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.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Simultaneous tectonic Descemet stripping endothelial keratoplasty and tectonic Bowman layer transplant for the management of corneal perforation

AIM:To report the outcomes of three cases of corneal perforation managed with simultaneous tectonic Descemet stripping endothelial keratoplasty(t-DSEK)and tectonic Bowman layer transplant(t-BLT)as an alternative to tectonic penetrating keratoplasty(t-PKP).METHODS:Three eyes of three patients receiving simultaneous t-DSEK and t-BLT for corneal perforation were included.The technique for DSEK was modified depending on individual requirements.The t-BLT technique was standardised using an 8 mm graft and fixated with a running suture.Success was measured by the ability of this procedure to close a corneal perforation.RESULTS:All three cases achieved tectonic eye globe restoration and remained stable during the minimum 3-month observation period.Reinterventions were relatively common:2 cases required amniotic membrane transplant for persistent epithelial defects.One case required DSEK rebubbling.One case developed angle closure glaucoma requiring surgical peripheral iridectomy.CONCLUSION:Simultaneous t-DSEK and t-BLT may be a useful strategy for the management of corneal perforation as an alternative management to t-PKP for selected cases.

Corneal neuromediator profiles following laser refractive surgery

Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

White-to-white corneal diameter: normal values in healthy Iranian population obtained with the Orbscan II

AIMTo determine the normative values of white-to-white corneal diameter with Orbscan II Topography System and to compare right and left eyes data in the normal young population.

Post photorefractive keratectomy corneal ectasia

Dear Editor,We write to describe two cases of corneal ectasia occurred after photorefractive keratectomy.Due to the wide diffusion of refractive surgery,many ophthalmologists attempted to identify the risk factors and prevention methods to avoid such severe complication of this technique.

Corneal epithelial defects following vitreoretinal surgery:incidence and outcomes from the DISCOVER study

AIM:To investigate the incidence,risk factors,clinical course,and outcomes of corneal epithelial defects(CED)following vitreoretinal surgery in a prospective study setting.METHODS:This was a post-hoc analysis of all participants in DISCOVER intraoperative optical coherence tomography study.Subjects with CED 1 d after surgery without intraoperative corneal debridement was defined as the postoperative CED group.Subjects who underwent intraoperative debridement were defined as intraoperative debridement group.Eyes were matched 2:1 with controls(eyes without postoperative CED)for comparative assessment.The primary outcomes were the incidence of CED on postoperative day one and the incidence of required intraoperative debridement.Secondary outcomes included time to defect closure,delayed healing(>2 wk),visual acuity(VA)and presence of scarring at one year and cornea consult.RESULTS:This study included 856 eyes that underwent vitreoretinal surgery.Intraoperative corneal debridement was performed to 61(7.1%)subjects and postoperative CED developed spontaneously in 94(11.0%)subjects.Significant factors associated with postoperative CED included prolonged surgical duration(P=0.003),diabetes mellitus(P=0.04),postoperative ocular hypotension(P<0.001).Prolonged surgical duration was associated with intraoperative debridement.Delayed defect closure time(>2 wk)was associated with corneal scar formation at the end of the 1 y in all epithelial defect subjects(P<0.001).The overall rate of corneal scarring for all eyes undergoing vitrectomy was 1.8%.CONCLUSION:Prolonged duration of surgery is the strongest factor associated with both intraoperative debridement and spontaneous postoperative CED.Delayed defect closure is associated with a greater risk of corneal scarring at one year.The overall rate of corneal scarring following vitrectomy is low at<2%.

Trans-epithelial accelerated corneal cross-linking for keratoconus in children

The aim of the study is to evaluate the safety and effi cacy of trans-epithelial accelerated corneal cross-linking（TE-ACXL） in children with progressive keratoconus.Retrospective,case-series of 23 eyes of 14 children who underwent TE-ACXL.Evaluations were performed at baseline and 1,3,6,12 and 18 mo postoperatively.Mean follow-up time of 23.82±3.15 mo and mean age was 13.7±1.4 y（range 11 to 16 y）.Mean preoperative uncorrected distance visual acuity changed from 0.92±0.45 log MAR（20/160） to 0.71±0.40 log MAR（20/100）（P=0.001）.Mean keratometry（Km） changed from 53.87± 6.03 to 53.00±5.81（P=0.001）.Pachymetry did not have significant changes at last follow-up（P=0.30）.The mean preoperative sphere was-5.58±2.48 and-4.89±4.66 D（P=0.11） at last follow-up;refractive cylinder from-5.58±2.48 to-5.02±2.23（P=0.046）.In conclusion,tomographic and refractive stability are shown in over 91% of eyes with pediatric progressive keratoconus who underwent TE-ACXL.

Bilateral retrocorneal hyaline scrolls secondary to asymptomatic congenital syphilis: A case report

BACKGROUND Retrocorneal hyaline scrolls are a rare phenomenon.We report a case of bilateral retrocorneal hyaline scrolls that were likely induced by asymptomatic congenital syphilis.CASE SUMMARY A 71-year-old woman presented with blurred vision due to cataracts.Slit-lamp microscopy revealed bilateral hyaline scrolls with a dichotomous branching pattern extending to the anterior chamber or rods attaching to the rough posterior surface of the cornea.The patient was positive for syphilis-specific antibodies,with no ocular or systemic evidence of congenital or acquired syphilis.Binocular cataract,retrocorneal scroll,and corneal endothelial gutta were considered.The scroll of the right eye was removed during cataract surgery and further observed using hematoxylin–eosin staining and scanning electron microscopy.The cornea of the right eye remained transparent,and the residual scroll seemed stable,however,the corneal endothelial density declined at 13 mo after surgery.In vivo confocal microscopy revealed coalescence of corneal guttae at the level of the corneal endothelium or adhesion to the posterior surface of the endothelium,with enlarged endothelial cells in both eyes.Activated keratocytes in the stroma and a highly reflective acellular structure at the level of the Descemet’s membrane were observed.The removed scroll had a cartilage-like hardness and a circularly arranged fiber-like acellular structure.CONCLUSION Occult congenital syphilis could induce corneal endothelial gutta and theformation of retrocorneal scrolls without other signs of ocular syphilis.

AB022.Biosynthetic implants for corneal regeneration in patients at high risk of rejecting donor transplantation

Background:Patients with inflammation or severe corneal pathology are often at high risk of rejecting the human donor corneas that they receive during transplantation.Our goal was to determine whether cell-free implants incorporating phosphorylcholine-based polymer,2-methacryloyloxyethyl phosphorylcholine(MPC),which has inflammation suppressing properties,can support repair and regeneration of ulcerated,high-risk corneas.Methods:Interpenetrating networks of recombinant human collagen and MPC(RHC-MPC)were fabricated into corneal implants in a certified and monitored cleanroom.An open-label,first-in-human observational study was conducted following ISO 14971 and 14155:2011,the Declaration of Helsinki and relevant laws of Ukraine and India,after respective ethical approval and trial registration.Seven unilaterally blind patients,aged 36 to 76 years old,diagnosed with conditions putting them at high risk of rejecting conventional corneal transplantation,and capable of providing informed written consent were grafted and followed up for an average of two years.However,RHC like native collagen is a large macromolecule and difficult to process and is non-customisable.Hence,small,customisable analogs to collagen comprising collagen-like peptides(CLP)conjugated to polyethylene glycol(PEG)were developed.These CLP-PEG analogs like RHC were combined with MPC into implants and tested in mini-pig models with alkali burned corneas,a high-risk condition.Results:One patient had an unrelated infection that necessitated re-grafting and was excluded from the study.The RHC-MPC implants in the remaining six patients were stably integrated throughout the entire observational period.There was regeneration of the cornea epithelium and stroma.Significant vision improvement was observed in in patients with damaged corneas due to infection.By two weeks post-operation,RHC-MPC implanted corneas of patients with active ulcers were free from the symptoms of pain,irritation and photophobia.Over the two-year follow-up period,sensitivity to touch improved,suggesting that the implants were able to promote nerve regeneration.The results seen in the clinical trial were reproduced in corneal grafts comprising MPC and the CLP-PEG collagen analog.Both CLP-PEG-MPC and control CLP-PEG only implants promoted regeneration of corneal epithelium,stroma and nerves.However,the alkali-burned corneas grafted with CLP-PEG-MPC implants retained the thickness of their healthy contralateral controls.Control corneas with CLP-PEG implants without the MPC however,were significantly thicker.Conclusions:These results demonstrate that collagen or its synthetic analog comprising CLP-PEG,can promote regeneration.The incorporation of MPC appears to suppress inflammation in pathologies that constitute conditions with a high-risk for graft rejection.Regeneration was able to occur in inflamed corneas as evidenced by CLP-PEG only grafts,but long-term follow-up is needed to determine if the chronic inflammation may influence graft failure over time.

Analysis of corneal nerve plexus in corneal confocal microscopy images

Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).

Effect of dexamethasone intravitreal implant in a corneal graft rejection

Dear Sir,I am Dr. Nilufer Yesilirmak, from the Department of Cornea, Bascom Palmer Eye Institute, Miami, Florida,USA. We wrote to report a reduction of graft rejection with dexamethasone intravitreal implant （Ozurdex ） in a case with aphakia.

Paediatric cornea crosslinking current strategies:A review

Background:In the general population,1 in 2000 people has keratoconus.Indians and other people from Southeast Asia have a higher incidence of keratoconus.Children with keratoconus typically present earlier in life and with a more severe disease.Rubbing the eyes has been identified as a risk factor.Children have a higher incidence and a faster rate of keratoconus progression.Visual rehabilitation in children with keratoconus is challenging.They have a low compliance with contact lens use.Many of these children require penetrating keratoplasty at an early age.Therefore,stopping the progression of keratoconus in children is of paramount importance.Main text:Compared to treatment,keratoconus progression prophylaxis is not only preferable,but also easier.Corneal collagen cross-linking has been shown to be safe and effective in stopping its progression in children.The Dresden protocol,which involves central corneal deepithelization(7-9 mm),saturation of the stroma with riboflavin(0.25%),and 30 min UV-A exposure,has proven to be the most successful.Two significant disadvantages of the typical Dresden regimen are the prolonged operating time and the significant post-operative pain.Accelerated-CXL(9 mW/cm^(2) x 10 min)has been studied to reduce operative time and has been shown to be equally effective in some studies.Compared to accelerated CXL or traditional CXL,epi-off procedures,transepithelial treatment without the need for de-epithelialization and without postoperative discomfort,have been shown to be safer but less effective.Corneal crosslinking should only be performed after treating children with active vernal keratoconjunctivitis.Corneal opacity,chronic corneal edema,sterile infiltrates,and microbial keratitis have been reported after cross-linking of corneal collagen.Conclusions:The"Dresden protocol",also known as the conventional corneal cross-linking approach,should be used to halt the progression of keratoconus in young patients.However,if the procedure needs to be completed more rapidly,accelerated corneal crosslinking may be considered.Transepithelial corneal cross-linking has been proven to be less effective at stabilizing keratoconus,although being more safer.

Cellular therapy of the corneal stroma: a new type of corneal surgery for keratoconus and corneal dystrophies

Cellular therapy of the corneal stroma,with either ocular or extraocular stem cells,has been gaining a lot of interest over the last decade.Multiple publications from different research groups are showing its potential benefits in relation to its capacity to improve or alleviate corneal scars,improve corneal transparency in metabolic diseases by enhancing the catabolism of the accumulated molecules,generate new organized collagen within the host stroma,and its immunosuppressive and immunomodulatory properties.Autologous extraocular stem cells do not require a healthy contralateral eye and they do not involve any ophthalmic procedures for their isolation.Mesenchymal stem cells have been the most widely assayed and have the best potential to differentiate into functional adult keratocytes in vivo and in vitro.While embryonic stem cells have been partially abandoned due to ethical implications,the discovery of the induced pluripotent stem cells(iPSC)has opened a new and very promising field for future research as they are pluripotent cells with the capacity to theoretically differentiate into any cell type,with the special advantage that they are obtained from adult differentiated cells.Cellular delivery into the corneal stroma has been experimentally assayed in vivo in multiple ways:systemic versus local injections with or without a carrier.Encouraging preliminary human clinical data is already available although still very limited,and further research is necessary in order to consolidate the clinical applications of this novel therapeutic line.

Artificial neural network to guide intracorneal ring segments implantation for keratoconus treatment:a pilot study

Background:To analyze the clinical results of an artificial neural network(ANN)that has been processed in order to improve the predictability of intracorneal ring segments(ICRS)implantation in keratoconus.Methods:This retrospective,comparative,nonrandomized,pilot,clinical study included a cohort of 20 keratoconic eyes implanted with intracorneal ring segments KeraRing(Mediphacos,Belo Horizonte,Brazil)using the ANN(ANN group)and 20 keratoconic eyes implanted with KeraRing using the manufacturer’s nomograms(nomogram group).Uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA)(visual acuity is expressed in decimal value and in LogMAR value in brackets),manifest refraction,corneal topography,tomography,aberrometry,pachymetry and volume analysis(Sirius System.CSO,Firenze,Italy)were performed during the preoperative visit;and the two groups,ANN group and nomogram group,did not differ significantly preoperatively in all of the parameters evaluated.These preoperative values were compared with the results obtained at the third-month visit.Mann-Whitney test and Wilcoxon test were used for the statistical analyses.Results:The spherical equivalent and the keratometric values decreased significantly in both groups.The CDVA improved from 0.60±0.23(0.22 LogMAR)pre-operatively to 0.73±0.21(0.14 LogMAR)post-operatively in the ANN group(p<0.005),and from 0.54±0.19(0.27 LogMAR)pre-operatively to 0.62±0.19(0.21 LogMAR)post-operatively in the nomogram group(p<0.01),with statistically significant difference between the two groups(p<0.05),being better in the ANN group.Coma-like aberrations decreased significantly in the ANN group,while in the nomogram group they did not change significantly,but no statistically significant difference was found between the two groups.Conclusions:ANN to guide ICRS provides an increase in the visual acuity,reduction in the spherical equivalent and improvement in the optical quality of keratoconus patients.ANN gives better results when compared with the manufacturer’s nomograms in terms of better corrected vision and reduction of the coma-like aberrations.The constant inclusion of new cases will make the predictability of ANN increasingly better as the software finetunes its learning.

Artificial neural network to guide intracorneal ring segments implantation for keratoconus treatment:a pilot study

Background:To analyze the clinical results of an artificial neural network(ANN)that has been processed in order to improve the predictability of intracorneal ring segments(ICRS)implantation in keratoconus.Methods:This retrospective,comparative,nonrandomized,pilot,clinical study included a cohort of 20 keratoconic eyes implanted with intracorneal ring segments KeraRing(Mediphacos,Belo Horizonte,Brazil)using the ANN(ANN group)and 20 keratoconic eyes implanted with KeraRing using the manufacturer's nomograms(nomogram group).Uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA)(visual acuity is expressed in decimal value and in logMAR value in brackets),manifest refraction,corneal topography,tomography,aberrometry,pachymetry and volume analysis(Sirius System,CSO,Firenze,Italy)were performed during the preoperative visit;and the two groups,ANN group and nomogram group,did not differ significantly preoperatively in all of the parameters evaluated.These preoperative values were compared with the results obtained at the third-month visit.Mann-Whitney test and Wilcox on test were used for the statistical analyses.Results:The spherical equivalent and the keratometric values decreased significantly in both groups.The CDVA improved from 0.60±0.23(0.22 logMAR)preoperatively to 0.73±0.21(0.14 logMAR)postoperatively in the ANN group(P<0.005),and from 0.54±0.19(0.27 logMAR)preoperatively to 0.62±0.19(0.21 logMAR)postoperatively in the nomogram group(P<0.01),with statistically significant difference between the two groups(P<0.05),being better in the ANN group.Coma-like aberrations decreased significantly in the ANN group,while in the nomogram group they did not change significantly,but no statistically significant difference was found between the two groups.Con elusions:ANN to guide ICRS provides an increase in the visual acuity,reduction in the spherical equivalent and improvement in the optical quality of keratoconus patients.ANN gives better results when compared with the manu facturer's no mograms in terms of better corrected vision and reduction of the coma-like aberrations.The constant inclusion of new cases will make the predictability of ANN increasingly better as the software finetunes its learning.

Corneal surgery in keratoconus: which type, which technique, which outcomes?

Keratoconus is a disease characterized by progressive thinning,bulging,and distortion of the cornea.Advanced cases usually present with loss of vision due to high irregular astigmatism.A majority of these cases require surgical intervention.This review provides an update on the current treatment modalities of corneal surgery available for the management of advanced corneal ectasias.

单眼低度近视儿童双眼黄斑区视网膜和脉络膜血流密度分析

目的使用眼底相干光层析血管成像术(OCTA)测量单眼低度近视儿童双眼黄斑区视网膜、脉络膜血流密度,并探讨其临床意义。方法采用横断面研究,收集2022年6月至2023年2月大连市第三人民医院眼科门诊就诊的8~14岁单眼低度近视儿童45例(90眼)临床资料。经1%环喷托酯睫状肌麻痹后验光,将等效球镜度(SE)-3.00 D~-0.50 D纳入近视眼组,SE+0.25 D~<+2.00 D纳入非近视眼组。使用IOL Master 500测量眼轴(AL)、平均角膜曲率半径(CR),计算轴率比(AL/CR)。使用海德堡SD-OCT进行黄斑区水平线性扫描并获取中心凹下脉络膜厚度(SFCT)值。使用OCTA模块获取3 mm×3 mm的视网膜脉络膜血流图像,通过Image J图形处理软件获取浅层视网膜血管丛(SCP)血流密度、深层视网膜血管丛(DCP)血流密度、脉络膜毛细血管层(CC)血流密度及中心凹无血管区(FAZ)面积。采用Pearson相关分析各血流指标与年龄、AL、CR、AL/CR、SFCT的相关性。结果近视眼组SE和SFCT均小于未近视眼组,而AL和AL/CR均大于未近视眼组,差异均有统计学意义(均P<0.05)。近视眼组DCP血流密度小于非近视眼组,差异有统计学意义(P<0.01);其他血流指标2组比较无统计学差异(均P>0.05)。Pearson相关分析结果显示,近视眼组SCP、DCP血流密度与SE呈正相关(r分别为0.611、0.731,均P<0.05);与AL呈负相关(r分别为-0.568、-0.712,均P<0.05);与AL/CR呈负相关(r分别为-0.557、-0.564,均P<0.05)。非近视眼组SCP、DCP血流密度与AL/CR呈负相关(r分别为-0.615、-0.656,均P<0.05)。2组CC血流密度、FAZ面积与年龄、SE、AL、CR、AL/CR、SFCT无相关性(均P>0.05)。结论单眼低度近视儿童近视眼与非近视眼比较,DCP血流密度降低;近视眼视网膜血流密度与SE、AL、AL/CR相关,非近视眼视网膜血流密度仅与AL/CR相关。

The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)of<15 in the lower eyelid of each eye,and non-invasive tear break-up time(NI-TBUT)<10s,who were randomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with P<0.001.Multivariate analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,NIBUT,and OSDI.There was a significant difference between ILux®and MMGE(P<0.001)at follow-up from the first to the twelfth month in MGS,NI-BUT,and OSDI scores.No adverse events were reported.CONCLUSION:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.