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Preoperative skin antiseptic preparation is the gold standard for prevention of surgical infection. However, improper use of antiseptics may lead to severe ocular damage. Currently, the most common surgical antiseptics can be divided into aqueous-based and alcohol-based disinfectants, with chlorhexidine and iodine/iodophors being the two major components. Chlorhexidine has a persistent antimicrobial effect and is resistant to neutralization by blood or organic products in surgical wounds. Nevertheless, due to its toxicity to the ears, meninges, and eyes, application of chlorhexidine should be prohibited in these surgical fields. Iodine/iodophor is better tolerated by the ocular surface and is the recommended antiseptic for ophthalmic or head and neck surgeries close to the periocular area. Alcohol is less pricey and has a rapid antiseptic effect, though its desiccating effect and flammability restrict the use in mucosal or laser surgeries. The single or combined use of these antiseptics may inadvertently induce severe ocular damage, especially during time-consuming head and neck surgeries with prone, hyperextension, or lateral tilt positions, or surgeries under general anesthesia. Apart from the choice of antiseptics, appropriate selection and attachment of bio-occlusive dressings are key to avoiding antiseptic-related ocular injuries. In this review, we provided a comprehensive summary of the characteristics of antiseptics used in surgical settings and the possible mechanisms and outcomes of antiseptic-related ocular injuries. The prevention, diagnosis, and acute management of these complications were also discussed.

To investigate the structure–function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure–function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA.

The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs.

Inherited retinal degenerations (IRDs) are a group of phenotypically and genotypically heterogeneous disorders with substantial socioeconomic impact. In this cohort study, we tried to address the genetic characteristics and epidemiology of IRDs in Taiwan. Totally, 312 families with IRDs were identified and recruited and genetic testing was performed via probe capture-based NGS targeting 212 IRD-related genes. Statistical analysis was based on the proband of each affected family. Disease-causing genotypes were identified in 178 families (57.1%). ABCA4 variants were the most common cause of disease in this cohort (27 families, 15.2%), whereas CYP4V2 variants were the most common cause for the single phenotype—Bietti’s crystalline dystrophy (12 families, 3.8%). Some variants such as ABCA4:c.1804C>T, CYP4V2:c.802-8_810delinsGC, and EYS:c6416G>A were population-specific disease-causing hotspots. Probands affected by ABCA4, RPGR, RP1L1, and CEP290 sought medical help earlier while patients affected by EYS and CYP4V2 visited our clinic at an older age. To evaluate the representativeness of our cohort in the genetic epidemiology of IRDs in Taiwan, our demographic data were compared with that of the total IRD population in Taiwan, obtained from the National Health Insurance Research Database. This is currently the largest-scale, comprehensive study investigating the genetic characteristics and epidemiology of IRD in Taiwan. These data could help patients and caregivers to adopt precision genomic medicine and novel gene therapies in near future.

Purpose: To study the surgical outcome of therapeutic penetrating keratoplasty (TPK) for medically uncontrolled microbial keratitis at a tertiary hospital in Taiwan over a 14-year period. Methods: This is a retrospective case series study. Patients who underwent TPK at National Taiwan University Hospital in 2001–2014 were included. Patients were divided into 3 diagnostic groups: bacterial keratitis, fungal keratitis, and acanthamoeba keratitis. Each of the following criteria was evaluated: graft clarity at 1 month and 1 year postoperatively, cure of the disease, and anatomical success rate. Results: A total of 107 TPKs were included. TPK eradicated the infection in 57/62 (91.9%) of bacterial keratitis, 33/41 (80.5%) of fungal keratitis, and 9/10 (90.0%) of acanthamoeba keratitis. 22/57 grafts (38.6%) of bacterial keratitis, 22/38 grafts (57.9%) of fungal keratitis, and 5/10 grafts (50.0%) of acanthamoeba keratitis remained clear at 1 year postoperatively. The 1-year graft survival rate did not significantly differ among these 3 groups. The leading causes of graft failure were late endothelial decompensation and graft reinfection. A higher percentage of graft clarity was achieved in grafts

Purpose: Corneal avascularity is critical for corneal transparency; therefore, a tailored process has been presumed to minimize corneal neovascularization (NV). In most cell types, the transcription of vascular endothelial growth factor (VEGF) is up-regulated, and the stability of VEGF mRNA is sustained by human antigen R (HuR) during hypoxia; however, whether such response applies to corneal epithelial cells is unclear. Methods: Human corneal epithelial cells (HCECs) and MCF-7 cells that serves as the control were incubated under 0.5% oxygen, and the levels of VEGF and HuR were examined time-dependently. The alteration of HuR was also examined in vivo using the closed-eye contact lens-induced corneal neovascularization rabbit model and immunohistochemistry. Additionally, the expression of HuR was modulated by transfection of plasmids encoding HuR or siRNA targeting HuR to validate the role of HuR in VEGF expression. Results: We found that, unlike in control cells, the level of VEGF was not up-regulated, and the HuR expression was declined in HCECs following hypoxia. The HuR immunostaining intensities were decreased in corneal epithelial cells of rabbits wearing contact lenses. In addition, HuR overexpression restored the ability of HCECs to up-regulate VEGF under hypoxia; however, knockdown of HuR suppressed hypoxia-induced VEGF in control cells but did not further decrease VEGF in HCECs. These findings suggest that HCECs may modulate HuR to suppress hypoxia-mediated up-regulation of VEGF. Conclusion: Our study revealed a distinct regulation of VEGF via HuR in HCECs following hypoxia, which likely contributes to minimizing corneal NV and/or maintenance of corneal avascularity. Keywords: Human corneal epithelial cells (HCECs), Corneal avascularity, Corneal neovascularization, Vascular endothelial growth factor (VEGF), Human antigen R protein (HuR)

Clinical registries have been developed for decades in the field of ophthalmology, and they are especially well-suited to the study of keratoplasty practices. A comprehensive donor/recipient registry system can provide insight into donor, recipient, and surgical factors associated with immediate and long-term outcomes and adverse reactions. Furthermore, linkage with demographic databases can elucidate relationships with social determinants of health and potentially shape public policy. The vast sample size and multicenter nature of registries enable researchers to conduct sophisticated multivariate or multilayered analyses. In this review, we aim to emphasize the importance of registry data for keratoplasty practice and 1) summarize the structure of current keratoplasty registries; 2) examine the features and scientific contributions of the registries from Australia, the United Kingdom, Singapore, the Netherlands, Sweden, Eye Bank Association of America, and European Cornea and Cell Transplant registries; 3) compare registry-based studies with large single-site clinical studies; 4) compare registry-based studies with randomized control studies; and 5) make recommendations for future development of keratoplasty registries. Keratoplasty registries have increased our knowledge of corneal transplant practices and their outcomes. Future keratoplasty registry-based studies may be further strengthened by record linkage, data sharing, and international collaboration.

AimThis study aimed to test whether human platelet lysate (HPL) has neurotrophic ability for corneal nerve regeneration.MethodsWe measured the neurotrophic factors in human peripheral serum (HPS) and two commercially available HPLs, UltraGRO and PLTMax. In vitro, we compared the growth rates, neuronal differentiation and immunostaining of neuron markers in mouse neuroblastoma cell line (Neuro-2a) and primary culture of mouse trigeminal ganglion cells that were cultivated in different concentrations of fetal bovine serum, HPS and HPL. In vivo, we created corneal wounds on Sprague Dawley rats with a rotating burr and evaluated the effects of topical HPL on wound healing and corneal nerve regeneration by in vivo confocal microscopy and corneal aesthesiometry.ResultsHPLs had significantly higher concentrations of various neurotrophic factors compared with HPS (pConclusionHPL has significantly higher concentrations of neurotrophic factors compared with HPS. It showed not only in vitro but also in vivo corneal neurotrophic abilities. Our results suggest that HPL may have a potential role in the treatment of diseases related to corneal nerve damage or degeneration.

PURPOSE To determine the role of IQ-domain GTPase-activating protein1 (IQGAP-1) in tight junctions of human corneal epithelial cells (HCECs) and its effect against P. aeruginosa (PAK) invasion. MATERIAL AND METHODS Primary human corneal epithelial cells (HCECs), immortalized HCECs, and IQGAP-1 RNA knockdown HCECs (siHCECs) were used. Confocal microscopy, transepithelial electrical resistance (TER), trypan blue exclusion assay and gentamicin invasion assay were done. RESULTS In primary and immortalized HCECs, IQGAP-1 co-localized with zonular occludin-1 (ZO-1) and actin. Enhanced actin and ZO-1 aggregation were seen in siHCECs. IQGAP-1 knockdown significantly increased TER of immortalized HCECs (P < .0001). Cell viability after PAK infection increased for siHCECs for up to 4 h after infection. PAK intracellular invasion was significantly lowered by 50% in siHCECs at 1 h post-infection. CONCLUSION IQGAP-1 knockdown increased the strength and integrity of tight junctions and may provide an early protective effect against P. aeruginosa invasion.

Purpose To investigate the demographics, risk factors, microbiology, and resistance pattern at a tertiary hospital and to detect the shifting trend over 2 decades. Design A retrospective observational case series. Methods We reviewed all records of patients with microbial keratitis (MK) that were hospitalized in National Taiwan University Hospital between 2007 and 2016. Demographics, predisposing factors, pathogens, and clinical courses were compared to our previous study conducted from 1992 to 2001. Antibiotic susceptibility was compared with those conducted from 1994 to 2005. Results The percentage of patients 60 years and older in the MK population was increasing (P = 2.1E-21). The proportion of trauma-related MK declined while MK related to chronic ocular or systemic disorders rose. The prevalence of nontuberculous mycobacteria (NTM) showed a decreasing trend (P = .0032), whereas Microsporidia has been increasingly detected. The 2 most common bacterial isolates were Pseudomonas aeruginosa (35.2%) and Staphylococcus species (13.2%). Management of these infection did not differ in common pathogens between the 2 decades. The susceptibility of Staphylococcus species to oxacillin reduced significantly (P = .002) and there was an increase in methicillin-resistant Staphylococcus aureus keratitis. Conclusions Contact lens wear remained the most common predisposing factor, with Pseudomonas species as the major pathogen. However, chronic disorder–related MK was on the rise along with an increasing trend of oxacillin resistance in Staphylococcus species. We found a decreasing trend in NTM keratitis while Microsporidia keratitis was considered as an emerging ocular disease. Though gram-negative isolates remained susceptible to all antibiotics tested, antibiotic resistance was more common in gram-positive isolates.

The study aims to evaluate the therapeutic effects of dermatologic tacrolimus ointment on eyelids to treat refractory vernal keratoconjunctivitis (VKC). This institutional study examined the effects of steroid treatment for 10 patients diagnosed with severe VKC refractory to steroid treatment. Patients received 0.1% dermatologic topical tacrolimus treatment on their eyelids once or twice daily for concomitant atopic dermatitis. The therapeutic outcomes were evaluated according to change in severity of clinical findings recorded with serial external ocular photography and change in requirement for steroid treatment. Clinical signs and symptoms improved substantially after tacrolimus treatment. Significant reduction in size of papillae, decrease of discharge, improvement in hyperemia, and shield ulcer healing with re-epithelization were observed in all patients. Six out of 10 (60%) patients did not receive steroid treatment. Long-term maintenance of tacrolimus was required to prevent episodic exacerbation. Patients’ only treatment-related complaints were of mild burning sensations during medication application to eyelids, and this sensation disappeared a few days after treatment. Application of 0.1% dermatologic tacrolimus ointment to eyelids is effective and safe in the treatment of refractory VKC in patients with concomitant atopic dermatitis. This treatment may serve as a substitute for or decrease the requirement of steroid treatment.

Background/aimsTo evaluate the utility rate, indication, outcome, and cost of refrigeration and glycerol cryopreservation for storing anterior corneal buttons during endothelial keratoplasty for subsequent use in tectonic lamellar patch grafting.MethodAnterior corneal buttons collected after precutting or prestripping during endothelial keratoplasty from January 2014 to December 2019 were preserved using the following protocol: (1) refrigeration for up to 4 weeks at 4°C in Optisol-GS and (2) glycerol cryopreservation for up to 2 years. The utility rate, outcome and cost of these cryopreserved anterior corneal buttons were retrospectively examined.ResultsDuring the 6-year study period, 26 anterior corneal buttons were refrigerated and 49 were cryopreserved for extended use. The utility rates for the refrigerated and cryopreserved anterior corneal buttons were 69.2% and 73.5%, respectively. Their average preservation periods were 0.53±0.05 and 12.76±0.94 months, respectively. Noninfection-related perforation was the leading indication for using the extendedly preserved anterior corneal buttons. The average postoperative follow-up periods were 10.03±2.91 and 14.35±2.17 months for refrigerated and cryopreserved anterior corneal buttons. Secondary keratoplasty was required by 7 of 18 (38.9%) and 6 of 36 (16.7%) patients receiving refrigerated and cryopreserved anterior corneal buttons, respectively. None of our patients developed graft infection from donor tissues.ConclusionCryopreservation can safely extend the utility of anterior corneal buttons. This method not only reduced the wastage of the limited donor tissue but also was cost-effective.

Background Full-thickness macular hole (FTMH) is a rare complication in retinitis pigmentosa (RP) patients and may increase intraoperative challenges. Furthermore, lens capsular flap transplantation and inverted internal limiting membrane (ILM) flap were reported to close complicated FTMH successfully. Here, we present a case of bilateral advanced RP complicated by a FTMH treated with a novel lens capsular flap transplantation and inverted internal limiting membrane flap. Case presentation A 46-year-old presented to our hospital with a complaint of progressively blurred vision and metamorphopsia in both eyes. Spectral-domain optical coherence tomography revealed a FTMH with retinoschisis in the right eye and another FTMH in the left eye. ILM peeling with inverted ILM flap technique was performed on the right eye and ILM peeling with anterior lens capsular flap technique was performed on the left eye. Post-operative follow-up showed successful closure of the FTMH and improved vision in both eyes. Conclusions In our present case, flap-assisted techniques for retinitis pigmentosa with macular hole result in excellent visual and anatomic outcomes.

Background: In most of the world, corneas from hepatitis B surface antigen (HBsAg)-positive donors have been considered unsuitable for transplantation because of assumed risk of disease transmission. Methods: In Taiwan, an HBV endemic area, corneas from HBsAg-positive donors can be allocated to recipients who are seropositive for HBsAg or antibody against HBsAg (anti-HBs). Between January, 2015 and December, 2019, we evaluated HBV DNA in serum and corneo-scleral rims retrieved from HBsAg-positive and HBsAg-negative donors. We assessed donor serum HBsAg, anti-HBs, hepatitis B core antibody (anti-HBc) and HBV DNA to predict the presence of their corneo-scleral HBV DNA. We conducted a look-back study of recipients transplanted with corneo-scleral HBV DNA-positive donor grafts. Their HBV serological profiles were examined to identify possible post-transplantation hepatitis B transmission. Findings: Forty-five and 125 corneal grafts from 28 HBsAg-positive and 85 HBsAg-negative donors, respectively, were included. The donor corneo-scleral rim HBV DNA-positive rate was significantly greater in HBsAg-positive donor grafts (80·0%) compared to that of the HBsAg-negative grafts (6·4%, [ P

The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype&ndash, phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p &lt, 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C&gt, T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C&gt, T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants.

Radial keratoneuritis (RK) is a common feature of Acanthamoeba keratitis (AK). In vivo confocal microscopy (IVCM) is noninvasive and provides real-time images for the diagnosis of corneal diseases by allowing the visualization of corneal structures and morphologies of living organisms at the cellular level. Images of AK with RK obtained using commercial white light IVCM devices have not been frequently evaluated. In the present study, a white light IVCM device was used to evaluate the corneal findings and describe spatial changes in the corneal nerves at different depths in cases of early-stage AK with RK.In this retrospective, observational study, white light IVCM images focused on RK were evaluated for Acanthamoeba cysts/trophozoites, corneal deposits, and altered corneal nerves, with special emphasis on three-dimensional spatial changes in the corneal nerves at different depths.Seventeen eyes of 17 patients exhibiting early-stage AK with RK were included in the study. Acanthamoeba cysts/trophozoites were observed in the corneal epithelium of 13 eyes and stroma of 7 eyes. Alterations in the corneal nerve morphology and density were observed from the basal epithelial layer to the stromal layer in 12 eyes. Acanthamoeba trophozoites were attached to the corneal stromal nerves in five eyes.These findings suggest that white light IVCM can identify consistent corneal findings, particularly spatial changes in the corneal nerves, in cases of early-stage AK with RK.

Researchers demonstrated an elegant ability for red discrimination in zebra finches. It is interested to understand whether red activates exhibit much stronger response than other colors in neural network levels. To reveal the question, local field potentials (LFPs) was recorded and analyzed in two visual pathways, the thalamofugal and the tectofugal pathways, of zebra finches. Human studies demonstrate visual associated telencephalons communicate with higher order brain areas such as prefrontal cortex. The present study determined whether a comparable transmission occurs in zebra finches. Telencephalic regions of the thalamofugal (the visual Wulst) and the tectofugal pathway (the entopallium) with their higher order telencephalon, nidopallium caudolateral (NCL) were simultaneously recorded. LFPs of relay nuclei (the nucleus rotundus, ROT) of tectofugal pathway were also acquired. We demonstrated that LFP powers in the tectofugal pathway were higher than those in the thalamofugal pathway when illuminating blue lights. In addition, the LFP synchronization was stronger between the entopallium and NCL. LFPs also revealed a higher Granger causality from the direction of entopallium to NCL and from ROT to entopallium. These results suggest that zebra finches’ tectofugal pathway predominately processing color information from ROT to NCL, relayed by entopallium, and blue could trigger the strongest response.

Purpose To develop and compare deep learning (DL) algorithms to detect keratoconus on the basis of corneal topography and validate with visualization methods. Methods We retrospectively collected corneal topographies of the study group with clinically manifested keratoconus and the control group with regular astigmatism. All images were divided into training and test datasets. We adopted three convolutional neural network (CNN) models for learning. The test dataset was applied to analyze the performance of the three models. In addition, for better discrimination and understanding, we displayed the pixel-wise discriminative features and class-discriminative heat map of diopter images for visualization. Results Overall, 170 keratoconus, 28 subclinical keratoconus and 156 normal topographic pictures were collected. The convergence of accuracy and loss for the training and test datasets after training revealed no overfitting in all three CNN models. The sensitivity and specificity of all CNN models were over 0.90, and the area under the receiver operating characteristic curve reached 0.995 in the ResNet152 model. The pixel-wise discriminative features and the heat map of the prediction layer in the VGG16 model both revealed it focused on the largest gradient difference of topographic maps, which was corresponding to the diagnostic clues of ophthalmologists. The subclinical keratoconus was positively predicted with our model and also correlated with topographic indexes. Conclusions The DL models had fair accuracy for keratoconus screening based on corneal topographic images. The visualization mentioned in the current study revealed that the model focused on the appropriate region for diagnosis and rendered clinical explainability of deep learning more acceptable. Translational relevance These high accuracy CNN models can aid ophthalmologists in keratoconus screening with color-coded corneal topography maps.

To determine the role of transmembrane mucins in blocking fluorescein ingress to the corneal epithelium and its deficiency in contributing to corneal fluorescein punctate staining.A dry eye model was established by extirpating lacrimal and Harderian glands in rabbits to correlate the expression of mucins with fluorescein-stained areas on the corneal button using immunofluorescence. Expression of transmembrane mucins was promoted in human corneal epithelial cells (HCECs) by culturing with the mucin-promoting medium (MPM) or diquafosol treatment. Conversely, the expression of mucins was downregulated by knockdown with short hairpin RNA. The role of mucin1 extracellular domain in fluorescein ingress was further verified by overexpression of N-terminally truncated mucin1 in HCECs.In the rabbit dry eye model, the expression level of mucin1 was significantly decreased in superficial corneal epithelial cells where fluorescein punctate staining was observed. Upregulation of mucin1 and mucin16 in HCECs promoted by MPM or by diquafosol treatment impeded intracellular fluorescein ingress. Downregulation of mucin1 and mucin16 enhanced fluorescence ingress in HCECs after fluorescein staining. Overexpression of truncated mucin1 did not alter the fluorescein intensity of fluorescein-stained HCECs, supporting the notion that the ability of mucin1 to block fluorescein ingress was primarily mediated by its extracellular domain. Minimal inherent expression of mucin16 in the rabbit cornea limited the validation of its role in blocking fluorescein ingress in vivo.Transmembrane mucin1 blocks fluorescein ingress in the corneal epithelium, explaining how fluorescein staining is positive when the level of transmembrane mucins is disturbed in dry eyes.

Objectives In vivo confocal microscopy was used to observe the morphological presentations and anatomical correlations between corneal neovascularization (NV) and intracorneal lipid deposition in a rabbit model of contact lens (CL)-induced lipid keratopathy secondary to corneal NV. Methods Rabbits were divided into 3 groups: (1) 8-week normal diet, (2) 8-week high-cholesterol diet, and (3) 4-week normal diet followed by 4-week high-cholesterol diet. Corneal NV was induced by closed-eye CL. The formation and maturation of corneal NV were shown by immunohistochemical staining against CD31 and high-molecular-weight melanoma-associated antigen. In vivo confocal microscopy identified corneal NV and lipid deposition. Acquired images for each eye were arranged and mapped into subconfluent montages. Results In group 1, corneal NV sprouting formed from the peripheral to the central cornea by the end of week 4. Pericytes around vessels were shown after 2 weeks of CL wear. In group 2, lipid deposition started from the peripheral cornea and progressively covered the whole cornea. In group 3, lipid deposition was found first in the central cornea after 2 weeks of high-cholesterol diet and progressed to cover the peripheral cornea. In vivo confocal microscopy demonstrated four different patterns of intracorneal lipid deposition: spindle shapes arranged randomly or in parallel, amorphous shapes, multiangular shapes, and mixed types. Intracorneal lipid deposition was distributed from basal corneal epithelium to deep stroma. Conclusions Intracorneal lipids tend to accumulate around newly formed corneal NV but can extend to the area covered with mature NV. In vivo confocal microscopy can demonstrate various shapes and depths of intracorneal lipid deposition.

Purpose To evaluate the complications and the treatment results of SmartPlug-related complications. Methods Retrospective review of all patients from a single medical hospital who received SmartPlug (Medennium, Inc., Irvine, CA) insertions from October 2007 to February 2014. All patients who developed SmartPlug-related canaliculitis and pyogenic granuloma were analyzed. Lacrimal irrigation with antibiotics was performed in most patients. Results Six hundred thirty-one eyes received SmartPlug insertion and 18 eyes developed SmartPlug-related complications (14 canaliculitis and 4 pyogenic granuloma). The mean time interval from insertion to development of the complications is 3.0 (0.5-6.9) years. Sixteen eyes received lacrimal irrigation with antibiotics, and all the eyes showed improvement without recurrence. The other two eyes had recurrence of granuloma pyogenica only after surgical excision. Conclusions SmartPlug-related complications, including canaliculitis and granuloma pyogenica, required long-term follow-up. Most of the complications can be cured by lacrimal irrigation of antibiotics.

BackgroundThis study examined whether corneas from bacteremic donors could be used for corneal transplant.MethodsCorneas donated to the National Eye Bank of Taiwan between 1 January 2014 and 30 June 2017 were included in this study. All the corneas had corneoscleral rim cultures during the retrieval process and were hypothermic preserved in the Optisol-GS storage medium. A microbial work-up flow chart was used for the sterility check of all grafts. Bacteremic donors were defined as those whose last blood culture before corneal donation was positive. The microbial contamination rates, the endothelial cell densities, the tissue utility rates and early complications after transplants were compared between the corneas from bacteremic versus non-bacteremic donors.Results697 corneas from 356 donors were analysed, 70 of which were from bacteremic donors. The microbial contamination rates of the corneas from bacteremic and non-bacteremic donors (7.1% vs 9.1%)(p=0.30) were close. None of the contaminated corneas grew the same bacterial strains as those from their blood cultures. The corneas from bacteremic donors and non-bacteremic donors have similar endothelial cell densities (2931±297 cells/mm2 vs 2903 ± 470 cells/mm2) (p=0.63). Corneas from bacteremic and non-bacteremic donors shared a similar utility rate (98.6% vs 99.4%)(p=0.41). None of the corneas caused infectious complications after transplants.ConclusionOur study showed that corneas from bacteremic and non-bacteremic donors have equally low contamination rates and are of the same quality in terms of endothelial cell density and safety.

Purpose To report an outbreak of microsporidial keratoconjunctivitis resulting from a swimming pool in Taiwan. Design Retrospective case series. Methods The records of 13 teenagers (15 eyes) contracting microsporidial keratoconjunctivitis after swimming in a local swimming pool were reviewed. Corneal scrapings were collected in all eyes at a tertiary referred hospital in June 2017. Gram stain, modified Kinyoun acid-fast stain, polymerase chain reaction (PCR), and gene analysis of the microsporidian 16S ribosomal RNA (rRNA) were examined in all 15 cases. Results Symptoms occurred 1–12 days after the water contact. At presentation, all eyes showed nonpurulent conjunctivitis and small, plaque-like epithelial lesions peripherally (n = 6), centrally (n = 3), both peripherally and centrally (n = 5), or centrally with superficial punctate keratopathy (n = 1). During the follow-up period, 10 eyes developed central superficial punctate keratopathy (n = 6) or subepithelial haze or infiltrates, which were distributed centrally (n = 2) or peripherally (n = 3), following development of plaque-like epithelial lesions. The results of Gram stain and modified Kinyoun's acid-fast stain were confirmatory in 10 cases (67%). All 15 cases yielded positive PCR results and were all identified to be Vittaforma corneae. All followed-up eyes healed without sequelae using topical levofloxacin and betamethasone eye drops. Conclusions Microsporidial keratoconjunctivitis can develop from contact with swimming pool water. The clinical course initially manifested as rapidly resolving conjunctivitis and peripheral plaque-like epithelial lesions, followed by paracentral or central plaque-like epithelial lesions, which evolved into subepithelial haze or infiltrates.

PURPOSE: To report a case of bilateral non-tuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE) that was successfully treated with oral and topical fortified antibiotics. METHODS: Case report and literature review. RESULTS: An otherwise healthy 21-year-old woman presented with culture-proven bilateral Mycobacterium abscessus keratitis 8 days after undergoing SMILE, showing multiple white stromal infiltrates in the interface in both eyes. Progressive, diffuse flap edema followed by pocket abscess, exudation in the anterior chamber, granulation tissue formation in the pocket, intrastromal neovascularization, and eventually partial resolution of corneal opacity were noted after topical and oral antibiotic treatment for 6 months. Her corrected distance visual acuity was 20/32 and 20/50 in the right and left eyes, respectively, 12 months after initial presentation. CONCLUSIONS: This is the first report of successful medical management of bilateral non-tuberculous mycobacterial keratitis after SMILE. The manifestations are different from and even more difficult to treat than those of keratitis after LASIK. [ J Refract Surg. 2018;34(9):633–636.]

Background/aimWe investigated the microstructural changes in white matter of adults with amblyopia using diffusion spectrum imaging with systematic tract-based automatic analysis of the whole brain.MethodsTen adults with amblyopia (six women and four men, 33.6±10.6 years old on average) and 20 age- and sex-matched normal-sighted controls were enrolled. The mean generalised fractional anisotropy (GFA) was measured in 76 white matter tracts and compared between the experimental and control groups using a threshold-free cluster-weighted method andt-test. A 2-percentile cut-off was used to identify segments with the greatest differences between the two groups.ResultsParticipants with amblyopia had significantly lower GFA values than the controls in 11 segments located in nine white matter tracts, which included the following: left arcuate fasciculus, left frontal aslant tract, left fornix and left inferior fronto-occipital fasciculus of the association fibres; left thalamic radiations of the auditory nerve and bilateral optic radiations of the projection fibres; and genu and middle temporal gyrus of the callosal fibres. Amblyopic participants had statistically higher GFA values in the bilateral uncinate fasciculus than those of the controls.ConclusionThis preliminary study using whole-brain tractographic analysis of white matter reveals association between abnormal early visual processing and alterations in brain architecture, which may be related to various higher-level deficits, such as audiovisual integration and hand−eye coordination in patients with amblyopia.

PURPOSE To assess the surgical and clinical outcomes of anterior lamellar keratoplasty using anterior corneal buttons from Descemet stripping automated endothelial keratoplasty (DSAEK) donor tissue. METHODS Retrospective data from 8 patients with unilateral limbal dermoids, treated between February 2011 and January 2016 at National Taiwan University Hospital, were analyzed. Donor corneas for DSAEK were divided into anterior and posterior lamellae using a 350-μm microkeratome. Anterior corneal buttons were stored for up to 4 weeks in storage media before being used as patch grafts for anterior lamellar keratoplasty. RESULTS Corneoscleral integrity was preserved in all cases. Three of the 8 patients showed improved best-corrected visual acuity after surgery. Three patients' astigmatism reduced by more than 0.75 diopters. All 8 patients had satisfactory cosmesis after surgery. Neovascularization at the graft-host junction and graft edema was noted in 1 patient and was treated using bevacizumab injection and topical steroid. CONCLUSIONS Anterior corneal buttons obtained from DSAEK can be used as patch grafts for surgical management of limbal dermoids. This procedure achieved satisfactory cosmetic and visual outcomes in our study. This procedure may potentially allow one corneal tissue to be received by multiple patients.

PURPOSE: The aim of this study is to evaluate the effects of air-lifting on the stemness, junctional protein formation, and cytokeratin expression of rabbit limbal stem cells cultivated in vitro, and to find out the proper timing of air-lifting before transplantation as limbal epithelial cell sheets for the treatment of limbal insufficiency. MATERIALS AND METHODS: Limbal epithelial cells were isolated from the limbus of New Zealand white rabbits and cultivated in vitro. After the cells became confluent, different durations of air-lifting (0, 1, 2, 4, and 7 days) were performed. At the end of cultivation, immunohistochemistry on cryosections was performed and observed by fluorescein microscopy and in vitro confocal microscopy for cytokeratins (K3, K10, K12, K13, and K14), junctional and structural proteins (ZO-1, p120, and actin) and stem cell markers (ABCG2 and P63). Scanning electron microscopy was used for observing the microstructure of superficial cells. Transepithelial electrical resistance (TEER) was used to measure the transepithelial permeability. RESULTS: The expression of K3, K10, K12, K13, K14, and ABCG2 showed no differences in pattern and location among different groups of airlifting. A time-dependent increase in corneal epithelial thickness was found after air-lifting. In vitro confocal microscopy demonstrated that K3, p120, and ZO-1 were expressed on the apical cell layer, whereas P63 and ABCG2 were expressed more on the basal epithelial layer. Scanning electron microscopy of the superficial layer demonstrated that airlifting induced time-dependent increase in the size of surface epithelial cells and triggered cellular differentiation. TEER results demonstrated a time-dependent increase of transepithelial electric resistance. CONCLUSIONS: During limbal epithelial cell expansion in vitro, air-lifting can increase cellular stratification, enlarge surface cells, trigger cellular differentiation, and increase the transepithelial barrier. However, the expression of cellular junctional, stem cell and cytokeratin markers seems to have no obvious differences in pattern and localization.

To determine the role of IQ-domain GTPase-activating protein1 (IQGAP-1) in tight junctions of human corneal epithelial cells (HCECs) and its effect againstPrimary human corneal epithelial cells (HCECs), immortalized HCECs, and IQGAP-1 RNA knockdown HCECs (siHCECs) were used. Confocal microscopy, transepithelial electrical resistance (TER), trypan blue exclusion assay and gentamicin invasion assay were done.In primary and immortalized HCECs, IQGAP-1 co-localized with zonular occludin-1 (ZO-1) and actin. Enhanced actin and ZO-1 aggregation were seen in siHCECs. IQGAP-1 knockdown significantly increased TER of immortalized HCECs (IQGAP-1 knockdown increased the strength and integrity of tight junctions and may provide an early protective effect against

To compare the sensitivity of two genotypes of P. aeruginosa to various disinfectant solutions and analyze the attached bacteria on worn cosmetic contact lenses (cosCLs).In this prospective study, healthy volunteers wore etafilcon (brown), nelfilcon (gray), or hilafilcon (black) cosCLs and microbial adhesion analysis was performed. A rub-off test determined pigment dislodgement. Disinfectant sensitivity to Optifree Replenish (Alcon), Optifree Pure Moist (Alcon), Renu Fresh (BauschLomb), and AoSept Plus (Ciba Vision) was tested at various disinfection times and compared between various genotypes and Type III secretion (T3S) system mutants.Of the 1152 cosCLs collected, 364 were culture positive (32%). The highest rate of culture-positive lens was hilafilcon (chi square, P = 0.0001). Hilafilcon also had a significantly greater number of isolates than etafilcon (P 0.0001). Hilafilcon was the only lens to fail the rub-off test. Cytotoxic strains were significant more resistant to Renu Fresh than were invasive strains, even at 100% of recommended disinfection time (P = 0.0005). Of the tested disinfectants, Renu Fresh was significantly less effective in killing both genotypes of P. aeruginosa compared to AoSept Plus at all time points (25%, 50%, 75%, and 100% recommended disinfection time, P = 0.0001, 0.0001, 0.0005, and 0.0005, respectively). When the T3S system was dysfunctional, mutant strains were all susceptible to disinfectants (P = 0.0001 for both invasive and cytotoxic strains).Pseudomonas species is commonly found on cosCLs of asymptomatic individuals. Wearers of cosCLs that dislodge pigments may be predisposed to microbial contamination. Cytotoxic strains are more resistant to disinfectant solutions, especially to Renu Fresh. P. aeruginosa disinfectant resistance requires a functional T3S system.

Corneal endothelial dysfunction causes corneal edema and severe visual impairments that may lead to permanent blindness. Although corneal endothelial keratoplasty is currently the treatment-of-choice to restore vision, it faces several difficulties, including worldwide shortage of donor corneas, progressive loss of endothelial cells after surgery, and extensive damage of endothelial cells during surgical manipulation. With further understanding of the corneal endothelial cell biology and advances in the field of pharmacological treatment, tissue engineering, cell or stem cell therapy, different strategies have been developed to treat corneal endothelial disorders.

Purpose: Radial keratoneuritis (RK) is a common feature of Acanthamoeba keratitis (AK). In vivo confocal microscopy (IVCM) is noninvasive and provides real-time images for the diagnosis of corneal diseases by allowing the visualization of corneal structures and morphologies of living organisms at the cellular level. Images of AK with RK obtained using commercial white light IVCM devices have not been frequently evaluated. In the present study, a white light IVCM device was used to evaluate the corneal findings and describe spatial changes in the corneal nerves at different depths in cases of early-stage AK with RK. Methods: In this retrospective, observational study, white light IVCM images focused on RK were evaluated for Acanthamoeba cysts/trophozoites, corneal deposits, and altered corneal nerves, with special emphasis on three-dimensional spatial changes in the corneal nerves at different depths. Results: Seventeen eyes of 17 patients exhibiting early-stage AK with RK were included in the study. Acanthamoeba cysts/trophozoites were observed in the corneal epithelium of 13 eyes and stroma of 7 eyes. Alterations in the corneal nerve morphology and density were observed from the basal epithelial layer to the stromal layer in 12 eyes. Acanthamoeba trophozoites were attached to the corneal stromal nerves in five eyes. Conclusion: These findings suggest that white light IVCM can identify consistent corneal findings, particularly spatial changes in the corneal nerves, in cases of early-stage AK with RK.

PurposeTo determine the correlation between superior limbic keratoconjunctivitis (SLK) and selected tear cytokines and to evaluate the efficacy of these cytokines in monitoring the response of patients with SLK to either medical treatment alone or in combination with conjunctival resection.DesignA cohort study.MethodsTwenty-five eyes of 13 patients with SLK were assigned to either medically responsive or surgical treatment groups depending on their responses 1 month after initial medical treatment. Treatment efficacy was assessed by improvements in clinical grading and decreases in the levels of tear cytokines.ResultsFourteen eyes were improved by medical treatment alone, whereas satisfactory outcomes were achieved for the remaining 11 eyes after surgical management. The overall grading prior to medical treatment was lower in medically responsive group compared with surgical treatment group (p=0.0139). Among the examined tear cytokines, monocyte chemoattractant protein (MCP)-1 was positively associated with the severity of clinical grading (p=0.0251). While both treatments significantly decreased the levels of MCP-1 and interleukin-6, surgical treatment also decreased the levels of interferon-γ and tumour necrosis factor-α. Notably, overall cytokine levels after surgical treatment were lower than those after medical treatment alone.ConclusionsSince an association of tear MCP-1 level with the clinical grading and treatment response of SLK was observed in this study, tear MCP-1 may be a potential indicator of SLK disease severity. According to the degree to which the tear cytokine levels were decreased, surgical treatment appears to be an effective treatment modality for patients with SLK who are refractory to medical treatment alone.

Purpose: To analyze the outcomes of Acanthamoeba keratitis (AK) in terms of different clinical presentations in a tertiary hospital in Taiwan over a 20- year period. Methods: This is a retrospective case series. Patients with AK diagnosed at the National Taiwan University Hospital between January 1996 and December 2015 were identified. A diagnosis of AK was made on the basis of positive Acanthamoeba smear/cultures or pathological identification of Acanthamoeba cysts on keratoplasty specimens. Patient demographics, clinical presentations, treatment courses, and final visual outcomes were collected and analyzed. Visual acuity, postoperative complications and graft survivals were measured as outcomes. Results: Of the 62 patients with AK in our study, 64.5% were medically treated while 35.5% underwent surgical treatment. In those with ring infiltrate, 52.4% patients could be successfully treated with medications. In eyes receiving penetrating keratoplasty, postoperative complications were more common in therapeutic penetrating keratoplasty (TPK) than those in optical penetrating keratoplasty (OPK) group (82.4% versus 40%, p = 0.04). The graft size was larger in TPK than that in OPK group (8.56 versus 7.83 mm, p = 0.002). Furthermore, post-operative glaucoma, which was the major complication, was found to be associated with larger graft size (p = 0.02) and dilated pupil/iris atrophy (p = 0.01). Conclusion: Even in advanced cases with ring infiltrate, eradication of infection with anti-amoebic drugs is possible. In those requiring keratoplasty, the surgical timing should be made meticulously considering graft size and signs of dilated pupil/iris atrophy in terms of post-operative glaucoma. Keywords: Acanthamoeba keratitis, Penetrating keratoplasty, Post-keratoplasty glaucoma