AIM:To describe the surgical procedure of fusiform penetrating keratoplasty(FPK)using multiple trephines of different sizes for treating patients with severe infectious keratitis.METHODS:Fourteen eyes underwent FPK,an...AIM:To describe the surgical procedure of fusiform penetrating keratoplasty(FPK)using multiple trephines of different sizes for treating patients with severe infectious keratitis.METHODS:Fourteen eyes underwent FPK,and 15 eyes received conventional penetrating keratoplasty(PK)were included in the study.The best-corrected visual acuity(BCVA),refractive outcomes,endothelial cell density,and postoperative complications were recorded.RESULTS:The FPK group was followed for an average of 15.3±2.1mo,whereas the PK group was followed for 16.1±1.9mo.The corneal ulcers were elliptical-shaped in all 14 eyes in the FPK group.The mean BCVA(logMAR,0.26±0.13)showed no statistically significant differences from that in the PK group(logMAR,0.21±0.12,P>0.05)at 1y after surgery.But the mean curvature,mean astigmatism,and mean spherical equivalent in the FPK group were lower than those in the PK group(P<0.05).Peripheral anterior synechia was observed in one patient in the FPK group,whereas 6 patients in the PK group.Suture loosening and neovascularization were observed in 4 and 5 eyes in the PK group,respectively.No graft immune rejection or elevation of intraocular pressure was observed in the two groups.CONCLUSION:For patients with elliptical-shaped corneas or corneal ulcers,FPK can avoid disrupting of corneal limbus,reduce the risk of postoperative complications,and can result in satisfactory visual quality.展开更多
The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional...The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.展开更多
AIM:To examine the change of iris volume measured by CASIA2 anterior segment optical coherence tomography(ASOCT)in glaucoma patients with or without type 2 diabetes mellitus(T2DM)and explore if there is a correlation ...AIM:To examine the change of iris volume measured by CASIA2 anterior segment optical coherence tomography(ASOCT)in glaucoma patients with or without type 2 diabetes mellitus(T2DM)and explore if there is a correlation between hemoglobin A1c(HbA1c)level and iris volume.METHODS:In a cross-sectional study,72 patients(115 eyes)were divided into two groups:primary open angle glaucoma(POAG)group(55 eyes)and primary angle-closure glaucoma(PACG)group(60 eyes).Patients in each group were separately classified into patients with or without T2DM.Iris volume and glycosylated HbA1c level were measured and analyzed.RESULTS:In the PACG group,diabetic patients'iris volume was significantly lower than those of non-diabetics(P=0.02),and there was a significant correlation between iris volume and HbA1c level in the PACG group(r=-0.26,P=0.04).However,diabetic POAG patients'iris volume was noticeably higher than those of non-diabetics(P=0.01),and there was a significant correlation between HbA1c level and iris volume(r=0.32,P=0.02).CONCLUSION:Diabetes mellitus impact iris volume size,as seen by increased iris volume in the POAG group and decreased iris volume in the PACG group.In addition,iris volume is significantly correlated with HbA1c level in glaucoma patients.These findings imply that T2DM may compromise iris ultrastructure in glaucoma patients.展开更多
AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among th...AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among the glaucoma patients,54 were treated with medication,while 25 remained untreated.Central corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation coefficient.RESULTS:The CNFD was reduced in glaucoma groups compared to healthy subjects(P<0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients.As the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P<0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P<0.001).In the absence of medication,CNFD in males was lower than that in females(P<0.05).Among patients under medication therapy,CNFD remained consistent between males and females.CONCLUSION:Antiglaucoma eye drops affect the microstructure of corneal nerves.IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.展开更多
AIM: To study the clinical observation of removal of the necrotic corneal tissue combined with conjunctival flap covering surgery under the guidance of the AS-OCT in treatment of fungal keratitis. METHODS:A retrospect...AIM: To study the clinical observation of removal of the necrotic corneal tissue combined with conjunctival flap covering surgery under the guidance of the AS-OCT in treatment of fungal keratitis. METHODS:A retrospective study was done to 10 patients (10 eyes) who had accepted removal of the necrotic corneal tissue combined with conjunctival flap covering surgery for fungal keratitis,the diagnosis by corneal scraping and smear examination or confocal microscopy check hyphae. Local and systemic antifungal therapy more than one week for all patients, corneal ulcer enlarge or no shrink. Slit lamp microscope examination the diameter of corneal ulcer about 2mm-4mm. Anterior segment optical coherence tomography (AS-OCT)examine the depth of corneal ulcer between 1/3-1/2, infiltrate corneal stroma about 20um-80um,the diameter of corneal ulcer about 3mm-6mm.Type-B ultrasonic exclusion endophthalmitis. Complete removal lesions until transparent of stoma, make conjunctival flap equal or greater than ulcer 1mm nearby conjunctiva. Continued antifungal therapy. The vision, fungal recurrence, conjunctival flap rollback or desquamate were analysed. ' RESULTS:Ten patients had success done this surgery, the corneal ulcer was not enlarge and healing afteroperation. 7 cases were bridging conjunctival flap and 3cases were single conjunctival flap. Preoperation vision above 0.1 had 8 cases,7 cases had vision above 0.1 one week after surgery, while 1 cases vision droped from 0.3 to 0.05.There was not recurrent for fungal,2 cases conjunctival flap rollback:1 case was bridging and 1case was single flap, no conjunctival flap desquamate. CONCLUSION: It is safe and effective to perform removal of the necrotic corneal tissue combined with conjunctival flap covering surgery under the guidance of the AS-OCT in treatment of fungal keratitis which werenot sensitive or aggravate for antifungal drugs.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. M...AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.展开更多
AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections...AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections.METHODS: This study applied a retrospective analysis of 3690 bacterial isolates from ocular specimens, which were obtained from the conjunctiva, cornea, aqueous humor, vitreous body, and other ocular sites of the patients at Shandong Eye Institute in northern China from January 2013 to December 2017. The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics. In the analysis of antibiotic sensitivities, the bacteria were divided into four groups according to gram staining, and statistical methods were used to compare their antibiotic sensitivities. RESULTS: Among the 3690 isolated bacterial strains, Staphylococcus epidermidis(2007, 54.39%) accounted for the highest proportion. As for the total isolates, their sensitivity rate to gatifloxacin was up to 90.01%, with four types of gram-stained bacteria being all highly sensitive to it, but their sensitivity rate to levofloxacin was only 51.91%. The sensitivity rate of gram-negative bacilli(G-B) to levofloxacin was 83.66%, significantly higher than the other three types of gram-stained bacteria(P<0.05). Gram-positive cocci (G+C, 97.95%) and gram-positive bacilli(G+B, 97.54%) were more sensitive to vancomycin than gram-negative cocci(G-C, 70.59%) and G-B(68.57%;P<0.05). For fusidic acid, the sensitivity rates of G+C(89.83%) and G+B(73.37%) were significantly higher than that of G-B(29.83%;P<0.05). The gram-negative bacteria's sensitivity rate to cefuroxime was as low as 59.25%, but only G-B was less sensitive to cefuroxime(57.28%), while G-C was still highly sensitive(89.29%). The sensitivity rate of gram-positive bacteria to moxifloxacin was as high as 80.28%, but only G+C was highly sensitive to moxifloxacin(81.21%), while G+B was still less sensitive(32.00%). CONCLUSION: Staphylococcus epidermidis is the predominant isolate in all ocular specimens with bacteria. Gatifloxacin is more suitable for topical prophylactic use than levofloxacin in ophthalmology when necessar y. Vancomycin and fusidic acid both have better effects on gram-positive bacteria than gram-negative bacteria. More accurate antibiotic sensitivity analysis results can be obtained when a more detailed bacterial classification and more appropriate statistical methods are performed.展开更多
AIM: To compare long-term postoperative outcomes of manual and femtosecond assisted corneal trephination in deep anterior lamellar keratoplasty(FS-DALK) for keratoconus.METHODS: In the retrospective study, 17 consecut...AIM: To compare long-term postoperative outcomes of manual and femtosecond assisted corneal trephination in deep anterior lamellar keratoplasty(FS-DALK) for keratoconus.METHODS: In the retrospective study, 17 consecutive eyes that underwent vertical side cut incision FS-DALK and 22 eyes that underwent trephine incision DALK were collected over a 2-year period. Main measurements included postoperative uncorrected-visual acuity(UCVA), corrected distance visual acuity(CDVA), refractive sphere and cylinder, manifest refraction spherical equivalent(MRSE), flat and steep corneal keratometry(K1 and K2), endothelial cell density(ECD), and time of epithelium healing and suture removal.RESULTS: Groups were comparable for diagnosis and preoperative visual acuity. Follow-up averaged 23 mo(range, 12-36 mo). At 12 mo, the mean UCVA was better in the manual-DALK group(P=0.039), and the refractive sphere was lower in the FS-DALK group(P=0.040). MRSE between groups differed at 1, 6, and 12 mo postoperatively(P=0.047, 0.025, 0.042, respectively). Mean CDVA, cylinder, K1, K2,corneal astigmatism, ECD, and time of epithelium healing were similar between groups. Stability of MRSE, ECD, and K1 returned sooner after FS-DALK. Initial loosened suture removal time was earlier in the manual-DALK group(P=0.042) while complete suture removal time was similar(P=0.122).CONCLUSION: Manual and femtosecond assisted corneal trephination in DALK are options for advanced keratoconus. FS-DALK do not result in improved visual acuity but it is more stable during the follow-up period. FSDALK in the present form show limited benefit, so surgical design and parameters still need to be optimized and explored.展开更多
AIM: To identify the current indications and the trend shifts for penetrating keraboplasty (PKP) in Shandong. METHODS: The medical charts of all patients who underwent PKP at Shandong Eye Institute from June 1, 2005 t...AIM: To identify the current indications and the trend shifts for penetrating keraboplasty (PKP) in Shandong. METHODS: The medical charts of all patients who underwent PKP at Shandong Eye Institute from June 1, 2005 to May 31, 2010 were analysed retrospectively. RESULTS: A total of 875 patients (875 eyes) received PKP in this 5-year period, accounting for 61.6% of all corneal transplantation surgeries. The leading indications for PKP were infectious keratitis (37.1%), HSK (19.1%), keratoconus (11.2%), bullous keratopathy (8.5%), regrafting (6.7%) and corneal scarring (4.8%). The percentage of PKP for keratoconus declined year by year, whereas the percentage of bullous keratopathy had a mild annual increase. Fungal infections accounted for 65.2% of the infectious keratitis cases, remaining the leading cause of corneal infection. In addition, 54.1% of bullous keratopathy cases were associated with cataract surgery. The leading initial diagnoses associated with regrafting were infectious keratitis (38.9%), HSK (18.6%) and corneal burn (16.9%). The major causes of regrafting included graft endothelial dysfunction (39.0%), graft ulcer (28.8%) and primary disease recurrence (15.3%). CONCLUSION: Infectious keratitis remained the leading indication for PKP in Shandong, and fungal infections were still the major cause of corneal infections. There was an increasing trend in the percentage of PKP cases indicated for bullous keratopathy but a decline in the same for keratoconus. Even with a decline in the overall proportion among all corneal transplantation surgeries, PKP is still the major corneal transplant choice in Shandong.展开更多
AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression o...AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression of GPR91 in MU tissues was evaluated using quantitative realtime reverse transcription polymerase chain reaction（qRTPCR） and immunohistochemistry（IHC）. Succinate was used to activate GPR91 signaling, and the effect of GPR91 on the expression of interleukin-1β（IL-1β）, NLRP3, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-13（MMP-13） in human peripheral blood mononuclear cells（PBMCs） was determined. The influence of GPR91 on the nuclear factor-κB（NF-κB） signaling in PBMCs was investigated by detecting the phosphorylation of p65. Moreover, the expression of IL-1β, VEGF, MMP-13 and phosphorylated p65（p-p65） in the tissues of MU was examined by qRT-PCR or IHC.RESULTS： GPR91 mRNA expression showed a higher level in the MU group than in the healthy control group. IHC analysis also revealed that the expression of GPR91 was elevated in patients with MU compared with healthy controls. Moreover, ligation of GPR91 with succinate promoted the lipopolysaccharide-induced production of NLRP3, IL-1β, VEGF and MMP-13 in PBMCs through increased phosphorylation of p65. Pharmacological inhibition of the NF-κB signaling reversed GPR91 induced production of NLRP3, IL-1β, VEGF and MMP-13. These findings, coupled with the elevated amounts of IL-1β, VEGF, MMP-13 and p-p65 observed in the MU biopsies, constituted a rational basis for the involvement of GPR91 in the pathogenesis of MU.CONCLUSION： This study indicates the increased succinate receptor GPR91 in conjunctival or corneal tissues is involved in the pathogenesis of MU through elevated NF-κB activity, which may provide a new therapeutic target for MU.展开更多
AIM:To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane(rh NGF-AM)on corneal epithelial and nerve regeneration in rabbit model.METHODS:Freshly prepared human amniotic membrane(AM...AIM:To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane(rh NGF-AM)on corneal epithelial and nerve regeneration in rabbit model.METHODS:Freshly prepared human amniotic membrane(AM)were immersed into PBS buffer containing 100 or 500μg/mL rh NGF for 15,30,and 60 min at 4℃.The in vitro release kinetics of rh NGF was measured with ELISA.For in vivo evaluation,the AM were immersed with 500μg/mL rh NGF for 30 min.Fifty-seven rabbits were selected to establish corneal epithelial defect model.In addition to the 19 rabbits in control group,38 rabbits received AM transplantation with or without rh NGF after the removal of central epithelium.Corneal epithelial defect area,sub-epithelial nerve fiber density,corneal sensitivity,rh NGF contents in resident AM and corneas were measured after the surgery.RESULTS:rh NGF was sustained release from the AM within 14 d in vitro,with the positive correlation with initial immersion concentration.The immersion of AM in 500μg/mL rh NGF for 30 min achieved the most stable release within 14 d.After transplantation in rabbit cornea,a high concentration of rh NGF in resident rh NGF-AM and cornea was maintained within 8 d.Corneal epithelial healing,nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rh NGF-AM transplantation when compared to simple AM transplantation(all P<0.05).CONCLUSION:Simple immersion of AM achieves the sustained release of rh NGF,and promotes corneal epithelial wound healing and nerve regeneration,as well as the recovery of corneal sensitivity in rabbit.展开更多
AIM:To investigate the association of axial length(AL),lens thickness(LT),and lens vault(LV)with postoperative anterior chamber angle metrics after laser peripheral iridotomy(LPI).METHODS:Prospective observational stu...AIM:To investigate the association of axial length(AL),lens thickness(LT),and lens vault(LV)with postoperative anterior chamber angle metrics after laser peripheral iridotomy(LPI).METHODS:Prospective observational study of 69 patients(97 eyes)were diagnosed as primary angle-closure suspect(PACS),primary angle closure(PAC)or primary angle-closure glaucoma(PACG).AL,LT,anterior central chamber depth(ACD),angle opening distance(AOD),trabecular iris angle(TIA),and angle recess area(ARA)were measured before and 1 wk after LPI.The association between AL,LT,LV with ACD,AOD,TIA,ARA were analyzed by comparing the differences between preoperative and postoperative measurements for anterior segment biometric parameters.RESULTS:ACD,AOD,TIA,and ARA were significantly increased after LPI(all P<0.05).Greater LT was significantly associated with greater postoperative increases in ACD,AOD,TIA,and ARA(all P<0.05).AL was not significantly associated with changes of anterior segment biometric parameters.Greater LV was significantly associated with greater postoperative increases in ACD,AOD,and TIA(all P<0.05),but was not significantly associated with changes of ARA.CONCLUSION:Greater baseline LT and LV measurements are associated with greater increases in anterior segment biometric parameters after laser peripheral iridotomy.AL are not associated with the change of anterior segment biometric parameters.展开更多
AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chin...AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.展开更多
AIM: To determine the proliferative potential and the maintenance of stem cell activity in stored human limbal tissues, and correlate this with the preservation time, cell viability and the expression of stem cell mar...AIM: To determine the proliferative potential and the maintenance of stem cell activity in stored human limbal tissues, and correlate this with the preservation time, cell viability and the expression of stem cell markers. METHODS: Thirty limbal rims were split into 4 parts and stored in corneal preservation medium at 4 degrees C for 0, 1, 4, or 7 days. The limbal stem cell and mitotic markers P63, CK19, proliferating cell nuclear antigen (PCNA), and Ki67 were determined by immunohistochemical staining. The proliferative potential of limbal epithelial cells was assessed by cell viability, the ability of generating stratified epithelium, and colony forming assay. RESULTS: The stored tissues maintained limbal stratified structure to 7 days and exhibited comparable expression level of stem cell and mitotic markers. The proportion of viable cells decreased with the prolonged preservation time, while colony forming efficiency decreased from the 1st day and disappeared at the 4th day. When inoculated on amniotic membrane, the cells preserved for 1 day formed a stratified epithelium, while the cells from 4 days' preservation formed a discontinuous layer. CONCLUSION: The colony forming efficiency of limbal epithelial stem/progenitor cells decreased rapidly with the increasing preservation time, while the expression level of markers and capacity of forming epithelial monolayer on amniotic membrane decreased gradually. The limbal epithelial stem cells lost their function earlier than the lost expression level of stem cell markers. This may help us to better choose the appropriate preservation grafts for future limbal stem cell transplantation.展开更多
AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood...AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.展开更多
AIM: Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Many studies suggest that age-related maculopathy susceptibility 2 (ARMS2) is ...AIM: Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Many studies suggest that age-related maculopathy susceptibility 2 (ARMS2) is a second major susceptibility gene for AMD. At present, there is no functional information on this gene. Therefore, the purpose of the present study was to detect the expression of ARMS2 in retinal pigment epithelium (RPE) cells and to investigate the effect of ARMS2 on the phagocytosis function of RPE cells. METHODS: Immunofluorescence and reverse transcriptase PCR were used to demonstrate the presence and location of ARMS2 in ARPE-19 (human retinal pigment epithelial cell line, ATCC, catalog No.CRL-2302) cells. siRNA was used to knock down ARMS2 mRNA, and the effects of the knockdown on the phagocytosis function of the ARPE-19 cells were evaluated via Fluorescence Activated Cell Sorting (FACS). RESULTS: ARMS2 was present in ARPE-19 cells, localized in the cytosol of the perinuclear region. The expression of ARMS2 mRNA (messenger RNA) in ARPE-19 cells transfected with ARMS2-siRNA (small interfering RNA, 0.73+/- 0.08) was decreased compared with normal cells (1.00+/- 0.00) or with cells transfected with scrambled siRNA (0.95+/- 0.13) (P<0.05). After incubation of RPE cells with a latex beads medium for 12, 18, or 24 hours, the fluorescence intensities were 38.04 +/- 1.02, 68.92 +/- 0.92, and 78.00 +/- 0.12 in the ARMS2-siRNA-transfected groups, respectively, and 77.98 +/- 5.43, 94.87 +/- 0.60, and 98.30 +/- 0.11 in the scrambled siRNA-transfected groups, respectively. The fluorescent intensities of the same time points in the two groups were compared using Student's t-test, and the p values were all less than 0.001 at the three different time points. CONCLUSION: There is endogenous expression of ARMS2 in ARPE-19 cells. ARMS2 plays a role in the phagocytosis function of RPE cells, and this role may be one of the mechanisms that participates in the development of AMD.展开更多
AIM: To evaluate the treatment selections and outcomes of keratoconus and discuss the grading treatment of keratoconus.METHODS: Medical records of 1162 patients(1863 eyes) with keratoconus treated with rigid gas perme...AIM: To evaluate the treatment selections and outcomes of keratoconus and discuss the grading treatment of keratoconus.METHODS: Medical records of 1162 patients(1863 eyes) with keratoconus treated with rigid gas permeable(RGP), corneal collagen crosslinking, and keratoplasty were reviewed. The patients were grouped according to the CLEK Study. The advanced group was further divided into a <60 D group and >60 D group. The best-corrected visual acuity(BCVA) and topographic data before and after treatment were recorded.RESULTS: In the 761 eyes with steep K<52 D, nonsurgical management accounted for 83.4%, while in the 735 eyes with steep K>60 D, surgical management accounted for 90.6%. A total of 618 eyes had improved BCVA at the final fol ow-up point(>18 mo, P<0.001). When steep K was <52 D, the BCVA in the RGP group was better than those with lamellar keratoplasty(LKP;P=0.028). When steep K was >52 D, the BCVA and topographic astigmatism outcomes showed no differences among the treatment groups. When steep K was >60 D, the BCVA in eyes treated with LKP was worse than those with steep K<60 D(P=0.025). The incidence of steep K progression in the RGP group was higher in advanced group(20.0% vs 10.8%, P=0.019). The probability of future keratoplasty in RGP was higher in advanced group(14.8% vs 7.0%, P=0.027). The incidence of steep K progression in the corneal collagen crosslinking(CXL) group was higher in advanced group(32.3% vs 8.5%, P=0.007). Multivariate logistic regression revealed the following related factors for treatment options: steep K [odds ratio(OR)=1.208, 95%CI: 1.052-1.387], TA(OR=1.171, 95%CI: 1.079-1.270), and TCT(OR=0.978, 95%CI: 0.971-0.984). The level of steep K, TA, and TCT all relates to the treatment choices of both keratoplasty and non-keratoplasty, while steep K provided the highest diagnostic accuracy(AUC=0.947, P<0.001).CONCLUSION: Steep K is an important grading treatment indicator. When steep K is <52 D, RGP lenses should be recommended. It is the best time for LKP when the steep K ranges from 52 to 60 D.展开更多
AIM:To describe the design and clinical application of a corneal donor dehydrator which can quickly dehydrate corneas and keep its original shape.METHODS:The corneal donor material is placed on stainless steel beads w...AIM:To describe the design and clinical application of a corneal donor dehydrator which can quickly dehydrate corneas and keep its original shape.METHODS:The corneal donor material is placed on stainless steel beads with different diameters in the dehydrating box to make the cornea the same shape as the steel ball.Then,the cornea is placed inside the dehydrater for rapid dehydrating using the internal cleaning and ventilation system.Totally 83 eyes underwent deep anterior lamellar keratoplasty(DALK)using corneal donor tissue preserved with corneal dehydrater,and 60 patients(60 eyes)received DALK by the same surgeon using corneal donor tissue preserved with glycerol were included in the control group.The best corrected visual acuity(BCVA),the thickness and transparency of the corneal buttons were recorded.RESULTS:After the completion of dehydrating,all the donor corneas maintained a normal shape without any shrinkage or distortion,and the average intraoperative rehydration time was 43.3±12.1 s during operation.The mean BCVA of the dehydrater group was 0.30±0.18 at 1 wk and 0.32±0.16 at 1 mo,which were statistically better than that of the control group(P<0.001).The score of corneal buttons transparency were lower than that of the control group with statistical difference(P<0.001).The thickness of corneal buttons at 1 wk and at 1 mo in the dehydrater group was significantly better than that of the control group respectively(P<0.001).One week after operation,no corneal button turbidity or edema was observed in both groups.CONCLUSION:The dehydrater can quickly dehydrate the corneal material in a clean and airtight environment and maintain the original shape of the corneal donor during the dehydrating process.This dehydrater is recommended for long-term high-quality preservation in areas where corneal materials cannot be used within a reasonable time period.展开更多
AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal...AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS: In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n=25). Grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4(+) T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS: Rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4(+) T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adhered to the corneal endothelium. Blood vessels in iris increased and were filled with lymphocytes. And lymphocytes were detected to migrate through endothelial cell gap out of vessels. When allograft rejection occurred, macrophages attached to endothelial cells with large number of lymphocytes and macrophages infiltrating in iris. CONCLUSION: Lymphocyte infiltration and activation occurred in iris-ciliary body after allogenic PK, and the lymphocytes could migrate from iris blood vessel to the anterior chamber, which might play an important role in corneal allograft immune rejection.展开更多
基金Supported by the National Natural Science Foundation of China (No.81900907,No.81870639)Taishan Scholar Program (No.20231255).
文摘AIM:To describe the surgical procedure of fusiform penetrating keratoplasty(FPK)using multiple trephines of different sizes for treating patients with severe infectious keratitis.METHODS:Fourteen eyes underwent FPK,and 15 eyes received conventional penetrating keratoplasty(PK)were included in the study.The best-corrected visual acuity(BCVA),refractive outcomes,endothelial cell density,and postoperative complications were recorded.RESULTS:The FPK group was followed for an average of 15.3±2.1mo,whereas the PK group was followed for 16.1±1.9mo.The corneal ulcers were elliptical-shaped in all 14 eyes in the FPK group.The mean BCVA(logMAR,0.26±0.13)showed no statistically significant differences from that in the PK group(logMAR,0.21±0.12,P>0.05)at 1y after surgery.But the mean curvature,mean astigmatism,and mean spherical equivalent in the FPK group were lower than those in the PK group(P<0.05).Peripheral anterior synechia was observed in one patient in the FPK group,whereas 6 patients in the PK group.Suture loosening and neovascularization were observed in 4 and 5 eyes in the PK group,respectively.No graft immune rejection or elevation of intraocular pressure was observed in the two groups.CONCLUSION:For patients with elliptical-shaped corneas or corneal ulcers,FPK can avoid disrupting of corneal limbus,reduce the risk of postoperative complications,and can result in satisfactory visual quality.
基金supported by the National Natural Science Foundation of China(82371032,82070923)the Major Basic Research Project of the Natural Science Foundation of Shandong Province(ZR2023ZD60)+1 种基金the Taishan Scholar Program(20231255)the Academic Promotion Program of Shandong First Medical University(2019RC009).
文摘The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.
基金Supported by Natural Science Foundation of Shandong Province(No.ZR2020MH172)。
文摘AIM:To examine the change of iris volume measured by CASIA2 anterior segment optical coherence tomography(ASOCT)in glaucoma patients with or without type 2 diabetes mellitus(T2DM)and explore if there is a correlation between hemoglobin A1c(HbA1c)level and iris volume.METHODS:In a cross-sectional study,72 patients(115 eyes)were divided into two groups:primary open angle glaucoma(POAG)group(55 eyes)and primary angle-closure glaucoma(PACG)group(60 eyes).Patients in each group were separately classified into patients with or without T2DM.Iris volume and glycosylated HbA1c level were measured and analyzed.RESULTS:In the PACG group,diabetic patients'iris volume was significantly lower than those of non-diabetics(P=0.02),and there was a significant correlation between iris volume and HbA1c level in the PACG group(r=-0.26,P=0.04).However,diabetic POAG patients'iris volume was noticeably higher than those of non-diabetics(P=0.01),and there was a significant correlation between HbA1c level and iris volume(r=0.32,P=0.02).CONCLUSION:Diabetes mellitus impact iris volume size,as seen by increased iris volume in the POAG group and decreased iris volume in the PACG group.In addition,iris volume is significantly correlated with HbA1c level in glaucoma patients.These findings imply that T2DM may compromise iris ultrastructure in glaucoma patients.
基金Supported by the National Natural Science Foundation of China(No.82371058)the Natural Science Foundation of Shandong Province(No.ZR2020MH172)+2 种基金the Ophthalmology New Technology Incubation Fund Program(Ophthalmology Incubation Fund Phase II Project[2022]No.[005])Medicine Science and Technology Development Program of Shandong Province(No.202107020108)Qingdao Science and Technology Beneficiary Program(No.24-1-8-smjk-16-nsh).
文摘AIM:To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy(IVCM).METHODS:This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals.Among the glaucoma patients,54 were treated with medication,while 25 remained untreated.Central corneal images were evaluated by IVCM,and then ACCMetrics was used to calculate the following parameters:corneal nerve fiber density(CNFD),branch density(CNBD),fiber length(CNFL),total branch density(CTBD),fiber area(CNFA),fiber width(CNFW),and fractal dimension(CNFrD).The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman’s rank correlation coefficient.RESULTS:The CNFD was reduced in glaucoma groups compared to healthy subjects(P<0.01).Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients.As the number of medications and usage count increased,CNFD,CNBD,CNFL,CTBD,CNFA,and CNFrD experienced a decline,while CNFW increased(all P<0.01).For the brinzolamide-therapy group,there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups(P<0.001).In the absence of medication,CNFD in males was lower than that in females(P<0.05).Among patients under medication therapy,CNFD remained consistent between males and females.CONCLUSION:Antiglaucoma eye drops affect the microstructure of corneal nerves.IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.
文摘AIM: To study the clinical observation of removal of the necrotic corneal tissue combined with conjunctival flap covering surgery under the guidance of the AS-OCT in treatment of fungal keratitis. METHODS:A retrospective study was done to 10 patients (10 eyes) who had accepted removal of the necrotic corneal tissue combined with conjunctival flap covering surgery for fungal keratitis,the diagnosis by corneal scraping and smear examination or confocal microscopy check hyphae. Local and systemic antifungal therapy more than one week for all patients, corneal ulcer enlarge or no shrink. Slit lamp microscope examination the diameter of corneal ulcer about 2mm-4mm. Anterior segment optical coherence tomography (AS-OCT)examine the depth of corneal ulcer between 1/3-1/2, infiltrate corneal stroma about 20um-80um,the diameter of corneal ulcer about 3mm-6mm.Type-B ultrasonic exclusion endophthalmitis. Complete removal lesions until transparent of stoma, make conjunctival flap equal or greater than ulcer 1mm nearby conjunctiva. Continued antifungal therapy. The vision, fungal recurrence, conjunctival flap rollback or desquamate were analysed. ' RESULTS:Ten patients had success done this surgery, the corneal ulcer was not enlarge and healing afteroperation. 7 cases were bridging conjunctival flap and 3cases were single conjunctival flap. Preoperation vision above 0.1 had 8 cases,7 cases had vision above 0.1 one week after surgery, while 1 cases vision droped from 0.3 to 0.05.There was not recurrent for fungal,2 cases conjunctival flap rollback:1 case was bridging and 1case was single flap, no conjunctival flap desquamate. CONCLUSION: It is safe and effective to perform removal of the necrotic corneal tissue combined with conjunctival flap covering surgery under the guidance of the AS-OCT in treatment of fungal keratitis which werenot sensitive or aggravate for antifungal drugs.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
基金Supported by the National Natural Science Foundation of China (No.81370990)the Young and MiddleAged Scientists Research Awards Fund of Shandong Province, China (No. BS2013YY013, No. BS2015YY014)the Science and Technology Foundation of Shinan District, Qingdao, Shandong Province, China (No. 2013-13-014-YY)
文摘AIM： To uncover the mutations profile of transforming growth factor beta-induced （TGFBI） gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS： Forty-two subjects （6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients） of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS： We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy （GCD） （including 3 families and 8 sporadic patients） and lattice corneal dystrophy （LCD） （including 2 families and 9 sporadic patients）. The next phenotypes were corneal dystrophy of Bowman layer （CDB） （1 family and 1 sporadic patient） and epithelial basement membrane dystrophy （EBMD） （1 sporadic patient）. Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient, CONCLUSION： GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD, Our findings extend the mutational spectrum of TFGBI , and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.
基金Supported by the National Natural Science Foundation of China(No.81670839)the Shandong Medical and Health Science and Technology Development Program(No.2016WS0265)the Qingdao People’s Livelihood Science and Technology Project(No.16-6-2-14-nsh)
文摘AIM: To provide statistical evidence for the use of antibiotics in ophthalmology by assessing the distribution and antibiotic sensitivity of bacterial isolates from ocular specimens with suspected microbial infections.METHODS: This study applied a retrospective analysis of 3690 bacterial isolates from ocular specimens, which were obtained from the conjunctiva, cornea, aqueous humor, vitreous body, and other ocular sites of the patients at Shandong Eye Institute in northern China from January 2013 to December 2017. The parameters assessed mainly included the distribution of isolated bacteria and the results of susceptibility tests for antibiotics. In the analysis of antibiotic sensitivities, the bacteria were divided into four groups according to gram staining, and statistical methods were used to compare their antibiotic sensitivities. RESULTS: Among the 3690 isolated bacterial strains, Staphylococcus epidermidis(2007, 54.39%) accounted for the highest proportion. As for the total isolates, their sensitivity rate to gatifloxacin was up to 90.01%, with four types of gram-stained bacteria being all highly sensitive to it, but their sensitivity rate to levofloxacin was only 51.91%. The sensitivity rate of gram-negative bacilli(G-B) to levofloxacin was 83.66%, significantly higher than the other three types of gram-stained bacteria(P<0.05). Gram-positive cocci (G+C, 97.95%) and gram-positive bacilli(G+B, 97.54%) were more sensitive to vancomycin than gram-negative cocci(G-C, 70.59%) and G-B(68.57%;P<0.05). For fusidic acid, the sensitivity rates of G+C(89.83%) and G+B(73.37%) were significantly higher than that of G-B(29.83%;P<0.05). The gram-negative bacteria's sensitivity rate to cefuroxime was as low as 59.25%, but only G-B was less sensitive to cefuroxime(57.28%), while G-C was still highly sensitive(89.29%). The sensitivity rate of gram-positive bacteria to moxifloxacin was as high as 80.28%, but only G+C was highly sensitive to moxifloxacin(81.21%), while G+B was still less sensitive(32.00%). CONCLUSION: Staphylococcus epidermidis is the predominant isolate in all ocular specimens with bacteria. Gatifloxacin is more suitable for topical prophylactic use than levofloxacin in ophthalmology when necessar y. Vancomycin and fusidic acid both have better effects on gram-positive bacteria than gram-negative bacteria. More accurate antibiotic sensitivity analysis results can be obtained when a more detailed bacterial classification and more appropriate statistical methods are performed.
基金Supported by the Innovation Project of Shandong Academy of Medical Sciences。
文摘AIM: To compare long-term postoperative outcomes of manual and femtosecond assisted corneal trephination in deep anterior lamellar keratoplasty(FS-DALK) for keratoconus.METHODS: In the retrospective study, 17 consecutive eyes that underwent vertical side cut incision FS-DALK and 22 eyes that underwent trephine incision DALK were collected over a 2-year period. Main measurements included postoperative uncorrected-visual acuity(UCVA), corrected distance visual acuity(CDVA), refractive sphere and cylinder, manifest refraction spherical equivalent(MRSE), flat and steep corneal keratometry(K1 and K2), endothelial cell density(ECD), and time of epithelium healing and suture removal.RESULTS: Groups were comparable for diagnosis and preoperative visual acuity. Follow-up averaged 23 mo(range, 12-36 mo). At 12 mo, the mean UCVA was better in the manual-DALK group(P=0.039), and the refractive sphere was lower in the FS-DALK group(P=0.040). MRSE between groups differed at 1, 6, and 12 mo postoperatively(P=0.047, 0.025, 0.042, respectively). Mean CDVA, cylinder, K1, K2,corneal astigmatism, ECD, and time of epithelium healing were similar between groups. Stability of MRSE, ECD, and K1 returned sooner after FS-DALK. Initial loosened suture removal time was earlier in the manual-DALK group(P=0.042) while complete suture removal time was similar(P=0.122).CONCLUSION: Manual and femtosecond assisted corneal trephination in DALK are options for advanced keratoconus. FS-DALK do not result in improved visual acuity but it is more stable during the follow-up period. FSDALK in the present form show limited benefit, so surgical design and parameters still need to be optimized and explored.
基金Supported by National Natural Science Foundation of China(No.30630063)
文摘AIM: To identify the current indications and the trend shifts for penetrating keraboplasty (PKP) in Shandong. METHODS: The medical charts of all patients who underwent PKP at Shandong Eye Institute from June 1, 2005 to May 31, 2010 were analysed retrospectively. RESULTS: A total of 875 patients (875 eyes) received PKP in this 5-year period, accounting for 61.6% of all corneal transplantation surgeries. The leading indications for PKP were infectious keratitis (37.1%), HSK (19.1%), keratoconus (11.2%), bullous keratopathy (8.5%), regrafting (6.7%) and corneal scarring (4.8%). The percentage of PKP for keratoconus declined year by year, whereas the percentage of bullous keratopathy had a mild annual increase. Fungal infections accounted for 65.2% of the infectious keratitis cases, remaining the leading cause of corneal infection. In addition, 54.1% of bullous keratopathy cases were associated with cataract surgery. The leading initial diagnoses associated with regrafting were infectious keratitis (38.9%), HSK (18.6%) and corneal burn (16.9%). The major causes of regrafting included graft endothelial dysfunction (39.0%), graft ulcer (28.8%) and primary disease recurrence (15.3%). CONCLUSION: Infectious keratitis remained the leading indication for PKP in Shandong, and fungal infections were still the major cause of corneal infections. There was an increasing trend in the percentage of PKP cases indicated for bullous keratopathy but a decline in the same for keratoconus. Even with a decline in the overall proportion among all corneal transplantation surgeries, PKP is still the major corneal transplant choice in Shandong.
基金Supported by National Natural Science Foundation of China (No.81530027 No.81500767+3 种基金 No.81570821)Natural Science Foundation of Shandong Province (No. ZR2018PH020 No.ZR2015YL037)the Innovation Project of Shandong Academy of Medical Sciences
文摘AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression of GPR91 in MU tissues was evaluated using quantitative realtime reverse transcription polymerase chain reaction（qRTPCR） and immunohistochemistry（IHC）. Succinate was used to activate GPR91 signaling, and the effect of GPR91 on the expression of interleukin-1β（IL-1β）, NLRP3, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-13（MMP-13） in human peripheral blood mononuclear cells（PBMCs） was determined. The influence of GPR91 on the nuclear factor-κB（NF-κB） signaling in PBMCs was investigated by detecting the phosphorylation of p65. Moreover, the expression of IL-1β, VEGF, MMP-13 and phosphorylated p65（p-p65） in the tissues of MU was examined by qRT-PCR or IHC.RESULTS： GPR91 mRNA expression showed a higher level in the MU group than in the healthy control group. IHC analysis also revealed that the expression of GPR91 was elevated in patients with MU compared with healthy controls. Moreover, ligation of GPR91 with succinate promoted the lipopolysaccharide-induced production of NLRP3, IL-1β, VEGF and MMP-13 in PBMCs through increased phosphorylation of p65. Pharmacological inhibition of the NF-κB signaling reversed GPR91 induced production of NLRP3, IL-1β, VEGF and MMP-13. These findings, coupled with the elevated amounts of IL-1β, VEGF, MMP-13 and p-p65 observed in the MU biopsies, constituted a rational basis for the involvement of GPR91 in the pathogenesis of MU.CONCLUSION： This study indicates the increased succinate receptor GPR91 in conjunctival or corneal tissues is involved in the pathogenesis of MU through elevated NF-κB activity, which may provide a new therapeutic target for MU.
基金Supported by the Academic Promotion Program of Shandong First Medical University(No.2019ZL001)。
文摘AIM:To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane(rh NGF-AM)on corneal epithelial and nerve regeneration in rabbit model.METHODS:Freshly prepared human amniotic membrane(AM)were immersed into PBS buffer containing 100 or 500μg/mL rh NGF for 15,30,and 60 min at 4℃.The in vitro release kinetics of rh NGF was measured with ELISA.For in vivo evaluation,the AM were immersed with 500μg/mL rh NGF for 30 min.Fifty-seven rabbits were selected to establish corneal epithelial defect model.In addition to the 19 rabbits in control group,38 rabbits received AM transplantation with or without rh NGF after the removal of central epithelium.Corneal epithelial defect area,sub-epithelial nerve fiber density,corneal sensitivity,rh NGF contents in resident AM and corneas were measured after the surgery.RESULTS:rh NGF was sustained release from the AM within 14 d in vitro,with the positive correlation with initial immersion concentration.The immersion of AM in 500μg/mL rh NGF for 30 min achieved the most stable release within 14 d.After transplantation in rabbit cornea,a high concentration of rh NGF in resident rh NGF-AM and cornea was maintained within 8 d.Corneal epithelial healing,nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rh NGF-AM transplantation when compared to simple AM transplantation(all P<0.05).CONCLUSION:Simple immersion of AM achieves the sustained release of rh NGF,and promotes corneal epithelial wound healing and nerve regeneration,as well as the recovery of corneal sensitivity in rabbit.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2020MH172)the Demonstration and Guidance Project of Science and Technology Benefiting People in Qingdao(No.20-3-4-39-nsh)。
文摘AIM:To investigate the association of axial length(AL),lens thickness(LT),and lens vault(LV)with postoperative anterior chamber angle metrics after laser peripheral iridotomy(LPI).METHODS:Prospective observational study of 69 patients(97 eyes)were diagnosed as primary angle-closure suspect(PACS),primary angle closure(PAC)or primary angle-closure glaucoma(PACG).AL,LT,anterior central chamber depth(ACD),angle opening distance(AOD),trabecular iris angle(TIA),and angle recess area(ARA)were measured before and 1 wk after LPI.The association between AL,LT,LV with ACD,AOD,TIA,ARA were analyzed by comparing the differences between preoperative and postoperative measurements for anterior segment biometric parameters.RESULTS:ACD,AOD,TIA,and ARA were significantly increased after LPI(all P<0.05).Greater LT was significantly associated with greater postoperative increases in ACD,AOD,TIA,and ARA(all P<0.05).AL was not significantly associated with changes of anterior segment biometric parameters.Greater LV was significantly associated with greater postoperative increases in ACD,AOD,and TIA(all P<0.05),but was not significantly associated with changes of ARA.CONCLUSION:Greater baseline LT and LV measurements are associated with greater increases in anterior segment biometric parameters after laser peripheral iridotomy.AL are not associated with the change of anterior segment biometric parameters.
基金Supported by China Postdoctoral Science Foundation Funded Project(No.2017M612211)the National Natural Science Foundation of China(No.81300742+2 种基金No.81600721)the Shandong Province Medical and Health Technology Development Project(No.2016WS0265)the Science and Technology Plan of Qingdao(No.15-9-1-35-jch)
文摘AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.
基金National Natural Science Foundation of China (No.81170816)Specialized Research Fund for the Doctoral Program of Higher Education (No.20113706110004)Qingjun Zhou is partially supported by the TaishanScholar Program of Jinan City, China (No.20081148)
文摘AIM: To determine the proliferative potential and the maintenance of stem cell activity in stored human limbal tissues, and correlate this with the preservation time, cell viability and the expression of stem cell markers. METHODS: Thirty limbal rims were split into 4 parts and stored in corneal preservation medium at 4 degrees C for 0, 1, 4, or 7 days. The limbal stem cell and mitotic markers P63, CK19, proliferating cell nuclear antigen (PCNA), and Ki67 were determined by immunohistochemical staining. The proliferative potential of limbal epithelial cells was assessed by cell viability, the ability of generating stratified epithelium, and colony forming assay. RESULTS: The stored tissues maintained limbal stratified structure to 7 days and exhibited comparable expression level of stem cell and mitotic markers. The proportion of viable cells decreased with the prolonged preservation time, while colony forming efficiency decreased from the 1st day and disappeared at the 4th day. When inoculated on amniotic membrane, the cells preserved for 1 day formed a stratified epithelium, while the cells from 4 days' preservation formed a discontinuous layer. CONCLUSION: The colony forming efficiency of limbal epithelial stem/progenitor cells decreased rapidly with the increasing preservation time, while the expression level of markers and capacity of forming epithelial monolayer on amniotic membrane decreased gradually. The limbal epithelial stem cells lost their function earlier than the lost expression level of stem cell markers. This may help us to better choose the appropriate preservation grafts for future limbal stem cell transplantation.
基金Supported by the National Natural Science Foundation of China(No.81271036No.81500751)+1 种基金the Key Research Project of Shandong Province,China(No.2015GSF118121)the Natural Science Foundation of Shandong Province,China(No.ZR2015PH062)
文摘AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.
基金Supported by National Natural Science Foundation of China(No.30901637)Qingdao Sci-Tec Bureau, China(No.08-2-1-3-nsh)
文摘AIM: Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Many studies suggest that age-related maculopathy susceptibility 2 (ARMS2) is a second major susceptibility gene for AMD. At present, there is no functional information on this gene. Therefore, the purpose of the present study was to detect the expression of ARMS2 in retinal pigment epithelium (RPE) cells and to investigate the effect of ARMS2 on the phagocytosis function of RPE cells. METHODS: Immunofluorescence and reverse transcriptase PCR were used to demonstrate the presence and location of ARMS2 in ARPE-19 (human retinal pigment epithelial cell line, ATCC, catalog No.CRL-2302) cells. siRNA was used to knock down ARMS2 mRNA, and the effects of the knockdown on the phagocytosis function of the ARPE-19 cells were evaluated via Fluorescence Activated Cell Sorting (FACS). RESULTS: ARMS2 was present in ARPE-19 cells, localized in the cytosol of the perinuclear region. The expression of ARMS2 mRNA (messenger RNA) in ARPE-19 cells transfected with ARMS2-siRNA (small interfering RNA, 0.73+/- 0.08) was decreased compared with normal cells (1.00+/- 0.00) or with cells transfected with scrambled siRNA (0.95+/- 0.13) (P<0.05). After incubation of RPE cells with a latex beads medium for 12, 18, or 24 hours, the fluorescence intensities were 38.04 +/- 1.02, 68.92 +/- 0.92, and 78.00 +/- 0.12 in the ARMS2-siRNA-transfected groups, respectively, and 77.98 +/- 5.43, 94.87 +/- 0.60, and 98.30 +/- 0.11 in the scrambled siRNA-transfected groups, respectively. The fluorescent intensities of the same time points in the two groups were compared using Student's t-test, and the p values were all less than 0.001 at the three different time points. CONCLUSION: There is endogenous expression of ARMS2 in ARPE-19 cells. ARMS2 plays a role in the phagocytosis function of RPE cells, and this role may be one of the mechanisms that participates in the development of AMD.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2015YL037)the Innovation Project of Shandong Academy of Medical Sciences(No.2018-21)。
文摘AIM: To evaluate the treatment selections and outcomes of keratoconus and discuss the grading treatment of keratoconus.METHODS: Medical records of 1162 patients(1863 eyes) with keratoconus treated with rigid gas permeable(RGP), corneal collagen crosslinking, and keratoplasty were reviewed. The patients were grouped according to the CLEK Study. The advanced group was further divided into a <60 D group and >60 D group. The best-corrected visual acuity(BCVA) and topographic data before and after treatment were recorded.RESULTS: In the 761 eyes with steep K<52 D, nonsurgical management accounted for 83.4%, while in the 735 eyes with steep K>60 D, surgical management accounted for 90.6%. A total of 618 eyes had improved BCVA at the final fol ow-up point(>18 mo, P<0.001). When steep K was <52 D, the BCVA in the RGP group was better than those with lamellar keratoplasty(LKP;P=0.028). When steep K was >52 D, the BCVA and topographic astigmatism outcomes showed no differences among the treatment groups. When steep K was >60 D, the BCVA in eyes treated with LKP was worse than those with steep K<60 D(P=0.025). The incidence of steep K progression in the RGP group was higher in advanced group(20.0% vs 10.8%, P=0.019). The probability of future keratoplasty in RGP was higher in advanced group(14.8% vs 7.0%, P=0.027). The incidence of steep K progression in the corneal collagen crosslinking(CXL) group was higher in advanced group(32.3% vs 8.5%, P=0.007). Multivariate logistic regression revealed the following related factors for treatment options: steep K [odds ratio(OR)=1.208, 95%CI: 1.052-1.387], TA(OR=1.171, 95%CI: 1.079-1.270), and TCT(OR=0.978, 95%CI: 0.971-0.984). The level of steep K, TA, and TCT all relates to the treatment choices of both keratoplasty and non-keratoplasty, while steep K provided the highest diagnostic accuracy(AUC=0.947, P<0.001).CONCLUSION: Steep K is an important grading treatment indicator. When steep K is <52 D, RGP lenses should be recommended. It is the best time for LKP when the steep K ranges from 52 to 60 D.
基金National Natural Science Foundation of China(No.81870639,No.82070923,No.81900907)Taishan Scholar Program(No.tspd20150215,No.tsqn201812150)the Academic Promotion Program of Shandong First Medical University(No.2019RC009)。
文摘AIM:To describe the design and clinical application of a corneal donor dehydrator which can quickly dehydrate corneas and keep its original shape.METHODS:The corneal donor material is placed on stainless steel beads with different diameters in the dehydrating box to make the cornea the same shape as the steel ball.Then,the cornea is placed inside the dehydrater for rapid dehydrating using the internal cleaning and ventilation system.Totally 83 eyes underwent deep anterior lamellar keratoplasty(DALK)using corneal donor tissue preserved with corneal dehydrater,and 60 patients(60 eyes)received DALK by the same surgeon using corneal donor tissue preserved with glycerol were included in the control group.The best corrected visual acuity(BCVA),the thickness and transparency of the corneal buttons were recorded.RESULTS:After the completion of dehydrating,all the donor corneas maintained a normal shape without any shrinkage or distortion,and the average intraoperative rehydration time was 43.3±12.1 s during operation.The mean BCVA of the dehydrater group was 0.30±0.18 at 1 wk and 0.32±0.16 at 1 mo,which were statistically better than that of the control group(P<0.001).The score of corneal buttons transparency were lower than that of the control group with statistical difference(P<0.001).The thickness of corneal buttons at 1 wk and at 1 mo in the dehydrater group was significantly better than that of the control group respectively(P<0.001).One week after operation,no corneal button turbidity or edema was observed in both groups.CONCLUSION:The dehydrater can quickly dehydrate the corneal material in a clean and airtight environment and maintain the original shape of the corneal donor during the dehydrating process.This dehydrater is recommended for long-term high-quality preservation in areas where corneal materials cannot be used within a reasonable time period.
基金National Natural Science Foundation of China (No.30872817, 30630063, and 30271394)National Basic Research Program of China (No.2009CB526506)+1 种基金Taishan Scholar Program,China(No.ts20081148)Department of Science and Technology of Shandong Province,China(No.2006GG220233)
文摘AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS: In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n=25). Grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4(+) T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS: Rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4(+) T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adhered to the corneal endothelium. Blood vessels in iris increased and were filled with lymphocytes. And lymphocytes were detected to migrate through endothelial cell gap out of vessels. When allograft rejection occurred, macrophages attached to endothelial cells with large number of lymphocytes and macrophages infiltrating in iris. CONCLUSION: Lymphocyte infiltration and activation occurred in iris-ciliary body after allogenic PK, and the lymphocytes could migrate from iris blood vessel to the anterior chamber, which might play an important role in corneal allograft immune rejection.
