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Vascular endothelial growth factor（VEGF）, fibroblast growth factor（FGF）, nerve growth factor（NGF）, epidermal growth factor and interferon are important endogenous proteins that regulate cell proliferation, differentiation and regeneration. Biological products targeting growth factors are used in the treatment of ocular diseases such as wet age-related macular degeneration, corneal injury and neurotrophic keratitis. Anti-VEGF drugs can regulate the proliferation of vascular endothelia, reduce the edema and exudation of retinal tissue，which are the main therapeutic agents for wet age-related macular degeneration and diabetic retinopathy. The basic FGF (b-FGF) can promote the proliferation, differentiation, and migration of corneal epithelial cells, accelerating the healing of the corneal injury and reduces corneal inflammation；and bovine b-FGF has been approved for the treatment of corneal injuries. The NGF promotes the growth, development, and differentiation of central and peripheral neurons, thus accelerating the repair of nerve damage；and the European Medicines Agency approved the use of nerve growth factor for the treatment of neurotrophic keratitis in 2017. Recent clinical studies show that patients with moderate or severe neurotrophic keratitis achieved complete corneal healing following 8 weeks of NGF therapy. Epidermal growth factor derivative eye drops have been approved for the treatment of corneal epithelial injuries. Recombinant human interferon has been clinically used in the treatment of ocular viral infections. This article reviews the research progress in the development of new cell growth factor drugs for the treatment of ophthalmic diseases, to provide insights for expanding the application of cell growth factors in ophthalmology.

To determine corneal foreign body (FB) location together with corneal wound depth and width by using anterior segment optical coherence tomography (AS-OCT) after uncomplicated FB removal. Method: This prospective study was conducted with patients injured by a superficial metallic corneal FB. Under slit-lamp examination, after determining its location, the FB was removed with a 27-G needle. The depth and width of the corneal wound and the thinnest stromal thickness at the wound site were measured initially using AS-OCT. Measurements were repeated to assess the wound healing process at one week and at two months following FB removal. Results: Totally, 63 eyes of 63 patients were included in this study. The average age was 35.8 ± 11.0 years, and 96.8% of the patients were men. In terms of location of the FBs, 26 (41.3%) were in the central region, 21 (33.3%) were in the paracentral region, and 16 (25.4%) were in peripheral regions. The mean depth and width of the corneal wounds were 117.0 ± 42.5 µm and 332.9 ± 99.4 µm, respectively. The mean percentage of corneal wound depth was 18.9 ± 6.1%. In 20 patients who presented for follow-up, it was observed that the width of the wound increased and the thinnest stromal thickness at the wound site decreased over the two months. Conclusion: The AS-OCT findings of the present study showed that the corneal FBs generally affected the anterior cornea with less than approximately 0.2 mm depth and 0.5 mm width. In addition, FBs were commonly located in the central and paracentral cornea.

Introduction To report a late onset, deep stromal and endothelial corneal scar in a keratoconus patient after corneal collagen cross-linking (CXL). Case description Observational case report. A 29-year-old man with bilateral keratoconus received an accelerated (A-CXL 10*9) epithelium-off CXL procedure in the left eye. 6-months postoperatively, a 2.2 × 1.2 mm inferocentral corneal scar was detected, which was located in the posterior stroma ranging from approximately 350 µm until the endothelium, therefore was situated below the demarcation line. A topical corticosteroid treatment did not influence the magnitude or configuration of the scar. Visual acuity was never affected, which includes the examination 12 months postoperatively. Conclusions We report a case of a late onset deep stromal and endothelial corneal scar 6 months after accelerated CXL as postoperative complication without affecting visual acuity.

This evidence-based practice change project examined the use of supine positioning as a substitute for lateral positioning after sedation for endoscopic procedures for the purpose of preventing corneal injuries in this patient population.This study used a pre and post implementation design.Retrospective data was collected over 12 months, including 4,422 endoscopic procedures for comparison to the prospective data collected after implementing the practice change, which totaled eight months and 3080 procedures.Incidence rates for corneal injury and eye irritation were 0.158% before the practice change, with a decrease in incidence to 0.097% after the change. Using a two-sided Fisher's exact test, the results were not statistically significant (P =.05). Additionally, linear regression showed a slight downward trend with implementation; however, these results were also not statistically significant.The intervention did not have a statistically significant impact on the incidence of corneal injury. It is possible that more than one risk factor was contributing to corneal injury in this setting and the intervention only addressed one potential risk factor.

The study aims to investigate the role of the lipid mediator resolvin D1 (RvD1) in bacterial keratitis in a murine model.The effect of RvD1 on Pseudomonas aeruginosa-stimulated human corneal epithelial cells (HCECs) and mouse macrophages and dendritic cells (DCs) was assessed. C57BL/6 mouse corneas were abraded and treated with RvD1 after stimulation with P. aeruginosa, following which cytokine production level in the cornea and drainage lymph nodes was compared with that in controls. Corneal opacity and thickness were assessed using anterior segment photographs, and optical coherence tomography and corneal infiltrates were analyzed using immunohistochemistry for neutrophils.RvD1 significantly inhibited pro-inflammatory cytokine production in HCECs, mouse macrophages, and DCs. Corneal opacity and corneal thickness were reduced, and the development of corneal infiltrates, specifically neutrophils, was also significantly inhibited by RvD1 in response to stimulation with P. aeruginosa.RvD1 inhibits P. aeruginosa-induced corneal inflammation. This finding supports a potential therapeutic approach for patients with bacterial keratitis.

Corneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.A cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.We assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.We did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.National Eye Institute.

PURPOSE To report the outcomes of two-piece microkeratome-assisted MK for eyes with full-thickness traumatic corneal scars and otherwise functional endothelium following corneal penetrating injury. DESIGN Interventional case series METHODS: : In this single-center study, 41 consecutive eyes with traumatic corneal scars that underwent two-piece microkeratome-assisted mushroom keratoplasty were evaluated. The two-piece mushroom graft consisted of an anterior lamella of 9-mm diameter and a posterior lamella of 6-mm diameter. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density and postoperative complication rates. RESULTS Of the 41 total cases, 38 eyes (93%) reached Snellen vision ≥20/100, 36 (88%) reached ≥20/60, 29 (71%) reached ≥20/40 and 13 (32%) reached ≥20/25 2 years following MK. Excluding eyes with vision-impairing comorbidities, baseline logMAR BSCVA (1.41±0.73) significantly improved annually during the first 2 years (p < 0.001) reaching 0.16±0.13 at year 2 which subsequently remained stable up to 10 years (p = 0.626). RA exceeded 4.5 diopters in 2 cases (5%) after wound revision for high-degree astigmatism in 5 cases. Endothelial cell loss was 35.1% at 1 year with an annual decline of 2.9% over 10 years. Elevation in IOP was observed postoperatively in 7 eyes of which 6 had pre-existing glaucoma. The 10-year cumulative risk for graft rejection and failure was 8.5% and 10% respectively. CONCLUSION Two-piece microkeratome-assisted MK for traumatic corneal scars can allow excellent visual rehabilitation with relatively stable ECL and low rates of immunologic rejection and graft failure.

PURPOSE: Topical, local anesthetic eye drops in conjunction with antibiotics are commonly used to reduce ocular pain and treat patients in emergency clinics; however, their effects on corneal healing are poorly understood. This study examined whether regular or diluted proparacaine eye drops given in combination with common ophthalmic antibiotics affect corneal wound healing parameters using in vitro and in vivo models. METHODS: Primary human corneal fibroblasts generated from donor corneas and New Zealand white rabbits were used. Regular (0.5%) and diluted (0.05%) proparacaine eye drops, twice daily for 3 days, were applied to cultures and rabbit eyes, with or without ophthalmic antibiotics (polymyxin B sulfate and trimethoprim). Trypan blue, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and scratch wound assays measured cellular viability, proliferation, and migration, respectively, in vitro. Slit lamp biomicroscopy, tonometry, fluorescein eye test, hematoxylin and eosin (H&E) staining, and 4′,6-diamidino-2-phenylindole (DAPI) immunofluorescence were used for in vivo studies. RESULTS: Both regular and diluted proparacaine affected wound healing response in the cornea in vitro and in vivo in a time-dependent manner. Adjunct antibiotic treatments had additive effects characterized by reduced corneal fibroblast viability, proliferation, and migration in vitro and corneal epithelial recovery in vivo. Regular proparacaine with antibiotics showed most pronounced effects on corneal wound healing parameters, and diluted proparacaine without antibiotics had minimal negative effects in vitro and in vivo. CONCLUSION: Both methods of regular (0.5%) and diluted (0.05%) proparacaine topical application to the cornea are safe, but impede corneal wound healing in vitro and in vivo. Adjunct antibiotic treatments had additive negative effects on corneal wound repair.

A 20-year-old male patient presented to our tertiary eye centre with post-traumatic cataract in the right eye, 3 months after penetrating trauma with metal wire while working with electric cables. The corneal laceration had been repaired soon after trauma elsewhere and the patient had some gain of

Biomechanical properties of corneal scar are strongly correlated with many corneal diseases and some types of corneal surgery, however, there is no elasticity information available about corneal scar to date. Here, we proposed an acoustic radiation force optical coherence elastography system to evaluate corneal scar elasticity. Elasticity quantification was first conducted on ex vivo rabbit corneas, and the results validate the efficacy of our system. Then, experiments were performed on an ex vivo human scarred cornea, where the structural features, the elastic wave propagations, and the corresponding Young’s modulus of both the scarred region and the normal region were achieved and based on this, 2D spatial distribution of Young’s modulus of the scarred cornea was depicted. Up to our knowledge, we realized the first elasticity quantification of corneal scar, which may provide a potent tool to promote clinical research on the disorders and surgery of the cornea.

Corneal transparency, necessary for vision and depending on the high organization of stromal extracellular matrix, is maintained by keratocytes. Severe or continuous corneal injuries determine exaggerated healing responses resulting in the formation of irreversible fibrotic scars and vision impairment. Soluble guanylate cyclase (sGC) stimulation demonstrated antifibrotic effects in both experimental fibrosis and human lung and skin fibroblasts. Here, we assessed whether sGC stimulation with BAY 41-2272 could attenuate transforming growth factor β1 (TGFβ1)-induced myofibroblast differentiation of human corneal keratocytes. Cells were challenged with TGFβ1, with/without BAY 41-2272 preincubation, and subsequently assessed for viability, proliferation, migration, chemoinvasion, as well for the expression of myofibroblast/fibroblast activation markers and contractile abilities. Treatment with BAY 41-2272 did not affect keratocyte viability, while preincubation of cells with the sGC stimulator was able to inhibit TGFβ1-induced proliferation, wound healing capacity, and invasiveness. BAY 41-2272 was also able to attenuate TGFβ1-induced myofibroblast-like profibrotic phenotype of keratocytes, as demonstrated by the significant decrease in ACTA2, COL1A1, COL1A2, FN1 and PDPN gene expression, as well as in α-smooth muscle actin, α-1 chain of type I collagen, podoplanin, vimentin and N-cadherin protein expression. Finally, BAY 41-2272 significantly counteracted the TGFβ1-induced myofibroblast-like ability of keratocytes to contract collagen gels, reduced phosphorylated Smad3 protein levels, and attenuated gene expression of proinflammatory cytokines. Collectively, our data show for the first time that BAY 41-2272 is effective in counteracting keratocyte-to-myofibroblast transition, thus providing the rationale for the development of sGC stimulators as novel promising modulators of corneal scarring and fibrosis.

Purpose: analgesic drugs, including nonselective opioids and non-steroidal anti-inflammatory drugs, should be used with great precautions to relieve pain after trauma to the corneal epithelium because of their unfavorable effects on wound healing. Biphalin is a synthetic opioid peptide that has been demonstrated to possess a strong analgesic effect on rodents. The purpose of this study is to investigate the effects of biphalin on human corneal epithelial wound healing. Methods: an immortalized human corneal epithelial cell (HCEC) culture was used to analyze the effects of biphalin on wound healing. The toxicity of biphalin at various concentrations was measured by the MTT assay. The effects of 1 μM and 10 μM biphalin on wound closure, cell migration and proliferation were tested in an in vitro scratch assay of HCECs. Naloxone, a non-selective competitive opioid receptor antagonist, was also used to inhibit the effects of biphalin in all experiments. Results: biphalin did not cause any toxic effect on HCECs at concentrations lower than 100 μM at various incubation time points. Biphalin significantly increased wound healing at 1 μM concentration in an in vitro scratch assay of HCECs (P < 0.05). It also significantly increased migration of HCECs (P < 0.01). There was no significant difference between the biphalin and control groups of HCECs in the Ki67 proliferation assay. Conclusion: biphalin, which is a synthetic opioid peptide, promotes corneal epithelial wound healing by increasing cell migration. This role should be evaluated in further in vivo and clinical studies. / Objet: les analgésiques, dont les morphiniques non-sélectifs et les anti-inflammatoires non stéroïdiens (AINS) devraient être utilisés avec beaucoup de précautions pour traiter la douleur dans les lésions de l’épithélium cornéen du fait de leurs effets indésirables sur la cicatrisation. La Biphaline est un peptide morphinique de synthèse dont on a démontré qu’il possède un effet analgésique puissant chez les rongeurs. Le but de cette étude est d’évaluer les effets de la Biphaline sur les lésions de l’épithélium cornéen humain. Méthodes: une culture de cellules épithéliales immortalisées de cornée humaine (HCEC) a été utilisée pour tester les effets de la Biphaline sur la cicatrisation. La toxicité de la Biphaline a été mesurée à diverses concentrations par essai MTT. L’effet de 1 μM et de 10 μM de Biphaline ont été testées sur la cicatrisation dans un essai in vitro de grattage de HCEC et séparément de migration et de prolifération cellulaire. La Naloxone, un antagoniste compétitif non sélectif des récepteurs morphiniques, fut aussi utilisée pour inhiber les effets de la Biphaline dans toutes les expériences. Résultats: la Biphaline ne produit aucun effet toxique sur les HCEC aux concentrations inférieures à 100 μM aux différents temps d’incubation. La Biphaline augmente significativement la cicatrisation à la concentration de 1 μM dans un test de grattage in vitro d’HCEC (p < 0,05). Elle accroît également significativement la migration des HCEC (p < 0,01). Il n’y a pas de différence significative entre la Biphaline et le groupe témoin de HCEC au test de prolifération Ki67. Conclusion: la Biphaline, un peptide morphinique de synthèse, favorise la cicatrisation de l’épithélium cornéen par l’augmentation de la migration cellulaire. Ce rôle serait à évaluer par des études in vivo et cliniques ultérieures., NA

This case report aims to describe a modified continuous suturing technique for firm fixation of a human amniotic membrane graft in a patient with persistent epithelial defect (PED) after a chemical eye injury. As a result of this technique, the amniotic membrane (AM) was firmly fixed to the corneal surface with eight continuous and locked episcleral sutures that resembled an octagon graft. This technique was performed in a 14-year-old patient with PED after a chemical corneal burn. Three weeks after the surgery, the PED was completely healed. This simple continuous suturing technique can allow firm and stable fixation of AM grafts on the ocular surface in cases of PED after chemical burn. It may prevent early loss of the graft and facilitate corneal epithelial wound healing.

To compare the therapeutic effects of different forms of nintedanib ophthalmic preparations on neovascularization corneal alkali burns in rats.Forty rat models of left eye corneal alkali burns were constructed, and the five groups (NNTH had a stronger inhibitory effect on corneal neovascularization (CNV) in alkali-burned rats while reducing the level of inflammatory factors. NNTH had a longer drug duration of release than nanoformulations in vitro. Nintedanib at low concentrations (8 μM) had no significant cytotoxicity to HCECs but significantly induced apoptosis and inhibited the expression of VEGFA and CD31 and the migration of HUVECs.Nanomorphic thermoreversible hydrogel is superior among the nintedanib ophthalmic preparations, showing better inhibition of CNV in alkali-burned eyeballs and it blocked the migration and proangiogenic ability of HUVECs.

Corneal wounds resulting from injury, surgeries, or other intrusions not only cause pain, but also can predispose an individual to infection. While some inflammation may be beneficial to protect against microbial infection of wounds, the inflammatory process, if excessive, may delay corneal wound healing. An examination of the literature on the effect of inflammation on corneal wound healing suggests that manipulations that result in reductions in severe or chronic inflammation lead to better outcomes in terms of corneal clarity, thickness, and healing. However, some acute inflammation is necessary to allow efficient bacterial and fungal clearance and prevent corneal infection. This inflammation can be triggered by microbial components that activate the innate immune system through toll-like receptor (TLR) pathways. In particular, TLR2 and TLR4 activation leads to pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activation. Similarly, endogenous molecules released from disrupted cells, known as damage-associated molecular patterns (DAMPs), can also activate TLR2, TLR4 and NFκB, with the resultant inflammation worsening the outcome of corneal wound healing. In sterile keratitis without infection, inflammation can occur though TLRs to impact corneal wound healing and reduce corneal transparency. This review demonstrates the need for acute inflammation to prevent pathogenic infiltration, while supporting the idea that a reduction in chronic and/or excessive inflammation will allow for improved wound healing.

Corneal injury due to ocular trauma or infection is one of the most challenging vision impairing pathologies. The aim of the work was to study the effect of biodegradable silk fibroin-based scaffolds containing GDNF on the corneal regeneration process. During cultivate the highest keratocytes proliferative activity was registered with scaffolds containing 250 ng/ml and 500 ng/ml GDNF. In mice with an experimental model of epithelial-stromal damage to the cornea, silk fibroin-based scaffolds containing GDNF in various concentrations were used (in groups 1, 2 and 3 silk fibroin-based scaffolds containing GDNF in a concentration of 50 ng/ml, 250 ng/ml and 500 ng/ml, respectively; in group 4 - silk fibroin-based scaffolds without GDNF; in group 5 - a solution of GDNF with concentration of 500 ng/ml; group 6- control). The area of the corneal epithelial defect in groups 2, 3, and 5 was less than in the other groups. The most pronounced positive immunohistochemical reaction with antibodies to Bcl2, Bax, phosphoERK1/2 and phospho-JNK1/2, Ki67, Gap43 was observed in groups 2 and 3. Thus, silk fibroin-based scaffolds with GDNF stimulate the epithelialization process, proliferative activity of epithelial cells and keratocytes, accelerate the formation of the stromal nerve plexus and exhibit anti-apoptotic activity.

Background: This review summarized prophylactic retinectomy technique and its effect on anatomic and functional outcomes in severe open globe injuries (OGIs). Methods: A comprehensive search in PubMed (MEDLINE), Embase, Scopus, and EuropePMC databases was performed up until 8 January 2020. Enrolled studies include case series, studies involving pars plana vitrectomy (PPV) combined with retinectomy in severe penetrating injuries with or without IOFB, perforating injuries, and globe ruptures. Primary outcome was best-corrected visual acuity (BCVA) ⩾20/200 at the end of the study. Secondary outcomes were the rate of proliferative retinopathy (PVR), globe survival rate and retinal reattachment rate. Results: A total of seven studies, involving 275 eyes with severe OGIs, is included in this study. Meta-analysis indicates that final BCVA ⩾20/200 was achieved in 61% (95% CI 49%–73%). Meta-regression analysis showed that improvement was inversely affected by the presence of pre-operative direct macular injury ( p = 0.001) and corneal scar ( p = 0.015). The proportion of pre-operative BCVA Conclusion: Early PPV combined with retinectomy was associated with acceptable visual improvement and anatomical success.

PURPOSE: Bioactive substrates can be used therapeutically to enhance wound healing. Here, we evaluated the effect of an in-situ thermoresponsive hydrogel from decellularized porcine cornea ECM, COMatrix (COrnea Matrix), for application as an ocular surface bandage for corneal epithelial defects. METHODS: COMatrix hydrogel was fabricated from decellularized porcine corneas. The effects of COMatrix hydrogel on attachment and proliferation of human corneal epithelial cells (HCECs) were evaluated in vitro. The effect of COMatrix on the expressions of the inflammatory genes, IL-1β, TNF-α, and IL-6 was assessed by RT-PCR. The in-situ application and also repairing effects of COMatrix hydrogel as an ocular bandage was studied in a murine model of corneal epithelial wound. The eyes were examined by optical coherence tomography (OCT) and slit-lamp microscopy in vivo and by histology and immunofluorescence post-mortem. RESULTS: In vitro, COMatrix hydrogel significantly enhanced the attachment and proliferation of HCECs relative to control. HCECs exposed to COMatrix had less induced expression of TNF-α (P

The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic collapse around the world. Effective treatments to mitigate this viral infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells (HCEC) in culture challenged with IFNγ as models of the eye surface to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 Spike (S) protein to angiotensin-converting enzyme 2 (ACE2). We found that the lipid mediators, elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i) decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ-stimulated HCEC. There was also a concomitant decrease in the binding of Spike RBD with the lipid treatments. Using RNA-seq analysis, we uncovered that the lipid mediators also attenuated the expression of pro-inflammatoy cytokines participating in hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to open therapeutic avenues to counteract virus attachment and entrance to the body.

Existing knowledge regarding golf-associated eye injuries (GEIs) is sparse. The purpose of this study was to characterize the types of GEIs, examine the mechanisms of injury, describe the characteristics of GEI victims, and determine the incidence of GEIs during the 2002-2021 period using the National Electronic Injury Surveillance System (NEISS) database.Deidentified patient records were analyzed. Each GEI was assigned into a specific category of diagnosis, and the mechanism of injury was determined. National estimates were collected for each year, and simple linear regression modeling was used to determine trends over time. Furthermore, patient variables for sex, race, and age were analyzed.The NEISS query provided a total of 379 GEIs for analysis. GEIs were most common in adult males, with a decreasing, although not statistically significant, trend during this period (β = -17.88, p = 0.110). Children were more likely to have a GEI caused by a golf club while adults were more likely to have one caused by the surrounding environment. Across all age groups, contusions and corneal abrasions were the most common GEIs, constituting 50.4% (190/377) of all eye injuries, followed by foreign body injuries (9%, 34/377) and then irritation/inflammation of the eye (8%, 30/377). The most common mechanism of injury among all players involved adverse interactions with the environment (37.7%, 142/377).Contradictory to existing literature, we show that minor GEIs are more common than severe ones. Rather than golf clubs or balls, environmental elements are the leading cause of GEIs.

In primary care practices and emergency departments, approximately 2% to 3% of visits are related to eye conditions. The most common diagnoses are corneal abrasion, corneal foreign body, conjunctivitis, external hordeolum (stye), and subconjunctival hemorrhage. This section addresses hordeolum, chalazion, conjunctivitis, corneal abrasion, and corneal foreign body. A thorough history and physical examination are crucial for patients with these conditions, and frequently are sufficient for diagnosis. Conservative therapies are first-line treatments for hordeolum and chalazion, including application of warm compresses, eyelid scrubs, and eyelid massage. Conjunctivitis is the most common etiology of red eye and has infectious and noninfectious causes. Bacterial conjunctivitis typically resolves in 1 to 2 weeks, but can be managed with topical antibiotic solutions or ointments. Viral conjunctivitis management involves frequent handwashing and use of cool compresses and artificial tears. Corneal abrasion is the most common eye injury seen in emergency departments, and corneal foreign body is the second most common. Topical antibiotics and cycloplegics are mainstay therapies for corneal abrasion, with consideration of topical nonsteroidal anti-inflammatory drugs for pain management. Follow-up visits are recommended for select patients. Management of corneal foreign body requires prompt removal of the object, pain management, consideration of prophylactic antibiotics, and follow-up when appropriate.

The process of corneal wound healing is complex and induces scar formation. Corneal scarring is a leading cause of blindness worldwide. The fibrotic healing of a major ocular wound disrupts the highly organized fibrillar collagen arrangement of the corneal stroma, rendering it opaque. The process of regaining this organized extracellular matrix (ECM) arrangement of the stromal layer to restore corneal transparency is complicated. The surface retention capacity of ocular drugs is poor, and there is a large gap between suitable corneal donors and clinical requirements. Therefore, a more efficient way of treating corneal scarring is needed. The eight major classes of interventions targeted as therapeutic tools for healing scarred corneas include those based on exosomes, targeted gene therapy, microRNAs, recombinant viral vectors, histone deacetylase inhibitors, bioactive molecules, growth factors, and nanotechnology. This review highlights the recent advancements in molecular therapeutics to restore a cornea without scarring. It also provides a scope to overcome the limitations of present studies and perform robust clinical research using these strategies.

Substance P (SP) is a tachykinin expressed by various cells in the nervous and immune systems. SP is predominantly released by neurons and exerts its biological and immunological effects through the neurokinin receptors, primarily the neurokinin-1 receptor (NK1R). SP is essential for maintaining ocular surface homeostasis, and its reduced levels in disorders like diabetic neuropathy disrupt the corneal tissue. It also plays an essential role in promoting corneal wound healing by promoting the migration of keratocytes. In this review, we briefly discuss the structure, expression, and function of SP and its principal receptor NK1R. In addition, SP induces pro-inflammatory effects through autocrine or paracrine action on the immune cells in various ocular surface pathologies, including dry eye disease, herpes simplex virus keratitis, and Pseudomonas keratitis. We provide an in-depth review of the pathogenic role of SP in various ocular surface diseases and several new approaches developed to counter the immune-mediated effects of SP either through modulating its production or blocking its target receptor.

Corneal blindness due to scarring is conventionally treated by corneal transplantation, but the shortage of donor materials has been a major issue affecting the global success of treatment. Pre-clinical and clinical studies have shown that cell-based therapies using either corneal stromal stem cells (CSSC) or corneal stromal keratocytes (CSK) suppress corneal scarring at lower levels. Further treatments or strategies are required to improve the treatment efficacy. This study examined a combined cell-based treatment using CSSC and CSK in a mouse model of anterior stromal injury. We hypothesize that the immuno-regulatory nature of CSSC is effective to control tissue inflammation and delay the onset of fibrosis, and a subsequent intrastromal CSK treatment deposited collagens and stromal specific proteoglycans to recover a native stromal matrix. Using optimized cell doses, our results showed that the effect of CSSC treatment for suppressing corneal opacities was augmented by an additional intrastromal CSK injection, resulting in better corneal clarity. These in vivo effects were substantiated by a further downregulated expression of stromal fibrosis genes and the restoration of stromal fibrillar organization and regularity. Hence, a combined treatment of CSSC and CSK could achieve a higher clinical efficacy and restore corneal transparency, when compared to a single CSSC treatment.

Background Corneal neovascularization (CNV) is an important disease that causes blindness. Secretogranin III (Scg3) has emerged as a new influencing factor of neovascularization. This study analyzed the Scg3 antibody’s inhibitory effect on CNV and and explored its preliminary mechanism. Methods Human umbilical vein endothelial cells (HUVECs) were treated with Scg3 and anti-Scg3. Cell proliferation, wound healing migration and tube formation assays were performed. Healthy adult New Zealand rabbits were randomly selected to be alkali burned and establish the corneal neovascularization (CNV) model. The rabbits were randomly divided into 3 groups (the high concentration group, low concentration group and control group). Different doses of anti-Scg3 and PBS were administered to the rabbits. Clinical examinations, immunostaining, quantitative real-time polymerase chain reaction (qPCR) and western blotting analyses were performed postoperatively. Results In the in vitro study, the Scg3 antibody mixture inhibited Scg3-induced endothelial cell proliferation and angiogenesis. In the in vivo study, significant CNV was observed in the control group. Confocal microscopy also revealed considerable active neovascularization in the control group. There was no obvious CNV growth in the high concentration group. Additionally, CD31, LYVE1 and CD45 expression was significantly inhibited after treatment with a high concentration of Scg3 antibody. The qPCR and western blotting analyses revealed that the levels of ERK in the low concentration group and high concentration group were higher than those in the control group at 7 days and 14 days. The levels of VEGF in the control group were significantly increased compared with those in the high concentration group. In all three groups, the levels of Akt were not significantly different at any time point. Conclusion The expression of Scg3 could affect the growth of HUVECs in vitro. Treatment with a high concentration (0.5 µg/mL) of Scg3 antibody reduced the inflammatory response and inhibited the growth of corneal neovascularization after corneal alkali burn injury in rabbits. The MEK/ERK pathway might play an important role in the inhibitory effect of anti-Scg3.

Limbus-derived stromal/mesenchymal stem cells (LMSCs) are vital for corneal homeostasis and wound healing. However, despite multiple pre-clinical and clinical studies reporting the potency of LMSCs in avoiding inflammation and scarring during corneal wound healing, the molecular basis for the ability of LMSCs remains unknown. This study aimed to uncover the factors and pathways involved in LMSC-mediated corneal wound healing by employing RNA-Sequencing (RNA-Seq) in human LMSCs for the first time. We characterized the cultured LMSCs at the stages of initiation (LMSC−P0) and pure population (LMSC−P3) and subjected them to RNA-Seq to identify the differentially expressed genes (DEGs) in comparison to native limbus and cornea, and scleral tissues. Of the 28,000 genes detected, 7800 DEGs were subjected to pathway-specific enrichment Gene Ontology (GO) analysis. These DEGs were involved in Wnt, TGF-β signaling pathways, and 16 other biological processes, including apoptosis, cell motility, tissue remodeling, and stem cell maintenance, etc. Two hundred fifty-four genes were related to wound healing pathways. COL5A1 (11.81 ± 0.48) and TIMP1 (20.44 ± 0.94) genes were exclusively up-regulated in LMSC−P3. Our findings provide new insights involved in LMSC-mediated corneal wound healing.

The objective of this study was to develop and evaluate an effective topical formulation to promote corneal epithelial wound healing. Ascorbyl glucoside (AA-2G), a stable prodrug of AA, was formulated in solid in oil (S/O) nanodispersions by emulsifying AA-2G solutions in cyclohexane using Span 85 as an emulsifying agent and freeze-drying emulsions to produce AA-2G - surfactant complex. The complexes were then dispersed in castor oil to produce S/O nanodispersions which were evaluated in terms of their particle size, polydispersity index, encapsulation efficiency, morphology, physical stability as well as the transcorneal permeation and accumulation of AA-2G. The same preparation procedure was used to prepare S/O nanodispersions of AA. S/O nanodispersions of AA and AA-2G were formulated into oily drops that were tested for efficacy in promoting wound healing after corneal epithelial depredation. AA-2G was loaded efficiently in S/O nanodispersions (EE 99%) in the form of spherical nanoparticles. S/O nanodispersions were physically stable and resulted in improved permeation (18x) and accumulation (7x) of AA-2G in transcorneal diffusion experiments in comparison to AA-2G solutions. Oily eye drops of AA-2G and AA showed no irritation and significant improvement in epithelial healing in vivo in comparison to AA-2G and AA solutions.

Mesenchymal stem cells (MSCs) represent a population of adult stem cells that have potent immunoregulatory, anti-inflammatory, and antiapoptotic properties. In addition, they have ability to migrate to the site of inflammation or injury, where they contribute to the regeneration and healing process. For these properties, MSCs have been used as therapeutic cells in several models, including treatment of damages or disorders of the ocular surface. If the damage of the ocular surface is extensive and involves a limbal region where limbal stem cell reside, MSC therapy has been proved as the effective treatment approach. Although the anti-inflammatory properties of MSCs have been well characterized, mechanisms of antiapoptotic action of MSCs are not well recognized. Using a chemically damaged cornea in a mouse model, we showed that the injury decreases expression of the gene for antiapoptotic molecule Bcl-2 and increases the expression of proapoptotic genes Bax and p53. These changes were attenuated by local transplantation of MSCs after corneal damage. The antiapoptotic effect of MSCs was tested in an in vitro model of co-cultivation of corneal explants with MSCs. The apoptosis of corneal cells in the explants was induced by proinflammatory cytokines and was significantly inhibited in the presence of MSCs. The antiapoptotic effect of MSCs was mediated by paracrine action, as confirmed by separation of the explants in inserts or by supernatants from MSCs. In addition, MSCs decreased the expression of genes for the molecules associated with endoplasmic reticulum stress Atf4, Bip, and p21, which are associated with apoptosis. The results show that MSCs inhibit the expression of proapoptotic genes and decrease the number of apoptotic cells in the damaged corneas, and this action might be one of the mechanisms of the therapeutic action of MSCs.

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Objectives Corneal abrasions are common ophthalmic presentations to emergency departments. Among emergency physicians and ophthalmologists, there are highly variable practice patterns with regard to management of resultant pain and discomfort. The goal of this study was to review and analyze the efficacy and safety of topical pain therapies for corneal abrasions, including topical anesthetics, nonsteroidal anti-inflammatory drugs (NSAIDs), cycloplegics, steroids, pressure patching, and the use of a bandage contact lens (BCL). Methods The review followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The protocol was established a priori and published on PROSPERO (CRD42020201288). MEDLINE, EMBASE, CENTRAL, and Web of Science were searched until December 31, 2020. Primary studies comparing topical pain therapies to another therapy or control were included. Primary outcomes included percentage of corneal abrasions healed at 24, 48, and 72 hours, as well as pain control at 24 and 48 hours. Secondary outcomes included use of oral analgesia and incidence of complications. Risk of bias was assessed using validated tools. Quality of evidence was assessed using the GRADE methodology. Results Overall, 33 studies (31 randomized controlled trials [RCTs], two cohort studies) comprising 4,167 patients with corneal abrasions were analyzed. Only the data for topical NSAIDs were of adequate evidence from which to draw conclusions; topical NSAIDs demonstrated significantly reduced pain scores at 24 hours (standardized mean differences [SMD] -0.69, 95% CI = -0.98 to -0.41) and 48 hours (SMD = -0.56, 95% CI = -1.02 to -0.10) as well as 53% (95% CI = 34% to 67%) lower oral analgesia use compared to control. Based on available data, topical anesthetics, cycloplegics, patching, and the use of a BCL did not result in any significant difference in pain scores or use of oral analgesia, while no studies examined topical steroids. No interventions resulted in healing delays or significantly higher rates of complications compared to controls. Conclusions There was strong evidence to support that topical NSAIDs reduce pain associated with corneal abrasions in the first 48 hours and the need for oral analgesia. The existing evidence was insufficient to support or refute the use of topical anesthetics, cycloplegics, steroids, or BCL for pain control in corneal abrasions. Pressure patching was ineffective at pain reduction and may increase the risk of complications. Delays in healing or other complications were not significantly different between any intervention or control for simple, uncomplicated corneal abrasions; however, larger RCTs are required to identify any differences in rare complications.

This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.

Amniotic membrane (AM) transplantation is often used as a treatment for corneal repair, but AM is prone to dissolving and shedding after surgery; multiple transplants will cause pain and financial burden. In this work, human amniotic membrane was firstly decellularized to obtain an AM extracellular matrix (dAM). This dAM was homogenized and extracted to obtain the dAM extract (simplified as dAME). Different forms of administration for corneal injury were performed as liquid drops (diluted dAME), in situ gels (using temperature-dependent Poloxamer 407 as the matrix), and tablets (poly(vinyl alcohol) as the matrix). The cytocompatibility of dAME was evaluated using corneal epithelial cells, corneal stromal cells and fibroblasts as cell models. The results showed that dAME is biocompatible to all these cells. Cells exhibited normal morphology and growth state at a dAME concentration of up to 160 μg mL−1. In vivo, dAME exhibited increased wound healing efficiency in severe corneal injury, being characterized with a shorter healing time for epithelium and a faster recovery for stromal opacity and thickness, compared with those of the control eyes. Different forms of administration have different effects on corneal repair; among them, in situ gels achieved the best therapeutic efficiency. Their biological mechanism was detected via quantitative real-time polymerase chain reaction (qRT-PCR) technology. It was confirmed that dAME plays important roles in promoting the mRNA expression of leucine-rich and immunoglobulin-like domains 1 (LRIG1) and in inhibiting the mRNA of transforming growth factor-β1 (TGF-β1).

Corneal neovascularization (CNV) is the major cause of blindness after eye injury; however, only several drugs can be applied and the invasive administration ways (i.e., intravitreal injection and subconjunctival injection) are used. Resveratrol is a highly effective anti-VEGF agent against CNV. However, its applications are limited due to its strong hydrophobicity and instability. Here, we developed a resveratrol-loaded ocular lamellar crystalline gel (ROLG) for high inhibition of CNV. ROLGs were composed of resveratrol, glyceryl monooleate (GMO), ethanol, and water, and their lamellar crystalline structures were identified by polarizing light microscopy and small-angle X-ray scattering. High drug loading (4.4 mg/g) of ROLGs was achieved due to the hydrogen bonding between GMO and resveratrol. Resveratrol showed sustained release with 67% accumulative release in 7 h, which was attributed to the slow erosion of gels. Resveratrol in ROLGs had a high corneal permeation 3 times higher than resveratrol in hyaluronic acid suspensions (RHSs). ROLGs were administered to rats only once a day because of their strong retention on the cornea surface. ROLGs were safe due to the very little contact of ethanol in ROLGs to the cornea. CNV post-rat corneal alkaline injury was highly inhibited by ROLGs, resulting from the attenuation of corneal VEGF expression and then corneal healing was improved. The ROLG was a promising ocular medicine for the prevention of CNV.

Introduction The current study was designed to test the potential role of recombinant human MG53 (rhMG53) protein on protecting against alkaline-induced corneal injury in mice. Materials and Methods A round filter paper with 2-mm diameter was soaked in 1 mol/L of NaOH solution. The mouse alkaline injury was generated by placing the filter paper directly on the cornea for 30 seconds and washed with 30-mL saline; 10 µL of rhMG53 solution (20 µg/mL) or saline control was topically administrated on the mouse corneas (twice per day for 10 days). Re-epithelialization was measured by fluorescein staining and imaged by a slit lamp equipped with a digital camera. Clinical neovascularization and opacity scores were measured every day after injury. Ten days after injury, mice were sacrificed and corneas were dissected out for flat mount staining of CD31 for neovascularization. Results MG53 was present in both dog aqueous humor and human tears. mg53-/- corneas were more susceptible to alkaline-induced corneal injury. Topical treatment of rhMG53 improved re-epithelialization, suppressed neovascularization, and fibrosis induced by alkaline injury. Conclusions rhMG53 may be an effective means to treat corneal wounding.

BACKGROUND: Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the management options for corneal abrasion. A comprehensive summary and synthesis of the evidence on antibiotic prophylaxis in traumatic corneal abrasion is thus far unavailable, therefore we conducted this review to evaluate the current evidence regarding this important issue. OBJECTIVES: To assess the safety and efficacy of topical antibiotic prophylaxis following corneal abrasion. Our objectives were 1) to investigate the incidence of infection with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion; and 2) to investigate time to clinical cure, defined as complete healing (re‐epithelialization) of the epithelium, with antibiotics versus placebo or alternative antibiotics in people with corneal abrasion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4), Ovid MEDLINE, Embase.com, PubMed, the Latin American and Caribbean Health Sciences Literature database (LILACS), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 April 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing antibiotic with another antibiotic or placebo in children and adults with corneal abrasion due to any cause. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for the prespecified outcomes using the GRADE classification. MAIN RESULTS: Our search of the electronic databases yielded 8661 records. We screened 7690 titles and abstracts after removal of duplicates. We retrieved 32 full‐text reports for further review. We included two studies that randomized a total of 527 eyes of 527 participants in the review. One study was conducted in Denmark, and one was conducted in India. The two studies did not examine most of our prespecified primary and secondary outcomes. The first study was a parallel‐group RCT comparing chloramphenicol ocular ointment with fusidic acid ocular gels (frequency was not clearly reported). This study enrolled 153 participants older than 5 years of age with corneal abrasion in Denmark with a one‐day follow‐up duration. No participants had secondary infection in the fusidic acid group, whereas three (4.1%) participants in the chloramphenicol group had a slight reaction (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.01 to 2.79; 144 participants; very low certainty evidence). Thirty‐one (44.3%) participants in the fusidic acid arm and 34 (46.6%) participants in the chloramphenicol arm were cured (defined as the area of abrasion zero and no infection) at day 1 (RR 0.94, 95% CI 0.65 to 1.34; 144 participants; very low certainty evidence). Without providing specific data, the study reported that the degree of pain was not affected by the interventions received. The most common adverse events reported were itching and discomfort of the eye, which occurred in approximately one‐third of participants in each group (low certainty evidence). A second multicenter, two‐arm RCT conducted in India enrolled 374 participants older than 5 years of age with corneal abrasion who presented within 48 hours after injury. This study investigated the effect of a three‐day course of either ocular ointment combinations of chloramphenicol‐clotrimazole or chloramphenicol‐placebo (all three times daily). At day 3, 169 (100%) participants in the chloramphenicol‐clotrimazole arm and 203 (99%) out of 205 participants in the chloramphenicol‐placebo arm were cured without any complication, defined as complete epithelialization of the cornea without evidence of infection (RR 1.01, 95% CI 0.99 to 1.03; 374 participants; very low certainty evidence). Four participants assigned to the chloramphenicol‐placebo arm experienced mild adverse events: two participants (1%) had mild chemosis and irritation, and two (1%) had small single sterile corneal infiltrates (low certainty evidence). AUTHORS' CONCLUSIONS: Given the low to very low certainty of the available evidence, any beneficial effects of antibiotic prophylaxis in preventing ocular infection or accelerating epithelial healing following a corneal abrasion remain unclear. Moreover, the current evidence is insufficient to support any antibiotic regimen being superior to another. There is a need for a well‐designed RCT assessing the efficacy and safety of ocular antibiotics in the treatment of corneal abrasion with a particular focus on high‐risk populations and formulation of interventions.

Background Apoptosis signal-regulating kinase 1-interacting protein 1 (AIP1) participates in inflammatory neovascularization induction. NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS), leading to an imbalance in nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and NLR family pyrin domain containing 6 (NLRP6) expression. The mechanisms of AIP1, NOX4, ROS and inflammasomes in corneal neovascularization were studied herein. Methods C57BL/6 and AIP1-knockout mice were used in this study. The alkali burn procedure was performed on the right eye. Adenovirus encoding AIP1 plus green fluorescence protein (GFP) (Ad-AIP1-GFP) or GFP alone was injected into the right anterior chamber, GLX351322 was applied as a NOX4 inhibitor, and then corneal neovascularization was scored. The expression of related genes was measured by quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining. 2′,7′-Dichlorofluorescin diacetate staining was used to determine the ROS levels. Results The expression of AIP1 was decreased, while that of cleaved interleukin-1β (clv-IL-1β) and vascular endothelial growth factor A (VEGFa) was increased after alkali burn injury. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. NLRP3/NLRP6 expression was imbalanced after alkali burns. GLX351322 reversed the imbalance in NLRP3/NLRP6 by reducing the ROS levels. This treatment also reduced the expression of clv-IL-1β and VEGFa, suppressing neovascularization. Conclusions AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burn injury. Based on the pathogenesis of corneal neovascularization, these findings are expected to provide new therapeutic strategies for patients. Plain English summary Corneal alkali burn injury is a common type of ocular injury that is difficult to treat in the clinic. The cornea is a clear and avascular tissue. Corneal neovascularization after alkali burn injury is a serious complication; it not only seriously affects the patient’s vision but also is the main reason for failed corneal transplantation. Corneal neovascularization affects approximately 1.4 million patients a year. We show for the first time that AIP1 and NOX4 can regulate corneal inflammation and neovascularization after alkali burns. The expression of AIP1 was decreased, while that of clv-IL-1β and VEGFa was increased after alkali burns. We tried to elucidate the specific molecular mechanisms by which AIP1 regulates corneal neovascularization. NOX4 activation was due to decreased AIP1 expression in murine corneas with alkali burns. NOX4 expression was increased, the imbalance in NLRP3/NLRP6 was exacerbated, and corneal neovascularization was increased significantly in AIP1-knockout mice compared with those in C57BL/6 mice after alkali burns. These effects were reversed by AIP1 overexpression. Additionally, NLRP3/NLRP6 expression was unbalanced, with NLRP3 activation and NLRP6 suppression in the corneal alkali burn murine model. Eye drops containing GLX351322, a NOX4 inhibitor, reversed the imbalance in NLRP3/NLRP6 by reducing ROS expression. This treatment also reduced the expression of clv-IL-1β and VEGFa, reducing neovascularization. Therefore, we provide new gene therapeutic strategies for patients. With the development of neovascularization therapy, we believe that in addition to corneal transplantation, new drug or gene therapies can achieve better results.

PurposeTo determine whether a community health worker (CHW) program increases referrals to local eye care providers and ultimately reduces the incidence of corneal ulcers.DesignCluster-randomized trial performed from 2014 to 2017 in rural South India.MethodsThis was a community-based study that included all inhabitants of 42 rural South Indian communities. CHWs were trained to diagnose corneal abrasions and assist participants in seeking care at a local vision center. Given the nature of the intervention, the trial was not masked. The main outcome measure was incident corneal ulcer, defined as an active infiltrate or evidence of a new opacity, as assessed by means of penlight examination during an annual door-to-door census.ResultsTwenty-one study clusters were randomized to the CHW intervention and 21 to no intervention. Vision centers diagnosed 195 corneal abrasions from the intervention clusters during the 2-year study (rate, 223 per 100,000 person-years; 95% CI, 28-1743) and 62 from the control clusters (rate, 62 per 100,000 person-years; 95% CI, 8-496; incidence rate ratio, 3.57; 95% CI, 2.01-6.35; P < .001). The estimated incidence of corneal ulceration during the study period was 60 per 100,000 person-years (95% CI, 25-141) in the intervention group and 32 per 100,000 person-years (95% CI, 13-80) in the control group (incidence rate ratio, 1.86; 95% CI, 0.5-6.4; P=.32).ConclusionsA CHW program resulted in 3.5 times more referrals to local eye care providers for corneal abrasions, but no difference could be detected in the incidence of corneal ulceration. CHW programs provide a mechanism for increasing referrals to eye hospitals.Trial registrationClinicalTrials.gov ID: NCT02284698.