Repeatability,interocular correlation and agreement of optic nerve head vessel density in healthy eyes:a sweptsource optical coherence tomographic angiography study

AIM:To assess the repeatability,interocular correlation,and agreement of quantitative swept-source optical coherence tomography angiography(OCTA)optic nerve head(ONH)parameters in healthy subjects.METHODS:Thir ty-three healthy subjects were enrolled.The ONH of both eyes were imaged four times by a swept-source-OCTA using a 3 mm×3 mm scanning protocol.Images of the radial peripapillary capillary were analyzed by a customized Matlab program,and the vessel density,fractal dimension,and vessel diameter index were measured.The repeatability of the four scans was determined by the intraclass correlation coefficient(ICC).The most well-centered optic disc from the four repeated scans was then selected for the interocular correlation and agreement analysis using the Pearson correlation coefficient,ICC and Bland-Altman plots.RESULTS:All swept-source-OCTA ONH parameters exhibited certain repeatability,with ICC>0.760 and coefficient of variation(CoV)≤7.301%.The obvious interocular correlation was observed for papillary vessel density(ICC=0.857),vessel diameter index(ICC=0.857)and fractal dimension(ICC=0.906),while circumpapillary vessel density exhibited moderate interocular correlation(ICC=0.687).Bland-Altman plots revealed an agreement range of-5.26%to 6.21%for circumpapillary vessel density.CONCLUSION:OCTA ONH parameters demonstrate good repeatability in healthy subjects.The interocular correlations of papillary vessel density,fractal dimension and vessel diameter index are high,but the correlation for circumpapillary vessel density is moderate.

Ocular syphilis:a case series of four patients and a review of the literature

Background:The incidence of syphilis has been increasing in the United States over the last two decades,with a more recent increase among women.Ocular syphilis is an uncommon but important complication of syphilis,most often presenting as posterior or panuveitis in late or latent syphilis of unknown duration.Untreated ocular syphilis may lead to permanent vision loss,underscoring the importance of appropriate evaluation and treatment of ocular syphilis.Case Description:In a retrospective,non-contiguous case series,we highlight four patients diagnosed and treated with ocular syphilis at a single institution.Four presentations of ocular syphilis are illustrated:anterior and intermediate uveitis,optic neuritis,posterior uveitis,and panuveitis.All patients initially presented with a decreased visual acuity(VA).One patient had a previous diagnosis of human immunodeficiency virus(HIV).Three patients were treated with intravenous(IV)penicillin and one patient with IV ceftriaxone.All had a return to their baseline VA after their course of treatment.Conclusions:Syphilis may go undetected without a high index of clinical suspicion due to its nonspecific presentations.All patients with ocular inflammation should have syphilis testing as a part of their infectious workup with both treponemal and non-treponemal testing.Patients diagnosed with syphilis and are not known to be HIV-negative should undergo testing for HIV due to the high rate of co-infection.Early diagnosis and prompt treatment after onset of symptoms may contribute to a more favorable prognosis for ocular syphilis.

Improving the training abilities of ophthalmic educators: the Ophthalmology Foundation’s initiatives

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.

Comparison of success rate and intraocular pressure spikes between selective laser trabeculoplasty and micropulse laser trabeculoplasty in African American and Hispanic patients

AIM:To examine the efficacy and safety of micropulse laser trabeculoplasty(MLT)versus selective laser trabeculoplasty(SLT)in a large cohort of primarily African American and Hispanic patients.METHODS:A single center retrospective comparative cohort review conducted at Cook County Health facilities that included patients with a diagnosis of open angle glaucoma or ocular hypertension who received an SLT or MLT procedure between January 2017 and May 2021.RESULTS:Totally 131 eyes of 99 patients were analyzed.The 77 eyes received SLT and 54 received MLT.Seven out of 77 eyes in the SLT group(9.1%)and 1 out of 54 eyes in the MLT group(1.9%)had an IOP spike(defined as>5 mm Hg)at either 1h or 1wk after procedure(P=0.05,Chisquared test with Haldane-Anscombe correction).The procedure failure rate at one year was 50%for SLT and 48%for MLT(P=0.31).CONCLUSION:MLT has a significantly lower incidence of pressure spikes and a similar treatment failure rate at 1-year post-procedure,demonstrating that it is a reasonable alternative compared to SLT.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population:a new approach

AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Corneal neurotization: a narrative review of techniques, outcomes, and surgical considerations

Background and Objective:Corneal neurotization is a novel surgical technique used to restore corneal sensation in patients with neurotrophic keratopathy.Neurotrophic keratopathy is a disorder characterized by dysfunction of the ophthalmic division of the trigeminal nerve,which provides sensory innervation to the cornea.Without sensation,the cornea is at risk of infection,ulceration,perforation,and ultimately,vision loss.Corneal neurotization has emerged as an innovative technique to reinnervate anesthetized corneas by transferring a healthy donor nerve to the affected eye around the corneoscleral limbus.As the field of corneal neurotization rapidly grows,there is a need to synthesize the existing body of literature on corneal neurotization and identify important areas for further research.In this review,we will discuss neurotrophic keratopathy and its current management strategies,followed by an overview of corneal neurotization techniques,outcomes,surgical considerations,and future directions.Methods:PubMed and Google Scholar searches were conducted to retrieve and analyze relevant original papers and reviews on neurotrophic keratopathy and corneal neurotization up until April 2022.Key Content and Findings:Currently,numerous techniques for corneal neurotization exist,including direct nerve transfers,as well as indirect neurotization via interposition nerve grafts.So far,corneal neurotization has been shown to be highly successful in restoring corneal sensation,improving visual acuity,and improving corneal epithelial health.To date,there have been no significant differences in outcomes between direct versus indirect neurotization techniques,different donor nerves,or autologous versus allogeneic interposition grafts.However,there is some evidence that corneal neurotization procedures may be more successful in pediatric patients.Conclusions:Corneal neurotization shows great promise in treating neurotrophic corneas and represents the first management option to date that addresses the underlying pathophysiological mechanism of neurotrophic keratopathy by restoring corneal sensation.As the use of corneal neurotization continues to broaden,additional studies will become important to compare techniques in a systematic manner,with larger sample sizes,as well as standardized outcome measures and follow-up time.

Visual impact of sub-Tenon anesthesia during combined phacoemulsification and vitrectomy surgery

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.

Ophthalmology residency training in Jordan:an evaluation of quality and comparison with international standards

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.

Comment on:Recurrence after spontaneous separation of epiretinal membrane in a young woman:a case report

Dear Editor,Herein,we provide a commentary on the recently published article by Zeng QZ and Yu WZ[1].This case report provides interesting novel insights into the recurrence of epiretinal membrane(ERM)following self-separation in a young patient.In addition to the study,we have been investigating spontaneous ERM release for many years and have recently published a related paper[2].

Ocular surface in patients with different degrees of myopia

AIM:To investigate the clinical features of the ocular surface in patients with different degrees of myopia.METHODS:A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June,2023.After completing the Ocular Surface Disease Index(OSDI)score scale,measurements were taken for refraction,biometric parameters and ocular surface parameters.The prevalence,severity and related parameters of the dry eye among different groups based on axial length(AL)were compared.Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters.RESULTS:Statistically significant differences were observed in refractive error,corneal thickness,anterior chamber depth,and subfoveal choroidal thickness among the groups(all P<0.05).With the increase in AL,the incidence and severity of dry eye increased significantly(P<0.05).Moreover,the tear film break-up time(BUT)shortened(P<0.05),and the corneal fluorescein staining(CFS)points increased significantly(P<0.05).OSDI scores were positively correlated with AL and spherical equivalent(SE;both P<0.05);BUT was negatively correlated with AL,SE,and corneal astigmatism(AST;all P<0.05);Schirmer I test(SIT)results were negatively correlated with AL and SE(both P<0.05).CONCLUSION:AL elongation is a risk factor for dry eye onset in myopic participants.The longer the AL,the more severe the dry eye is,with the increased CFS spots and tear film instability.Additionally,SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

BACKGROUND Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple lineages.In humans,their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or organs.Studies suggested that mesenchymal stem cells(MSCs),necessary for repair and regeneration via transplantation,require doses ranging from 10 to 400 million cells.Furthermore,the limited expansion of MSCs restricts their therapeutic application.AIM To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy protocols.METHODS Human umbilical cord(hUC)tissue derived MSCs were obtained and re-cultured.These cultured cells were subjected to the following evaluation pro-cedures:Immunophenotyping,immunocytochemical staining,trilineage differentiation,population doubling time and number,gene expression markers for proliferation,cell cycle progression,senescence-associatedβ-galactosidase assay,human telomerase reverse transcriptase(hTERT)expression,mycoplasma,cytomegalovirus and endotoxin detection.RESULTS Analysis of pluripotent gene markers Oct4,Sox2,and Nanog in recultured hUC-MSC revealed no significant differences.The immunophenotypic markers CD90,CD73,CD105,CD44,vimentin,CD29,Stro-1,and Lin28 were positively expressed by these recultured expanded MSCs,and were found negative for CD34,CD11b,CD19,CD45,and HLA-DR.The recultured hUC-MSC population continued to expand through passage 15.Proliferative gene expression of Pax6,BMP2,and TGFb1 showed no significant variation between recultured hUC-MSC groups.Nevertheless,a significant increase(P<0.001)in the mitotic phase of the cell cycle was observed in recultured hUC-MSCs.Cellular senescence markers(hTERT expression andβ-galactosidase activity)did not show any negative effect on recultured hUC-MSCs.Additionally,quality control assessments consistently confirmed the absence of mycoplasma,cytomegalovirus,and endotoxin contamination.CONCLUSION This study proposes the development of a novel protocol for efficiently expanding stem cell population.This would address the growing demand for larger stem cell doses needed for cellular transplantation and will significantly improve the feasibility of stem cell based therapies.

Comment on: Effect of intubation in patients with functional epiphora after endoscopic dacryocystorhinostomy

Dear Editor,We read with interest the article by Han et al[1]in which they retrospectively assessed the effect of bicanalicular intubation for functional epiphora after a failed endoscopic dacryocystorhinostomy(DCR).They confirmed the post-DCR“functional obstruction”based on fluorescein dye disappearance(FDDT)and irrigation test[1].

Medical and surgical approach to ocular surface reconstruction

Ocular surface disease(OSD)can have a severe impact on patients as it can lead to visual impairment and persistent discomfort.Ocular surface reconstruction(OSR)is an approach to the management of ocular diseases that cause structural damage to the ocular surface.OSR encompasses both medical and surgical treatment options.In this review,we discuss the medical and surgical strategies used in OSR.Medical management often aims to treat tear insufficiency,inflammation,and keratinization.Surgical treatments may be employed for a variety of reasons,including failure of medical management.This may include improving the oculo-palpebral structures in order to improve lid positioning and tear film.Additional therapies focus on improving tear production,such as through salivary gland transplantation.In situations where the ocular surface is so severely damaged that there is loss of limbal stem cells,limbal stem cell transplant(LSCT)may be indicated.Other surgeries such as amniotic membrane transplant(AMT)and conjunctival flaps(CFs)can help promote corneal healing.Finally,in severe situations where the cornea is beyond salvage,corneal transplantation,such as a penetrating keratoplasty(PKP),can be considered.OSR often requires a combination of medical and surgical approaches targeted to each specific patient’s presentation in order to achieve optimal outcomes.

Ocular cicatricial pemphigoid:diagnosis and systemic management

Ocular cicatricial pemphigoid(OCP)is a subcategory of mucous membrane pemphigoid(MMP)where the conjunctiva is the main site of inflammation.It is a chronic and autoimmune disease characterized by acute and chronic conjunctivitis that can progress to severe conjunctival cicatrization,corneal opacification,ocular surface keratinization,and eyelid abnormalities.OCP can lead to structural damage that can result in visual impairment,visual loss,and blindness,and can have a significant impact in a patient’s quality of life.Patients may manifest with varying symptoms,degrees of severity and may have different rates of progression.Early diagnosis and appropriate systemic immunosuppression are of utmost importance for prompt and adequate disease control.Various systemic immunomodulatory therapies(IMTs),including anti-metabolites,alkylating,and biologic agents have been utilized to achieve inflammation control and remission.Careful monitoring of disease progression is important to assess response and to modify and escalate therapy if needed.Treatment to alleviate symptoms of dry eye disease and address trichiasis and other eyelid abnormalities is recommended as well.A multidisciplinary approach to optimize clinical care is recommended in the management of patients with OCP.This review will address the immunopathogenesis,clinical features,keys to diagnosis and staging of patients with OCP.It will highlight the current immunomodulators utilized for disease management and proposed stepladder strategies.This review will discuss the updated roles of combination therapy,novel use of biologics as well as the recent use of adrenocorticotropic hormone(ACTH)analog in severe recalcitrant cases.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Progress of mesenchymal stem cell therapy for neural and retinal diseases

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.

Alpha lipoic acid protects lens from H_2O_2-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes

Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H2O2）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2,0.2 mM of H2O2 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 H2O2 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 H2O2 in inducing cataract and apoptosis.Furthermore.0.2 mM ol H2O2 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 H2O2.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H2O2-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.

Clinical features and treatment outcomes of endogenous Klebsiella endophthalmitis:a 12-year review

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.

Differentiation potential of human adipose tissue derived stem cells into photoreceptors through explants culture and enzyme methods

AIM： To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells （ADSCs） generated by enzyme （EN） and explant （EX） culture methods.METHODS： We investigated potentials of human orbital ADSCs to differentiate into photoreceptors through EN and EX culture methods. EN and EX orbital ADSCs were obtained from the same donor during rehabilitative orbital decompression, and then were subject to a 3-step induction using Noggin, DKK-1, IGF-1 and b-FGF at different time points for 38d. Stem cell, eye-field and photoreceptor-related gene and protein markers were measured by reverse transcription-polymerase chain reaction （RT-PCR） and immunofluorescent （IMF） staining.RESULTS： Both EX and EN orbital ADSCs expressed CD133, a marker of cell differentiation. Moreover, PAX6 and rhodopsin, markers of the retinal progenitor cells, were detected from EX and EN orbital ADSCs. In EX orbital ADSCs, PAX6 mRNA was detected on the 17th day and then the rhodopsin mRNA was detected on the 24th day. In contrast, the EN orbital ADSCs expressed PAX6 and rhodopsin mRNA on the 31st day. EX orbital ADSCs expressed rhodopsin protein on the 24th day, while EN orbital ADSCs expressed rhodopsin protein on the 31st day. CONCLUSION： Orbital ADSCs isolated by direct explants culture show earlier and stronger expressions of markers towards eye field and retinal photoreceptor differentiation than those generated by conventional EN method.

Long-term outcomes of penetrating keratoplasty in keratoconus: analysis of the factors associated with final visual acuities

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.

Retinal detachment repair through multifocal intraocular lens-overcoming visualization challenge of the peripheral retina

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.