Infectious keratitis in pediatric population aged less than two years: a tertiary eye institute experience.

BACKGROUND: Infectious keratitis is a serious ocular condition, which can lead to corneal scarring, vision loss, and even blindness. Pediatric infectious keratitis accounts for about 13% of all cases, although there is a lack of comprehensive data regarding keratitis in less than two years of age population group. This study was aimed to determine predisposing factors, clinical characteristics, microbial profile, and management of infectious keratitis in a population of children aged less than two years. MATERIALS AND METHODS: A retrospective study was carried out in a tertiary eye institute over a period of 18 years from July 2005 to December 2022. Collected data was analyzed for demographics, predisposing factors, clinical features, and treatment methods. RESULTS: Fifty-seven cases of keratitis were identified. Age of the patients ranged from 1 to 24 months (Median: 6, interquartile range: 2-10). Thirty cases were male (52.6%). Predisposing factors were identified in 39 cases (68.4%): consisting of prior ocular trauma (n = 15), previous intraocular surgery (n = 11), ocular surface disease (n = 10), nasolacrimal duct obstruction (n = 4), prematurity (n = 3), developmental delay (n = 2), TORCH infection (n = 1), and contact lens (n = 1). Corneal thinning was observed in 29 eyes (50.9%), which progressed to perforation in 13 eyes (22.8%). Three patients developed endophthalmitis (95% CI, 1.5-13.4%). Most eyes had negative smear (60.4%) and culture (59.6%) results. Pseudomonas aeruginosa was the most common microorganism (11 of 21). Candida albicans was isolated in one case. In vitro susceptibility results showed good coverage of the combined ceftazidime and vancomycin regimen (100%). Surgical procedures were carried out in 35 eyes (61.4%) and 15 eyes required tectonic procedures (26.3%). CONCLUSION: Despite good coverage of medical treatment over cultured isolates, surgical tectonic intervention was required in nearly a quarter of cases to resolve the corneal infection. This finding indicates the necessity of prompt patient referring, corneal sampling and initiation of the treatment.

All about traumatic cataracts: narrative review.

Ocular trauma is an important cause of monocular blindness worldwide. Injury to the lens after blunt or penetrating trauma is common and can result in vision impairment. Selecting the most appropriate therapeutic approaches depends on factors such as patients' age, mechanism of trauma, and underlying clinical conditions. Early management, especially within childhood, is essential because of the difficulties involved in examination; anatomical variations; as well as accompanying intraocular inflammation, amblyopia, or vitreoretinal adhesions. The objective of this study was to provide a comprehensive review of the epidemiology and clinical management of traumatic cataract, highlighting the significance of accurate diagnosis and selection of the optimal therapeutic approach.

In praise of povidone-iodine application in ophthalmology.

Polyvinyl pyrrolidone or povidone-iodine (PVP-I) is a water-soluble complex formed by the combination of iodine and a water-soluble polymer, polyvinyl pyrrolidone. This complex exerts bactericidal, fungicidal, and virucidal action by gradually releasing free iodine at the site of application to react with pathogens. In ophthalmology, PVP-I is used as a disinfectant and antiseptic agent for preoperative preparation of the skin and mucous membranes and for treating contaminated wounds. PVP-I has been shown to reduce effectively the risk of endophthalmitis in various ocular procedures, including cataract surgery and intravitreal injections; however, it has also been used in the treatment of conjunctivitis, keratitis, and endophthalmitis, with promising results especially in low-resource situations. PVP-I has been associated with complications such as postoperative eye pain, persistent corneal epithelial defects, ocular inflammation, and an attendant risk of keratitis. In cases of poor PVP-I tolerance, applying PVP-I at lower concentrations or using alternative antiseptics such as chlorhexidine should be considered. We provide an update on the efficacy of PVP-I in the prophylaxis and treatment of conjunctivitis, keratitis, and endophthalmitis and a comprehensive analysis of the current literature regarding the use of PVP-I in the management of these ocular conditions. Also, PVP-I-related adverse effects and toxicities and its alternatives are discussed. The goal is to present a thorough evaluation of the available evidence and to offer practical recommendations for clinicians regarding the therapeutic usage of PVP-I in ophthalmology.

The Potential of Mesenchymal Stem/Stromal Cell Therapy in Mustard Keratopathy: Discovering New Roads to Combat Cellular Senescence.

Mesenchymal stem/stromal cells (MSCs) are considered a valuable option to treat ocular surface disorders such as mustard keratopathy (MK). MK often leads to vision impairment due to corneal opacification and neovascularization and cellular senescence seems to have a role in its pathophysiology. Herein, we utilized intrastromal MSC injections to treat MK. Thirty-two mice were divided into four groups based on the exposure to 20 mM or 40 mM concentrations of mustard and receiving the treatment or not. Mice were clinically and histopathologically examined. Histopathological evaluations were completed after the euthanasia of mice after four months and included hematoxylin and eosin (H&E), CK12, and beta-galactosidase (ß-gal) staining. The treatment group demonstrated reduced opacity compared to the control group. While corneal neovascularization did not display significant variations between the groups, the control group did register higher numerical values. Histopathologically, reduced CK12 staining was detected in the control group. Additionally, ß-gal staining areas were notably lower in the treatment group. Although the treated groups showed lower severity of fibrosis compared to the control groups, statistical difference was not significant. In conclusion, it seems that delivery of MSCs in MK has exhibited promising therapeutic results, notably in reducing corneal opacity. Furthermore, the significant reduction in the ß-galactosidase staining area may point towards the promising anti-senescence potential of MSCs.

From the diagnosis of infectious keratitis to discriminating fungal subtypes; a deep learning-based study.

Infectious keratitis (IK) is a major cause of corneal opacity. IK can be caused by a variety of microorganisms. Typically, fungal ulcers carry the worst prognosis. Fungal cases can be subdivided into filamentous and yeasts, which shows fundamental differences. Delays in diagnosis or initiation of treatment increase the risk of ocular complications. Currently, the diagnosis of IK is mainly based on slit-lamp examination and corneal scrapings. Notably, these diagnostic methods have their drawbacks, including experience-dependency, tissue damage, and time consumption. Artificial intelligence (AI) is designed to mimic and enhance human decision-making. An increasing number of studies have utilized AI in the diagnosis of IK. In this paper, we propose to use AI to diagnose IK (model 1), differentiate between bacterial keratitis and fungal keratitis (model 2), and discriminate the filamentous type from the yeast type of fungal cases (model 3). Overall, 9329 slit-lamp photographs gathered from 977 patients were enrolled in the study. The models exhibited remarkable accuracy, with model 1 achieving 99.3%, model 2 at 84%, and model 3 reaching 77.5%. In conclusion, our study offers valuable support in the early identification of potential fungal and bacterial keratitis cases and helps enable timely management.

Artificial Intelligence and Infectious Keratitis: Where Are We Now?

Infectious keratitis (IK), which is one of the most common and catastrophic ophthalmic emergencies, accounts for the leading cause of corneal blindness worldwide. Different pathogens, including bacteria, viruses, fungi, and parasites, can cause IK. The diagnosis and etiology detection of IK pose specific challenges, and delayed or incorrect diagnosis can significantly worsen the outcome. Currently, this process is mainly performed based on slit-lamp findings, corneal smear and culture, tissue biopsy, PCR, and confocal microscopy. However, these diagnostic methods have their drawbacks, including experience dependency, tissue damage, cost, and time consumption. Diagnosis and etiology detection of IK can be especially challenging in rural areas or in countries with limited resources. In recent years, artificial intelligence (AI) has opened new windows in medical fields such as ophthalmology. An increasing number of studies have utilized AI in the diagnosis of anterior segment diseases such as IK. Several studies have demonstrated that AI algorithms can diagnose and detect the etiology of IK accurately and fast, which can be valuable, especially in remote areas and in countries with limited resources. Herein, we provided a comprehensive update on the utility of AI in IK.

Post-laser refractive surgery keratitis: A concise narrative review.

Laser refractive surgery (LRS) is a specialized surgical discipline within ophthalmology that focuses on vision correction via laser techniques. LRS requires a high rate of accuracy and exactitude to improve the visual outcome and minimize complications, which may lead to delayed visual recovery. Keratitis, either infectious or noninfectious, is a post-LRS complication that requires early diagnosis and proper interventional measures. In this narrative review, we summarize different aspects of keratitis following LRS. This literature review aims to provide a thorough understanding of the causes of post-LRS infectious keratitis and its appropriate management for successful outcomes.

Impact of coronary artery bypass grafting surgery on the chorioretinal biomicroscopic characteristics.

BACKGROUND: Most patients with cardiovascular disorders suffer from coronary artery diseases, which can be treated successfully using coronary artery bypass grafting (CABG). One of the unpleasant events following CABG is postoperative vision loss (POVL). Vulnerability of retinal vessels to hemodynamic changes, an expectable event following CABG, may contribute to the development of POVL, which might be associated with the changes in the choroidal and retinal structures. AIM: To investigate postoperative changes in chorioretinal and peripapillary nerve fiber layer (NFL) thickness, and progression of diabetic and hypertensive retinopathy after CABG. METHODS: In this prospective, cross-sectional study, 49 eyes in 25 candidates for CABG underwent both ophthalmic and cardiovascular examinations within 6 mo prior to and 9 mo after surgery. RESULTS: Among the study participants, 56% were male with a mean age of 62.84 years ± 10.49 years (range 33-80 years). Diabetes mellitus was observed in eight participants (32%). None of the patients suffered from postoperative anterior or posterior ischemic optic neuropathy, central retinal artery occlusion, and cortical blindness. The mean value of the preoperative best corrected visual acuity was 0.11 ± 0.10 logMAR (range, 0-0.4), which worsened to 0.15 ± 0.08 logMAR (range, 0-0.4) after CABG (P = 0.031). No significant difference was observed between the pre- and postsurgical choroidal (P = 0.853) and macular (P = 0.507) thickness, NFL thickness in the subfoveal (P > 0.999) and peripapillary areas (P = 0.659), as well as the severity of diabetic and hypertensive retinopathy. CONCLUSION: CABG may reduce visual acuity without affecting ocular structures. Postoperative vision reduction might be attributable to molecular or cellular variations, changes in visual pathway function, or central nervous system.

Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair.

PURPOSE: Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model. METHODS: Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining. RESULTS: hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks). CONCLUSIONS: Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.

A Case Series of Infectious Keratitis After Corneal Cross-linking.

PURPOSE: To present the 7-year experience of a tertiary eye hospital while exploring possible risk factors and incidence of infectious keratitis in patients undergoing standard corneal cross-linking (CXL). METHODS: This retrospective cohort study included patients with progressive keratoconus undergoing standard CXL in the Farabi Eye Hospital and all other patients who had undergone CXL in other facilities and were diagnosed as having infectious keratitis in the 7-year period of the study. RESULTS: Among the total of 4,863 eyes that underwent CXL, 6 eyes developed infectious keratitis, yielding an incidence rate of 0.12%. Additionally, 13 eyes from 10 patients with a CXL history in other facilities who developed infectious keratitis were included. The mean age was 23.75 years, and 75% of patients were men and 25% were women. Gram-positive bacteria and Staphylococcus aureus were the most prevalent pathogens. Meibomian gland dysfunction, dry eye disease, or blepharitis were present in 12 patients. Medical treatment did not arrest the disease progress in 5 patients, which eventually required cases to undergo keratoplasty. CONCLUSIONS: This study supports the need for proper patient selection by using a comprehensive medical history. It also highlights the imperative role of rigorous patient education and follow-up, particularly in the first postoperative week. Finally, the study emphasizes aggressive early therapy for patients with suspicious findings. [J Refract Surg. 2023;39(8):564-572.].

Cellular senescence implication in mustard keratopathy.

Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.

Application of biomaterials and nanotechnology in corneal tissue engineering.

Corneal diseases are among the most common causes of blindness worldwide. Regardless of the etiology, corneal opacity- or globe integrity-threatening conditions may necessitate corneal replacement procedures. Several procedure types are currently available to address these issues, based on the complexity and extent of injury. Corneal allograft or keratoplasty is considered to be first-line treatment in many cases. However, a significant proportion of the world's population are reported to have no access to this option due to limitations in donor preparation. Thus, providing an appropriate, safe, and efficient synthetic implant (e.g., artificial cornea) may revolutionize this field. Nanotechnology, with its potential applications, has garnered a lot of recent attention in this area, however, there is seemingly a long way to go. This narrative review provides a brief overview of the therapeutic interventions for corneal pathologies, followed by a summary of current biomaterials used in corneal regeneration and a discussion of the nanotechnologies that can aid in the production of superior implants.

Outbreak of methanol-induced optic neuropathy in early COVID-19 era; effectiveness of erythropoietin and methylprednisolone therapy.

BACKGROUND: Methanol is a highly toxic, non-potable alcohol. Outbreaks of methanol toxicity occur due to its fraudulent addition to alcoholic beverages as a cheaper substitute for ethanol. Recently, alongside the coronavirus disease 2019 (COVID-19) pandemic, rumors circulated on social media that consuming alcohol can prevent or cure the virus, leading to a COVID-19 and methanol-induced optic neuropathy (MON) syndemic. AIM: To investigate the impact of erythropoietin (EPO) on the outcomes of patients diagnosed with MON. METHODS: In this prospective study, 105 patients presenting with acute bilateral visual loss secondary to methanol intoxication were enrolled from March to May 2020 at Farabi Eye Hospital. A comprehensive ocular examination was conducted for all participants. Recombinant human EPO and methylprednisolone were administered intravenously to all patients for three consecutive days. RESULTS: The mean age of the participants was 39.9 years (± 12.6). Ninety-four patients were male and eleven were female. The mean pre-treatment best corrected visual acuity (BCVA) improved from 2.0 ± 0.86 to 1.39 ± 0.69 logarithm of the minimum angle of resolution post-treatment (P < 0.001), with significant improvement observed in all age categories and genders (P < 0.001). Visual acuity improvement was also significant regardless of whether the patient presented before or after 72 h (P < 0.001), and the post-treatment BCVA remained significant at all monthly follow-up visits (P < 0.001). CONCLUSION: EPO and methylprednisolone therapy have been shown to be effective in improving visual outcomes in patients with MON when administrated within the first month of exposure. Public awareness efforts are necessary to prevent further outbreaks of methanol toxicity in the current COVID-19 era.

Clinical Features, Risk Factors, and Management of Candida Keratitis.

BACKGROUND/AIMS: To determine the clinical features, predisposing factors, and management of infectious keratitis caused by Candida spp. METHODS: Retrospective chart review. RESULTS: The medical records of 52 patients (54 eyes) with Candida keratitis were available for statistical analysis. Thinning of the corneal stroma was identified in 34 eyes (63.0%), and corneal perforation occurred in 16 eyes (29.6%). Corneal thinning and perforation were more common in Candida albicans compared with non-albicans (P-val < .001, P = .09, respectively). The most common predisposing factors for Candida keratitis were topical steroid use (21 patients, 40.4%), previous corneal transplantation (17 patients, 32.7%), and preexisting ocular surface disease (15 patients, 28.8%). Fourteen eyes (25.9%) required cyanoacrylate glue application and 10 eyes (18.5%) underwent therapeutic penetrating keratoplasty (TPK). CONCLUSION: Local immunosuppression and ocular surface disease play an important role in Candida keratitis. C. albicans appears to be more invasive compared with non-albicans spp.

Cellular senescence and ophthalmic diseases: narrative review.

PURPOSE: Cellular senescence is a state of permanent growth arrest whereby a cell reaches its replicative limit. However, senescence can also be triggered prematurely in certain stressors including radiation, oxidative stress, and chemotherapy. This stress-induced senescence has been studied in the context of promoting inflammation, tumor development, and several chronic degenerative diseases of aging. Emerging research has elucidated the role of senescence in various ocular diseases. METHODS: The literature search was performed using PubMed with using the query (senescence OR aging) AND (eye disease OR ocular disease OR ophthalmic disease OR cornea OR glaucoma OR cataract OR retina) on October 20th, 2022. No time restriction was proposed. Articles were excluded if they were not referenced in English. RESULTS: Overall, 51 articles regarding senescence and ocular diseases were found and summarized in this study. Several signaling pathways have been implicated in the development of senescence. Currently, senescence has been linked to various corneal and retinal pathologies, as well as cataract and glaucoma. Given the number of pathologies, senolytics, which are small molecules with the ability to selective targeting of senescent cells, can be used as therapeutic or prophylactic agents. CONCLUSIONS: Senescence has been shown to underlie the pathogenesis of numerous ocular diseases. The overall literature on senescence and ocular disease is growing rapidly. There is an ongoing debate whether or not cellular senescence detected in experiments contributes in a significant way to diseases. Research on understanding the mechanism of senescence from ocular cells and tissues is just beginning. Multiple animal models are required to test potential senolytics. Currently, no studies exist to date which have demonstrated the benefits of senolytic therapies in human studies.

Ocular graft-versus-host disease (oGVHD): From A to Z.

Allogeneic hematopoietic stem cell transplantation is a definitive therapy for a variety of disorders. One of the complications is acute graft-versus-host disease (aGVHD), which has a high mortality rate. Patients can also develop chronic graft-versus-host disease (cGVHD), a more indolent yet afflicting condition that affects up to 70% of patients. Ocular involvement (oGVHD) is one of the most prevalent presentations of cGVHD and can manifest as dry eye disease, meibomian gland dysfunction, keratitis, and conjunctivitis. Early recognition of ocular involvement using regular clinical assessments as well as robust biomarkers can aid in better management and prevention. Currently, the therapeutic strategies for the management of cGVHD, and oGVHD in particular, have mainly focused on the control of symptoms. There is an unmet need for translating the preclinical and molecular understandings of oGVHD into clinical practice. Herein, we have comprehensively reviewed the pathophysiology, pathologic features, and clinical characteristics of oGVHD and summarized the therapeutic landscape available to combat it. We also discuss the direction of future research regarding a more directed delineation of pathophysiologic underpinnings of oGVHD and the development of preventive interventions.

Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." RESULTS: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. CONCLUSIONS: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

Bacillary Layer Detachment in Diabetic Retinopathy: A Case Report.

To our knowledge, this is the first report to describe bacillary layer detachment (BLD) in a patient with diabetic retinopathy treated with anti-vascular endothelial growth factor. We present the case of a 55-year-old diabetic female who was referred to our hospital complaining of decreased vision in her left eye for 2 weeks. Fundus examination of both eyes was compatible with diabetic retinopathy. Spectral-domain optical coherence tomography of the left eye showed a large dome-shaped cystic space with marginal septa, splitting the myoid zone, consistent with the BLD phenotype. A single dose of intravitreal bevacizumab injection was administered. After 4 weeks, BCVA was improved significantly with complete resolution of BLD. Underlying choroidal ischemia in patients with different vascular disorders like diabetes mellitus may lead to photoreceptor stress and BLD. This study adds to the growing literature, which describes BLD as a marker of fluid accumulation in relation to several macular diseases.

Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery.

INTRODUCTION: Mesenchymal stem cells (MSCs) are novel, promising agents for treating ocular surface disorders. MSCs can be isolated from several tissues and delivered by local or systemic routes. They produce several trophic factors and cytokines, which affect immunomodulatory, transdifferentiating, angiogenic, and pro-survival pathways in their local microenvironment via paracrine secretion. Moreover, they exert their therapeutic effect through a contact-dependent manner. AREAS COVERED: In this review, we discuss the characteristics, sources, delivery methods, and applications of MSCs in ocular surface disorders. We also explore the potential application of MSCs to inhibit senescence at the ocular surface. EXPERT OPINION: Therapeutic application of MSCs in ocular surface disorders are currently under investigation. One major research area is corneal epitheliopathies, including chemical or thermal burns, limbal stem cell deficiency, neurotrophic keratopathy, and infectious keratitis. MSCs can promote corneal epithelial repair and prevent visually devastating sequelae of non-healing wounds. However, the optimal dosages and delivery routes have yet to be determined and further clinical trials are needed to address these fundamental questions.

Concise Review: Bioengineering of Limbal Stem Cell Niche.

The corneal epithelium is composed of nonkeratinized stratified squamous cells and has a significant turnover rate. Limbal integrity is vital to maintain the clarity and avascularity of the cornea as well as regeneration of the corneal epithelium. Limbal epithelial stem cells (LESCs) are located in the basal epithelial layer of the limbus and preserve this homeostasis. Proper functioning of LESCs is dependent on a specific microenvironment, known as the limbal stem cell niche (LSCN). This structure is made up of various cells, an extracellular matrix (ECM), and signaling molecules. Different etiologies may damage the LSCN, leading to limbal stem cell deficiency (LSCD), which is characterized by conjunctivalization of the cornea. In this review, we first summarize the basics of the LSCN and then focus on current and emerging bioengineering strategies for LSCN restoration to combat LSCD.