Prevalence and Outcomes of High versus Low Ratio Plasma to Red Blood Cell Resuscitation in a Multi-Institutional Cohort of Severely Injured Children.

BACKGROUND: The benefit of targeting high ratio fresh frozen plasma (FFP):red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP:RBC transfusion and the association with outcomes in children presenting in shock. METHODS: A post-hoc analysis of a 24-institution prospective observational study (4/2018-9/2019) of injured children <18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (>1:2) ratio FFP:RBC. Nonparametric Kruskal-Wallis and chi-square were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths. RESULTS: Of 135 children with median (IQR) age 10 (5,14) years and weight 40 (20,64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (MTP; low-38%, high-46%, p = .34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = .01); however, hospital mortality was similar (low-24%, high-20%, p = .65) as was the risk of extended ventilator, ICU, and hospital days (all p > .05). CONCLUSION: Despite increased injury severity, patients who received a high ratio of FFP:RBC had comparable rates of mortality. These data suggest high ratio FFP:RBC resuscitation is not associated with worst outcomes in children who present in shock. MTP activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer.

PURPOSE: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety. METHODS: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test. RESULTS: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug. CONCLUSION: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial.

Prevalence and clinical characteristics of neurotrophic keratopathy in hispanic population in northeastern Mexico.

PURPOSE: To evaluate the prevalence and clinical characteristics of neurotrophic keratopathy (NK) in northeastern Mexico. METHODS: Retrospective cross-sectional study in which NK patients admitted to our ophthalmology clinic between 2015 and 2021 were consecutively enrolled. Data regarding demographics, clinical characteristics, and comorbidities were collected at the time diagnosis of NK was made. RESULTS: In the period from 2015 to 2021, a total of 74,056 patients were treated and of these 42 had a diagnosis of neurotrophic keratitis. The prevalence found was 5.67 [CI95 3.95-7.38] in 10,000 cases. The mean age observed was 59 ± 17.21 years occurring more frequently in males in 59% and with corneal epithelial defects in 66.7%. The most frequent antecedents were the use of topical medications in 90%, the presence of diabetes mellitus 2 in 40.5% and systemic arterial hypertension in 26.2%. A higher proportion of male patients with corneal alterations and a higher proportion of female patients with corneal ulcerations and/or perforation were observed. CONCLUSION: Neurotrophic keratitis is an underdiagnosed disease with a broad clinical spectrum. The antecedents that were contracted corroborate what was reported in the literature as risk factors. The prevalence of the disease in this geographical area was not reported, so it is expected to increase over time when searching for it intentionally.

Crystalloid volume is associated with short-term morbidity in children with severe traumatic brain injury: An Eastern Association for the Surgery of Trauma multicenter trial post hoc analysis.

OBJECTIVE: This study examined differences in clinical and resuscitation characteristics between injured children with and without severe traumatic brain injury (sTBI) and aimed to identify resuscitation characteristics associated with improved outcomes following sTBI. METHODS: This is a post hoc analysis of a prospective observational study of injured children younger than 18 years (2018-2019) transported from the scene, with elevated shock index pediatric-adjusted on arrival and head Abbreviated Injury Scale score of ≥3. Timing and volume of resuscitation products were assessed using χ 2t test, Fisher's exact t test, Kruskal-Wallis, and multivariable logistic regression analyses. RESULTS: There were 142 patients with sTBI and 547 with non-sTBI injuries. Severe traumatic brain injury patients had lower initial hemoglobin (11.3 vs. 12.4, p < 0.001), greater initial international normalized ratio (1.4 vs. 1.1, p < 0.001), greater Injury Severity Score (25 vs. 5, p < 0.001), greater rates of ventilator (59% vs. 11%, p < 0.001) and intensive care unit (ICU) requirement (79% vs. 27%, p < 0.001), and more inpatient complications (18% vs. 3.3%, p < 0.001). Severe traumatic brain injury patients received more prehospital crystalloid (25% vs. 15%, p = 0.008), ≥1 crystalloid boluses (52% vs. 24%, p < 0.001), and blood transfusion (44% vs. 12%, p < 0.001) than non-sTBI patients. Among sTBI patients, receipt of ≥1 crystalloid bolus (n = 75) was associated with greater ICU need (92% vs. 64%, p < 0.001), longer median ICU (6 vs. 4 days, p = 0.027) and hospital stay (9 vs. 4 days, p < 0.001), and more in-hospital complications (31% vs. 7.5%, p = 0.003) than those who received <1 bolus (n = 67). These findings persisted after adjustment for Injury Severity Score (odds ratio, 3.4-4.4; all p < 0.010). CONCLUSION: Pediatric trauma patients with sTBI received more crystalloid than those without sTBI despite having a greater international normalized ratio at presentation and more frequently requiring blood products. Excessive crystalloid may be associated with worsened outcomes, including in-hospital mortality, seen among pediatric sTBI patients who received ≥1 crystalloid bolus. Further attention to a crystalloid sparing, early transfusion approach to resuscitation of children with sTBI is needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Customizable Collagen Vitrigel Membranes and Preliminary Results in Corneal Engineering.

Corneal opacities are a leading cause of visual impairment that affect 4.2 million people annually. The current treatment is corneal transplantation, which is limited by tissue donor shortages. Corneal engineering aims to develop membranes that function as scaffolds in corneal cell transplantation. Here, we describe a method for producing transplantable corneal constructs based on a collagen vitrigel (CVM) membrane and corneal endothelial cells (CECs). The CVMs were produced using increasing volumes of collagen type I: 1X (2.8 µL/mm2), 2X, and 3X. The vitrification process was performed at 40% relative humidity (RH) and 40 °C using a matryoshka-like system consisting of a shaking-oven harboring a desiccator with a saturated K2CO3 solution. The CVMs were characterized via SEM microscopy, cell adherence, FTIR, and manipulation in an ex vivo model. A pilot transplantation of the CECs/CVM construct in rabbits was also carried out. The thickness of the CVMs was 3.65-7.2 µm. The transparency was superior to a human cornea (92.6% = 1X; 94% = 2X; 89.21% = 3X). SEM microscopy showed a homogenous surface and laminar organization. The cell concentration seeded over the CVM increased threefold with no significant difference between 1X, 2X, and 3X (p = 0.323). The 2X-CVM was suitable for surgical manipulation in the ex vivo model. Constructs using the CECs/2X-CVM promoted corneal transparency restoration.

Human Colonization with Antibiotic-Resistant Bacteria from Nonoccupational Exposure to Domesticated Animals in Low- and Middle-Income Countries: A Critical Review.

Data on community-acquired antibiotic-resistant bacterial infections are particularly sparse in low- and middle-income countries (LMICs). Limited surveillance and oversight of antibiotic use in food-producing animals, inadequate access to safe drinking water, and insufficient sanitation and hygiene infrastructure in LMICs could exacerbate the risk of zoonotic antibiotic resistance transmission. This critical review compiles evidence of zoonotic exchange of antibiotic-resistant bacteria (ARB) or antibiotic resistance genes (ARGs) within households and backyard farms in LMICs, as well as assesses transmission mechanisms, risk factors, and environmental transmission pathways. Overall, substantial evidence exists for exchange of antibiotic resistance between domesticated animals and in-contact humans. Whole bacteria transmission and horizontal gene transfer between humans and animals were demonstrated within and between households and backyard farms. Further, we identified water, soil, and animal food products as environmental transmission pathways for exchange of ARB and ARGs between animals and humans, although directionality of transmission is poorly understood. Herein we propose study designs, methods, and topical considerations for priority incorporation into future One Health research to inform effective interventions and policies to disrupt zoonotic antibiotic resistance exchange in low-income communities.

The evolution of the modified osteo-odonto-keratoprosthesis, its reliability, and long-term visual rehabilitation prognosis: An analytical review.

An exhaustive search of the world's literature was performed to analyze all case reports and series on the modified osteo-odonto-keratoprosthesis (MOOKP) published up to January 2022. The demographic profile, the primary indication for surgery, surgical technique variations, postoperative medical management, long-term functional and anatomical outcomes, and intra- and postoperative complications were analyzed and compared. Additionally, some of the authors' (GI, VP, and GA) unpublished MOOKP cases were studied. An extensive literature search yielded 37 case series and case reports. Overall, 958 patients were analyzed. The most common indication for surgery was autoimmune disease (39.1%), closely followed by chemical injury (38.8%). The most common intraoperative complications (21.67%) included maxillofacial, vitreous hemorrhage/vitritis, and mucosal. The most common postoperative complications (78.4%) were lamina and oral mucosa-associated, secondary glaucoma, and choroid/retinal detachment. Follow-up periods ranged from one to 364 months (median: 36.7 months). Altogether, 78% of patients achieved a visual acuity of 20/400 or better at the end of the follow-up period, and 91.2% improved at least temporarily after MOOKP surgery. Mean anatomic success at the end-of-follow-up for all patients was 88.25% (range, 50-100%). The long-term anatomic and functional success of the MOOKP makes it a reliable option for visual rehabilitation in patients with bilateral corneal blindness and end-stage ocular surface disease. This review aims to describe the evolution of the MOOKP procedure, analyzing all published case series for its long-term reliability, visual and anatomical outcomes, complications, and future directions.

Virtual Visits for Outpatient Burn Care During the COVID-19 Pandemic.

Burn-injured patients must frequently travel long distances to regional burn centers, creating a burden on families and impairing clinical outcomes. Recent federal policies in response to the coronavirus pandemic have relaxed major barriers to conducting synchronous videoconference visits in the home. However, the efficacy and benefits of virtual visits relative to in-person visits remained unclear for burn patients. Accordingly, a clinical quality assurance database maintained during the coronavirus pandemic (3/3/2020 to 9/8/2020) for virtual and/or in-person visits at a comprehensive adult and pediatric burn center was queried for demographics, burn severity, visit quality, and distance data. A total of 143 patients were included in this study with 317 total outpatient encounters (61 virtual and 256 in-person). The savings associated with the average virtual visit were 130 ± 125 miles (mean ± standard deviation), 164 ± 134 travel minutes, $104 ± 99 driving costs, and $81 ± 66 foregone wage earnings. Virtual visit technical issues were experienced by 23% of patients and were significantly lower in pediatric (5%) than in adult patients (44%; P = .006). This study is the first to assess the efficacy of synchronous videoconference visits in the home setting for outpatient burn care. The findings demonstrate major financial and temporal benefits for burn patients and their families. Technical issues remain an important barrier, particularly for the adult population. A clear understanding of these and other barriers may inform future studies as healthcare systems and payors move toward improving access to burn care through remote healthcare delivery services.

Groundwater-surface water interactions and flux of organic matter and nutrients in an urban, Mediterranean stream.

The chemical quality of dissolved organic matter (DOM) and the speciation of nitrogen exported from urban catchments is of great importance to biogeochemical cycling in riverine and coastal receiving waters. Many urban streams in Mediterranean climates have a flashy hydrologic regime, which would suggest a rapid pulsing and shunting of solutes downstream. However, the role of these systems both as passive pipes for solute transport or as reactors for DOM and nutrient transformation is still an open question for urban, Mediterranean streams. To address this question, we evaluated changes in concentrations of inorganic and organic solutes and DOM optical properties in Alvarado Creek, a perennially-flowing, urban, first-order tributary of the San Diego River in San Diego, CA, USA, during dry weather (baseflow) conditions and during four storm events in 2016-2018. Chloride and sulfate concentrations corroborate the supposed saline groundwater supply that maintains perennial flow and brackish nature in this urban stream. During dry weather, high proportions of protein-like fluorescent component (AC4) and downstream decreases in total dissolved nitrogen (TDN) and nitrate imply in-stream processing (nitrification and denitrification). By contrast, storm hysteresis curves indicate that the supply of DOM and TDN was not exhausted over the duration of a storm event, whereas nitrate was eventually depleted, presumably because nitrification could not keep up with the export of nitrate from source areas. Rapid decreases in chloride during the storm hydrograph coincided with a shift in specific ultraviolet absorbance (SUVA) and fluorescence index (FI) to more terrestrially-derived and aromatic carbon sources, most likely from interflow of stormwater through vadose zone soils. On an annual basis, the export of microbially-derived DOM during dry weather was higher than the export of terrestrially-derived DOM during storm events; both represent important carbon inputs to coastal waters.

Phytochemical Profile and Antioxidant and Antiproliferative Activity of Sedum dendroideum on Pterygium Fibroblasts.

BACKGROUND: Sedum dendroideum has antioxidant effects that are beneficial for different diseases. We aimed to analyze the antiproliferative activity of S. dendroideum in human pterygium fibroblasts (HPFs). METHODS: HPFs were treated for 24 h with 0-1000 µg/mL of S. dendroideum lyophilized to analyze its effect on cell viability using the CellTiter assay. RNA from HPF treated with 250 µg/mL of S. dendroideum lyophilized was isolated, and the expression of VEGF and CTGF genes was evaluated by qPCR. A dermal fibroblast cell line (HDFa) was used as a healthy control. The total phenolic content, antioxidant activity, and chemical profile of S. dendroideum lyophilized were determined. RESULTS: Viability of HPF decreased after 24 h treatment of S. dendroideum in a dose-dependent manner. The expression of VEGF and CTGF significantly decreased (P < 0.01) in HPF treated with 250 µg/mL of S. dendroideum when compared with untreated HPF. The total phenolic concentration in the S. dendroideum lyophilized was 33.67 mg gallic acid equivalents (GAE)/g. Antioxidant activity was 384.49 mM Trolox equivalents/mL. The main phenolic compounds identified by HPLC analysis were the kaempferol-3-O-glycoside, kaempferol-3-O-rhamnoside, kaempferol-3-O-neohesperidoside-7-O-α-rhamnopyranoside, and kaempferol-3-O-glycoside-7-O-rhamnoside. CONCLUSIONS: S. dendroideum decreases the proliferation of HPF and the expression of VEGF and CTGF. The phenolic compound concentration, antioxidant activity, and phytochemical profile may play a role in these effects.

Overcoming PD-1 Inhibitor Resistance with a Monoclonal Antibody to Secreted Frizzled-Related Protein 2 in Metastatic Osteosarcoma.

Secreted frizzled-related protein 2 (SFRP2) promotes the migration/invasion of metastatic osteosarcoma (OS) cells and tube formation by endothelial cells. However, its function on T-cells is unknown. We hypothesized that blocking SFRP2 with a humanized monoclonal antibody (hSFRP2 mAb) can restore immunity by reducing CD38 and PD-1 levels, ultimately overcoming resistance to PD-1 inhibitors. Treating two metastatic murine OS cell lines in vivo, RF420 and RF577, with hSFRP2 mAb alone led to a significant reduction in the number of lung metastases, compared to IgG1 control treatment. While PD-1 mAb alone had minimal effect, hSFRP2 mAb combination with PD-1 mAb had an additive antimetastatic effect. This effect was accompanied by lower SFRP2 levels in serum, lower CD38 levels in tumor-infiltrating lymphocytes and T-cells, and lower PD-1 levels in T-cells. In vitro data confirmed that SFRP2 promotes NFATc3, CD38 and PD-1 expression in T-cells, while hSFRP2 mAb treatment counteracts these effects and increases NAD+ levels. hSFRP2 mAb treatment further rescued the suppression of T-cell proliferation by tumor cells in a co-culture model. Finally, hSFRP2 mAb induced apoptosis in RF420 and RF577 OS cells but not in T-cells. Thus, hSFRP2 mAb therapy could potentially overcome PD-1 inhibitor resistance in metastatic osteosarcoma.

High-Fat Diet Drives an Aggressive Pancreatic Cancer Phenotype.

BACKGROUND: Emerging evidence indicates associations between high-fat diet (HFD), metabolic syndrome (MetS), and increased risk of pancreatic cancer. However, individual components of an HFD that increase cancer risk have not been isolated. In addition, a specific pattern of cytokine elevation by which MetS drives pancreatic tumor progression is not well described. We hypothesized that oleic acid (OA), a major component of HFD, would augment pancreatic neoplastic processes. METHODS: An orthotopic pancreatic cancer model with Panc02 cells was used to compare the effect of low-fat diet to OA-based HFD on cancer progression. Tumors were quantitated, analyzed by immunohistochemistry. In addition, serum cytokine levels were quantitated. Proliferation, migration assays, and expression of epithelial-to-mesenchymal transition factors were evaluated on Panc02 and MiaPaCa-2 pancreatic cancer cells cultured in high concentrations of OA. RESULTS: HFD tumor-bearing mice (n = 8) had an 18% weight increase (P < 0.001) and increased tumor burden (P < 0.05) compared with the low-fat diet tumor-bearing group (n = 6). HFD tumors had significantly increased angiogenesis (P < 0.001) and decreased apoptosis (P < 0.05). Serum of HFD mice demonstrated increased levels of glucagon and glucagon-like peptide-1. Two pancreatic cancer cell lines cultured in OA demonstrated significant increases in proliferation (P < 0.001) and a >2.5-fold increase in cell migration (P < 0.001) when treated with OA. Panc02 treated with OA had increased expression of epithelial-to-mesenchymal transition factors SNAI-1 (Snail) and Zeb-1(P < 0.01). CONCLUSIONS: High-fat conditions in vitro and in vivo resulted in an aggressive pancreatic cancer phenotype. Our data support further investigations elucidating molecular pathways augmented by MetS conditions to identify novel therapeutic strategies for pancreatic cancer.

Resident-Driven Wellness Initiatives Improve Resident Wellness and Perception of Work Environment.

BACKGROUND: Resident burnout is associated with increased adverse patient events and increased incidence of resident depression and suicide when compared to the general population. We hypothesized that resident-driven assessment and implementation of wellness measures would allow implementation of desired interventions and facilitate improvement in wellness. METHODS: A wellness intervention team was established to address resident wellness and job satisfaction. A needs assessment to determine desired interventions as well as a three-part anonymous 5-point Likert scale survey was developed and distributed to general surgery residents. Following implementation of three measures, a postintervention survey was administered at 6 and 15 mo to the same cohort. Analysis of variance test was used to evaluate for significant difference between preintervention and postintervention surveys. RESULTS: Three interventions were implemented: two protected weekday personal days per year, modernization of resident workspace, and additional meal funds. There were statistically significant changes in perceptions of wellness opportunities (3.14 versus 3.88 and 3.7; P < 0.05), time for wellness (2.53 versus 3.42 and 3.2; P < 0.05), work/life balance satisfaction (2.86 versus 3.71 and 3.41; P < 0.05), and improved quality of life (2.67 versus 3.3 and 3.0; P < 0.05) in both 6-mo and 15-mo postintervention responses. CONCLUSIONS: Implementation of resident-selected wellness measures was found to influence overall resident satisfaction and improved perception of the working environment. Several scores of wellness items showed sustained improvement at 15 mo. These results suggest that resident-driven wellness interventions can positively affect working conditions for residents.

Update on indications, complications, and outcomes of scleral contact lenses.

Background: The role of scleral contact lenses (SCLs) has increasingly expanded since the first lens was fitted more than a century ago. While it was initially prescribed for the management of severely compromised corneas, the indications for modern SCL use have expanded to include less severe diseases. In this review, we aimed to provide an up-to-date overview of the current indications, complications, and outcomes for the various types of SCLs. Methods: In this narrative review, we thoroughly searched the PubMed/MEDLINE database for literature published from January 1980 to November 2021. Only relevant up-to-date English references were included. Furthermore, the figures in this manuscript were derived from our unit's patient documentation. Results: Currently, SCLs can successfully be used to manage ocular surface diseases, visually rehabilitate irregular corneas, and correct irregular refractive errors. Although newer materials have yielded the same visual outcomes with fewer complications, these consequences still occur in approximately one-third of contact lens wearers, including difficulties in insertion and/or removal, discomfort or pain, and developing either halos, blurriness, or haze. Even though most of these complications are minor and can be easily treated, a good practice is essential to avoid sight-threatening complications such as microbial keratitis. Conclusions: SCLs are indispensable in ophthalmic clinics. The development of better-quality SCLs has increased the number of indications and improved the achievable visual rehabilitation. The future of developing improvements in SCL design, materials, and fit, and the expansion of their indication range is promising.

Long-term outcomes of pediatric laparoscopic needled-assisted inguinal hernia repair: A 10-year experience.

PURPOSE: Laparoscopic inguinal hernia repair (LIHR) has gained wide acceptance over the past decade, although studies with longer term follow-up are lacking. We present one of the largest cohorts of children undergoing laparoscopic needle-assisted repair (LNAR) with long-term follow-up. METHODS: A clinical quality database was maintained for children ≤14 years of age who underwent laparoscopic needle-assisted repair between 2009 and 2017 with review of follow-up through 2019. De-identified data was reviewed. RESULTS: 1023 patients with 1457 LNAR were included during the 10-year period. Mean age at surgery was 2.56 years (2 days to14 years). The overall hernia recurrence rate was 0.75% (11/1457). A total of four postoperative hydroceles required intervention. Preterm infant repair done <60w post conceptional age had a significantly lower recurrence rate (0.63%) than other patients (0.82%) (p < 0.01). 64.2% of patients had clinical follow-up over a period of 11 years with a mean follow-up of 5.97 years. CONCLUSION: We present a large cohort study of consecutive pediatric laparoscopic hernia repairs followed over an 11-year period. LNAR is safe and effective for term and preterm patients with similar complication rates to other techniques, including open repair. Additionally, our results suggest that preterm infants may have superior outcomes with this method. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.

The molecular basis of neurotrophic keratopathy: Diagnostic and therapeutic implications. A review.

Neurotrophic keratopathy (NK) is a degenerative corneal disease produced by different factors, including infection, trauma, and neurogenesis, that lead to trigeminal nerve damage and impaired corneal sensitivity. Extensive epithelial breakdown, impaired corneal epithelial healing and corneal ulceration, stromal melting, and perforation are main NK features. The proliferation of the corneal epithelium is endogenously regulated by a balance between adrenergic cAMP-dependent and cholinergic cGMP-dependent pathways. A careful balance of epitheliotropic neuromediators and neurotrophic factors expressed by corneal nerves and epithelial cells, respectively, is required to maintain corneal homeostasis. Even in its early stages, NK can cause reduced vision secondary to epithelial disturbance. Diagnosing NK is challenging, requiring the acquisition of a thorough clinical history and a comprehensive neurological and ophthalmic examination. Following suspicion of a clinical NK diagnosis, corneal sensitivity must be assessed qualitatively with the wisp of the cotton-tipped applicator and quantitatively through Cochet-Bonnet esthesiometry (CBE). A myriad of therapies is used for NK, and new, more specific modalities are being developed and investigated. Medical treatment with topical recombinant human nerve growth factor and surgical treatment through corneal neurotization are promising therapies aiming to target NK pathophysiology. Coexistent ocular surface disorders must be managed concomitantly to improve its prognosis. This review describes the up-to-date knowledge of the molecular basis regarding the pathogenesis of NK, and the novel target-specific therapeutic approaches based on this molecular mechanism.