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.

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.

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.

Research advances in pathogenic mechanisms underlying air pollution-induced ocular surface diseases

Background:The harmful effect of aerial fine particulate matter(PM_(2.5))has been a serious public health issue and has attracted worldwide attention,especially in developing countries.Main Text:Numerous previous clinical and experimental studies have demonstrated that PM_(2.5) has a clear pathogenic effect on diseases related to the respiratory and cardiovascular systems.Recent researches have pointed out that PM_(2.5) plays a pivotal role in the occurrence and progression of ocular surface diseases.The current studies have shown that PM_(2.5) may promote the appearance of conjunctivitis,keratitis,blepharitis,dry eye,meibomian gland dysfunction(MGD)and other ocular surface diseases through regulating a series of mechanisms such as inflammation,immune reaction,oxidative stress,autophagy,cell migration,and epigenetics.Conclusions:This review aims to summarize the current research progress on the pathogenic mechanism of PM_(2.5)-related ocular surface diseases.

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.

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.

Changes in Tear-Film Status and Ocular Surface Disease Index Score Following Prolonged Use of Face Mask

Background: Dry eye is characterized by tear film instability, decreased tear volume and a high Ocular Surface Disease Index (OSDI) score. Face masks have been linked to dry eye complaints in recent studies. Purpose: To evaluate the changes in tear-film status and Ocular Surface Disease Index (OSDI) score following prolonged use of face mask. Design: Cross-sectional study. Method: Patients between 18 to 70 years using masks regularly for at least 2 hours/day for at least 5 days/week from different eye-care centres in Dhaka were included. All subjects were divided into 4 groups. Mask use lasted approximately 2 hours/day in Group 1, 4 hours/day in Group 2, 6 hours/day in Group 3 and 8 hours or more/day in Group 4. Evaluation of symptoms, tear- film stability and tear volume was done by Ocular Surface Disease Index (OSDI) scores, Tear-film Break-Up Time (TBUT) and Schirmer-1 test. Average of right & left eye’s Tear-film Break Up time (TBUT) and Schirmer-1 value were noted. Results: Total 100 patients were enrolled (n = 100). The TBUT (p < 0.001) and Schirmer-1 measurement (p = 0.01) were significantly lesser and Ocular Surface Disease Index (OSDI) score were significantly higher in patients using face-masks for longer time (p < 0.001). Conclusion: Patients who wore masks for prolonged time had tear film instability, reduced tear volume and higher Ocular Surface Disease Index (OSDI) score.

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM:To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life(QOL)in patients after allogeneic hematopoietic stem cell transplantation(ALLO-HSCT).METHODS:Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020.They completed two questionnaires:the Ocular Surface Disease Index(OSDI)and the quality-of-life scale for Chinese patients with visual impairment(SQOL-DV1).Ocular conditions and systemic conditions were also assessed.RESULTS:Eye damage was correlated with total bilirubin(P=0.005),and gamma-glutamyl transferase(GGT)(P=0.021).There was no significant correlation between the overall QOL score and OSDI(P=0.8226)or SQOLDV1(P=0.9526)scores.The OSDI and the overall QOL score were not correlated with ocular conditions,including best-corrected visual acuity(BCVA),intraocular pressure,Schirmer tear test II,sodium fluorescein staining,tear film breakup time,and tear meniscus height.SQOLDV1 was correlated with BCVA(P=0.0007),sodium fluorescein staining(P=0.007),and tear film breakup time(P=0.0146).CONCLUSION:In some patients,early ocular symptoms are not evident after ALLO-HSCT,while ocular surface complications can be observed after a comprehensive ophthalmological examination.Especially for those with elevated total bilirubin or GGT,regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease(o GVHD),especially for patients with elevated total bilirubin or GGT.

Eye reflux:an ocular extraesophageal manifestation of gastric reflux

AIM： To suspect laryngopharyngeal reflux（LPR） in patients with ocular surface disease（OSD）. METHODS： The present study evaluated a group of subjects with OSD assessing the Ocular Surface Disease Index（OSDI） and the Reflux Symptom Index（RSI） to detect patients with suspected LPR and define a possible relationship between tests.RESULTS： Two hundred and ninety subjects（175 females, mean age： 60.41±15.68y） were consecutively visited at ophthalmologist offices. One hundred and one（34%） patients had pathological RSI（〉13） and consequently a suspected LPR.CONCLUSION： The current study shows that suspected LPR may be common（34%） in patients with OSD and a suspected LPR may be considered in OSD patients when RSI score is 〉13 and OSDI score is 〉42.

Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid

AIM： To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy（IVCM） in patients with ocular cicatricial pemphigoid（OCP）.· METHODS： A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence（DIF） biopsies and indirect immunofluorescence（IIF） were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response.·RESULTS： A total of 12 consecutive OCP patients（7male, 5 female; mean age 60.42 ±10.39y） were recruited.All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95 ±2.85y（range： 5mo to 10y）. The Foster classification varied from stage I to IV and 20 eyes（83%） were within or greater than Foster stage Ⅲ on presentation. Two of the 12patients（17%） demonstrated positive DIF; 3 of the 12（25%） patients reported positive IIF. The mean duration of the follow-up period was 20.17 ±11.88mo（range： 6 to48mo）. IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented asocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes（75%） remained stable, 6 eyes（25%） had recurrent conjunctivitis and cicatrization in 2 eyes（8%） was progressing.· CONCLUSION： As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up.

Inflammation and dry eye disease——where are we?

The presence of inflammation in dry eye disease(DED)results in increased patient symptomatology,ocular surface damage and worsening tear dysfunction.It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease.This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED,inflammation and meibomian gland dysfunction(MGD).The clinical evaluation of eyes with such changes,markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

Cryopreserved limbal lamellar keratoplasty for peripheral corneal and limbal reconstruction

This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty（CLLK） for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean age of 41±23.9 y were included. The average follow-up was 12.1±5.6 mo. Stable ocular surface was achieved in all eyes at last follow-up. Epithelialization originated from both recipient and graft in 9 eyes. We conclude that CLLK compensates for the shortage of donor corneas and cryopreserved limbal grafts provide epithelialization sources in ocular surface reconstruction.

Topographic tear film trend and new parameters for noninvasive break up time test

AIM:To evaluate the quantitative and qualitative results of the noninvasive tear film break-up time(NI-BUT)test and investigate the predictive ability of the new NIBUT parameter in discriminating between normal Ocular Surface Disease Index(OSDI;scores≤12)and abnormal OSDI(scores≥13).METHODS:A total of 341 eyes of 341 volunteers who applied for routine eye outpatient control were included in the prospective study.All participants'noninvasive first tear film break-up time(NIF-BUT),noninvasive average tear film break-up time(NIAvg-BUT)and average value of the first three break-up time(A3F-BUT)were analyzed.A3F-BUT,the new NI-BUT parameter,is calculated by adding the NIF-BUT value to the 2^(nd )break-up time value that has a difference of at most 1 second from the NIF-BUT value and to the 3^(rd) break-up time and then dividing the respective sum by 3.Receiver operating characteristic(ROC)curve and forward logistic regression analyses were performed to determine the parameter that had the best predictive ability between the OSDI groups.RESULTS:The NI-BUT values of 255 eyes of 255 volunteers included in the study were analyzed statistically.The mean NIF-BUT,NIAvg-BUT,and A3F-BUT values were calculated as 5.3±3.0,8±3.1,and 5.8±3.0 seconds,respectively.All three parameters were found to be significantly lower in the abnormal OSDI group(P=0.014,0.034,and 0.011,respectively).The area under the curve(AUC)of the A3F-BUT to predict abnormal OSDI was AUC=0.625(0.529-0.720),P=0.011 and NIF-BUT was AUC=0.599(0.502-0.696),P=0.043.The A3F-BUT parameter and NIF-BUT parameters were found to be significantly efficient in discriminating abnormal OSDI.CONCLUSION:The new parameter for the NI-BUT test has more predictive ability in the discrimination of OSDI groups.

Pterygium associated with light-emitting diode use:a case report

Background:Pterygium is a sun-related ocular surface disease secondary to ultraviolet(UV)radiation exposure.Outdoor occupational UV exposure is known to occur secondary to sun exposure.We present a unique case of pterygium associated with indoor occupational light-emitting diode(LED)exposure not previously described in the literature.Case Description:A mobile phone repairer presented with blurred vision and a superotemporal pterygium of his dominant left eye associated with a magnifying glass LED work lamp was diagnosed.This was excised routinely with conjunctival autografting to the defect.Histopathology confirmed benign pterygium and recovery was uncomplicated with resolution of blur.Conclusions:The development of pterygium in our patient may have arisen due to the LED lamp’s wavelengths possibly falling within the UV as well as the upper end of the visible light radiation spectrum.Given the increasing reliance on LED light sources in modern life,ocular conditions arising from exposure to these radiation sources may now need to be listed in the differential diagnoses of patients with pterygium.Appropriate UV protection counselling for these types of lights may also now need to be considered.