Immediate and Delayed Effects of Punctal Plug Insertion on Tear Meniscus Height in Severe Aqueous-Deficient Dry Eye.

PURPOSE: The aim of this study was to assess the immediate and delayed effects of tear punctal occlusion with punctal plugs on tear meniscus height (TMH) in severe aqueous-deficient dry eye (ADDE) disease. METHODS: Consecutive patients with severe ADDE related to Sjögren syndrome or ocular graft-versus-host disease underwent inferior and superior occlusion with punctal plugs. TMH was measured using the LacryDiag ocular surface analyzer platform before, 10 minutes, and at least 1 month after punctal occlusion. The corneal fluorescein staining (CFS) score was graded with the Oxford scale (from 0 to 5). Ocular symptoms were graded with a visual analog scale (from 1 to 10). RESULTS: We included 24 eyes of 24 patients (mean age 61 ± 9 years; mean follow-up 7 ± 5 months). The mean TMH was 0.19 ± 0.06 mm at baseline and increased significantly to 0.41 ± 0.13 mm (P < 0.001) and 0.46 ± 0.17 mm (P < 0.001) at 10 minutes after punctal plug insertion and at the end of follow-up, respectively. The median CFS score decreased from 3 ± 1 before plug insertion to 1 ± 2 at the end of follow-up (P < 0.001). Many patients (67%; n = 16) reported subjective improvement of symptoms. TMH was negatively correlated with the CFS score and visual analog scale score assessing symptoms. CONCLUSIONS: Upper and lower punctal occlusion increased TMH in patients with severe ADDE as soon as 10 minutes after plug insertion. TMH remained stable over time, which led to the relief of symptoms and reduced corneal staining.

Paradoxical inflammatory blepharitis in a patient with Crohn's disease.

We report the case of a 15-year-old boy with severe inflammatory blepharitis who was being treated with a TNFα inhibitor for Crohn's disease (CD). This case shows the potential utility of a skin biopsy in distinguishing metastatic CD associated with granulomatous blepharitis from a paradoxical blepharitis induced by anti-TNFα. It also demonstrates that ustekinumab can be considered in patients with CD who cannot tolerate TNFα inhibitors because of cutaneous paradoxical reactions.

P33-A110†Ex vivo models of corneal epithelial regeneration in bioreactor: respective roles of limbal, conjunctival and corneal epithelia.

PURPOSE: Human corneas preserved in bioreactor (BR) are characterized by not only a better endothelial viability, but also a more differentiated and stratified epithelium compared to corneas preserved in organoculture. By using corneal preservation in BR, we aimed to analyze the respective contribution of corneal (C), limbal (L), and conjunctival (Conj) epithelia in corneal epithelial regeneration. METHODS: Five pairs of corneas from body donation to Science were used with a death-to-collection time <20 hours. A 3- to 5-mm-wide conjunctival flange was kept intact. Five patterns were set up by complete mechanical removal of 1, 2, or 3 epithelia (-): C-L+Conj+, C-L-Conj+, C-L+Conj-, C+L-Conj-, C-L-Conj- (control) (n=2 for each pattern). The L epithelia was destroyed by scraping and thermocoagulation. Corneas were then kept in BR (21mmHg, 2.5µl/min of Corneamax Eurobio, 31°C) for 3 weeks to allow epithelial regeneration. The epithelium was then analyzed using immunofluorescence (IF) on flat mounted cornea by targeting CK12 (corneal epithelium) and CK15 (limbal epithelium). Cell nuclei were counterstained with DAPI. Corneal transparency was quantified using a transparometer. RESULTS: No epithelium was reconstituted in the C-L-Conj- control group. In the other 4 models including the C-L-Conj+ group, the cornea was transparent and covered by a pluristratified corneal epithelium, characterized by CK12 expression. CONCLUSION: In this BR model, conjunctival epithelial cells alone allowed the regeneration of a typical corneal epithelium whereas corneal epithelium was able to migrate to the limbus and conjunctiva. We hypothesize that all 3 ocular surface epithelia contain stem cells or progenitors able to migrate throughout the cornea and restore the corneal epithelium independently of each other. The main difference between our ex vivo model and in vivo situation is the absence of neovascularization. This suggests that the main cause of limbic insufficiency is due to the loss of the anti-angiogenic barrier rather than the loss of limbic stem cells.

Double-Docking Technique for Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty: A Retrospective Consecutive Case Series Study of Advanced Keratoconus.

PURPOSE: The aim of this study was to report the clinical outcomes and prognosis of femtosecond laser (FSL)-assisted double-docking deep anterior lamellar keratoplasty (DD-DALK) for advanced keratoconus (AK). METHODS: Records of consecutive patients with keratoconus who underwent FSL-assisted DALK (DD-DALK) were reviewed. RESULTS: We analyzed 37 eyes from 37 patients who underwent DD-DALK. Sixty-eight percent of eyes had a successful big-bubble formation and 27% had a manual dissection to achieve the DALK deep dissection. Stromal scarring was associated with not achieving a big bubble. Intraoperative conversion to penetrating keratoplasty was conducted in 2 cases (5%). The best-corrected visual acuity improved from a median (± interquartile range) of 1.55 ±0.25 logMAR preoperatively to 0.2 ±0.2 logMAR ( P < 0.0001). The median postoperative spherical equivalent was -5.75 ±2.75 D with a median astigmatism of -3.5 ±1.3 D. BCVA, SE, and astigmatism were not statistically different between patients who underwent DD-DALK and patients who underwent manual DALK. Stromal scarring was associated with big-bubble (BB) formation failure ( P = 0.003). All patients with failed BB requiring manual dissection had anterior stromal scarring. CONCLUSIONS: DD-DALK is safe and reproducible. The success rate of BB formation is hampered by stromal scarring.

Retinal Nerve Fiber Layer Thickness/Minimum Rim Width Ratio Differentiates Glaucoma From Other Optic Neuropathies.

PRCIS: Global peripapillary retinal nerve fiber layer thickness (pRNFL)/Bruch membrane opening-minimum rim width (BMO-MRW) ratio is an objective and effective parameter to separate glaucomatous optic neuropathies (GONs) from nonGONs (NGONs). PURPOSE: This study was undertaken to evaluate the diagnostic capability of the pRNFL/ BMO-MRW ratio to differentiate GONs from NGONs. PATIENTS AND METHODS: This retrospective study included patients with an optic neuropathy (ON), visual loss for>6 months and a confirmed single etiology. pRNFL thickness and BMO-MRW were measured with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The diagnostic accuracies of pRNFL, BMO-MRW and the global pRNFL/BMO-MRW ratio were evaluated with the areas under receiver operating characteristics curves. RESULTS: One eye each from 171 patients was investigated: 50 primary open angle glaucomas, 15 normal pressure glaucomas, 50 optic neuritises, 15 nonarteritic anterior ischemic ONs, 24 compressive ONs, 10 dominant optic atrophies, and 7 nutritional ONs. The global pRNFL/BMO-MRW ratio had the highest area under receiver operating characteristics curve [0.97 vs. 0.92; P =0.01]. It was able to distinguish between GONs and NGONs with a cutoff value of 0.34. Increased mean deviation of the visual field-defect severity was associated with a higher ratio for GONs and a lower ratio for NGONs. CONCLUSION: Compared with NGONs and for the same degree of pRNFL thinning, lower BMO- MRW was found to be a specific marker of glaucoma, reflecting the neuroglial architecture changes within the optic nerve head typical of glaucoma and supporting fundamental pathophysiological differences.

Severe Corneal Involvement Associated With Mpox Infection.

This article discusses 2 cases of severe corneal involvement during mpox.

Cystoid macular oedema after descemet membrane endothelial keratoplasty.

AIMS: To determine the incidence and risk factors of cystoid macular oedema (CMO) following descemet membrane endothelial keratoplasty (DMEK) with or without combined cataract surgery (triple-DMEK). METHODS: We reviewed the records of patients who underwent DMEK surgery alone or triple-DMEK performed at the Rothschild Foundation Hospital (Paris, France) between January 2019 and March 2020. Patients with pre-existing CMO observed on the preoperative macular optical coherence tomography (OCT) were excluded. Spectral-domain OCT was performed in patients with postoperative visual impairment. Data regarding comorbidities, intraoperative characteristics and postoperative treatments or complications were collected and analysed. Univariate and multivariate analyses were performed. RESULTS: Twenty three of 246 eyes (9.36%) developed clinically significant (cs)-CMO after DMEK. Triple-DMEK was not associated with a higher risk to develop CMO (12.2% in DMEK alone and 6.1% in triple-DMEK). Pseudophakic bullous keratopathy (PBK ; 39.1% vs 9%; OR=3.5 (1.0 to 11.8), p=0.045) and epiretinal membrane (ERM; 39.1% vs 7.7%; OR=10.5 (3.4 to 32.3), p<0.001) were more frequently observed in patients who developed CMO. The occurrence of hyphaema during surgery was statistically associated with postoperative CMO (13% vs 1.3%; OR=7.1 (1.0 to 48.8) p=0.045). Peroperative epithelial debridement was statistically associated with postoperative CMO (65.2% vs 33.2%, p=0.005), but only in univariate analysis. CONCLUSIONS: We identified a clinically significant CMO incidence of 9.35% after DMEK. Patients with a history of ERM, PBK and intraoperative hyphaema may be at risk of developing CMO after DMEK surgery and should be monitored.

Predictive factors of graft detachment and rebubbling after descemet membrane endothelial keratoplasty.

PURPOSE: To identify risk and predictive factors associated with the need of rebubbling in the eye of patients who underwent a descemet membrane endothelial keratoplasty (DMEK). METHODS: The records of patients who underwent DMEK were retrospectively analyzed. Data regarding comorbidities, intraoperative characteristics, and postoperative treatments or complications were collected. The central corneal thickness (CCT) was measured by optical coherence tomography before and the day after DMEK. Univariate and multivariate analyses were performed. RESULTS: Of the 333 DMEK, rebubbling was performed in 119 cases (36%). Preoperative subepithelial fibrosis and a history of penetrating keratoplasty (PK) were associated with significantly more graft detachment [OR of 3.55 (2.02-6.32; P < 0.001) and 5.89 (2.00-21.86; P = 0.003), respectively]. A decreased CCT the day after surgery reduced by 5.7-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.93). Conversely, a 20% increase in the CCT the day after surgery increased by 4.5-fold the risk of rebubbling (sensitivity/specificity of 0.42/0.91). CONCLUSION: Variation of the CCT could be used as a predictive factor of rebubbling after DMEK. Patients with a 20% increase of CCT the day after surgery are at higher risk of graft detachment. Conversely, a reduced CCT the day after the surgery is associated with a reduced risk of rebubbling. Subepithelial fibrosis and history of PK were also identified as risk factors for rebubbling. Those predictive factors may help develop a customized approach for patients undergoing DMEK surgery.

Detecting Subclinical Corneal Edema Using Corneal Thickness Mapping in Patients Presenting Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To determine whether local corneal thickness changes observed with optical coherence tomography (OCT) can detect subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD). SETTING: Retrospective cohort study. METHODS: A series of patients presenting FECD who underwent cataract surgery alone (45 eyes) or with concomitant Descemet membrane endothelial keratoplasty (triple procedure; 117 eyes). The study reviewed medical records, collected the preoperative corneal thickness map and calculated the differences and ratio of corneal thickness measured at 5, 7, and 9 mm from the central corneal thickness. Area under the receiver operating characteristic curves (AUCs) were calculated and thresholds were selected to obtain a specificity of 90%. RESULTS: The median difference between 5- and 2-mm corneal thickness in the supra-nasal quadrant (∆5-2mmSN) was 38 µm (interquartile range 34-46) in the cataract group and 17 µm (2-38) in the triple procedure group (P < .001). The corneal thickness ratios of supra-nasal 5- to 2-mm (R5/2mmSN) and 7- to 2-mm (R7/2mmSN) were 1.07 (1.06-1.08) and 1.15 (1.13-1.17)] in the cataract group and 1.03 (1.00-1.06) and 1.09 (1.06-1.14) in the triple procedure group (P < .001). The probability of corneal edema was increased 7-fold with ∆5-2mm SN < 27 µm (AUC = 0.76) and 9.4- and 7.4-fold with R5/2mmSN and R7/2mmSN < 1.045 (AUC = 0.77) and 1.118 (AUC = 0.76), respectively. CONCLUSIONS: Local changes in corneal thickness may be useful in detecting preclinical corneal edema, especially in patients with FECD undergoing cataract surgery.

Meganuclease targeting HSV-1 protects against herpetic keratitis: Application to corneal transplants.

Herpes simplex virus (HSV) infection is a leading cause of corneal blindness. However, keratoplasty is only rarely proposed due to the high frequency of graft failure and associated recurrences. Gene therapy of the corneal graft might provide sustained protection against HSV infection. To test that hypothesis, we designed a meganuclease specific to an HSV-1 DNA sequence coding for major capsid protein (UL19) and selected an adeno-associated virus type-2 as the vector. Meganuclease was transduced into corneas and its effect was challenged in vitro, ex vivo, and then in vivo in a rabbit HSV-1-infection model of stromal keratitis and endotheliitis. In vivo, meganuclease exposure resulted in fewer infected stromal and endothelial cells, and protected against corneal opacification and edema. Ex vivo, HSV-1 infection rates of meganuclease-treated human corneas were drastically reduced. Furthermore, genetically engineered corneas transplanted in vivo into rabbit eyes protected against HSV-1 infection. This genome-editing technology targeting HSV-1 opens new opportunities to manage severe post-herpetic corneal blindness by providing infected patients with genetically protected corneal transplants.

EPHA2 biallelic disruption causes syndromic complex microphthalmia with iris hypoplasia.

Disruption of any of the ocular development steps can result in ocular defects such as microphthalmia, coloboma and anterior segment dysgeneses including aniridia and cataract. All of these anomalies can be isolated or seen in association with each other. Except for aniridia (almost exclusively due to PAX6 mutations), most of these congenital ocular malformations are related to a wide genetic heterogeneity, as hundreds of genes are implied in ocular development. Here we describe a patient presenting with bilateral microphthalmia, congenital cataract, corneal dystrophy and iris hypoplasia, associated with extra-ocular features, who underwent an analysis of 119 ocular development related genes. Genetic testing revealed the presence of two truncating variants in the EPHA2 gene. While EPHA2 mutations are mainly known to be responsible for isolated dominant congenital cataract, we report here the first case of complex anterior segment dysgenesis caused by a biallelic EPHA2 mutation. This gene should be screened in case of aniridia with a negative PAX6 testing, as the ocular features of our patient clearly mimic those of PAX6 mutated patients. This observation enlarges the phenotype associated with EPHA2 variations and rise the insight of a possible PAX6-EPHA2 interaction that needs further investigations. Moreover, despite a great variability in ocular and extra-ocular phenotypes, mutations type and inheritance pattern, a possible genotype-phenotype correlation can also be drawn for this gene.

Clinical course and treatment of archipelago keratitis: a Herpesviridae keratitis subtype.

PURPOSE: Archipelago keratitis (ApK) is a subtype of Herpesviridae stromal keratitis that consists of subepithelial nummular inflammatory infiltrates arranged in a radial centripetal pattern. This rare and poorly described form is not often recognised early. We report the first large series of ApK, with an analysis of clinical settings at presentation, evolution of the disease with time and a description of factors associated with recurrence. METHODS: The clinical records of 82 patients (83 eyes) with a diagnosis of ApK between 2011 and 2021 in two centres were reviewed. RESULTS: The median age of the 82 patients at referral was 37±28 years. ApK was unilateral in all but one case. A total of 76% of patients had at least one second diagnostic criteria suggesting a herpetic aetiology. Overall, 44 (53%) eyes exhibited least one recurrence after a median of 12 months. Recurrence was frequently associated with neovascularisation (HR 2.1, 95% CI 1.1 to 3.9; p=0.02) and tapering corticosteroids (HR 3.5, 95% CI 1.8 to 7.1; p<0.01) or valaciclovir use (HR=2.3, 95% CI 1.2 to 4.6; p=0.01). Antiviral treatment was used in all patients, whereas local anti-inflammatory drugs such as corticosteroids and/or ciclosporin were used in 73 (88%) cases. CONCLUSION: ApK is a Herpesviridae stromal keratitis that is typically unilateral in presentation and features a high risk of recurrence. Combined treatment with antiviral and anti-inflammatory drugs are usually required over the long term. Topical ciclosporin can be useful as a corticosteroid-sparing treatment.

Alleviation of Endoplasmic Reticulum Stress Enhances Human Corneal Epithelial Cell Viability under Hyperosmotic Conditions.

Tear hyperosmolarity plays an essential role in the initiation and progression of dry-eye disease. Under a hyperosmotic environment, corneal epithelial cells experience perturbations in endoplasmic reticulum function that can lead to proinflammatory signaling and apoptosis. In this study, we investigated the effect of tauroursodeoxycholic acid (TUDCA), a chemical chaperone known to protect against endoplasmic reticulum stress, on corneal epithelial cells exposed to hyperosmotic conditions. We found that the expression of the genes involved in the activation of the unfolded protein response and the pro-apoptotic transcription factor DDIT3 were markedly upregulated in patients with Sjögren's dry-eye disease and in a human model of corneal epithelial differentiation following treatment with hyperosmotic saline. Experiments in vitro demonstrated that TUDCA prevented hyperosmotically induced cell death by reducing nuclear DNA fragmentation and caspase-3 activation. TUDCA supplementation also led to the transcriptional repression of CXCL8 and IL5, two inflammatory mediators associated with dry-eye pathogenesis. These studies highlight the role of hyperosmotic conditions in promoting endoplasmic reticulum stress in the cornea and identify TUDCA as a potential therapeutic agent for the treatment of dry-eye disease.

Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential.

Glycans function as valuable markers of stem cells but also regulate the ability of these cells to self-renew and differentiate. Approximately 2% of the human genome encodes for proteins that are involved in the biosynthesis and recognition of glycans. In the present study, we evaluated the expression of a small subset of glycogenes in human limbal epithelial cells with distinct clonogenic potential. Individual clones were classified as abortive or clonogenic, based on the fraction of the terminal colonies produced; clones leading exclusively to terminal colonies were referred to as abortive while those with half or fewer terminal colonies were referred to as clonogenic. An analysis of glycogene expression in clonogenic cultures revealed a high content of transcripts regulating the galactose and mannose metabolic pathways. Abortive clones were characterized by increased levels of GCNT4 and FUCA2, genes that are responsible for the branching of mucin-type O-glycans and the hydrolysis of fucose residues on N-glycans, respectively. The expansion of primary cultures of human limbal epithelial cells for 10 days resulted in stratification and a concomitant increase in MUC16, GCNT4 and FUCA2 expression. These data indicate that the clonogenic potential of human limbal epithelial cells is associated with specific glycosylation pathways. Mucin-type O-glycan branching and increased fucose metabolism are linked to limbal epithelial cell differentiation.

Epithelial Regeneration in Human Corneas Preserved in an Active Storage Machine.

Purpose: To characterize the corneal epithelium (CE) and limbal epithelium (LE) of human corneas stored in an innovative active storage machine (ASM) after a period of organ culture (OC). Methods: Corneas unsuitable for graft and stored in a standard commercial OC medium for 2 to 5 weeks were transferred into our ASM for 14 days. The ASM actively maintained an overpressure on the endothelial side (20 mm Hg) while ensuring medium renewal. We compared three modalities of storage in the ASM's epithelial chamber: (1) alternating exposure to a supplemental hormonal epithelial medium (SHEM) and air (air-lifting), (2) continuous immersion in SHEM, and (3) continuous immersion in OC medium. Passive immersion of the whole cornea in OC medium or of the CE in SHEM with or without airlifting served as controls. Paired corneas were used for better comparability. Histology, differentiation (by immunolabeling), and ultrastructure were analyzed at the end. Results: The ASM with air-lifting was most effective in regenerating a pluristratified and differentiated CE (apical ZO-1 and MUC16 staining and regeneration of the glycocalyx). In addition, the LE was stratified with preserved expression of ABCB5. The ASM with immersion in SHEM or OC medium gave a less stratified and differentiated CE. In the three control groups, the epithelia, when present, were paucistratified and less differentiated. Conclusions: In human corneas previously stored in OC, the ASM regenerates a CE with differentiation characteristics close to normal. Translational Relevance: Regeneration of the epithelium of human corneas discarded by eye banks will increase tissue availability for research.

Pediatric Eye Injuries by Hydroalcoholic Gel in the Context of the Coronavirus Disease 2019 Pandemic.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has made alcohol-based hand sanitizers (ABHS) widely available in public places. This may warrant determining whether cases of unintentional ocular exposure are increasing, especially in children. Objective: To describe the epidemiologic trend of pediatric eye exposures to ABHS and to report the severity of the ocular lesions. Design, Setting, and Participants: Retrospective case series conducted from April 1, 2020, to August 24, 2020. Cases were retrieved from the national database of the French Poison Control Centers (PCC) and from a pediatric ophthalmology referral hospital in Paris, France. Cases of ocular exposure to chemical agents in children younger than 18 years during the study period were reviewed. Cases of ABHS exposure were included. Exposures: The following data were collected: age, sex, circumstances of exposure, symptoms, size of the epithelial defect at first examination, time between the incident and re-epithelialization, and medical and/or surgical management. Main Outcomes and Measures: Comparison of the number of eye exposures to ABHS in children between April to August 2020 and April to August 2019. Results: Between April 1 and August 24, 2020, there were 7 times more pediatric cases of ABHS eye exposures reported in the PCC database compared with the same period in 2019 (9.9% of pediatric eye exposures in 2020 vs 1.3% in 2019; difference, 8.6%; 95% CI, 7.4-9.9; P < .001). The number of cases occurring in public places increased in 2020 (from 16.4% in May to 52.4% in August). Similarly, admissions to the eye hospital for ABHS exposure increased at the same period (16 children in 2020 including 10 boys; mean [SD] age, 3.5 [1.4] years vs 1 boy aged 16 months in 2019). Eight of them presented with a corneal and/or conjunctival ulcer, involving more than 50% of the corneal surface for 6 of them. Two cases required amniotic membrane transplant. Conclusions and Relevance: These data support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population. To maintain good public compliance with hand disinfection, these findings support that health authorities should ensure the safe use of these devices and warn the parents and caregivers about their potential danger for children.

The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells.

Dynamic modification of nuclear and cytoplasmic proteins with O-linked ß-N-acetylglucosamine (O-GlcNAc) plays an important role in orchestrating the transcriptional activity of eukaryotic cells. Here, we report that the O-GlcNAc modification contributes to maintaining ocular surface epithelial homeostasis by promoting mucin biosynthesis and barrier function. We found that induction of human corneal epithelial cell differentiation stimulated the global transfer of O-GlcNAc to both nuclear and cytosolic proteins. Inflammatory conditions, on the other hand, were associated with a reduction in the expression of O-GlcNAc transferase at the ocular surface epithelia. Loss- and gain-of-function studies using small interfering RNA targeting O-GlcNAc transferase, or Thiamet G, a selective inhibitor of O-GlcNAc hydrolase, respectively, revealed that the presence of O-GlcNAc was necessary to promote glycocalyx barrier function. Moreover, we found that Thiamet G triggered a correlative increase in both surface expression of MUC16 and apical epithelial cell area while reducing paracellular permeability. Collectively, these results identify intracellular protein O-glycosylation as a novel pathway responsible for promoting the terminal differentiation of human corneal epithelial cells.

Role of CD147 (EMMPRIN/Basigin) in Tissue Remodeling.

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or basigin, is expressed in a variety of cell types. It is involved in the regulation of extracellular matrix (ECM) remodeling during physiological and pathological processes including wound healing, inflammatory diseases, and cancer. CD147 is a diagnostic and therapeutic target in cancer and inflammatory diseases, either directly or indirectly, by targeting CD147 partners. It can trigger matrix metalloproteinase inductions involved in ECM degradation, cell adhesion, and cell-cell interactions. It can also induce myofibroblast differentiation associated with ECM deposition and contraction. The shift from fibrosis to lysis, and vice versa, is poorly understood and could involve CD147. This article provides an overview of the role of CD147 in the regulation of ECM remodeling processes and discusses the involvement of the microenvironment in the modulation of its downstream effects. Understanding CD147 regulation could help identify new therapeutic intervention. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.

Neurotrophic keratitis: Frequency, etiologies, clinical management and outcomes.

PURPOSE: To determine neurotrophic keratitis (NK) frequency, etiologies and prognostic factors, and evaluate the outcome of its management. METHODS: In this retrospective epidemiologic study, we reviewed the electronic records of all patients consulting our tertiary referral eye hospital between November 2009 and October 2017. NK was defined as corneal hypoesthesia or anesthesia associated with epithelial irregularities. RESULTS: Among the 305,351 patients' files screened for eligibility, 335 (354 eyes) were included, yielding an NK frequency of 11/10,000 (0.11%). Their mean ± SD age was 63.1 ± 21.0 years. Eyes were equally divided among the Mackie classification 3 stages. The most frequent etiology was herpetic eye disease (114 eyes; 32.2%). A multifactorial cause was found for 121 (34.2%) eyes. Surgery required for 118 eyes (33.3%). Respective success rates for amniotic membrane transplantation (AMT) or matrix-regeneration of stages 2 and 3, and autologous serum of stage 1 were 57.2%, 63.6% and 21.7%, with mean healing times of 15.0, 16.3 and 85 days. The overall healing rate was 79.5%, with a mean of 44.8 days to healing. Advanced initial stage, diminished corrected-distance visual acuity (CDVA) and advanced age correlated with worse final CDVA. CONCLUSIONS: NK was more frequent than previously reported in the literature. Delayed diagnoses indicated we must increase ophthalmologists' awareness of this disease for patients with decreased corneal sensitivity and abnormal epithelium. To improve prognosis and final CDVA, NK-specific treatment should be initiated as soon as the diagnosis is suspected. Patient-centered combinations of different therapeutic components and close monitoring achieved promising results.