographic parameters was analyzed by Spearman rank correlation.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY201803). All patients were informed of the purpose and methods of the study and written informed consent was obtained before any medical examination.Results:The CD of the normal control group and stage Ⅰ, Ⅱ, Ⅲ keratoconus groups was 2 941(2 809, 3 072), 2 825(2 667, 3 030), 2 747(2 475, 2 903) and 2 370(2 142, 2 525) cells/mm 2, respectively.With the progression of keratoconus, CD decreased gradually, and there was a significant difference in CD among the four groups ( H=94.862, P<0.001). There were significant differences in CV and 6A among the four groups ( H=45.018, 20.421; both at P<0.001). CV was significantly higher in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ and Ⅱ keratoconus groups and 6A was significantly lower in stage Ⅲ keratoconus group than that of the normal control group and stage Ⅰ keratoconus group (all at P<0.05). With the progression of keratoconus, MAX, MIN, AVE and SD increased gradually, and there were significant differences in MAX, MIN, AVE and SD among the four groups ( H=37.905, 32.437, 110.182, 72.941; all at P<0.001). MAX and MIN in stage Ⅲ keratoconus group were significantly higher than those in stage Ⅰ keratoconus groups and normal control group (all at P<0.05). AVE and SD in stage Ⅲ keratoconus group were significantly higher than those in normal control group and stage Ⅰ and Ⅱ keratoconus groups (all at P<0.05). In patients with keratoconus, CD was moderately positively correlated with CCT ( rs=0.47, P<0.001) and TCT ( rs=0.53, P<0.001), and was moderately negatively correlated with mean keratometry (Km) ( rs=-0.59, P<0.001).6A was weakly positively correlated with CCT ( rs=0.18, P=0.01) and TCT ( rs=0.22, P=0.002), and was weakly negatively correlated with Km ( rs=-0.32, P<0.001). CV was weakly negatively correlated with CCT ( rs=-0.35, P<0.001) and TCT ( rs=-0.37, P<0.001), and was moderately positively correlated with Km ( rs=0.48, P<0.001). There was no correlation between CD, CV, 6A and ACD, or corneal volume. Conclusions:As the keratoconus progresses, the cornea protrudes and becomes thinner with CD and 6A decreasing while CV increasing.Corneal topographic parameters are related to the density and morphology of corneal endothelial cells.

Objective:To analyze and compare the corneal higher order aberration (HOA) after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).Methods:A non-randomized controlled study was conducted.Sixty myopic patients (60 eyes) who underwent FS-LASIK or SMILE correction at Shandong Eye Hospital from April 2018 to January 2020 were enrolled and the data from the right eye were collected for analysis.Thirty cases (30 eyes) who received FS-LASIK in FS-LASIK group and 30 cases (30 eyes) who received SMILE in SMILE group had a preoperative equivalent spherical diopter of (-5.36±1.11)D and (-4.93±1.03)D, respectively.The HOA of the 6-mm anterior surface, posterior surface, and whole cornea were measured before surgery and at 1, 3, 6, and 12 months after surgery using Pentacam.The root mean square values (μm) of total corneal HOA, spherical aberration, coma and trefoil were obtained.Differences in the above root mean square values at different time points were compared between the two groups.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY20180306). Written informed consent was obtained from each subject.Results:The preoperative and 1-, 3-, 6-, 12-month postoperative total HOA of the anterior corneal surface were (0.428±0.126), (0.775±0.169), (0.811±0.194), (0.759±0.214), (0.704±0.199)μm in the FS-LASIK group and (0.409±0.094), (0.656±0.148), (0.681±0.161), (0.668±0.175), (0.648±0.160)μm in the SMILE group, with a significant overall difference ( Fgroup=5.652, P=0.024; Ftime=107.169, P<0.01). Compared with SMILE group, the postoperative total HOA of anterior corneal surface and spherical aberration at different time points were increased in FS-LASIK group, showing statistically significant differences (all at P<0.05). Compared with before surgery, the postoperative total HOA of the anterior corneal surface and spherical aberration at different time points were increased in both groups, showing statistically significant differences (all at P<0.05). In the two groups, the 6- and 12-month postoperative total HOA of the anterior corneal surface were reduced in comparison with the 3-month postoperative ones of the anterior corneal surface, and the 12-month postoperative spherical aberrations of the anterior corneal surface were significantly reduced in comparison with the 1- and 3-month postoperative ones of the anterior corneal surface, showing statistically significant differences (all at P<0.05). There were significant differences in the coma and trefoil of the anterior corneal surface between before and after the operation (coma: Ftime=47.848, P<0.01; trefoil: Ftime=2.497, P=0.046). Compared with before surgery, the postoperative coma was significantly increased in the two groups (all at P<0.05). There were significant differences in total corneal HOA and spherical aberration at different postoperative time points between the two groups (total HOA: Fgroup=8.093, P=0.008; Ftime=125.019, P<0.01.spherical aberration: Fgroup=4.771, P=0.037; Ftime=34.033, P<0.01). Compared with SMILE group, the total corneal HOA and spherical aberration were significantly increased in FS-LASIK group at different postoperative time points (all at P<0.05). Compared with before surgery, postoperative total HOA of the anterior corneal surface and spherical aberration at different postoperative time points were significantly increased in both groups (all at P<0.05). In both groups, the 12-month postoperative corneal spherical aberration was significantly reduced in comparison with the 1- and 3-month postoperative ones (all at P<0.05). There was a significant difference in coma between before and after surgery ( Ftime=30.829, P<0.01). Compared with before surgery, the postoperative coma was significantly increased at different time points in both groups (all at P<0.05). Conclusions:Both FS-LASIK and SMILE increase the HOA of the anterior corneal surface and the whole cornea.Compared with FS-LASIK, SMILE introduces less HOA of the anterior corneal surface and the whole cornea as well as spherical aberrations.

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral allergic conjunctivitis common in school children.VKC is classified into palpebral-conjunctival type, limbal type and mixed type primarily based on clinical findings.Most allergic conjunctivitis does not impair vision, however, VKC probably causes visual impairment because of the involvement of cornea besides conjunctiva.Corneal lesions of VKC would lead to amblyopia in younger children.The term "vernal" in VKC indicates a seasonal onset, but 20%-60% patients are found onset throughout the year.In addition, misdiagnosis and improper treatment often lead to persistence or recurrence of VKC and other complications.Previous study has suggested that VKC is a hypersensitivity disease involved both type I and type IV, however, recent researchers found that immune factor, genetic factor and endocrine factor show close associations with the pathogenesis of VKC.The diagnosis of VKC depends on the clinical symptoms, pathological findings, infiltration of dendritic cells by laser scanning confocal microscopy and allergen tests.The treatment of VKC mainly focuses on symptom relief.In addition to anti-allergy, anti-inflammation and artificial tears, immunosuppressor has become a new trend.The pathogenesis and treatment progress of VKC are reviewed.

MicroRNA (miRNA) is a short noncoding RNA, which can regulate gene expression.miR-21 is one of the human miRNAs identified earlier.As an oncovirus, it is involved in the post-transcriptional regulation of gene and plays important roles in cell proliferation, apoptosis and differentiation.In addition, miR-21 promotes inflammatory responses and also plays a key role in regulating the function of immune system.Recent studies have shown that miR-21 could be detected in corneal fibroblasts cells, retinal pigment epithelial cells, retinal microvascular endothelial cells, retinal microglia and other eye-derived cells.Furthermore, miR-21 plays an important part in the development of various eye diseases including retinoblastoma, uveal melanoma, corneal alkali burn, proliferative vitreoretinopathy, diabetic retinopathy and uveitis.Further studies have shown that inhibited expression of miR-21 can treat retinoblastoma and rescue vision loss caused by corneal neovascularization and diabetic retinopathy, while overexpression of miR-21 can promote corneal epithelial healing and treat primary open-angle glaucoma and retinal degeneration.This review summarized the recent research progress of the role of miR-21 in eye diseases.

Objective:To investigate the risk factors and treatment outcome of recurrent Acanthamoeba keratitis (AK) after corneal transplantation. Methods:A serial case-observational study was carried out.Twenty-eight eyes of 28 patients with AK who underwent corneal transplantation in Shandong Eye Hospital from January 2012 to January 2019 were enrolled.All the eyes received corneal transplantation from failing to respond to topical and systemic anti- Acanthamoeba medical therapy, including 13 eyes that received penetrating keratoplasty (PKP) and 15 eyes that received lamellar keratoplasty (LKP). The corneal lesion was removed by a trephine with a diameter of 0.5 mm over infiltration area during PKP or LKP.The clinical features of recurrent AK were summarized, including recurrence time, site and signs, and the risk factors of AK recurrence were analyzed.Local and systemic anti- Acanthamoeba medical therapy was performed in all relapsed eyes, and secondary surgery was performed for the eyes with poor response to medication.The therapeutic outcome of recurrent AK was evaluated.The study adhered to the Declaration of Helsinki.This study protocol was approved by an Ethics Committee of Shandong Eye Hospital (No.201112). Results:In the 28 eyes, 7 eyes (25%) appeared recurrent AK after keratoplasty, including 2 eyes after PKP and 5 eyes after LKP.There was no significant difference in the recurrence rate between the two methods ( P=0.396). The recurrence rate of eyes that had used glucocorticoids drugs before operation was 57.14% (4/7), which was significantly higher in comparison with 14.29% (3/21) of eyes without glucocorticoids before surgery ( P=0.043). The recurrence rate of eyes with ulcer diameter ≥8.2 mm was 50.00% (5/10), which was significantly higher than 11.11% (2/18) of eyes with ulcer <8.2 mm ( P=0.036). The recurrent lesions began at the edge of implant bed accounted for 85.71% (6/7), and the recurrent lesions located below graft accounted for 14.29% (1/7). In 7 eyes with recurrent AK, 6 eyes were completely cured.Among recurrent AK eyes after LKP, 2 eyes were cured by long-term medical therapy, and 2 eyes were cured by extended-diameter LKP, and another 1 eye was cured by conjunctival flap covering surgery.One eye with recurrent AK after PKP was cured by extended-diameter PKP. Conclusions:The risk factors of recurrent AK after surgery are application of glucocorticoids before surgery and big lesions.Recurrent AK after surgery is curable by individualized therapy targeting to different clinical characteristics.

ObjectiveTo systematically review the efficacy of intervention by WeChat on medication compliance， psychotic symptom and recurrence rate of schizophrenic patients in community. MethodsDatabases including PubMed， the Cochrane Library， CBM， CNKI， Wanfang Data and VIP were searched electronically from January 1， 2011 to November 1， 2020 to collect randomized controlled trials （RCTs） about the effects of WeChat intervention on community schizophrenic patients. After two reviewers independently screened literature， extracted data and assessed the risk of bias of included studies， the meta-analysis was performed with Stata 12.0 software. ResultsA total of 381 articles were retrieved and finally 10 RCTs were included， including 1 251 patients with WeChat intervention group 641 cases and routine health education group 610 cases. Meta-analysis showed that compared with the conventional health education group， the WeChat intervention group had higher medication compliance （OR=3.05，95% CI：1.98~4.69，P<0.01）， lower PANSS score （SMD=-1.05，95% CI：-1.46~-0.64，P<0.01） and relapse rate （OR=0.34，95% CI：0.24~0.48，P<0.01）. ConclusionThe interactive intervention based on WeChat platform can effectively improve the medication compliance of patients with schizophrenia in the community， help to reduce the severity of psychotic symptoms and the recurrence rate.

Objective:To evaluate and compare the safety, efficacy, stability and predictability of laser-assisted subepithelial keratomileusis (LASEK) with femtosecond laser assisted in situ keratomileusis (FS-LASIK) for high myopic eyes.Methods:A non-randomized controlled clinical study was performed.The clinical data of 141 eyes of 75 patients who received LASEK or FS-LASIK for high myopia in Shandong Eye Hospital from January 2013 to December 2016 with complete medical data during 1-year following-up.The 56 eyes with the preoperative diopter of (-8.29±1.64)D received LASEK (LASEK group), and the 85 eyes with the preoperative diopter (-7.97±1.38)D underwent FS-LASIK (FS-LASIK group). Pre- and post-operative best corrected visual acuity (BCVA) and post-operative uncorrected visual acuity (UCVA) were recorded, and the spherical equivalent was examined by subjective optometry.The efficacy index, safety index, refractive stability, predictability and complications were assessed 6 months and 12 months after surgery.Efficacy index was defined as postoperative UCVA/preoperative BCVA; safety index was postoperative BCVA/preoperative BCVA; refractive stability was the difference of spherical equivalent between postoperative 6 months and 12 months, and predictability was the percentage of the eyes with the diopter ≤±0.50 D after surgery.This study protocol was approved by the Ethic Committee of Shandong Eye Hospital (No.SDSYKYY20180130).Results:There were no significant differences in efficacy index and safety index in both LASEK group and FS-LASIK group at 6 months and 12 months after surgery (all at P>0.05). The spherical equivalent was (0.08±0.30)D and (0.10±0.38)D in the LASEK group and (0.00±0.32)D and (0.01±0.35)D in the FS-LASIK group at 6 months and 12 months after surgery, and there were no significant differences between different time points in both LASEK group and FS-LASIK group ( t=0.376, P>0.05; t=0.227, P>0.05), showing a good refractive stability.At 12 months after surgery, the percentage of the eyes with spherical equivalent within ±0.50 D was 91.1% in the LASEK group and 96.4% in the FS-LASIK group, there was no significant difference between the two groups ( χ2=1.838, P>0.05). Four eyes in the LASEK group developed corneal haze at 12 months after the operation, and the postoperative BCVA was less than the preoperative BCVA. Conclusions:Both LASEK and FS-LASIK are safe, effective, stable and predictable for the correction of high myopic eyes.Corneal haze after LASEK is the main reason for the loss of BCVA.

Objective To investigate the clinical feature and treatment outcome of paediatric posttraumatic endophthalmitis.Methods A retrospective case study was performed.Twenty-six paediatric posttraumatic endophthalmitis children with 26 eyes were enrolled in Shandong Eye Hospital from April 2014 to April 2017.The clinical features,causes of trauma,time and mode of treatment,complications and visual acuity were analyzed.The subjects were graded according to the prognostic status,and the prognosis of the children was compared among different treatment time,vitrectomy time,operation frequency and antibiotic application.Results Of 26 cases,including 20 males and 6 females,aged from 1 year to 13 years,the average age was (6.56±3.25) years.The subjects were divided into infant group (2 cases,7.69％),preschool group (10 cases,38.46％) and school age group (14 cases,53.85％).The main cause of injury was wire,accounting for 34.62％ (9/26).Syringe needles accounted for 15.38％ (4/26).Fireworks accounted for 11.54％ (3/26).All of the 26 cases received vitrectomy,24 cases combined with lens extraction (92.31％).Among the 26 cases,8 cases had no primary visual acuity record;in the remaining 18 cases,the visual acuity at last follow-up was significantly improved when compared with the preoperative primary visual acuity (x2 =7.385,P =0.033).The positive rate of pathogenic bacteria culture in aqueous humor and vitreous humor was 23.08％ (6/26),gram-positive cocci was the main pathogenic bacteria of posttraumatic endophthalmitis,which account for 83.3％ (5/6).The prognostic grade was grade 1 in 15 cases (57.7％),grade 2 in 7 cases (26.9％) and grade 3 in 4 cases (15.4％).There were significant differences in the number of prognostic grading cases among children with different hospitalizing time or vitrectomy time (all at P＜0.05).The hospitalizing time,time of vitrectomy,number of operations and systemic application of antibiotics were positively correlated with the prognosis grade (rs =0.580,0.414,0.428,0.535;all at P ＜ 0.05).Conclusions Children with posttraumatic endophthalmitis should undergo vitrectomy as early as possible,which can receive better prognosis.