UbiA prenyltransferase domain-containing protein 1 (UBIAD1) variant c.695 A > G identified in a multigenerational Japanese family with Schnyder corneal dystrophy.

PURPOSE: We aimed to identify pathogenic variations in the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) gene in a Japanese family with Schnyder corneal dystrophy (SCD). STUDY DESIGN: Clinical study METHODS: Three clinically diagnosed SCD patients from a single pedigree participated. Patients 1 and 2 were 69- and 65-year-old sisters, and patient 3 was the 42-year-old daughter of patient 1. Blood samples from the patients were obtained for genetic analysis. Mutation screening of the two UBIAD1 exons was performed using polymerase chain reaction (PCR)-based DNA sequencing. RESULTS: All participants were found to be heterozygous for the pathogenic missense variation c.695 A > G (p.Asn232Ser) in exon 2 of UBIAD1. CONCLUSION: This is the first report on the pathogenic UBIAD1 variation c.695 A > G (p.Asn232Ser) in a Japanese population. SCD is a rare corneal dystrophy, and further research on additional cases will aid in the elucidation of disease mechanisms and development of therapeutic strategies.

Regular and irregular astigmatism of bullous keratopathy using Fourier harmonic analysis with anterior segment optical coherence tomography.

Bullous keratopathy (BK) is known to present with corneal edema and Descemet's folds, which can cause corneal astigmatism. However, no report quantitatively evaluated BK astigmatism by separating it into regular and irregular astigmatism. This study investigated the regular and irregular astigmatism of the anterior and posterior corneal surface with Fourier harmonic analysis and anterior segment optical coherence tomography. Preoperative data from 43 eyes of 41 BK patients who received corneal endothelial transplantation were compared with the data from 43 eyes of 43 subjects without corneal disease. Anterior and posterior cylinder power, central corneal thickness (CCT) and thinnest corneal thickness were significantly greater in BK. With Fourier harmonic analysis, BK eyes were found to have significantly larger anterior and posterior regular astigmatism, asymmetry component and higher-order irregularity. Asymmetry component and higher-order irregularity that accounted for the posterior irregular astigmatism increased as CCT increased in BK. Higher-order irregularity in the posterior cornea also positively correlated with worsening best corrected visual acuity. Subgroup analysis found significant correlations between CCT and posterior higher-order irregularity for intraocular surgery and laser iridotomy, but not Fuchs endothelial corneal dystrophy. This study has significance in that it revealed the characteristics of the corneal posterior irregular astigmatism of BK.

Impact of rigid gas-permeable contact lens on keratometric indices and corneal thickness of keratoconus eyes examined with anterior segment optical coherence tomography.

PURPOSE/AIM: Detecting keratoconus (KC) progression helps determine the surgical indication for corneal cross-linking (CXL). This retrospective observational study aimed to examine changes in keratometric indices and corneal thickness in patients with KC who used rigid gas-permeable (RGP) contact lenses. MATERIALS AND METHODS: This study involved 31 eyes (31 patients) diagnosed with KC. No patient had used RGP or any other type of contact lenses for at least 1 month. Corneal topographic data were obtained using three-dimensional anterior segment optical coherence tomography before and after >1 month of RGP lens use. RESULTS: The average and maximum keratometry values changed after using an RGP lens (-1.05 ± 1.92 D, p < 0.01 and -1.65 ± 4.20 D, p = 0.04, respectively); the spherical component of the anterior corneal surface became significantly smaller (p = 0.02). No change was observed in the central or thinnest corneal thickness values. Keratometric changes were greater in eyes with severe KC than in those with moderate KC (p = 0.014). CONCLUSIONS: Keratometry and spherical components of the anterior corneal surface values decreased after RGP lens use; keratometric changes were greater in eyes with severe KC than in those with moderate KC. Corneal progression indices, including corneal thickness, posterior keratometry, and irregular astigmatism values, mostly remained unchanged. It is important to consider these findings when evaluating corneal topography of KC and preparing CXL.

The effect of human platelet lysate on corneal nerve regeneration.

AIM: This study aimed to test whether human platelet lysate (HPL) has neurotrophic ability for corneal nerve regeneration. METHODS: We 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. RESULTS: HPLs had significantly higher concentrations of various neurotrophic factors compared with HPS (p<0.05). In Neuro-2a cells, 3% HPL was better at promoting neuronal growth and differentiation compared with HPS at the same concentration. HPL was also found to have superior neurotrophic effects compared with HPS in primary cultures of mouse trigeminal ganglion cells. In vivo, HPL-treated eyes had better corneal epithelial wound healing rate, nerve regeneration length and corneal touch threshold compared with eyes treated with artificial tears (p<0.05). CONCLUSION: HPL 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.

Corneal topography in keratoconus evaluated more than 30 years after penetrating keratoplasty: a Fourier harmonic analysis.

The aim of this observational study was to examine the characteristics of anterior and posterior corneal topography in keratoconic eyes more than 30 years after penetrating keratoplasty (PK). Patients who maintained clear grafts for more than 30 years after PK were included and divided into the keratoconus (KC) group or other diseases (Others) group, based on the primary indication. Twenty-six eyes of 26 patients were included. The KC group and the Others group included 14 eyes and 12 eyes, respectively. The KC group participants were younger at the time of surgery (P = 0.03). No differences were found in best-spectacle-corrected visual acuity, keratometric power, and central-corneal-thickness. Based on corneal topography using Fourier harmonic analyses, regular astigmatism in the anterior cornea was significantly larger (P = 0.047) and the spherical component in the posterior cornea was significantly lower (P = 0.01) in the KC group. The area under the receiver operating characteristic curve of the spherical component, regular astigmatism, asymmetry component, and higher-order irregularity were 66.07%, 63.10%, 57.14%, and 59.23%, respectively, in the anterior cornea and 80.65%, 52.98%, 63.10%, and 63.99%, respectively, in the posterior cornea. Our results suggested that Fourier harmonic analysis of corneal topography could be useful for patients with KC long after PK.

Eyelid sebaceous carcinoma: Validation of the 8th edition of the American Joint Committee on cancer T staging system and the prognostic factors for local recurrence, nodal metastasis, and survival.

PURPOSE: To investigate the clinicopathological features and prognostic factors for eyelid sebaceous gland carcinoma (SGC) in an ethnic Chinese population and to validate the performance of the T category of the 8th edition AJCC staging systems, with the aim of providing information for refinements. METHODS: Sixty-three patients with pathological diagnosis of SGC were enroled retrospectively. The clinicopathological features, treatments, and outcomes were collected. Prognostic factors associated with the outcome of local recurrence, regional lymph node metastasis, and tumour-related death were analysed. The performance analysis was performed by comparing the predictive value for survival and the monotonicity of gradients between the 7th and 8th staging systems. RESULTS: The distribution of T1:T2:T3:T4 tumours according to the 7th and 8th edition was 6:40:16:1 and 23:26:5:9, respectively. Positive surgical margin was a poor prognostic factor. Local recurrence was associated with more aggressive histopathological features and surrounding structure invasions. Regional lymph node metastasis was associated with larger tumours. The T category of 8th edition showed better predictability for local recurrence and regional lymph node metastasis, while the T category of 7th edition had better monotonicity of gradients. Tumours classified as T2c or worse had higher risk of regional lymph node metastasis, while tumours T3b or worse in the 8th edition had more tumour-related death. CONCLUSIONS: Patients with higher T category are at risk of regional lymph node metastasis and tumour-related death. Further refinement of the T category of AJCC staging system can focus on the predictability for local recurrence and the monotonicity of gradients.

Survival outcomes of eye-sparing surgery for adenoid cystic carcinoma of lacrimal gland.

PURPOSE: To survey adenoid cystic carcinoma of lacrimal glands in Asian population and investigate the predictability in prognosis following the 8th edition American Joint Committee on Cancer (AJCC) staging guideline. STUDY DESIGN: Retrospective study. METHODS: The clinical entities and surgical outcomes of the patients who were histologically confirmed with a diagnosis of lacrimal adenoid cystic carcinoma in National Taiwan University Hospital between January 1995 and December 2015 were retrospectively reviewed. RESULTS: Enrolled were 11 patients. The median follow-up was 7.2 years. Eight patients (72.7%) were diagnosed as T1 or T2 disease, and three patients (27.3%) were diagnosed as T3 or T4 disease according to the AJCC 8th edition guideline. Eye-sparing surgery with radiotherapy was performed in nine patients. Local recurrence was noted in six patients (54.5%) with median disease-free interval of 23.5 months. Six patients (54.5%) developed distant metastases, including lung, bone, and cranial invasions. Overall survival rate during the study period was 54.6%. Five-year overall survival was 81.8% and ten-year overall survival was 68.2%. The Log-rank test for overall survival and disease-free survival between patients with less than T3 disease (p=0.001) and patients with T3 or T4 disease (p=0.006) revealed significant differences. CONCLUSION: This study highlighted the aggressive nature of adenoid cystic carcinoma of lacrimal glands. Eye-sparing surgery with adjunctive radiotherapy may achieve relatively optimal disease control in diseases staged T1 or T2, but in advanced disease metastasis and mortality are usually inevitable.

En Face and Cross-sectional Corneal Tomograms Using Sub-micron spatial resolution Optical Coherence Tomography.

Accurate diagnosis of corneal pathology and morphological identification of different corneal layers require clear delineation of corneal three-dimensional structures and en face or cross-sectional imaging of palisade of Vogt (POV), neovascularization (NV) or corneal nerves. Here we report a prototype of full-field optical coherence tomography (FF-OCT) system with isotropic sub-micron spatial resolution in the en face and cross-sectional views. It can also provide three-dimensional reconstructed images and a large field of view (FOV) by stitching tomograms side by side. We validated the imaging power of this prototype in in vivo rat and rabbit eyes, and quantified anatomical characteristics such as corneal layer thickness, endothelial cell density and the intensity profile of different layers. This FF-OCT delineated the ridge-like structure of POV, corneal nerve bundles, and conjunctival vessels in rat eyes. It also clearly identified the vessel walls and red blood cells in rabbit model of corneal NV. The findings provided by this FF-OCT are expected to facilitate corneal disease diagnosis and treatment.

The corneal epitheliotrophic abilities of lyophilized powder form human platelet lysates.

PURPOSE: To evaluate whether lyophilized human platelet lysate (HPL) powder can preserve the growth factor concentrations and epitheliotrophic properties of liquid HPL, and potentially be used as a clinically-friendly treatment option. METHODS: Two commercialized liquid HPLs, UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were obtained and converted to lyophilized powder. After redissolution, lyophilized powder HPLs were compared with liquid HPLs, as well as human peripheral serum (HPS) and fetal bovine serum (FBS) in liquid or redissolved lyophilized powder forms. Concentrations of epidermal growth factor (EGF), transforming growth factor-ß1 (TGF-ß1), platelet-derived growth factor-AB (PDGF-AB) and platelet-derived growth factor-BB (PDGF-BB) were evaluated by enzyme-linked immunosorbent assay (ELISA). Human corneal epithelial cell line was incubated with the blood derivatives and evaluated for cell migration with scratch-induced directional wounding and proliferation with MTS assays. Cell differentiation was examined by transepithelial electrical resistance (TEER). Fluorescein staining and in vivo confocal microscopy were used to evaluate in vivo corneal epithelial wound healing in Sprague-Dawley rats that underwent corneal debridement and topical application of liquid and redissolved powder HPLs. RESULTS: Liquid form and redissolved lyophilized powder form HPLs had similar concentrations of EGF, TGF-ß1, PDGF-AB and PDGF-BB. In vitro experiments on cell migration, proliferation and differentiation and rat models on wound healing demonstrated no significant difference between the liquid and redissolved lyophilized powder forms for HPLs, HPS and FBS. In vivo confocal microscopy revealed similar wound healing process at different layers of cornea after corneal epithelial debridement between liquid form and redissolved lyophilized power form of HPLs. CONCLUSIONS: The redissolved lyophilized powder form of both commercialized HPLs showed similar growth factor concentrations and corneal epitheliotrophic abilities compared to the liquid form. Results suggest that the properties of liquid HPLs can be retained despite lyophilization and that lyophilized HPLs can be a treatment option for corneal epithelial disorders.

Effect of air-lifting on the stemness, junctional protein formation, and cytokeratin expression of in vitro cultivated limbal epithelial cell sheets.

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.

Serum components and clinical efficacies of autologous serum eye drops in dry eye patients with active and inactive Sjogren syndrome.

PURPOSE: Autologous serum eye drops are considered safe and efficient for the treatment of various ocular surface disorders, including dry eye diseases (DED) caused by the primary and secondary Sjogren syndrome (SS). However, the serum components in patients of SS may be different from those of normal patients and can thus lead to unpredictable therapeutic effects. This study divided the SS patients into active and inactive types based on the erythrocyte sedimentation rate and the presence or absence of active rheumatoid arthritis. METHODS: We compared the serum components of these two groups with standard and multiplex enzyme linked immunosorbent assay arrays and predicted the therapeutic effects of topical autologous serum for the treatment of DED with ocular surface disease index (OSDI) and Oxford Schema scale (OSS). RESULTS: Hyaluronic acid and transforming growth factor b1 levels were significantly higher in the active SS group compared to the inactive SS group (P < 0.01), whereas epidermal growth factors, insulin growth factor 1, and fibroblast growth factor b had no significant differences between these two groups. Active SS group had significantly higher expressions of interleukin (IL) 1 beta, IL 6, and tumor necrosis factor alpha compared to inactive SS patients (P < 0.05). There were no statistical differences in therapeutic effects between these two groups, as measured with the OSDI or OSS. CONCLUSION: Dividing the Sjogren dry eye patients into active and inactive groups may appear as a reasonable method to predict the quality of autologous serum eye drops, but there seems to be no significant predictability to the therapeutic effects.