Lysophosphatidic acid improves corneal endothelial density in tissue culture by stimulating stromal secretion of interleukin-1ß.

The short supply of donor corneas is exacerbated by the unsuitability of donors with insufficient endothelial cell density. Few studies have investigated promoting corneal endothelial cell proliferation to increase the endothelial cell density. We hypothesize that pre-transplantation treatment of proliferative tissue-cultivated corneas may increase corneal endothelial cell density. We observed that the airlift cultures were superior to immersion cultures with respect to both transparency and thickness. In this tissue culture system, we observed that lysophosphatidic acid increased the rabbit corneal endothelial cell density, number of BrdU-positive cells and improve wound healing. We also observed an indirect effect of lysophosphatidic acid on corneal endothelial cell proliferation mediated by the stimulation of interleukin-1ß secretion from stromal cells. Human corneal tissues treated with lysophosphatidic acid or interleukin-1ß contained significantly more Ki-67-positive cells than untreated group. The lysophosphatidic acid- or interleukin-1ß-treated cultured tissue remained hexagon-shaped, with ZO-1 expression and no evidence of the endothelial-mesenchymal transition. Our novel protocol of tissue culture may be applicable for eye banks to optimize corneal grafting.

Comparison of fungal and bacterial keratitis between tropical and subtropical Taiwan: a prospective cohort study.

BACKGROUND: Fungal keratitis (FK) has been shown to be a climate-sensitive disease. The differentiation between FK from bacterial keratitis (BK) was difficult. The purpose of this study was to compare the bacteriology and mycology between tropical and subtropical Taiwan and to investigate the independent risk factors for identification of fungi from bacteria. METHODS: Two hundred ninety-seven patients with clinical suspected microbial keratitis were prospectively enrolled. A fungal to bacteria rate (FBR), the number of fungi divided by bacteria identified, was determined to estimate the prevalence of fungi and bacteria. Clinical presentation, profiles of microorganisms, and predisposing risk factors were determined. Univariate and multivariate logistic regression analysis were used to investigate the independent risk factors. RESULTS: A total of 82 fungi and 143 bacteria were laboratory confirmed. The identification rate of fungus was higher in tropical Taiwan (p = 0.010). Among the fungi and bacteria confirmed, the FBR was 0.29 (22.4% vs. 77.6%) in subtropical Taiwan, and 0.70 (41.3% vs. 58.7%) in tropical Taiwan. Samples obtained in tropical area (p = 0.019), ocular trauma (p = 0.019), and plant exposure (p = 0.003) were independent risk factors for identification of fungus from bacteria. The predominant fungus isolated from corneal scraping were Fusarium solani (25%) and Trichosporon faecale (25%) in subtropical Taiwan; in tropical Taiwan was Fusarium spp. (50%). CONCLUSIONS: The identification rate of fungus was higher in tropical Taiwan than subtropical Taiwan. Awareness of the local epidemiology is crucial for early diagnosis of fungal keratitis in tropical area.

Clinical demographics of pterygium excision and prevalence of conjunctival intraepithelial neoplasia: a 15-year review.

PURPOSE: To find clinical demographics of pterygium surgery and prevalence of conjunctival intraepithelial neoplasia (CIN) in pterygium specimen. METHODS: This is a retrospective, institutional study. The records of patients who had received pterygium excision from 2000 to 2014 were reviewed. Patients after complete ophthalmic "examinations", surgical procedures, and pathological reports were enrolled. Surgical procedures, pathology, external eye photography, prevalence of CIN in specimen, and demographic data were described. RESULTS: Of 1787 pterygium cases, 928 were male and 859 were female. The mean age was 65.19 ± 14.21 years. Of these 1787 cases, 1435 (80.3%) cases had primary pterygium excision, while the others (n = 352; 19.7%) had pterygium excision for recurrence. Four cases presented CIN within pterygium tissue (0.22%). The mean age of pterygium patients with CIN was 57.75 ± 7.80 years. In stratified data, our patients who received primary and secondary pterygium excision were found prevalent in the eighth (28.2%) and seventh (26.1%) decade, respectively. Twelve percent of patients who underwent secondary pterygium excision had a recurrence and required another surgery. Patients requiring amniotic membrane transplantation (AMT) during primary pterygium excision were significantly younger (median, 58 years) than those (median, 67 years) without the assistance of AMT (p < 0.001). Similarly, AMT was utilized in younger patients (median, 56 years) during secondary pterygium excision, compared to those without AMT (median, 64 years) (p = 0.001). CONCLUSION: CIN combined with pterygium is very rare. However, the possibility of the development of ocular surface squamous neoplasia in pterygium tissue should not be ignored. Meticulous pathological investigation of the surgical samples is important.

Effect of Cross-Linking Density on the Structures and Properties of Carbodiimide-Treated Gelatin Matrices as Limbal Stem Cell Niches.

Given that human amniotic membrane is a valuable biological material not readily available for corneal epithelial tissue engineering, gelatin is considered as a potential alternative to construct a cellular microenvironment. This study investigates, for the first time, the influence of cross-linking density of carbodiimide-treated gelatin matrices on the structures and properties of artificial limbal stem cell niches. Our results showed that an increase in the carbodiimide concentration from 1.5 to 15 mM leads to an upward trend in the structural and suture strength of biopolymers. Furthermore, increasing number of cross-linking bridges capable of linking protein molecules together may reduce their crystallinity. For the samples treated with 50 mM of cross-linker (i.e., the presence of excess N-substituted carbodiimide), abundant N-acylurea was detected, which was detrimental to the in vitro and in vivo ocular biocompatibility of gelatin matrices. Surface roughness and stiffness of biopolymer substrates were found to be positively correlated with carbodiimide-induced cross-link formation. Significant increases of integrin ß1 expression, metabolic activity, and ABCG2 expression were noted as the cross-linker concentration increased, suggesting that the bulk crystalline structure and surface roughness/stiffness of niche attributed to the number of cross-linking bridges may have profound effects on a variety of limbal epithelial cell behaviors, including adhesion, proliferation, and stemness maintenance. In summary, taking the advantages of carbodiimide cross-linking-mediated development of gelatin matrices, new niches with tunable cross-linking densities can provide a significant boost to maintain the limbal stem cells during ex vivo expansion.

Expression of retinoic acid-binding proteins and retinoic acid receptors in sebaceous cell carcinoma of the eyelids.

BACKGROUND: Sebaceous cell carcinoma of the eyelid is a malignant tumor. However, the pathoetiology of sebaceous cell carcinoma is not clear. Retinoic acid (RA) signaling is essential for skin epidermal differentiation including the eyelids. In this study, we investigate the expression of ß-catenin, RA-binding proteins and RA receptors in sebaceous cell carcinoma of the eyelid and try to estimate their influence on its pathoetiology. METHODS: Retrospective, noncomparative, consecutive interventional case series. Sixteen cases of eyelid sebaceous gland carcinoma who received tumor excision at our hospital between 2001 and 2011 were included. Immunohistochemical staining for ß-catenin, cellular retinoic acid binding protein 1 (CRABP1), cellular retinoic acid binding protein 2 (CRABP2), fatty acid-binding protein 5 (FABP5), retinoic acid receptors (RAR-α, -ß, -γ), and retinoid X receptors (RXR-α, -ß, -γ) was performed on tissue samples obtained from tumor excision. RESULTS: Of the 16 sebaceous cell carcinoma cases reviewed, six were male and 10 female. The mean follow-up period was 6.7 ± 3.66 years (range, 0.3-13 years). Of these 16 cases, the expression of ß-catenin was significantly increased in sebaceous cell carcinoma cases. CRABP1 was similarly expressed in the sebaceous cell carcinoma and control groups. CRABP2 and FABP5 were expressed in hair follicles of lid skin in both groups, whereas the CRABP2 and FABP5 were aberrantly expressed in the tumor cells of the sebaceous glands. Notably, the expression of retinoic acid receptor (RAR-ß) and retinoid X receptors (RXR-ß, -γ) was significantly upregulated in sebaceous cell carcinoma of the eyelids. CONCLUSIONS: Our findings indicate that retinoic acid signaling is related to the pathogenesis of sebaceous cell carcinoma of the eyelids.

Epithelial phenotype in total sclerocornea.

PURPOSE: To understand whether the epithelial phenotype in total sclerocornea is corneal or conjunctival in origin. METHODS: Four cases of total sclerocornea (male:female = 1:3; mean age = 5.4 ± 4.3; 1-11 years old) who received penetrating keratoplasty (PKP) at our hospital between 2008 and 2011 were included. Corneal buttons obtained during PKP were used for transmission electron microscopy (TEM) as well as immunoconfocal microscopy for cytokeratins 3, 12, and 13, goblet cell mucin MUC5AC, connexin 43, stem cell markers p63 and ABCG2, laminin-5, and fibronectin. RESULTS: After a mean follow-up period of 38.8 ± 14.0 (12-54) months, the grafts remained clear in half of the patients. TEM examination revealed a markedly attenuated Bowman's layer in the scleralized corneas, with irregular and variably thinned collagen lamellar layers, and disorganization and random distribution of collagen fibrils, which were much larger in diameter compared with a normal cornea. Immunoconfocal microscopy showed that keratin 3 was expressed in all four patients, while p63, ABCG2, and MUC5AC were all absent. Cornea-specific keratin 12 was universally expressed in Patients 1 to 3, while mucosa (including conjunctiva)-specific keratin 13 was negative in these patients. Interestingly, keratin 12 and 13 were expressed in Patient 4 in a mutually exclusive manner. Linear expression of laminin-5 in the basement membrane zone and similar expression of fibronectin were observed. CONCLUSIONS: The epithelia in total sclerocornea are essentially corneal in phenotype, but in the event of massive corneal angiogenesis, invasion by the conjunctival epithelium is possible.

Comparison of Corneal Endothelial Cell Loss in Femtosecond Laser-assisted Cataract Surgery: Impact on Endothelial Cells in Different Regions.

PURPOSE: To compare changes in corneal endothelial parameters following femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification (CPS) in different corneal regions. SETTING: Chang Gung Memorial Hospital, Linkou, Taiwan, 2018- 2022. DESIGN: Single-center, retrospective. METHODS: Before and 1, 3, and 6 months post-op, specular microscopy was performed to measure endothelial cell density (ECD), corneal thickness, hexagonal cell rate (Hex), and coefficient of variation (CoV). Position 1 referred to the central cornea, Position 2 was nearest to the main wound, and Position 3 was at the peripheral zone diagonal to the main wound. RESULTS: This study analyzed 96 eyes in the FLACS group and 110 eyes in the CPS group. Preoperatively, Position 1 had lower ECD and CoV and higher Hex compared to the peripheral regions. FLACS patients had a significantly less phaco time and cumulative dissipated energy. At one month, FLACS patients showed a significantly smaller increase in corneal thickness at Positions 1 and 2. At 3 months, FLACS patients had lower endothelial cell loss (ECL) at Positions 1 and 3. ECL remained lower in FLACS patients at 6 months. The highest ECL was observed at Position 2 in both groups and was progressive up to 6 months. CONCLUSIONS: Following phacoemulcification, ECL varied in different corneal regions. At 3 months, the FLACS group exhibited significantly less ECL at the central cornea; however, the continued ECL at 6 months near the main wound suggested ongoing endothelial remodeling in the region.

Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial cells exposed to H2 O2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1ß, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A165 , with a dissociation constant of 2.2 × 10-14  M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.

Dry eye after LASIK with a femtosecond laser or a mechanical microkeratome.

PURPOSE: Dry eye is the most common complication after LASIK procedure and is associated with corneal denervation. We conducted the study to compare dry eye parameters and corneal sensitivity (CS) after laser in situ keratomileusis (LASIK) with a femtosecond laser (FS) or microkeratome (MK). METHODS: In this prospective, nonrandomized, comparative study, 87 consecutive patients with myopia were assigned to receive either LASIK surgery with an FS (n = 44) or MK-assisted LASIK surgery (n = 43). The groups were age and sex matched. Corneal sensitivity, Schirmer testing, tear breakup time (TBUT), conjunctival and corneal stainings, and a subjective questionnaire (Ocular Surface Disease Index [OSDI]) were evaluated preoperatively, at 1 week, and at 1, 3, and 6 months postoperatively. RESULTS: Preoperative spherical equivalent and sphere, calculated ablation depth, and suction time differed significantly between the two groups (p < 0.01, all comparisons). Postoperatively, CS decreased in both groups and gradually recovered. Schirmer test values were not significantly different throughout the postoperative time points between the groups. Laser in situ keratomileusis-induced corneal epitheliopathy was also increased after operation in both groups. However, there was no significant difference between the groups in corneal and conjunctival staining scores. The OSDI scores were increased postoperatively in both groups. After adjustment for the calculated ablation depth, TBUT was the only parameter that was statistically higher in the FS group than in the MK group (p = 0.03). CONCLUSIONS: Both FS- and MK-assisted LASIK reduced CS and TBUT and increased corneal staining and OSDI scores. However, TBUT was significantly higher in the FS group than in the MK group after operation.

Peripheral ulcerative keratitis in a patient with granulomatous rosacea.

A 24-year-old woman visited our emergency department due to intermittent dull pain in the right eye, blurred vision, foreign body sensation for 3 weeks, and progressive facial rash with pustules for 3 months. She had a history of recurring skin rash on her face and extremities since early adolescence. Peripheral ulcerative keratitis (PUK) was diagnosed based on slit-lamp examination and corneal topography and then granulomatous rosacea (GR) based on clinical manifestations and skin pathology. Topical prednisolone, artificial tears, oral doxycycline, oral prednisolone, and topical clindamycin were administered. After 1 month, PUK progressed to corneal perforation probably due to eye rubbing. The corneal lesion was repaired with a glycerol-preserved corneal graft. A dermatologist prescribed oral isotretinoin for 2 months in conjunction with topical betamethasone gradually tapered for 14 months. After 34 months of follow-up, no signs of skin and ocular recurrence were noted, and the cornea graft was intact. In conclusion, PUK may present with GR, and oral isotretinoin may be an effective therapy for PUK in the setting of GR.

Microbial Keratitis in Patients With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Experience From a Tertiary Centre in Taiwan.

PURPOSE: The purpose of this study was to analyze the clinical features, causative microorganisms, antibiotic susceptibility, and treatment outcomes in culture-proven microbial keratitis (MK) in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and to analyze the potential risk factors. METHODS: We reviewed the medical records of all patients with SJS/TEN who attended our department between 2009 and 2018. Patients with a diagnosis of MK who underwent corneal cultures were enrolled. Demographics; clinical characteristics including ocular findings, treatment, time between onset of SJS/TEN and keratitis; changes in visual acuity; culture results; and antibiotic susceptibility were analyzed. Culture results from prior conjunctival swabs and keratitis were also compared. RESULTS: Sixteen eyes from 12 patients (mean age 40.1 ± 27.7 years) with MK were identified. These patients had the most severe ocular involvement in the acute stage and had more severe ocular complications (SOCs) in the chronic stage compared with patients with SJS/TEN without MK. There were 26 infection episodes during 4.4 ± 6.9 (1.0-25.8) years of follow-up. Oral nonsteroidal anti-inflammatory drugs accounted for half of the causative drugs. Severe dry eye was the most common predisposing factor, followed by topical steroid use, trichiasis, and lid margin keratinization. Staphylococcus was the most common pathogen, and over half of the gram-positive bacteria were resistant to oxacillin/methicillin. Fungal infections (notably Candida ) accounted for nearly one-third of the causative microorganisms. Culture reports from periodic conjunctival swabs were not consistent with those from corneal scrapings. Recurrence of infection was associated with inferior visual outcome. CONCLUSIONS: Patients with SJS/TEN with SOCs are subject to recurrent corneal infections, which are responsible for deterioration of vision. Identifying the risk factors and aggressive treatment as early as possible is pivotal for infection control.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

PURPOSE: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Retrospective comparative case series. METHODS: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used. RESULTS: Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications. CONCLUSIONS: Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.

Up-regulation of heat shock protein 70-1 (Hsp70-1) in human limbo-corneal epithelial cells cultivated on amniotic membrane: A proteomic study.

Transplantation of cultivated human limbo-corneal epithelial (HLE) cells has been recognized as an effective stem cell (SC) therapy for treating corneal epithelial SC deficiency caused by burn or other diseases. With this technique, cryo-preserved human intact amniotic membrane (IAM) has been successfully used as a cell culture substrate and carrier, and is reported to preferentially preserve HLE stem/progenitor cells in vitro. However, little is known about what factors released by HLE cells are involved in the progenitor cell-preserving mechanism. Using proteomic method, we identified 13 proteins over-expressed by HLE cells cultured on IAM, which included heat shock protein 70-1 (Hsp70-1), Hsp-27, glutathione (GSH) S-transferase, annexin A2, galectin-7, and protein S100-A9. Increased Hsp70-1 expression was confirmed by Western blot and real-time PCR. The role of Hsp70-1 in promoting HLE cell survival was demonstrated by increased apoptosis index and increased cleaved poly ADP-ribose polymerase (CPARP) formation in hsp70-1-silenced, but not normal HLE cells after exposure to sublethal UVB irradiation or hydrogen peroxide. To understand the regulatory mechanism of Hsp70-1 expression in HLE cells, the role of transcription factor deltaNp63 (a well-recognized HLE stem cell; SC marker) was studied. We found that over-expression of deltaNp63α by plasmid vector induced a corresponding increase in Hsp70-1 protein production. Likewise, Hsp70-1 expression decreased in HLE cells after addition of deltaNp63α SiRNA. Immunoconfocal microscopy also revealed a paralleled expression of both proteins in corneal specimens. Thus, deltaNp63α-associated Hsp70-1 over-expression may promote HLE progenitor cell survival on IAM, possibly through the cytoprotective and anti-apoptotic effect of Hsp70-1.

Effect of hinge position on corneal sensation and dry eye parameters after femtosecond laser-assisted LASIK.

PURPOSE: To evaluate the effect of superior- versus nasal-hinged flaps on corneal sensation and dry eye after femtosecond laser-assisted LASIK. METHODS: A total of 43 patients who had undergone bilateral femtosecond laser-assisted LASIK for myopia were evaluated in a prospective, nonrandomized, contralateral eye study to compare the difference between different hinges on corneal sensation and dry eye. Corneal esthesiometry, Schirmer basic tear secretion test (BST), tear break-up time (BUT), ocular surface stainings, and the Ocular Surface Disease Index (OSDI) questionnaire were used to evaluate corneal sensation and dry eye parameters preoperatively as well as at 1 week and 1, 3, and 6 months postoperatively. RESULTS: Corneal sensation decreased significantly in both groups 1 week after surgery (P<.05 in the nasal hinge group; P<.01 in the superior hinge group) and gradually recovered over the first 3 months. No significant change was noted in BUT after surgery in either group (P>.05). Significant increases were noted in BST values at 1 and 3 months (P<.05) and 6 months (P<.01) postoperatively in both groups. Corneal fluorescein staining increased significantly in both groups at 1 week (P<.01) and returned to baseline by 6 months. Conjunctival Rose Bengal staining decreased significantly by 6 months in the superior hinge group only (P<.05). The OSDI significantly increased 1 week after surgery (P<.01) and did not completely return to baseline by 6 months postoperatively in either group (P<.05). No significant differences were noted in any of the parameters between groups at any time point (P>.05). CONCLUSIONS: Hinge position had no significant effect on corneal sensation or dry eye parameters. Aggressive dry eye regimens are needed for patients with preoperative dry eye.

Oxidation-mediated scaffold engineering of hyaluronic acid-based microcarriers enhances corneal stromal regeneration.

The functional design of scaffolding biomaterials with potent capabilities of promoting cell adhesion and proliferation is critically important for tissue repair and regeneration. Here, we exploit the effects of oxidation level of aldehyde hyaluronic acid (oHA) on gelatin microcarriers for repairing corneal injuries. Specifically, high oxidation levels can endow the microcarrier surface with large oHA grafting amount, smooth topography, and strong stiffness, consequently formulating biocompatible scaffolding materials with superior affinities for keratocyte attachment and growth. In a rabbit model of corneal alkali burn injury, single intracorneal injection of keratocytes/functionalized microcarriers with an appropriate oxidation level could effectively reduce corneal swelling (~62-fold improvement), recover ~94% collagen production and ~89% keratocan expression, and repair disordered collagenous stromal architecture after 4 weeks. These findings on the oxidation level effects of the aldehyde polysaccharide show a great potential use in the development of advanced scaffolds for efficient tissue engineering.

Amniotic membrane transplantation in a patient with impending perforated corneal ulcer caused by Streptococcus mitis: A case report and review of literature.

BACKGROUND: Streptococcus mitis (S. mitis) is an opportunistic pathogen that can lead to severe ocular infections. In previous reports, penetrating keratoplasty (PK) was usually adopted for the treatment of persistent corneal ulcers. This report describes an unusual case of nonhealing descemetocele caused by S. mitis treated by antibiotics plus amniotic membrane transplantation (AMT). CASE SUMMARY: A 63-year-old woman presented with a right persistent corneal ulcer that she had suffered from for the past 9 mo. The culture of a corneal scraping yielded S. mitis. The right eye descemetocele decreased in diameter from 3 to 0.8 mm after the continuous administration of topical vancomycin and ceftriaxone for 2 wk. Due to the slow healing, AMT was performed. Her corneal erosion healed and gradually became clear. Her visual acuity recovered from initially counting fingers to 100/200 at the last follow-up, 67 mo after AMT. CONCLUSION: Antibiotics plus AMT may be an effective alternative treatment other than PK to promote epithelialization and to reduce inflammation in the corneas complicated by S. mitis keratitis.

Fusarium Keratitis in Taiwan: Molecular Identification, Antifungal Susceptibilities, and Clinical Features.

We performed molecular identification and antifungal susceptibilities of pathogens and investigated clinical features of 43 culture-proven Fusarium keratitis cases from 2015-2020 in Taiwan. The pathogens were identified by sequencing of their internal transcribed spacer regions of ribosomal DNA and translation elongation factor 1α gene; their antifungal susceptibilities (to seven agents) were determined by broth microdilution method. We also collected clinical data to compare the drug susceptibilities and clinical features of Fusarium solani species complex (FSSC) isolates with those of other Fusarium species complexes (non-FSSC). The FSSC accounted for 76.7% pathogens, among which F. falciforme (32.6%) and F. keratoplasticum (27.9%) were the most common species. Among clinically used antifungal agents, amphotericin B registered the lowest minimal inhibitory concentration (MIC), and the new azoles efinaconazole, lanoconazole and luliconazole, demonstrated even lower MICs against Fusarium species. The MICs of natamycin, voriconazole, chlorhexidine, lanoconazole, and luliconazole were higher for the FSSC than the non-FSSC, but no significant differences were noted in clinical outcomes, including corneal perforation and final visual acuity. In Taiwan, the FSSC was the most common complex in Fusarium keratitis; its MICs for five tested antifungal agents were higher than those of non-FSSC, but the clinical outcomes did not differ significantly.

Application of a Deep Learning System in Pterygium Grading and Further Prediction of Recurrence with Slit Lamp Photographs.

BACKGROUND: The aim of this study was to evaluate the efficacy of a deep learning system in pterygium grading and recurrence prediction. METHODS: This was a single center, retrospective study. Slit-lamp photographs, from patients with or without pterygium, were collected to develop an algorithm. Demographic data, including age, gender, laterality, grading, and pterygium area, recurrence, and surgical methods were recorded. Complex ocular surface diseases and pseudopterygium were excluded. Performance of the algorithm was evaluated by sensitivity, specificity, F1 score, accuracy, and area under the receiver operating characteristic curve. Confusion matrices and heatmaps were created to help explain the results. RESULTS: A total of 237 eyes were enrolled, of which 176 eyes had pterygium and 61 were non-pterygium eyes. The training set and testing set were comprised of 189 and 48 photographs, respectively. In pterygium grading, sensitivity, specificity, F1 score, and accuracy were 80% to 91.67%, 91.67% to 100%, 81.82% to 94.34%, and 86.67% to 91.67%, respectively. In the prediction model, our results showed sensitivity, specificity, positive predictive value, and negative predictive values were 66.67%, 81.82%, 33.33%, and 94.74%, respectively. CONCLUSIONS: Deep learning systems can be useful in pterygium grading based on slit lamp photographs. When clinical parameters involved in the prediction of pterygium recurrence were included, the algorithm showed higher specificity and negative predictive value in prediction.

Clinical features and outcomes in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged < 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty-seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1-17 years); 51.1% were male. Thirty-three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often-implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3-42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long-term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post-inflammatory hypo-/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long-term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long-term sequelae requiring regular follow-up.