Cellular structural and functional imaging of donor and pathological corneas with label-free dual-mode full-field optical coherence tomography.

In this study, a dual-mode full-field optical coherence tomography (FFOCT) was customized for label-free static and dynamic imaging of corneal tissues, including donor grafts and pathological specimens. Static images effectively depict relatively stable structures such as stroma, scar, and nerve fibers, while dynamic images highlight cells with active intracellular metabolism, specifically for corneal epithelial cells. The dual-mode images complementarily demonstrate the 3D microstructural features of the cornea and limbus. Dual-modal imaging reveals morphological and functional changes in corneal epithelial cells without labeling, indicating cellular apoptosis, swelling, deformation, dynamic signal alterations, and distinctive features of inflammatory cells in keratoconus and corneal leukoplakia. These findings propose dual-mode FFOCT as a promising technique for cellular-level cornea and limbus imaging.

Photocurable and Temperature-Sensitive Bioadhesive Hydrogels for Sutureless Sealing of Full-Thickness Corneal Wounds.

Penetrating corneal wounds can cause severe vision impairment and require prompt intervention to restore globe integrity and minimize the risk of infection. Tissue adhesives have emerged as a promising alternative to suturing for mitigating postoperative complications. However, conventional water-soluble adhesives suffer formidable challenges in sealing penetrating corneal wounds due to dilution or loss in a moist environment. Inspired by the robust adhesion of mussels in aquatic conditions, an injectable photocurable bioadhesive hydrogel (referred to as F20HD5) composed of polyether F127 diacrylate and dopamine-modified hyaluronic acid methacrylate is developed for sutureless closure of corneal full-thickness wounds. F20HD5 exhibits high transparency, wound-sealing ability, proper viscosity, biodegradability, and excellent biocompatibility. It allows in situ cross-linking via visible light, thereby providing sufficient mechanical strength and adhesiveness. In vivo, the adhesive hydrogel effectively closed penetrating linear corneal incisions and corneal injuries with minimal tissue loss in rabbits. During the 56-day follow-up, the hydrogel facilitates the repair of the injured corneas, resulting in more symmetrical curvatures and less scarring in distinction to the untreated control. Thus, bioinspired hydrogel holds promise as an effective adhesive for sealing full-thickness corneal wounds.

A Structure-Aware Convolutional Neural Network for Automatic Diagnosis of Fungal Keratitis with In Vivo Confocal Microscopy Images.

Fungal keratitis (FK) is a common and severe corneal disease, which is widely spread in tropical and subtropical areas. Early diagnosis and treatment are vital for patients, with confocal microscopy cornea imaging being one of the most effective methods for the diagnosis of FK. However, most cases are currently diagnosed by the subjective judgment of ophthalmologists, which is time-consuming and heavily depends on the experience of the ophthalmologists. In this paper, we introduce a novel structure-aware automatic diagnosis algorithm based on deep convolutional neural networks for the accurate diagnosis of FK. Specifically, a two-stream convolutional network is deployed, combining GoogLeNet and VGGNet, which are two commonly used networks in computer vision architectures. The main stream is used for feature extraction of the input image, while the auxiliary stream is used for feature discrimination and enhancement of the hyphae structure. Then, the features are combined by concatenating the channel dimension to obtain the final output, i.e., normal or abnormal. The results showed that the proposed method achieved accuracy, sensitivity, and specificity of 97.73%, 97.02%, and 98.54%, respectively. These results suggest that the proposed neural network could be a promising computer-aided FK diagnosis solution.

Dual-crosslinked regenerative hydrogel for sutureless long-term repair of corneal defect.

Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.

Mechanoresponsive Drug Loading System with Tunable Host-Guest Interactions for Ocular Disease Treatment.

Conventional administration of eye drops often requires high dosages and/or repetitive treatments to achieve therapeutic efficacy. This is inefficient and may result in side effects or even toxicity. Although many delivery systems of ophthalmic drugs have been reported, most of them work in a fixed format in which both the type and dose of the loaded drugs cannot be changed upon demand. To overcome this limitation, a hybrid double network hydrogel system composed of methacryloyl gelatin, pluronic F127 diacrylate, and ß-cyclodextrin-modified oxidized dextran was developed. The hydrogels presented good mechanical strength and biocompatibility. In vitro assessments demonstrated that the hydrogels loaded with commonly used ophthalmic drugs could sustain the drug release for more than 21 days. This hydrogel system exhibited features of mechanoresponsive drug loading, and the capacity of drug loading could be significantly enhanced by macroscopically mechanical compression. Further in vivo evaluation of the drug delivery capacity showed that a dexamethasone-loaded hydrogel as a fornix insert effectively suppressed upregulation of proangiogenic factors and suture-induced corneal neovascularization in rats. This novel hydrogel system represents a promising drug delivery platform, which could potentially improve the treatments of ocular surface and other diseases.

Transcriptomic Profiling of Electroacupuncture Regulating the Molecular Network in Hippocampus of Rats with Cerebral Ischemia-Reperfusion Injury.

Objective: To explore the mechanism of electroacupuncture stimulation of the hand-taiyin meridian in regulating the molecular network of rats with cerebral ischemia-reperfusion injury based on transcriptomics. Methods: Male SD rats were randomly divided into sham operation group, model group, and electroacupuncture (EA) group. Middle cerebral artery embolization/reperfusion injury (MCAO/R) was used to establish the model group and EA group. The sham operation group only performed sham operation without modeling and any intervention, and the model group was bound daily. The EA group received electroacupuncture to stimulate the acupoints of hand-taiyin meridian for 14 days. Then, neurological scores, pathomorphological observations, and Tunel staining were performed. Finally, the affected hippocampus of the rat was used for transcriptome sequencing and RT-PCR detection. Results: After electroacupuncture intervention in rats, neurological function scores were improved, and neuronal apoptosis was reduced. The results of transcriptomics showed that a total of 1097 differentially expressed genes were obtained, of which 422 were upregulated and 675 were downregulated. The bioinformatics analysis showed that those differentially expressed genes were related to axon development, neuron projection development, neuron projection morphogenesis, plasma membrane cell projection morphogenesis, cell part morphogenesis, notch signaling pathway, long-term potentiation, MAPK signaling pathway, Hedgehog signaling pathway, and so on. The results of RT-PCR showed that Caspase 9 mRNA increased and BDNF, Grin2a, and PlexinD1 mRNA decreased after electroacupuncture intervention (P < 0.05). Conclusion: Electroacupuncture intervention on hand-taiyin meridian may reduce neurological function scores, inhibit neuron apoptosis, and enhance neuronal repair neuroreparation in MCAO/R rats, which may be related to the regulation of genes such as Caspase 9, BDNF, Grin2a, and PlexinD1.

[A case of Stevens-Johnson syndrome with binocular corneal perforation and multiple corneal transplantation which was difficult to control].

The 31-year-old female patient was admitted to the General Hospital of the Chinese People's Liberation Army for 3 days after the corneal transplantation of her right eye for 5 months.Four years ago, the patient developed red eyes, pain, dryness and photophobia after intravenous drip of cefuroxime sodium and metronidazole due to pelvic inflammation, accompanied by high fever, systemic rash and epidermal exfoliation, fingernail peeling, and mucosal ulceration in the eyes and mouth.Later, the patient received systemic hormone shock and point eye treatment in a local hospital, and the dry eyes gradually worsened. Despite continuous artificial tears and bandage mirror treatment, the corneal ulcer perforation in both eyes still occurred successively. After several penetrating keratografts and drug therapy, the ulcer and dissolution could not be prevented. He was admitted to our hospital due to corneal perforation in both eyes.Ophthalmic examination: visual acuity manual/15 cm in the right eye, intraocular pressure T-2, conjunctival sac stenosis, extensive corneal opacity and edema, ulcer about 8 mm, corneal perforation near the corneal limbus about 2 mm×5 mm below.The left eye had no light perception, a central corneal ulcer of about 8 mm, bulge of the posterior elastic layer, no anterior chamber, and atrophy of the eyeball.B-ultrasound showed choroidal detachment of the right eye.On the second day, the patient received right eye intraocular exploration, vitrectomy, ecotopic keratoscleral carrier Boston Ⅱ artificial keratoplasty, glaucoma valve implantation, autogenous ear cartilage implantation, conjunctival occlusion, and left eye lamellar keratoplasty, conjunctival occlusion.Postoperative visual acuity of right eye was -6.50 DS=0.12, intraocular pressure TN, ocular surface was stable.The left eye has no light perception and the ocular surface is stable.

Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty.

Keratoplasty is the gold standard treatment for visual impairment caused by corneal damage. The use of suturing as the bonding method is the source of many complications following keratoplasty. Currently available corneal adhesives do not have both adequate adhesive strength and acceptable biocompatibility. Herein, we developed a photocurable bioadhesive hydrogel which was composed of gelatin methacryloyl and oxidized dextran for sutureless keratoplasty. The bioadhesive hydrogel exhibited high light transmittance, resistance to enzymatic degradation and excellent biocompatibility. It also had higher adhesive strength than commercial adhesives (fibrin glue). In a rabbit model of lamellar keratoplasty, donor corneal grafts could be closely bonded to the recipient corneal bed and remained attached for 56 days by using of this in situ photopolymerized bioadhesive hydrogel. The operated cornea maintained transparent and noninflamed. Sutureless keratoplasty using bioadhesive hydrogel allowed rapid graft re-epithelialization, typically within 7 days. In vivo confocal microscopic and histological evaluation of the operated cornea did not show any apparent abnormalities in terms of corneal cells and ultrastructure. Thus, this bioadhesive hydrogel is exhibited to be an appealing alternative to sutures for keratoplasty and other corneal surgeries.

Changes in Anterior and Posterior Corneal Elevation in Patients With Allergic Conjunctivitis.

Purpose: To evaluate corneal elevation changes in patients with allergic conjunctivitis (AC) and to analyze their correlations with ocular allergy signs and corneal biomechanical alterations. Methods: Thirty patients (30 eyes) with AC and twenty normal subjects (20 eyes) were included in this prospective study. All participants underwent a complete ocular examination, including corneal tomography by Pentacam and corneal biomechanics evaluation by Corvis ST. AC patients were evaluated for their eye rubbing frequency and ocular allergic signs. Results: The elevation at the thinnest location (TE) and the central location (CE), the elevation difference at the thinnest location (TED) and the central location (CED), and the mean value of elevation difference in the central 4 mm zoom (MED) of both the anterior and posterior corneal surface were significantly higher in the AC group than in the normal group (p < 0.05 for all). In AC patients, only anterior corneal elevation parameters were positively correlated with eye rubbing frequency and ocular allergy sign severity (p < 0.05 for all), while the tomography and biomechanical index (TBI) was positively correlated with the elevation parameters of both the anterior and posterior corneal surfaces (p < 0.05 for all). Conclusion: AC patients carry an increased risk of corneal ectasia. Posterior corneal elevation parameters are sensitive and reliable predictors of keratoconus (KC) risk in AC patients. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04299399, identifier [NCT04299399].

Herpetic Keratitis Preceded by COVID-19 Vaccination.

The global Coronavirus Disease 2019 (COVID-19) pandemic has accelerated vaccine development at an unprecedented rate. A large population of people have received COVID-19 vaccines, while the vaccine safety data are limited. Here, we reported two cases of herpetic keratitis that occurred soon after receiving the inactivated COVID-19 vaccines. Case 1 was a 60-year-old woman who underwent penetrating keratoplasty (PKP) one year ago for corneal scarring caused by herpes simplex keratitis (HSK), and case 2 was a 51-year-old man with an unremarkable medical history. Both patients developed herpetic keratitis (HSK and varicella-zoster virus corneal endotheliitis, respectively) soon after receiving the inactivated COVID-19 vaccines (Sinovac). Herpetic keratitis was treated successfully with topical or plus oral antiviral ganciclovir. The short latency time in these two cases suggested that an inactivated COVID-19 vaccine may have a risk of triggering ocular herpes virus reactivation. Both clinicians and patients should be aware of this phenomenon. However, a causal relationship awaits confirmation.

Quantitative analysis of morphological and functional features in Meibography for Meibomian Gland Dysfunction: Diagnosis and Grading.

BACKGROUND: To explore the performance of quantitative morphological and functional analysis in meibography images by an automatic meibomian glands (MGs) analyser in diagnosis and grading Meibomian Gland Dysfunction (MGD). METHODS: A cross-sectional study collected 256 subjects with symptoms related to dry eye and 56 healthy volunteers who underwent complete ocular surface examination was conducted between January 1, 2019, and December 31, 2020. The 256 symptomatic subjects were classified into MGD group (n = 195) and symptomatic non-MGD group (n = 61). An automatic MGs analyser was used to obtained multi-parametric measurements in meibography images including the MGs area ratio (GA), MGs diameter deformation index (DI), MGs tortuosity index (TI), and MGs signal index (SI). Adjusted odds ratios (ORs) of the multi-parametric measurements of MGs for MGD, and the area under the receiver operating characteristic (AUC-ROC) curves of multi-parametric measurements for MGD diagnosing and grading were conducted. FINDINGS: When consider age, sex, ocular surface condition together, the estimated ORs for DI was 1.62 (95% CI, 1.29-2.56), low-level SI was 24.34 (95% CI, 2.73-217.3), TI was 0.76(95% CI, 0.54-0.90), and GA was 0.86 (95% CI, 0.74-0.92) for MGD. The combination of DI-TI-GA-SI showed an AUC = 0.82 (P < 0.001) for discriminating MGD from symptomatic subjects. The DI had a higher AUC in identifying early-stage MGD (grade 1-2), while TI and GA had higher AUCs in moderate and advanced stages (grade 3-5). Merging DI-TI-GA showed the highest AUCs in distinguish MGD severities. INTERPRETATION: The MGs area ratio, diameter deformation, tortuosity and signal intensity could be considered promising biomarkers for MGD diagnosis and objective grading. FUNDING: This work was supported by the Key-Area Research and Development Program of Guangdong Province (No. 2019B010152001), the National Natural Science Foundation of China under Grant (81901788) and Guangzhou Science and Technology Program (202002030412).

Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding.

Asymmetric neuronal expansion is thought to drive evolutionary transitions between lissencephalic and gyrencephalic cerebral cortices. We report that Neurog2 and Ascl1 proneural genes together sustain neurogenic continuity and lissencephaly in rodent cortices. Using transgenic reporter mice and human cerebral organoids, we found that Neurog2 and Ascl1 expression defines a continuum of four lineage-biased neural progenitor cell (NPC) pools. Double+ NPCs, at the hierarchical apex, are least lineage restricted due to Neurog2-Ascl1 cross-repression and display unique features of multipotency (more open chromatin, complex gene regulatory network, G2 pausing). Strikingly, selectively eliminating double+ NPCs by crossing Neurog2-Ascl1 split-Cre mice with diphtheria toxin-dependent "deleter" strains locally disrupts Notch signaling, perturbs neurogenic symmetry, and triggers cortical folding. In support of our discovery that double+ NPCs are Notch-ligand-expressing "niche" cells that control neurogenic periodicity and cortical folding, NEUROG2, ASCL1, and HES1 transcript distribution is modular (adjacent high/low zones) in gyrencephalic macaque cortices, prefiguring future folds.

Corneal biomechanical changes in allergic conjunctivitis.

BACKGROUND: To explore corneal biomechanical changes, identify related factors and determine early indicators of keratoconus (KC) development risk in allergic conjunctivitis (AC) patients. METHODS: A total of 50 patients, including 20 eyes without AC and 30 eyes with AC were enrolled in this study. All patients underwent a complete ocular examination, including evaluations of clinical manifestations of AC, corneal tomography and densitometry by Pentacam, corneal biomechanics by Corvis ST, and corneal and epithelial thickness mapping by RTvue optical coherence tomography (OCT). RESULTS: The index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), index of height decentration (IHD) and Belin/Ambrosio enhanced ectasia total deviation index (BAD-D) were significantly higher in the AC group than in the non-allergic conjunctivitis (NAC) group (P < 0.05). The tomography and biomechanical index (TBI) was also significantly higher in the AC group (P = 0.04). The average epithelial thickness in the 2-7 mm annulus was significantly thinner in the AC group than in the NAC group (P < 0.05). The average densitometry of the total cornea and the anterior layer were higher in the AC group than in the NAC group (P < 0.001). The ISV, IVA, KI, IHD and BAD-D were significantly correlated with the TBI and changes in corneal epithelial thickness in AC patients (P < 0.05). The changes in epithelial thickness were closely related to the eye rubbing frequency and allergic sign scores (P < 0.05). CONCLUSIONS: AC patients should be advised to routinely undergo corneal tomographic and biomechanical measurements, and the TBI could be used as an indicator of KC development risk in AC patients. TRIAL REGISTRATION: Corneal Biomechanical Changes of Allergic Conjunctivitis, NCT04299399 . Registered March 3, 2020 - Retrospectively registered.

Meridian-Specific and Post-Optical Deficits of Spatial Vision in Human Astigmatism: Evidences From Psycho-Physical and EEG Scalings.

Previous studies have demonstrated that orientation-specific deprivation in early life can lead to neural deficits of spatial vision in certain space, and can even result in meridional amblyopia (MA). Individuals with astigmatism are the optimal and natural models for exploring this asymmetric development of spatial vision in the human visual system. This study aims to assess the contrast sensitivity function (CSF) and EEG signals along two principal meridians in participants with regular astigmatism when being optimal optical corrected. Twelve participants with astigmatism (AST group, 20 eyes) and thirteen participants with (MA group, 19 eyes) were recruited in the current study. CSFs and spatial sweep visual evoked potentials (sVEP) were measured with vertical and horizontal sinewave gratings along two principal meridians monocularly. Area under log CSF (AULCSF), spatial frequency threshold corresponding to 80% contrast gratings (SF threshold at 80% ctr), and CSF acuity were calculated from CSF test. In addition, sVEP amplitudes and thresholds were calculated with the recursive least square method. Participants with astigmatism exhibited marked vertical-horizontal resolution disparities even after they were corrected with optimal optical corrections. CSF tests showed that AULCSF along weak meridian (measured with horizontal gratings) was lower than that along strong meridian (measured with vertical gratings) in both groups. Significant meridional disparity of CSF acuity was also found in both groups. In addition, the MA group showed larger meridional disparity compared to the AST group. Spatial sVEP thresholds also supported the existence of marked meridional disparity. Our results suggest that meridian-specific partial deprivation in early life might lead to monocularly asymmetric development of spatial vision in the human visual system. In terms of application, we tested the feasibility and reliability of adopting psychophysical and EEG scalings to investigate the asymmetric development of spatial vision related to astigmatism. These paradigms are potentially applicable to reduce and even eliminate the meridional disparity in the primary visual cortex by adopting perceptual learning or other vision-related interventions.

Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye.

This study aimed to investigate the protective effect of melatonin on the corneal epithelium in dry eye disease(DED) and explore its underlying mechanism. Human corneal epithelial(HCE) cells was exposure to t-butylhydroperoxide(tBH), C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Melatonin was used both in vivo and in vitro. Cell viability was detected by Cell Counting Kit-8 assay and Lactate Dehydrogenase Leakage. The change of cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and apoptosis was analyzed by flow cytometry. Western blot assays and immunofluorescence were carried out to measure protein changes. mRNA expression was investigated by RNA sequencing (RNA-Seq) and quantitative real-time PCR. The change of autophagic flux were observed through mCherry-GFP-LC3 transfection and electron microscopy(TEM). Clinical parameters of corneal epithelium defects, conjunctival goblet cells, tear volume, and level of ocular surface inflammation was recorded. Melatonin was able to reduce excessive ROS production and maintain mitochondrial function. TEM assay found melatonin rescued impaired autophagic flux under tBH. Moreover, melatonin significantly preserved cell viability, abolished LDH release, and decreased apoptosis. RNA-Seq indicated that melatonin greatly activating hemeoxygenase-1 (HO-1) expression. Interestingly, HO-1 ablation largely attenuated its protective effects. Besides, in dry eye mouse model, intraperitoneal injection of melatonin showed greatly improved clinical parameters, inhibited activated NLRP3 inflammation cascade, and increased density of goblet cells and tear volume. Thus, melatonin protects corneal epithelial cells from oxidative damage, maintain normal level of autophagy, and reduce inflammation via trigging HO-1 expression in DED.

Acellular Porcine Corneal Stroma May Not Be Optimal for Peripheral Keratoplasty: Reports of 2 Cases.

PURPOSE: Although acellular porcine corneal stroma (APCS) is a promising alternative to the human donor cornea for lamellar keratoplasty, here, we report 2 patients who exhibited persistent epithelial defects and sterile keratolysis after APCS transplantation to treat peripheral corneal diseases. METHODS: Two patients with different peripheral corneal diseases underwent lamellar keratoplasty by using D-shaped lamellar APCS as graft materials. Standard keratoplasty postoperative treatments, including topical antibiotic-corticosteroid, tacrolimus, and artificial tears, were applied. RESULTS: Patient 1 was a 7-year-old boy with limbal dermoid, and patient 2 was a 50-year-old man suffered from simultaneous Mooren ulcer with pterygium. Both patients developed persistent graft epithelial defects postoperatively, which were refractory to conventional nonsurgical therapies. The APCS grafts were noted to start sterile keratolysis at approximately 1 month after implantation and were completely dissolved within 3 months, leaving vascularized scars in the previously grafted area. CONCLUSIONS: These 2 cases demonstrated that given the high risk of postoperative persistent epithelial defect and sterile keratolysis, the application of APCS in peripheral keratoplasty may need further evaluation.

Heparin-Modified Amniotic Membrane Combined With Growth Factors for Promoting Corneal Wound Healing After Alkali Burn.

Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.

Evaluation of the Safety and Efficacy of a Low-Temperature Plasma Surgical System for Pterygium.

PURPOSE: Surgical excision is the standard treatment for pterygium. This study was conducted to evaluate the safety and efficacy of a novel technique using low-temperature plasma (LTP) for excision and hemostasis in pterygium surgery. METHODS: A prospective, comparative, and randomized clinical trial was conducted on 60 patients (60 eyes) undergoing pterygium excision with conjunctival autografts using fibrin glue. Patients were equally divided into the following 2 groups: a control group and a LTP group. Postoperative follow-up visits were scheduled on day 1, week 1, and months 1 and 3, and recurrence was evaluated at 1 year. Patients were examined for operative time, best corrected visual acuity, conjunctival autograft inflammation (CAI), graft stability (GS), pain, recurrence, and final appearance. Factors related to pterygium recurrence and final appearance were analyzed. RESULTS: Mean operative times were shorter in the LTP group (16.7 ± 3.4 min) than those in the control group (20.1 ± 4.7 min, P = 0.002). LTP eyes had milder CAI than control eyes at postoperative day 1 (P = 0.000) and week 1 (P = 0.000). Patients in the LTP group exhibited better GS (P = 0.01) and milder pain (P = 0.04) than those in the control group on day 1. Two control patients (6.7%) and no (0%) LTP patients experienced recurrence (P = 0.08). GS and CAI were the significant factors contributing to recurrence (GS: R = 0.425, P = 0.001; CAI: R = 0.309, P = 0.016). CONCLUSIONS: LTP to replace surgical blades and disposable cautery for ablation and hemostasis is safe and efficient for pterygium surgery, resulting in shorter operative time, milder inflammation, and better graft stability without increasing complication risk.

Conjunctival microvascular responses to anti-inflammatory treatment in patients with dry eye.

PURPOSE: This study characterized conjunctival microvascular morphological and haemodynamic responses after anti-inflammatory treatment in dry eye (DE). MATERIALS AND METHODS: Twenty-five patients with moderate DE (17 females and 8 males aged 48 ± 16 years) who underwent anti-inflammatory therapy (0.1% fluorometholone) and 25 healthy subjects (20 females and 5 males aged 48 ± 17 years) recruited as controls were enrolled. The conjunctival blood flow rate (BFR), blood flow velocity (BFV) and vessel diameter were measured by functional slit-lamp biomicroscopy (FSLB). DE symptoms and signs were assessed. All measurements were performed at baseline and at 30 and 60 days after commencement of treatment. RESULTS: At baseline, the conjunctival BFR, BFV, and vessel diameter were higher in the DE group than in the control group (p < 0.05). The BFR, BFV and corneal fluorescein staining (CFS) scores decreased at 60 days after therapy compared to at baseline and 30 days (all pcorrected < 0.05); Ocular surface diseases index (OSDI), the hyperaemia index (HI) and vessel diameters only showed significant decreases at 30 days. Moreover, significant increases in the noninvasive tear film break-up time (NI-BUT) and Schirmer I test score (ST) were observed. The CFS score correlated positively with BFV (r = 0.46), BFR (r = 0.58) and vessel diameter (r = 0.47). CONCLUSION: This study characterized conjunctival microvascular responses to anti-inflammatory treatment in DE patients. The results suggest that conjunctival BFV and BFR can be used as dynamic markers for treatment efficacy in DE.

Therapeutic effects of an anti-IL-6 antibody in fungal keratitis: Macrophage inhibition and T cell subset regulation.

Immune modulation plays a critical role in the pathogenesis of fungal keratitis (FK). However, the immune cell-mediated processes linking the innate immune response to the adaptive immune response are incompletely elucidated. IL-6 plays crucial roles in infectious and inflammatory processes in the cornea, regulating not only mononuclear macrophage differentiation but also lymphocyte activation, and IL-6 might be a useful target for immune intervention in FK. The frequencies of macrophages and T cells increased upon infection and were correlated with the severity of ocular pathogenesis. Additionally, protein profiling revealed that the expression of IL-6 and associated cytokines/chemokines was upregulated. Furthermore, anti-IL-6 intervention suppressed disease progression by reducing macrophage infiltration in the cornea and Th1, Th17, and Treg cell infiltration in draining lymph nodes (DLN) in an animal model of FK. Tocilizumab (TCZ), an antibody specific for IL-6, reduced the signal transducer and activator of transcription 3 (STAT3) activation in vivo and in vitro. In summary, fungal infection promoted macrophage and T cell activation via IL-6-mediated transcellular signaling to regulate immune cell migration and cytokine production, further demonstrating the role of IL-6 and providing a potential clinical therapeutic target in FK.