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.

Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Intra-and interobserver reliability of ocular surface analyzer LacryDiag

AIM:To invastigate intra-and interobserver reliability of interferometry,tear meniscus height(TMH)measurement and meibography(MBG)of an ocular surface analyzer,LacryDiag(Quantel Medical,France).METHODS:Five consecutive measurements and subsequent analysis of interferometry,TMH,and MBG were recorded by two examiners using the LacryDiag.To assess intra-and interobserver reliability,we used Cohen’s kappa for categorical variables(interferometry),or intraclass correlation coefficient for continuous variables(TMH,MBG).RESULTS:Thirty eyes of 30 examinees were included.For both observers,there was excellent intraobserver reliability for MBG(0.955 and 0.970 for observer 1 and 2,respectively).Intraobserver reliability for observer 1 was substantial for interferometry(0.799),and excellent for TMH(0.863).Reliability for observer 2 was moderate for interferometry(0.535)and fair to good for TMH(0.431).Interobserver reliability was poor for interferometry(0.074)and fair to good for TMH(0.680)and MBG(0.414).CONCLUSION:LacryDiag ocular surface analyzer in our study proves to be a reliable noninvasive tool for the evaluation of TMH and MBG.As for interferometry,poor interobserver reliability,fair to good intraobserver reliability for observer 1,and moderate for observer 2,leave room for improvement.

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.

Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

Autologous blood in the management of ocular surface disorders

Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders.This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders,encompassing its physiological basis,clinical applications,techniques,challenges,and future perspectives.The ocular surface,comprising the cornea,conjunctiva,and tear film,plays a critical role in maintaining visual function,and its disruption can lead to various pathological conditions.With its rich composition of growth factors,cytokines,and other bioactive molecules,autologous blood offers therapeutic potential in promoting corneal wound healing,reducing inflammation,and improving tear film stability.Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders,including persistent epithelial defects,neurotrophic keratopathy,and dry eye disease.However,challenges such as variability in treatment response,adverse effects,and optimal patient selection remain areas of concern.Further research is needed to elucidate the underlying mechanisms of action,refine treatment protocols,and explore synergistic approaches with other therapeutic modalities.Despite these challenges,autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders,offering new avenues for improving patient outcomes and quality of life.This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders.Current clinical trials are also summarized,and a comparison between autologous blood therapy and conventional eyedrops is attempted.Finally,safe techniques and protocols for autologous blood medicine are elucidated,and adverse effects and future perspectives of this novel therapy are reviewed.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients

AIM:To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction(MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a Lipi View interferometer.METHODS:Forty cases were randomized into control group A and treatment group B;the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery.The average non-invasive tear film break-up time(NITBUTav),first noninvasive tear film break-up time(NITBUTf),non-invasive measured tear meniscus height(NTMH),meibomian gland loss(MGL),lipid layer thickness(LLT)and partial blink rate(PBR)were measured preoperatively and 1wk,1 and 3mo postoperatively.RESULTS:The NITBUTav values of group A at 1wk(4.38±0.47),1mo(6.76±0.70),and 3mo(7.25±0.68)were significantly lower than those of group B(7.45±0.78,10.46±0.97,and 11.31±0.89;P=0.002,0.004,and 0.001,respectively).The NTMH values of group B at 1wk(0.20±0.01)and 1mo(0.22±0.01)were markedly higher than those of group A(0.15±0.01 and 0.15±0.01;P=0.008 and P<0.001,respectively);however,there was no difference at 3mo.The LLT of group B at 3mo[91.5(76.25-100.00)]significantly exceeded that of group A[65.00(54.50-91.25),P=0.017].No obvious intergroup difference was found in MGL or PBR(P>0.05).CONCLUSION:Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy.Preoperative cleaning,hot compresses,and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

Recent progress in N6-methyladenosine modification in ocular surface diseases

N6-methyladenosine(m6A)modification is a reversible process promoted by“writers”,inhibited by“erasers”,and processed by“readers”.During the last decade,increasing emphasis has been placed on the underlying roles of m6A modification owing to their great importance in biological significance.The abnormal regulation of m6A modification will lead to aberrant cellular behavior and various diseases.Recently,studies have demonstrated that m6A modification is closely associated with the genesis and progression of ocular surface diseases(OSDs).This review focus on the role of m6A modification and research progress in OSDs including fungal keratitis,herpes simplex keratitis,immunerelated keratoconjunctival diseases,pterygium,ocular chemical burns,and Graves’ophthalmopathy,which may provide new insights into and prospective applications for OSDs.

Ocular surface microbiota in patients with varying degrees of dry eye severity

AIM:To elucidate the profiles of commensal bacteria on the ocular surfaces of patients with varying severity of dry eye(DE).METHODS:The single-center,prospective,case-control,observational study categorized all participants into three distinct groups:1)control group(n=61),2)mild DE group(n=56),and 3)moderate-to-severe DE group(n=82).Schirmer’s tear secretion strips were used,and the bacterial microbiota was analyzed using 16S ribosomal ribonucleic acid gene sequencing.RESULTS:The three groups had significant differences in alpha diversity:the control group had the highest richness(Chao1,Faith’s phylogenetic diversity),the mild DE group showed the highest diversity(Shannon,Simpson),and the moderate-to-severe DE group had the lowest of the above-mentioned indices.DE severity was positively correlated with a reduction in beta diversity of the microbial community,with the moderate-to-severe DE group exhibiting the lowest beta diversity.Linear discriminant analysis effect size presented distinct dominant taxa that significantly differed between each.Furthermore,the exacerbation of DE corresponded with the enrichment of certain pathogenic bacteria,as determined by random forest analysis.CONCLUSION:As DE severity worsens,microbial community diversity tends to decrease.DE development corresponds with changes in microbial constituents,primarily characterized by reduced microbial diversity and a more homogenous species composition.

A narrative review of ocular surface disease considerations in the management of glaucoma

s from those searches were screened for relevance to our review topics.Publications were included if the subjects included glaucoma patients,and if ocular surface outcomes were described.Non-English papers were excluded.Key Content and Findings:Topical glaucoma medications frequently cause adverse effects on the ocular surface,both through direct action of the medications themselves as well as through toxicity from their associated preservatives.Optimization of the ocular surface may improve medication compliance rates.Traditional surgical treatments for glaucoma,such as trabeculectomy,can exacerbate OSD by disrupting the ocular surface but can also reduce the need for chronic medications.Optimization of ocular surface health is imperative in reducing trabeculectomy complication rates,while also potentially reducing the need for trabeculectomy in patients that are able to achieve intraocular pressure control through improved drop tolerability.The introduction of MIGS represents a promising alternative to existing therapies and has been shown to alleviate the overall medication burden.It would be reasonable to assume that decreasing the medication burden could reduce OSD prevalence and severity.However,more research is needed to directly assess the extent of improvement seen after MIGS.Conclusions:A comprehensive understanding of the importance of OSD in medical and surgical management of glaucoma is essential in optimizing patient care and improving outcomes.

Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P 【0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P 【0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.

Effects of estrogen replacement therapy on apoptosis and vascular endothelial growth factor expression in ocular surface epithelial cells:An experimental study

AIM:To investigate the effects of estrogen replacement therapy (ERT) on apoptosis and vascular endothelial growth factor (VEGF) expression in ocular surface in an experimental rat model.· METHODS:Forty female,Wistar rats were randomized in 4 groups in the study.Subcutaneous ERT (17β-estradiol,10g/kg/day) was administered to the first group without ovariectomy and to the second group with ovariectomy for three months.Third group had only ovariectomy and fourth group had sham operation.All rats were sacrificed in estrous cycles determined by vaginal smear test and their right eyes were enucleated at the end of the third month.Enucleated eyes were analyzed by immunohistochemical method for expressions of caspase-3,bcl-2,VEGF and TUNEL assay.· RESULTS:Caspase-3 expression of conjunctival epithelium was significantly higher in group 3 than group 1 (P =0.005),and group 2 (P =0.007).TUNEL score of conjunctival epithelium was significantly higher in group 3 than group 1 (P =0.006).TUNEL score of corneal epithelium was significantly higher in group 3 than group 2 (P =0.012),and group 4 (P =0.002).There was no significant difference between groups in that bcl-2 and VEGF expressions.· CONCLUSION:We determined increased apoptosis in ocular surface epithelial cells in ovariectomized rats.ERT and endogen estrogen decreased the apoptosis,and did not result in difference in VEGF expression between the groups.Estrogen may be beneficial for the treatment of apoptosis-mediated ocular surface disorders such as dry eye.Further studies are needed on this subject for a better understanding of the role of estrogen and to provide a new insight for treatment and prevention of apoptosis-mediated ocular surface disorders.

Factors affecting recurrence after surgical treatment in cases with ocular surface squamous neoplasia

AIM: To evaluate the risk factors leading to recurrence in patients with ocular surface squamous neoplasia(OSSN)METHODS: The records of 112 patients with OSSN who underwent treatment and follow-up between February 1999 and August 2018 were reviewed retrospectively.RESULTS: Totally 67 patients(59.8%) were male and 45 patients(40.2%) were female. The mean age at presentation was 63.7 y(range 22-87 y). Partial lamellar scleroconjunctivectomy(PLSC) was performed in 105(93.7%) cases and enucleation was performed in 7(6.3%) cases due to bulbus invasion as the first step treatment. Treatments used in addition to PLSC included cryotherapy in 78 eyes(74.3%), alcohol epitheliectomy in 57 eyes(54.3%) for presence of corneal involvement, and amniotic membrane transplantation in 17 eyes(16.2%) for ocular surface reconstruction. Topical mitomycin C was used in 10 patients(9.5%) and strontium-90(Str-90) treatment in 4(3.8%) patients because surgical margins were tumor positive at the histopathological examination. Postoperative histopathologic diagnoses were squamous cell carcinoma(52 cases), carcinoma in situ(44 cases), moderate conjunctival intraepithelial neoplasia(11 cases), and mild conjunctiva intraepithelial neoplasia(5 cases). At a mean follow-up of 20.1 mo, tumor recurrence was observed in 21(18.8%) cases. The rate of recurrence was found to be lower in cases that underwent supplemental cryotherapy compared to those that did not(P<0.001). There was no metastasis in any case. CONCLUSION: In our series, the recurrence rate is 18.8% and overall globe salvage rate is 90.2% for OSSN at relatively short-term follow-up.

The expression and distribution of α-Gal gene in various species ocular surface tissue

AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue.METHODS: α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence.RESULTS: A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue.CONCLUSION: This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.

Correlation of the retinopathy degree with the change of ocular surface and corneal nerve in patients with type 2 diabetes mellitus

AIM:To investigate the change of ocular surface and corneal nerve and their correlation in patients suffering from type 2 diabetes mellitus under different degrees of retinopathy.METHODS:Totally 129 type 2 diabetes mellitus patients(257 eyes)were included.They were divided into three groups:no diabetic retinopathy(NDR)group(33 cases,66 eyes),non-proliferative diabetic retinopathy(NPDR)group(32 cases,64 eyes),and proliferative diabetic retinopathy(PDR)group(34 cases,67 eyes).Healthy normal individuals were enrolled as controls(30 cases,60 eyes).Ocular Surface Disease Index(OSDI)questionnaire was completed by all subjects,and dry eye analyzer was applied to examine tear meniscus height(TMH),first tear break-up time(FTBUT),average tear break-up time(ATBUT),tear film lipid layer thickness classification,and meibomian gland loss(MGL)score.Corneal nerve fiber density(CNFD),corneal nerve branch density(CNBD),corneal nerve fiber length(CNFL),and corneal nerve fiber tortuosity(CNFT)were examined by in vivo confocal microscopy(IVCM).The differences and correlation among these parameters were analyzed.RESULTS:Total OSDI score,TMH,FTBUT,ATBUT,tear film lipid layer thickness,MGL score,CNFD,CNBD,CNFL,and CNFT were statistically different among the four groups(P<0.05).In NDR group,CNFL was positively correlated with TMH(r=0.493,both P<0.01)and ATBUT(r=0.437,P<0.05).CNFL in NPDR group was positively correlated with TMH(r=0.642,P<0.01)and ATBUT(r=0.6,P<0.01).CNFL in PDR group was positively correlated with TMH(r=0.364,P<0.05)and ATBUT(r=0.589,P<0.01),with low negative correlation with MGL score(r=-0.331,P<0.05).CONCLUSION:With the progression of diabetic retinopathy,TMH,BUT,lipid layer thickness,CNFL,CNFD,and CNBD gradually decreased,while total OSDI score,MGL score,and CNFT increased.CNFL is correlated with TMH and ATBUT in diabetic patients.

Reliability of Chinese web-based ocular surface disease index questionnaire in dry eye patients:a randomized,crossover study

AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean age:27.90±9.06 y)with DED completed paper-and web-based versions of C-OSDI questionnaires in a randomized crossover design.Ophthalmology examination and DED diagnosis were performed prior to the participants being invited to join the study.Participants were randomly designated to either group A(paper-based first and webbased second)or group B(web-based first and paper-based second).Final data analysis included participants that had successfully completed both versions of the C-OSDI.Demographic characteristics,test-retest reliability,and agreement of individual items,subscales,and total score were evaluated with intraclass correlation coefficients(ICC),Spearman rank correlation,Wilcoxon test and Rasch analysis.RESULTS:Reliability indexes were adequate,Pearson correlation was greater than 0.8 and ICCs range was 0.827 to 0.982;total C-OSDI score was not statistically different between the two versions.The values of mean-squares fit statistics were very low compared to 1,indicating that the responses to the items by the model had a high degree of predictability.While comparing the favorability 72%(182/254)of the participants preferred web-based assessment.CONCLUSION:Web-based C-OSDI is reliable in assessing DED and correlation with the paper-based version is significant in all subscales and overall total score.Webbased C-OSDI can be administered to assess individuals with DED as participants predominantly favored online assessment.

The association between demodex infestation and ocular surface manifestations in meibomian gland dysfunction

AIM： To investigate the association between ocular demodex folliculorum infestation and ocular surface manifestations in meibomian gland dysfunction（MGD）.METHODS： Eight-six patients with MGD were enrolled. All enrolled subjects were tested in the following sequence： ocular surface disease index（OSDI）, slit-lamp biomicroscope examination, corneal surface regularity index（SRI） and surface asymmetry index（SAI）, tear fluid collection, fluorescein tear film break-up time（F-BUT）, corneal fluorescein staining（CFS）, Schirmer I test（SIT） and demodex folliculorum counting. Tear matrix metalloproteinase（MMP）-9 activity was assessed using MMP-9 activity assay kit.RESULTS： Among 86 MGD patients, 40 were positive for demodex. The ocular demodex-positive group showed significantly increased scores of OSDI（25.96±13.74 vs 18.07±11.55, P=0.01）, lid margin abnormality（2.38±0.87 vs 1.98±0.91, P=0.04） and CFS（1.28±2.00 vs 0.94±1.36, P=0.01） compared to the ocular demodex-free group. The tear MMP-9 activity was higher in the ocular demodex-positive group（102.9±32.4 ng/mL） than the ocular demodex-free group（46.2±19.2 ng/mL, P=0.03）. There was no significant difference in meibum quality and expressibility, SRI, SAI, F-BUT and SIT between the two groups（P〉0.05 for each）. No significant correlation was noted between the number of demodex and ocular surface parameters in demodexpositive MGD group（P〉0.05 for each）.CONCLUSION： Ocular demodex folliculorum infestation may be associated with ocular discomfort and ocular surface damage in MGD.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.

Early changes to dry eye and ocular surface after smallincision lenticule extraction for myopia

AIM： To investigate the early changes in dry eye symptoms, tear function and ocular surface following small-incision lenticule extraction（SMILE） for myopia.·METHODS： Ninety-seven consecutive patients（193 eyes）who underwent SMILE for myopia were observed in this longitudinal and retrospective study. Parameters evaluated included： subjective dry eye symptoms（dryness, foreign body sensation and photophobia）, tear film breakup time（TBUT）, Schirmer Ⅰ test without anesthesia（S Ⅰ T）, tear meniscus height（TMH） and corneal fluorescein staining. Each parameter was evaluated before, and subsequently at 1d, 1wk, 1 and3 mo after surgery.·RESULTS： Compared with preoperative data, dryness was noted to be significantly increased at 1wk and 1mo postoperatively（P 〈0.01）. Symptoms of photophobia and foreign body sensation demonstrated significant differences at 1d and 1wk as compared with preoperative scores respectively（P 〈0.01）. These values were decreased at 1 and 3mo post-surgery（P 〉0.05）.Conversely the corneal staining scores were higher than the preoperative data at 1d, 1wk and 1mo（P 〈0.01）, but were close to the preoperative level at 3mo postoperatively. There was a significant decrease in TMH at 1wk and 1mo（P 〈0.01）, but the value was close to the preoperative level at 3mo postoperatively（P =0.16）. The examination outcomes of S Ⅰ T were significantly increased at 1d then reduced at 1wk after surgery（P 〈0.01）. Each value subsequently returned to the baseline value at 1 and 3mo（P 〉0.05）. TBUT was significantly decreased at all postoperative time points（P 〈0.01）.· CONCLUSION： SMILE resulted in mild dry eye symptoms, tear film instability and ocular surface damages; however, these complications can recover in a short period of time.

Effects of perioperative managements on ocular surface microbiota in intravitreal injection patients

AIM:To investigate the effects of on ocular surface microbiota in patients who received intravitreal injections.METHODS:Samples of ocular surface microbiota were obtained from 41 eyes of 41 patients who visited the Department of Ophthalmology.Patients were separated for three groups.Group A did not receive perioperative managements or intravitreal injection.Group B1 received only once and B2 received more than twice.In operating room,the samples were collected on the ocular surface.Operating taxonomic units(OTUs) clustering and alpha/beta diversity analysis was performed.The microbial 16S rRNA from samples were analyzed using the Hi Seq 2500 platform.RESULTS:Alpha diversity did not differ in each group,and beta diversity differed in the B2 group.Beta diversity showed a significant difference between Group A and B2(P=0.048).With the perioperative managements before intravitreal injection,the composition and relative abundance were altered.Top 10 microbiota on phylum and genus level,and then microbiota notably changed at genus level were listed.Gram-negative bacteria were varied more.Furthermore,Proteus was not found in Groups A and B1,but it was appeared after the patients received perioperative management and intravitreal injections in Group B2.CONCLUSION:With the perioperative managements,the balance of microbiota on the ocular surface is destroyed,and relative composition and abundance of microbiota on the ocular surface is obviously altered.The clinical doctors should pay more attention on the consequence of perioperative managements before intravitreal injection.