Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Ret...Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.展开更多
Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that dem...Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration.Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88.Motivated to study this retinal ganglion cell type,we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential.Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells.Interestingly,we find that ON-direction-selective retinal ganglion cells are resilient,but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments.Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.展开更多
AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and...AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.展开更多
Sir Nicholas Harold Lloyd Ridley has revolutionized the practice of ophthalmology by performing the firstintraocular lens （IOL） implantation in 1949. His scientific achievement was acknowledged thirty years later, w...Sir Nicholas Harold Lloyd Ridley has revolutionized the practice of ophthalmology by performing the firstintraocular lens （IOL） implantation in 1949. His scientific achievement was acknowledged thirty years later, which led to US Food and Drug Administration approval in 1981. Although the basic principles of IOL implantation have not changed since, many efforts have been invested in perfecting IOL design during the past decades.展开更多
AIM:To evaluate the recently described optical coherence tomography(OCT)based classification of epiretinal membrane(ERM)and its usefulness in predicting the functional outcome.METHODS:A retrospective observational rev...AIM:To evaluate the recently described optical coherence tomography(OCT)based classification of epiretinal membrane(ERM)and its usefulness in predicting the functional outcome.METHODS:A retrospective observational review of OCT scans of patients with the diagnosis of idiopathic ERM was carried out from January 2016 to June 2021.All consecutive images diagnosed with any stage of idiopathic ERM and fulfilled the eligibility criteria were included in the analysis.ERM was identified on OCT scans as a thin hyperreflective layer over the inner layers of retina.OCT scans of patients with ERM who underwent vitrectomy,were independently staged as per the new classification by two independent retinal surgeons to form a consensus on stage.Best corrected visual acuity(BCVA)in logMAR scale and central subfield thickness(CST)on pre-and post-operative spectral domain OCT scans were the variables noted for all patients at the time of diagnosis and at 6 and 12 mo follow up visit after undergoing intervention.Partial correlation coefficient was computed between BCVA(logMAR)and CST by ERM stage adjusting by baseline measures.RESULTS:Clinical charts of 74 patients with idiopathic ERM were assessed.Clinically significant improvement in BCVA overtime was observed with significant difference in median visual acuity of patients with StageⅡ-ⅣERM with P<0.001.The median CST of all patients with stageⅡ-ⅣERM showed similar consistent improvement with P<0.001 from baseline to 12^(th)month.Our results showed not only gain in visual acuity but also shift from baseline to anatomical normalization of CST in stageⅡ.We found a decrease in CST with difference of 166μm and 151μm in stageⅢand stageⅣrespectively.Our results remained consistent with the hypothesis of improved visual outcomes with all stages of ERM with adjusted moderate linear correlation between visual acuity and CST in stageⅡ-Ⅳ(r>0.3).CONCLUSION:Equally significant visual outcomes of patients with ERM stagedⅡ-Ⅳand therefore can be counselled for improved visual acuity after surgical removal of ERM with improvement up to 5 lines on Snellen's chart from the baseline.展开更多
AIM:To investigate the long-term results of penetrating keratoplasty(PK)in patients with keratoconus(KC)and to evaluate factors that might influence the final visual outcome.METHODS:We retrospectively reviewed the dat...AIM:To investigate the long-term results of penetrating keratoplasty(PK)in patients with keratoconus(KC)and to evaluate factors that might influence the final visual outcome.METHODS:We retrospectively reviewed the data of all patients with clinical KC who had undergone PK by a single corneal surgeon in a single center from May 1980to December 2005.The age of the patients,preoperative best-corrected visual acuity(BCVA),corneal thickness,death to preservation time,and preservation to transplantation time were recorded.Additionally,postoperative complications such as graft rejection,development of glaucoma and specular microscopy were checked during the follow-up.RESULTS:Sixty-nineeyesfrom69patientswerefinally included.The follow-up period was 8.64±6.13y.Graft rejection occurred in 4 eyes of 69 cases(5.8%),and the time to graft rejection was 2.1±1.3y.A Kaplan-Meier survival analysis showed that the estimated cumulative probability of graft rejection at 6,13,and 17y after PK were 95.6%,90.0%,and 78.8%,respectively.When we evaluated factors that might influence final BCVA in eyes,no disparity donor-host trephine size(same graft size)as well as higher spherical equivalent,and average Kvalue were associated with higher final BCVA.(P=0.006,0.051,0.092,and 0.021 in eyes with follow-up【8y;P=0.068,0.065,and 0.030 in eyes with follow-up≥8y,respectively).CONCLUSION:The long-term results of PK in patients with KC were favorable with a high percentage of good BCVA.Less myopic change and low average K-reading,as well as a surgical technique using the same size donor-recipient button may provide better visual outcomes particularly in patients with KC.展开更多
AIM:To investigate the visual impact of sub-Tenon anesthesia during combined phacoemulsification and vitrectomy surgery.METHODS:In this prospective case series, consecutive patients who underwent combined phacoemulsif...AIM:To investigate the visual impact of sub-Tenon anesthesia during combined phacoemulsification and vitrectomy surgery.METHODS:In this prospective case series, consecutive patients who underwent combined phacoemulsification and pars plana vitrectomy(PPV) under sub-Tenon anesthesia between October 2008 and September 2009 were enrolled. The patients were asked whether they could see the light of the operating microscope or not between various surgical steps with their contralateral eye being covered.RESULTS:A total of 163 eyes of 163 patients were enrolled in this study. After their contralateral eyes were covered, 152(93.3%) patients said that they could not see any light at least during one of the surgical steps. All eyes recovered to at least light perception on the first postoperative day. The incidence of no light perception during the surgery was not related to demographic factors, including age, gender, or type of ocular diseases.CONCLUSION:The incidence of no light perception during combined phacoemulsification and vitrectomy under sub-Tenon anesthesia was high in our study.Patients should be duly informed about this temporary but potential intraoperative event.展开更多
AIMTo evaluate Jordanian ophthalmology residency programs in achieving competencies outlined by the International Council of Ophthalmology (ICO) and residents' satisfaction with available training programs in Jord...AIMTo evaluate Jordanian ophthalmology residency programs in achieving competencies outlined by the International Council of Ophthalmology (ICO) and residents' satisfaction with available training programs in Jordan, and to highlight weakness points that may be improved and strengthened.展开更多
AIM:To review international guidelines and to share our infection control experience during the coronavirus disease 2019(COVID-19)pandemic at a tertiary eye centre in Hong Kong.METHODS:Infection control guidelines and...AIM:To review international guidelines and to share our infection control experience during the coronavirus disease 2019(COVID-19)pandemic at a tertiary eye centre in Hong Kong.METHODS:Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed.The measures at our hospital were drawn up as per international and local health authorities’guidelines and implemented with the collaboration of doctors,nurses and administrative staff.RESULTS:The aims of our infection control measures are to 1)minimize cross-infection within the hospital;2)protect and support hospital staff;3)ensure environmental control.To minimize the risk of cross-infection,outpatient attendance and elective surgery have been reduced by 40%,and general anesthesia procedures were reduced by 90%.Patients entering the hospital are screened for fever,travel history,contact and cluster history,and COVID-19 related symptoms.To protect and support hospital staff,we ensure provision of adequate personal protective equipment(PPE)and provide clear guidelines on the level of PPE needed,depending on the clinical situation.Other protective measures include provision of work uniforms,easy access to alcohol-based hand rub,opening new lunch areas,implementation of self-monitoring and self-reporting systems,and communication via online education and updates.Finally,environmental control is achieved by ensuring regular disinfection of the hospital premise,enhancing ventilation,and usage of disposable ophthalmic instruments.CONCLUSION:Our multi-pronged approach to infection control is,so far,successful in minimizing infection risks,while allowing the maintenance of essential ophthalmic services.展开更多
Our goal as medical educators is for our students to learn what they need to know and competently perform ophthalmic procedures.In addition,the students need to have good communication skills and behave professionally...Our goal as medical educators is for our students to learn what they need to know and competently perform ophthalmic procedures.In addition,the students need to have good communication skills and behave professionally and ethically(1,2).Most medical educators are not taught how to teach but rather learn by role-modeling their mentors.This can be good or bad depending on the mentor!In addition,the amount of knowledge and numbers of surgical procedures is ever increasing and yet,in most countries,the amount of time to train and become competent is not changing.Thus,our goal of creating competent ophthalmologists is ever more challenging.展开更多
Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to b...Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to be considered a gold standard.This study aims to introduce novel metrics to differentiate between KCN and healthy corneas using three-dimensional(3D)measurements of surface area and volume.Methods:This retrospective observational study examined KCN patients along with healthy control patients between the ages of 20 and 79 years old at the University of Maryland,Baltimore.The selected patients underwent a nine-line raster scan anterior segment optical coherence tomography(AS-OCT).ImageJ was used to determine the central 6 mm of each image and each corneal image was then divided into six 1 mm segments.Free-D software was then used to render the nine different images into a 3D model to calculate corneal surface area and volume.A two-tailed Mann-Whitney test was used to assess statistical significance when comparing these subsets.Results:Thirty-three eyes with KCN,along with 33 healthy control,were enrolled.There were statistically significant differences between the healthy and KCN groups in the metric of anterior corneal surface area(13.927 vs.13.991 mm^(2),P=0.046),posterior corneal surface area(14.045 vs.14.173 mm^(2),P<0.001),and volume(8.430 vs.7.773 mm3,P<0.001)within the central 6 mm.Conclusions:3D corneal models derived from AS-OCT can be used to measure anterior corneal surface area,posterior corneal surface area,and corneal volume.All three parameters are statistically different between corneas with KCN and healthy corneas.Further study and application of these parameters may yield new methodologies for the detection of KCN.展开更多
Background:With the rapid development of artificial intelligence(AI),large language models(LLMs)have emerged as a potent tool for invigorating ophthalmology across clinical,educational,and research fields.Their accura...Background:With the rapid development of artificial intelligence(AI),large language models(LLMs)have emerged as a potent tool for invigorating ophthalmology across clinical,educational,and research fields.Their accuracy and reliability have undergone tested.This bibliometric analysis aims to provide an overview of research on LLMs in ophthalmology from both thematic and geographical perspectives.Methods:All existing and highly cited LLM-related ophthalmology research papers published in English up to 24th April 2025 were sourced from Scopus,PubMed,and Web of Science.The characteristics of these publications,including publication output,authors,journals,countries,institutions,citations,and research domains,were analyzed using Biblioshiny and VOSviewer software.Results:A total of 277 articles from 1,459 authors and 89 journals were included in this study.Although relevant publications began to appear in 2019,there was a significant increase starting from 2023.He M and Shi D are the most prolific authors,while Investigative Ophthalmology&Visual Science stands out as the most prominent journal.Most of the top-publishing countries are high-income economies,with the USA taking the lead,and the University of California is the leading institution.VOSviewer identified 5 clusters in the keyword co-occurrence analysis,indicating that current research focuses on the clinical applications of LLMs,particularly in diagnosis and patient education.Conclusions:While LLMs have demonstrated effectiveness in retaining knowledge,their accuracy in image-based diagnosis remains limited.Therefore,future research should investigate fine-tuning strategies and domain-specific adaptations to close this gap.Although research on the applications of LLMs in ophthalmology is still in its early stages,it holds significant potential for advancing the field.展开更多
AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year ret...AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year retrospective,cross sectional case series on 18 cases of OSSN seen between January 2012 to June 2023.The patient’s demographics,presenting symptoms,tumor characteristics,histopathologic diagnosis,treatment,outcomes,and duration of follow-up were reviewed.RESULTS:Out of 33 identified cases of OSSN,only 18 were eligible for inclusion in the study.Mean age was 60.78y(range 31 to 80),with male predominance(66.67%).The left eye was most commonly affected(61.11%)with most presenting with fleshy mass(83.33%).Most tumors were located nasally(66.67%)and were predominantly papilliform(44.44%)in morphology with associated hyperpigmentation(38.89%).Squamous cell carcinoma(SCCA)was the most common histopathologic diagnosis(72.22%).The main primary treatment was surgical excision(94.44%)with or without adjunctive therapy,with only 1 patient undergoing first-line topical chemotherapy.Only 3 recurrences(16.67%)were noted with a median followup of 7.5mo.A statistically significant recurrence-free odds leaning towards the utilization of cryotherapy was noted.CONCLUSION:OSSN seen at the Philippine General Hospital is presented as a limbal papilliform mass,most commonly affecting elderly males.Surgical excision with adjuvant cryotherapy and/or chemotherapy is the preferred mode of treatment.展开更多
Red eye affects patients of all ages and is one of the most common ocular complaints seen in primary care and emergency rooms.Some conditions,like scleritis,keratitis,uveitis,or endophthalmitis,can be vision-threateni...Red eye affects patients of all ages and is one of the most common ocular complaints seen in primary care and emergency rooms.Some conditions,like scleritis,keratitis,uveitis,or endophthalmitis,can be vision-threatening and necessitate an immediate diagnosis and referral,but many others,like conjunctivitis or episcleritis,are benign and self-limiting.To prevent complications,such as irreversible vision loss or the spread of infection throughout the body,it is essential to accurately and promptly distinguish between benign and serious causes.With a broad range of etiologies covered,this review offers a thorough,evidence-based method for assessing red eye in primary care.For inflammatory,infectious,traumatic,and non-inflammatory disorders,we look at important clinical characteristics,diagnostic factors,and therapeutic approaches.Dry eye syndrome,pterygium,scleritis,episcleritis,keratitis,conjunctivitis,uveitis,blepharitis,hordeolum,endophthalmitis,orbital cellulitis,hyphema,trichiasis,and subconjunctival hemorrhage are among them.Whereas episcleritis usually responds to topical treatment,inflammatory conditions like scleritis and uveitis need systemic corticosteroids or immunosuppressive therapy.Infections such as keratitis,conjunctivitis,and endophthalmitis require treatments specific to the pathogen,while diseases like orbital cellulitis and hyphema may require hospitalization or surgery.External conditions like dry eye and blepharitis are treated conservatively with lubrication and cleanliness.This review aims to provide general practitioners with useful clinical tools for timely assessment,efficient triage,and referral by defining red flag symptoms,hallmark signs,and updated treatment protocols.Regular eye exams and patient education also improve results and lower recurrence.展开更多
Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical inte...Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases.However,the number of neurons still diminishes in many patients.Recently,stem cell therapy has been proposed as a viable option.Mesenchymal stem cells(MSCs),a widely-studied human adult stem cell population,have been discovered for more than 20 years.MSCs have been found all over the body and can be conveniently obtained from different accessible tissues:bone marrow,blood,and adipose and dental tissue.MSCs have high proliferative and differentiation abilities,providing an inexhaustible source of neurons and glia for cell replacement therapy.Moreover,MSCs also show neuroprotective effects without any genetic modification or reprogramming.In addition,the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation.These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders.Here,we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases.This review article will focus on multiple sclerosis,spinal cord injury,autism,glaucoma,retinitis pigmentosa and age-related macular degeneration.展开更多
Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley...Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H<sub>2</sub>O<sub>2</sub> induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.展开更多
AIM：To evaluate the efficacy and safety of three different concentrations of diluted atropine for the control of myopia in Korean children,and to assess the risk factors associated with rapid myopia progression.METH...AIM：To evaluate the efficacy and safety of three different concentrations of diluted atropine for the control of myopia in Korean children,and to assess the risk factors associated with rapid myopia progression.METHODS：A total of 285 children,with refractive errors within the range of-6 diopters（D）between 5 and 14 years of age were included.After using 0.01%,or 0.025%,or 0.05% atropine,for about 1y,changes in refraction,axial lengths and frequency of adverse events were analyzed.Logistic regression analyses were performed to evaluate the risk factors associated with rapid myopia progression.RESULTS：The changes in the mean spherical equivalent values were -0.134 D/mo in the before atropine group,-0.070 D/mo in the 0.01% atropine group,-0.047 D/mo in the 0.025% atropine group,and -0.019 D/mo in the 0.05% atropine group,with significant differences between the groups（P〈0.001）.The axial elongation was 0.046 mm/mo,0.037 mm/mo,0.025 mm/mo,and 0.019 mm/mo respectively,with significant differences between the groups（P=0.003）.The incidence of photophobia and near vision difficulty was not different among the three atropine groups（P=0.425and P=0.356,respectively）.Multivariate logistic regression analyses showed that only highly myopic parents were a significant predictive factor of rapid myopia progression in Korean children（odds ratio,8.155;95% confidence interval,3.626-18.342;P〈0.001）.CONCLUSION：Treatment with 0.01%,0.025% and 0.05% atropine solution inhibits myopia progression in Korean children in a dose-dependent manner.Children with highly myopic parents preferentially shows a rapid myopia progression rate.展开更多
AIM:To identify the clinical features and treatment outcomes of endogenous Klebsiella pneumoniae endophthalmitis and investigate prognostic factors of poor visual outcome.METHODS:The clinical records of all patients d...AIM:To identify the clinical features and treatment outcomes of endogenous Klebsiella pneumoniae endophthalmitis and investigate prognostic factors of poor visual outcome.METHODS:The clinical records of all patients diagnosed with endogenous Klebsiella endophthalmitis between January 2007 to December 2018 in Prince of Wales Hospital,Hong Kong,China were retrospectively reviewed.Thorough ophthalmological examination findings were recorded in the case note,including visual acuity testing,slit-lamp examination,indirect ophthalmoscopy and B-scan ultrasonography if media opacity precluded fundus viewing.RESULTS:A total of 18 eyes in 14 patients were identified.Bilateral involvement was noted in 4 patients(28.6%).Hepatobiliary sepsis was the source in 9 patients(64.3%).Culture of intraocular fluid was positive in 5 out of 18 eyes(27.8%).Mortality was noted in 2 patients(14.3%).Mean final visual acuity was 20/1500.Six out of 16 eyes had total loss of sight(37.5%)and 3 eyes required evisceration(18.8%).Multivariate linear regression revealed poor presenting visual acuity(P=0.031)and lack of fundus view due to vitritis(P=0.02)as prognostic factors of poor visual outcome.CONCLUSION:Visual outcome of endogenous Klebsiella endophthalmitis is poor.Poor presenting visual acuity and lack of fundus view predict poor visual outcome.High index of suspicion for endophthalmitis is important in Klebsiella sepsis patients with complaints of ocular symptoms.Ophthalmological screening is recommended in noncommunicable patients with Klebsiella sepsis.展开更多
AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r...AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.展开更多
文摘Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.
基金Institutional National Research Service Award T32 EY013360(to SM and SW)Research to Prevent Blindness(Career Development Award+8 种基金to PRW)BrightFocus Foundation(National Glaucoma Researchto PRW)Alcon Research Institute(Young Investigator Awardto PRW),and NIH Grants(EY032908,EY035684,EY036111to PRW)the Jefferey T.Fort Innovation Fund and Siteman Retina Research Fund(to RSA)the Hope Center Viral Vectors Core at Washington University School of Medicine,an unrestricted grant(to the Department of Ophthalmology and Visual Sciences)from Research to Prevent BlindnessVision Core Grant(P30 EY002687).
文摘Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss.In mice,there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration.Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88.Motivated to study this retinal ganglion cell type,we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential.Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells.Interestingly,we find that ON-direction-selective retinal ganglion cells are resilient,but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments.Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(No.2025ZR172).
文摘AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.
基金Supported in part by an unrestricted grant from Research to Prevent Blindness,Inc.The American Physician Fellowship for Medicine in Israel
文摘Sir Nicholas Harold Lloyd Ridley has revolutionized the practice of ophthalmology by performing the firstintraocular lens （IOL） implantation in 1949. His scientific achievement was acknowledged thirty years later, which led to US Food and Drug Administration approval in 1981. Although the basic principles of IOL implantation have not changed since, many efforts have been invested in perfecting IOL design during the past decades.
文摘AIM:To evaluate the recently described optical coherence tomography(OCT)based classification of epiretinal membrane(ERM)and its usefulness in predicting the functional outcome.METHODS:A retrospective observational review of OCT scans of patients with the diagnosis of idiopathic ERM was carried out from January 2016 to June 2021.All consecutive images diagnosed with any stage of idiopathic ERM and fulfilled the eligibility criteria were included in the analysis.ERM was identified on OCT scans as a thin hyperreflective layer over the inner layers of retina.OCT scans of patients with ERM who underwent vitrectomy,were independently staged as per the new classification by two independent retinal surgeons to form a consensus on stage.Best corrected visual acuity(BCVA)in logMAR scale and central subfield thickness(CST)on pre-and post-operative spectral domain OCT scans were the variables noted for all patients at the time of diagnosis and at 6 and 12 mo follow up visit after undergoing intervention.Partial correlation coefficient was computed between BCVA(logMAR)and CST by ERM stage adjusting by baseline measures.RESULTS:Clinical charts of 74 patients with idiopathic ERM were assessed.Clinically significant improvement in BCVA overtime was observed with significant difference in median visual acuity of patients with StageⅡ-ⅣERM with P<0.001.The median CST of all patients with stageⅡ-ⅣERM showed similar consistent improvement with P<0.001 from baseline to 12^(th)month.Our results showed not only gain in visual acuity but also shift from baseline to anatomical normalization of CST in stageⅡ.We found a decrease in CST with difference of 166μm and 151μm in stageⅢand stageⅣrespectively.Our results remained consistent with the hypothesis of improved visual outcomes with all stages of ERM with adjusted moderate linear correlation between visual acuity and CST in stageⅡ-Ⅳ(r>0.3).CONCLUSION:Equally significant visual outcomes of patients with ERM stagedⅡ-Ⅳand therefore can be counselled for improved visual acuity after surgical removal of ERM with improvement up to 5 lines on Snellen's chart from the baseline.
文摘AIM:To investigate the long-term results of penetrating keratoplasty(PK)in patients with keratoconus(KC)and to evaluate factors that might influence the final visual outcome.METHODS:We retrospectively reviewed the data of all patients with clinical KC who had undergone PK by a single corneal surgeon in a single center from May 1980to December 2005.The age of the patients,preoperative best-corrected visual acuity(BCVA),corneal thickness,death to preservation time,and preservation to transplantation time were recorded.Additionally,postoperative complications such as graft rejection,development of glaucoma and specular microscopy were checked during the follow-up.RESULTS:Sixty-nineeyesfrom69patientswerefinally included.The follow-up period was 8.64±6.13y.Graft rejection occurred in 4 eyes of 69 cases(5.8%),and the time to graft rejection was 2.1±1.3y.A Kaplan-Meier survival analysis showed that the estimated cumulative probability of graft rejection at 6,13,and 17y after PK were 95.6%,90.0%,and 78.8%,respectively.When we evaluated factors that might influence final BCVA in eyes,no disparity donor-host trephine size(same graft size)as well as higher spherical equivalent,and average Kvalue were associated with higher final BCVA.(P=0.006,0.051,0.092,and 0.021 in eyes with follow-up【8y;P=0.068,0.065,and 0.030 in eyes with follow-up≥8y,respectively).CONCLUSION:The long-term results of PK in patients with KC were favorable with a high percentage of good BCVA.Less myopic change and low average K-reading,as well as a surgical technique using the same size donor-recipient button may provide better visual outcomes particularly in patients with KC.
基金Supported in part by Science and Technology Project of Guangdong Province(No.2011B031800369)
文摘AIM:To investigate the visual impact of sub-Tenon anesthesia during combined phacoemulsification and vitrectomy surgery.METHODS:In this prospective case series, consecutive patients who underwent combined phacoemulsification and pars plana vitrectomy(PPV) under sub-Tenon anesthesia between October 2008 and September 2009 were enrolled. The patients were asked whether they could see the light of the operating microscope or not between various surgical steps with their contralateral eye being covered.RESULTS:A total of 163 eyes of 163 patients were enrolled in this study. After their contralateral eyes were covered, 152(93.3%) patients said that they could not see any light at least during one of the surgical steps. All eyes recovered to at least light perception on the first postoperative day. The incidence of no light perception during the surgery was not related to demographic factors, including age, gender, or type of ocular diseases.CONCLUSION:The incidence of no light perception during combined phacoemulsification and vitrectomy under sub-Tenon anesthesia was high in our study.Patients should be duly informed about this temporary but potential intraoperative event.
基金Supported in part by an unrestricted grant from Research to Prevent Blindness,Inc.New York,N.Y,USA
文摘AIMTo evaluate Jordanian ophthalmology residency programs in achieving competencies outlined by the International Council of Ophthalmology (ICO) and residents' satisfaction with available training programs in Jordan, and to highlight weakness points that may be improved and strengthened.
文摘AIM:To review international guidelines and to share our infection control experience during the coronavirus disease 2019(COVID-19)pandemic at a tertiary eye centre in Hong Kong.METHODS:Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed.The measures at our hospital were drawn up as per international and local health authorities’guidelines and implemented with the collaboration of doctors,nurses and administrative staff.RESULTS:The aims of our infection control measures are to 1)minimize cross-infection within the hospital;2)protect and support hospital staff;3)ensure environmental control.To minimize the risk of cross-infection,outpatient attendance and elective surgery have been reduced by 40%,and general anesthesia procedures were reduced by 90%.Patients entering the hospital are screened for fever,travel history,contact and cluster history,and COVID-19 related symptoms.To protect and support hospital staff,we ensure provision of adequate personal protective equipment(PPE)and provide clear guidelines on the level of PPE needed,depending on the clinical situation.Other protective measures include provision of work uniforms,easy access to alcohol-based hand rub,opening new lunch areas,implementation of self-monitoring and self-reporting systems,and communication via online education and updates.Finally,environmental control is achieved by ensuring regular disinfection of the hospital premise,enhancing ventilation,and usage of disposable ophthalmic instruments.CONCLUSION:Our multi-pronged approach to infection control is,so far,successful in minimizing infection risks,while allowing the maintenance of essential ophthalmic services.
文摘Our goal as medical educators is for our students to learn what they need to know and competently perform ophthalmic procedures.In addition,the students need to have good communication skills and behave professionally and ethically(1,2).Most medical educators are not taught how to teach but rather learn by role-modeling their mentors.This can be good or bad depending on the mentor!In addition,the amount of knowledge and numbers of surgical procedures is ever increasing and yet,in most countries,the amount of time to train and become competent is not changing.Thus,our goal of creating competent ophthalmologists is ever more challenging.
文摘Background:Traditional imaging approaches to keratoconus(KCN)have thus far failed to produce a standardized approach for diagnosis.While many diagnostic modalities and metrics exist,none have proven robust enough to be considered a gold standard.This study aims to introduce novel metrics to differentiate between KCN and healthy corneas using three-dimensional(3D)measurements of surface area and volume.Methods:This retrospective observational study examined KCN patients along with healthy control patients between the ages of 20 and 79 years old at the University of Maryland,Baltimore.The selected patients underwent a nine-line raster scan anterior segment optical coherence tomography(AS-OCT).ImageJ was used to determine the central 6 mm of each image and each corneal image was then divided into six 1 mm segments.Free-D software was then used to render the nine different images into a 3D model to calculate corneal surface area and volume.A two-tailed Mann-Whitney test was used to assess statistical significance when comparing these subsets.Results:Thirty-three eyes with KCN,along with 33 healthy control,were enrolled.There were statistically significant differences between the healthy and KCN groups in the metric of anterior corneal surface area(13.927 vs.13.991 mm^(2),P=0.046),posterior corneal surface area(14.045 vs.14.173 mm^(2),P<0.001),and volume(8.430 vs.7.773 mm3,P<0.001)within the central 6 mm.Conclusions:3D corneal models derived from AS-OCT can be used to measure anterior corneal surface area,posterior corneal surface area,and corneal volume.All three parameters are statistically different between corneas with KCN and healthy corneas.Further study and application of these parameters may yield new methodologies for the detection of KCN.
基金supported by Health and Medical Research Fund,Hong Kong(11220386,12230246).
文摘Background:With the rapid development of artificial intelligence(AI),large language models(LLMs)have emerged as a potent tool for invigorating ophthalmology across clinical,educational,and research fields.Their accuracy and reliability have undergone tested.This bibliometric analysis aims to provide an overview of research on LLMs in ophthalmology from both thematic and geographical perspectives.Methods:All existing and highly cited LLM-related ophthalmology research papers published in English up to 24th April 2025 were sourced from Scopus,PubMed,and Web of Science.The characteristics of these publications,including publication output,authors,journals,countries,institutions,citations,and research domains,were analyzed using Biblioshiny and VOSviewer software.Results:A total of 277 articles from 1,459 authors and 89 journals were included in this study.Although relevant publications began to appear in 2019,there was a significant increase starting from 2023.He M and Shi D are the most prolific authors,while Investigative Ophthalmology&Visual Science stands out as the most prominent journal.Most of the top-publishing countries are high-income economies,with the USA taking the lead,and the University of California is the leading institution.VOSviewer identified 5 clusters in the keyword co-occurrence analysis,indicating that current research focuses on the clinical applications of LLMs,particularly in diagnosis and patient education.Conclusions:While LLMs have demonstrated effectiveness in retaining knowledge,their accuracy in image-based diagnosis remains limited.Therefore,future research should investigate fine-tuning strategies and domain-specific adaptations to close this gap.Although research on the applications of LLMs in ophthalmology is still in its early stages,it holds significant potential for advancing the field.
文摘AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year retrospective,cross sectional case series on 18 cases of OSSN seen between January 2012 to June 2023.The patient’s demographics,presenting symptoms,tumor characteristics,histopathologic diagnosis,treatment,outcomes,and duration of follow-up were reviewed.RESULTS:Out of 33 identified cases of OSSN,only 18 were eligible for inclusion in the study.Mean age was 60.78y(range 31 to 80),with male predominance(66.67%).The left eye was most commonly affected(61.11%)with most presenting with fleshy mass(83.33%).Most tumors were located nasally(66.67%)and were predominantly papilliform(44.44%)in morphology with associated hyperpigmentation(38.89%).Squamous cell carcinoma(SCCA)was the most common histopathologic diagnosis(72.22%).The main primary treatment was surgical excision(94.44%)with or without adjunctive therapy,with only 1 patient undergoing first-line topical chemotherapy.Only 3 recurrences(16.67%)were noted with a median followup of 7.5mo.A statistically significant recurrence-free odds leaning towards the utilization of cryotherapy was noted.CONCLUSION:OSSN seen at the Philippine General Hospital is presented as a limbal papilliform mass,most commonly affecting elderly males.Surgical excision with adjuvant cryotherapy and/or chemotherapy is the preferred mode of treatment.
文摘Red eye affects patients of all ages and is one of the most common ocular complaints seen in primary care and emergency rooms.Some conditions,like scleritis,keratitis,uveitis,or endophthalmitis,can be vision-threatening and necessitate an immediate diagnosis and referral,but many others,like conjunctivitis or episcleritis,are benign and self-limiting.To prevent complications,such as irreversible vision loss or the spread of infection throughout the body,it is essential to accurately and promptly distinguish between benign and serious causes.With a broad range of etiologies covered,this review offers a thorough,evidence-based method for assessing red eye in primary care.For inflammatory,infectious,traumatic,and non-inflammatory disorders,we look at important clinical characteristics,diagnostic factors,and therapeutic approaches.Dry eye syndrome,pterygium,scleritis,episcleritis,keratitis,conjunctivitis,uveitis,blepharitis,hordeolum,endophthalmitis,orbital cellulitis,hyphema,trichiasis,and subconjunctival hemorrhage are among them.Whereas episcleritis usually responds to topical treatment,inflammatory conditions like scleritis and uveitis need systemic corticosteroids or immunosuppressive therapy.Infections such as keratitis,conjunctivitis,and endophthalmitis require treatments specific to the pathogen,while diseases like orbital cellulitis and hyphema may require hospitalization or surgery.External conditions like dry eye and blepharitis are treated conservatively with lubrication and cleanliness.This review aims to provide general practitioners with useful clinical tools for timely assessment,efficient triage,and referral by defining red flag symptoms,hallmark signs,and updated treatment protocols.Regular eye exams and patient education also improve results and lower recurrence.
基金Supported by Veterans Affairs(VA)Merit Review GrantSenior VA Research Career Scientist Award,Miami
文摘Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases.However,the number of neurons still diminishes in many patients.Recently,stem cell therapy has been proposed as a viable option.Mesenchymal stem cells(MSCs),a widely-studied human adult stem cell population,have been discovered for more than 20 years.MSCs have been found all over the body and can be conveniently obtained from different accessible tissues:bone marrow,blood,and adipose and dental tissue.MSCs have high proliferative and differentiation abilities,providing an inexhaustible source of neurons and glia for cell replacement therapy.Moreover,MSCs also show neuroprotective effects without any genetic modification or reprogramming.In addition,the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation.These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders.Here,we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases.This review article will focus on multiple sclerosis,spinal cord injury,autism,glaucoma,retinitis pigmentosa and age-related macular degeneration.
文摘Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H<sub>2</sub>O<sub>2</sub> induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.
基金Supported by the Catholic Medical Center Research Foundation made in the program year of 2018(No.5-2018-B0001-00006)
文摘AIM：To evaluate the efficacy and safety of three different concentrations of diluted atropine for the control of myopia in Korean children,and to assess the risk factors associated with rapid myopia progression.METHODS：A total of 285 children,with refractive errors within the range of-6 diopters（D）between 5 and 14 years of age were included.After using 0.01%,or 0.025%,or 0.05% atropine,for about 1y,changes in refraction,axial lengths and frequency of adverse events were analyzed.Logistic regression analyses were performed to evaluate the risk factors associated with rapid myopia progression.RESULTS：The changes in the mean spherical equivalent values were -0.134 D/mo in the before atropine group,-0.070 D/mo in the 0.01% atropine group,-0.047 D/mo in the 0.025% atropine group,and -0.019 D/mo in the 0.05% atropine group,with significant differences between the groups（P〈0.001）.The axial elongation was 0.046 mm/mo,0.037 mm/mo,0.025 mm/mo,and 0.019 mm/mo respectively,with significant differences between the groups（P=0.003）.The incidence of photophobia and near vision difficulty was not different among the three atropine groups（P=0.425and P=0.356,respectively）.Multivariate logistic regression analyses showed that only highly myopic parents were a significant predictive factor of rapid myopia progression in Korean children（odds ratio,8.155;95% confidence interval,3.626-18.342;P〈0.001）.CONCLUSION：Treatment with 0.01%,0.025% and 0.05% atropine solution inhibits myopia progression in Korean children in a dose-dependent manner.Children with highly myopic parents preferentially shows a rapid myopia progression rate.
文摘AIM:To identify the clinical features and treatment outcomes of endogenous Klebsiella pneumoniae endophthalmitis and investigate prognostic factors of poor visual outcome.METHODS:The clinical records of all patients diagnosed with endogenous Klebsiella endophthalmitis between January 2007 to December 2018 in Prince of Wales Hospital,Hong Kong,China were retrospectively reviewed.Thorough ophthalmological examination findings were recorded in the case note,including visual acuity testing,slit-lamp examination,indirect ophthalmoscopy and B-scan ultrasonography if media opacity precluded fundus viewing.RESULTS:A total of 18 eyes in 14 patients were identified.Bilateral involvement was noted in 4 patients(28.6%).Hepatobiliary sepsis was the source in 9 patients(64.3%).Culture of intraocular fluid was positive in 5 out of 18 eyes(27.8%).Mortality was noted in 2 patients(14.3%).Mean final visual acuity was 20/1500.Six out of 16 eyes had total loss of sight(37.5%)and 3 eyes required evisceration(18.8%).Multivariate linear regression revealed poor presenting visual acuity(P=0.031)and lack of fundus view due to vitritis(P=0.02)as prognostic factors of poor visual outcome.CONCLUSION:Visual outcome of endogenous Klebsiella endophthalmitis is poor.Poor presenting visual acuity and lack of fundus view predict poor visual outcome.High index of suspicion for endophthalmitis is important in Klebsiella sepsis patients with complaints of ocular symptoms.Ophthalmological screening is recommended in noncommunicable patients with Klebsiella sepsis.
基金Supported by the National Natural Science Foundation of China(No.81371005No.81428012)Tianjin Municipal Science and Technology Commission(No.15JCZDJC35600)
文摘AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.
