Assessment of the corneal biomechanical features of granular corneal dystrophy type 2 using dynamic ultra-high-speed Scheimpflug imaging.

PURPOSE: To evaluate the corneal biomechanical features of eyes with granular corneal dystrophy type 2 (GCD2) by analyzing corneal biomechanical indices obtained using a Corvis ST (CST) dynamic ultra-high-speed Scheimpflug imaging device. METHODS: In this retrospective case-control study, 35 CST parameters were compared in normal eyes (control) and eyes of patients with GCD2 treated at Osaka University Hospital, Osaka, Japan. The parameters included the Corvis Biomechanical Index (CBI), which is important in differentiating eyes with keratoconus from normal eyes. We measured the deposition rates of lesions in the central 7-mm region of the eye and assessed the correlation between the deposition rate and the CBI. RESULTS: Twenty-one eyes with GCD2 and 23 control eyes were analyzed. Eyes with GCD2 showed significantly less corneal stiffness in 15 CST parameters than did control eyes. In particular, the CBI was remarkably higher in eyes with GCD2 than in control eyes (P = 0.000006). Additionally, the deposition rate and the CBI were positively correlated. CONCLUSIONS: GCD2 eyes had softer corneas than did control eyes in most biomechanical CST parameters, and one of the parameters (the CBI) was linked to the rate of deposited lesions. Since IOP may be underestimated in GCD2 eyes, management should be especially careful in GCD2 cases complicated by glaucoma.

Co-ordinated ocular development from human iPS cells and recovery of corneal function.

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

Generation and validation of a PITX2-EGFP reporter line of human induced pluripotent stem cells enables isolation of periocular mesenchymal cells.

PITX2 (Paired-like homeodomain transcription factor 2) plays important roles in asymmetric development of the internal organs and symmetric development of eye tissues. During eye development, cranial neural crest cells migrate from the neural tube and form the periocular mesenchyme (POM). POM cells differentiate into several ocular cell types, such as corneal endothelial cells, keratocytes, and some ocular mesenchymal cells. In this study, we used transcription activator-like effector nuclease technology to establish a human induced pluripotent stem cell (hiPSC) line expressing a fluorescent reporter gene from the PITX2 promoter. Using homologous recombination, we heterozygously inserted a PITX2-IRES2-EGFP sequence downstream of the stop codon in exon 8 of PITX2 Cellular pluripotency was monitored with alkaline phosphatase and immunofluorescence staining of pluripotency markers, and the hiPSC line formed normal self-formed ectodermal autonomous multizones. Using a combination of previously reported methods, we induced PITX2 in the hiPSC line and observed simultaneous EGFP and PITX2 expression, as indicated by immunoblotting and immunofluorescence staining. PITX2 mRNA levels were increased in EGFP-positive cells, which were collected by cell sorting, and marker gene expression analysis of EGFP-positive cells induced in self-formed ectodermal autonomous multizones revealed that they were genuine POM cells. Moreover, after 2 days of culture, EGFP-positive cells expressed the PITX2 protein, which co-localized with forkhead box C1 (FOXC1) protein in the nucleus. We anticipate that the PITX2-EGFP hiPSC reporter cell line established and validated here can be utilized to isolate POM cells and to analyze PITX2 expression during POM cell induction.

Rubicon regulates A2E-induced autophagy impairment in the retinal pigment epithelium implicated in the pathology of age-related macular degeneration.

Waste product deposition and light stress in the retinal pigment epithelium (RPE) are crucial factors in the pathogenesis of various retinal degenerative diseases, including age-related macular degeneration (AMD), a leading cause of vision loss in elderly individuals worldwide. Given that autophagy in the RPE suppresses waste accumulation, determining the molecular mechanism by which autophagy is compromised in degeneration is necessary. Using polarized human RPE sheets, we found that bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), a major toxic fluorophore of lipofuscin, causes significant impairment of autophagy and the simultaneous upregulation of Rubicon, a negative regulator of autophagy. Importantly, this impairment was reversed in Rubicon-specific siRNA-treated RPE sheets. In a retinal functional analysis using electroretinograms (ERGs), mice with the RPE-specific deletion of Rubicon showed no significant differences from control cre-expressing mice but presented partially but significantly enhanced amplitudes compared with Atg7 knockout mice. We also found that an inflammatory reaction in the retina in response to chronic blue light irradiation was alleviated in mice with the RPE-specific deletion of Rubicon. In summary, we propose that upregulating basal autophagy by targeting Rubicon is beneficial for protecting the RPE from functional damage with ageing and the inflammatory reaction caused by light-induced cellular stress.

Corneal Opacity Induced by Light in a Mouse Model of Gelatinous Drop-Like Corneal Dystrophy.

Gelatinous drop-like corneal dystrophy (GDLD) is a severe inherited corneal dystrophy characterized by subepithelial corneal amyloid deposition. We had previously succeeded in identifying the responsible gene, TACSTD2, and subsequently found that the epithelial barrier function is significantly decreased. As with GDLD patients, the knockout mice showed severe loss of tight junction, progressive opacity, and neovascularization in the cornea. We devised an easy method to confirm the loss of the corneal barrier function even before corneal opacity is observed. Furthermore, by using knockout mice, we were able to verify clinical findings, such as the wound healing delay and light-induced acceleration of the disease. This mouse model should prove to be a highly useful tool for investigating the pathology of GDLD and for developing new therapies.

Transcription factor TFAP2B up-regulates human corneal endothelial cell-specific genes during corneal development and maintenance.

The corneal endothelium, which originates from the neural crest via the periocular mesenchyme (PM), is crucial for maintaining corneal transparency. The development of corneal endothelial cells (CECs) from the neural crest is accompanied by the expression of several transcription factors, but the contribution of some of these transcriptional regulators to CEC development is incompletely understood. Here, we focused on activating enhancer-binding protein 2 (TFAP2, AP-2), a neural crest-expressed transcription factor. Using semiquantitative/quantitative RT-PCR and reporter gene and biochemical assays, we found that, within the AP-2 family, the TFAP2B gene is the only one expressed in human CECs in vivo and that its expression is strongly localized to the peripheral region of the corneal endothelium. Furthermore, the TFAP2B protein was expressed both in vivo and in cultured CECs. During mouse development, TFAP2B expression began in the PM at embryonic day 11.5 and then in CECs during adulthood. siRNA-mediated knockdown of TFAP2B in CECs decreased the expression of the corneal endothelium-specific proteins type VIII collagen α2 (COL8A2) and zona pellucida glycoprotein 4 (ZP4) and suppressed cell proliferation. Of note, we also found that TFAP2B binds to the promoter of the COL8A2 and ZP4 genes. Furthermore, CECs that highly expressed ZP4 also highly expressed both TFAP2B and COL8A2 and showed high cell proliferation. These findings suggest that TFAP2B transcriptionally regulates CEC-specific genes and therefore may be an important transcriptional regulator of corneal endothelial development and homeostasis.

Homeostasis of SLC4A11 protein is mediated by endoplasmic reticulum-associated degradation.

The cornea is an important tissue that refracts light, and the corneal endothelium prevents edema of the corneal stroma by acting as a barrier and a pump for the transport of essential molecules/ions. Sodium bicarbonate transporter-like protein 11 (SLC4A11) is a transporter present in the corneal endothelium, and its mutation causes corneal endothelial disease. Here, we aimed to investigate the degradation pathway of SLC4A11. Quantitative PCR analysis revealed that two variants of SLC4A11 transcripts, variant 2 (SLC4A11-B) and variant 3 (SLC4A11-C), were expressed in human corneal endothelial tissues. Transient overexpression of these variants in HEK293T cells revealed that SLC4A11-B abundantly localized to the cell membrane. Furthermore, SLC4A11-B-transfected HEK293T cells expressed the mature glycosylated forms and immature non-glycosylated forms of SLC4A11. Cycloheximide chase experiments revealed that mature SLC4A11 showed high degradation stability; however, degradation of immature SLC4A11-B was significantly faster than that of immature SLC4A11-C. Therefore, we performed further degradation analysis of the SLC4A11 mutants, which are classified into ER-retained and cell surface-associated mutants similar to the wild type. Compared to the wild type, ER-retained mutants S213P and W240P showed delayed degradation but the cell surface-associated mutants showed minimal degradation. Further analysis using proteasome inhibitors revealed that degradation of immature SLC4A11 was delayed after treatment with the proteasome inhibitors, MG-132 and bortezomib, and was mediated by poly-ubiquitination. Moreover, the degradation of immature SLC4A11 protein was suppressed by Eeyarestatin I, an ER-associated protein degradation (ERAD) inhibitor. Collectively, these data suggest that SLC4A11 protein is degraded via ERAD.

Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) due to corneal endothelial cell degeneration is a major cause of corneal transplantation. It is characterized by abnormal deposition of extracellular matrix (ECM), such as corneal guttae, accompanied by a loss of endothelial cells. Although recent studies have revealed several genomic factors, the molecular pathophysiology of FECD has not yet been revealed. In this study, we establish a cellular in vitro model by using immortalized corneal endothelial cells obtained from late-onset FECD and control patients and examined the involvement of epithelial mesenchymal transition (EMT) on excessive ECM production. We demonstrate that the EMT-inducing genes ZEB1 and SNAI1 were highly expressed in corneal endothelial cells in FECD and were involved in excessive production of ECM proteins, such as type I collagen and fibronectin through the transforming growth factor (TGF)-ß signaling pathway. Furthermore, we found that SB431542, a specific inhibitor of TGF-ß type I ALK receptors, suppressed the expression of ZEB1 and Snail1 followed by reduced production of ECM. These findings suggest that increased expression levels of ZEB1 and Snail1 in FECD cells were responsible for an increased responsiveness to TGF-ß present in the aqueous humor and excessive production of ECM. In addition, these results suggest that the regulation of EMT-related genes by blocking the TGF-ß signaling pathway may be a feasible therapeutic strategy for FECD.

Ultrasonic wave properties of human bone marrow in the femur and tibia.

Ultrasonic wave properties of human bone marrow obtained in the femur and tibia were measured using an ultrasound pulse technique. The measured frequency range was 4-10 MHz, and the temperature range was 30 °C-40 °C. The sound velocity was 1410 m/s, and the attenuation coefficient was 4.4 dB/cm at 36 °C (10 MHz). These values decreased with temperature. Site dependence and individual differences in elderly human bone marrow were negligible. The slopes of the attenuation coefficient were estimated by a power law. The values of the exponent n were 2.0 (30 °C-38 °C) and 2.3 (40 °C).

Corneal endothelial cell fate is maintained by LGR5 through the regulation of hedgehog and Wnt pathway.

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a target of Wnt signaling, is reportedly a marker of intestine, stomach, and hair follicle stem cells in mice. To gain a novel insight into the role of LGR5 in human corneal tissue, we performed gain- and loss-of-function studies. The findings of this study show for the first time that LGR5 is uniquely expressed in the peripheral region of human corneal endothelial cells (CECs) and that LGR5((+)) cells have some stem/progenitor cell characteristics, and that in human corneal endothelium, LGR5 is the target molecule and negative feedback regulator of the Hedgehog (HH) signaling pathway. Interestingly, the findings of this study show that persistent LGR5 expression maintained endothelial cell phenotypes and inhibited mesenchymal transformation (MT) through the Wnt pathway. Moreover, R-spondin-1, an LGR5 ligand, dramatically accelerated CEC proliferation and also inhibited MT through the Wnt pathway. These findings provide new insights into the underlying homeostatic regulation of human corneal endothelial stem/progenitor cells by LGR5 through the HH and Wnt pathways.

A novel mutation (p.Glu1389AspfsX16) of the phosphoinositide kinase, FYVE finger containing gene found in a Japanese patient with fleck corneal dystrophy.

PURPOSE: The phosphoinositide kinase, FYVE finger containing (PIKFYVE) gene has been identified as a gene responsible for fleck corneal dystrophy (FCD). The purpose of this study is to report a novel mutation of the PIKFYVE gene in a Japanese patient with fleck corneal dystrophy. METHODS: Slit-lamp microscopy, corneal topography, and optical coherence tomography were performed for the clinical examination of the patient's eye. For genetic analysis, peripheral blood was obtained from the patient and her sister. DNA was extracted from the blood and subjected to mutation analysis by sequencing of the PIKFYVE gene. The sequencing results were validated with a PCR-fragment length polymorphism analysis. RESULTS: A 63-year-old woman presented at our clinic with complaints of decreased vision and metamorphopsia in her right eye occurring 1 month before presentation. Both eyes exhibited small, dot-like, white flecks scattered throughout all layers of the corneal stroma, which corresponds to the typical FCD phenotype. The opacities were relatively dominant at the peripheral region of the cornea, yet were found throughout the entire cornea. Sequence analysis revealed that the patient has a heterozygous c.4166_4169delAAGT mutation located at exon 24 of the PIKFYVE gene that may cause p.Glu1389AspfsX16 flame-shift mutation, which has never before been reported for FCD. CONCLUSIONS: To the best of our knowledge, this is the first study to show that a novel mutation (p.Glu1389AspfsX16) causing the truncation of the PIKFYVE protein causes fleck corneal dystrophy in the Japanese population.

An outbreak of serotype 19A pneumococcal pneumonia in a relief facility in Japan.

An outbreak of serotype 19A Streptococcus pneumoniae occurred among the residents of a relief facility. Pneumonia developed in 5 of 99 residents (attack rate, 5.1%). We obtained pharyngeal specimens from non-onset residents, and S. pneumoniae was isolated from 6 individuals (6.4%), 5 of whom had serotype 19A.

Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: implications in the pathogenesis of gelatinous drop-like corneal dystrophy.

Gelatinous drop-like dystrophy (GDLD) is a rare autosomal recessive form of corneal dystrophy characterized by subepithelial amyloid depositions on the cornea. Previous clinical and laboratory observations have strongly suggested that epithelial barrier function is significantly decreased in GDLD. Despite the decade-old identification of the tumor-associated calcium signal transducer 2 (TACSTD2) gene as a causative gene for GDLD, the mechanism by which the loss of function of this causative gene leads to the pathological consequence of this disease remains unknown. In this study, we investigated the functional relationship between the TACSTD2 gene and epithelial barrier function. Through the use of immunoprecipitation and a proximity ligation assay, we obtained evidence that the TACSTD2 protein directly binds to claudin 1 and 7 proteins. In addition, the loss of function of the TACSTD2 gene leads to decreased expression and change in the subcellular localization of tight junction-related proteins, including claudin 1, 4, 7, and ZO1 and occludin, both in diseased cornea and cultured corneal epithelial cells. These results indicate that loss of function of the TACSTD2 gene impairs epithelial barrier function through decreased expression and altered subcellular localization of tight junction-related proteins in GDLD corneas.

Two novel mutations of TACSTD2 found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization.

PURPOSE: To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD). METHODS: Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis. Plasmid vectors harboring normal and mutated TACSTD2 were transfected to the immortalized human corneal epithelial cells to identify the subcellular localization of the normal and mutated TACSTD2 gene products. RESULTS: Sequencing analysis of TACSTD2 revealed two novel homozygous mutations (c.840_841insTCATCATCGCCGGCCTCATC and c.675C>A which may result in frameshift (p.Ile281SerfsX23) and nonsense (p.Tyr225X) mutations, respectively) in the 3 GDLD patients. Protein expression analysis showed that the mutated gene product was distributed diffusely in the cytoplasm, whereas the normal gene product accumulated at the cell-to-cell borders. CONCLUSIONS: This study reports two novel mutations in 3 GDLD families and expands the spectrum of mutations in TACSTD2 that may cause pathological corneal amyloidosis.

Clinical and microbiological evaluation of hemodialysis-associated pneumonia (HDAP): should HDAP be included in healthcare-associated pneumonia?

Although hemodialysis-associated pneumonia (HDAP) was included among the healthcare-associated pneumonias (HCAP) in the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guideline, little information relevant to clinical epidemiology, especially microbiological characteristics, is available. This study aimed to reveal microbiological characteristics and clinical outcomes of HDAP and to assess whether HDAP should be included in the HCAP category. We retrospectively analyzed 69 HDAP patients [42 with moderate and 27 with severe disease based on A-DROP (age, dehydration, respiratory failure, orientation disturbance, and low blood pressure)] in whom sputum cultures were performed at our hospital between 2007 and 2009. The most common pathogens were Staphylococcus aureus (37.7%), which were composed of methicillin-resistant S. aureus (MRSA) (27.5%) and methicillin-sensitive S. aureus (MSSA) (10.1%), followed by Streptococcus pneumoniae (10.1%), Klebsiella pneumoniae (8.7%), Haemophilus influenzae (7.2%), and Moraxella catarrhalis (5.8%). This distribution mostly resembled the microbiological characteristics of HCAP reported previously, except that the frequency of multi-drug-resistant (MDR) gram negatives such as Pseudomonas aeruginosa (2.9%) was clearly lower and that of MRSA was higher. There were no significant differences in microbiological findings, including the incidence of MDR pathogens, between the two severity groups. Despite most cases (82.6%) receiving only monotherapy, the prognosis (30-day survival and in-hospital mortality rates were 88.4% and, 17.4%, respectively) was similar to the past HCAP reports, but there were no significant correlations between prognosis and presence of MDR pathogens (30-day mortality rates 18.2% in MDR positive vs. 8.5% in MDR negative; p = 0.242). Assessment for not only MDR pathogens, but also severity of illness by the A-DROP system made it possible to conduct stratification based on prognosis. Our results suggest that HDAP should be included in the HCAP category, while understanding that there are some differences.

Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling.

PURPOSE: Vernal keratoconjunctivitis (VKC) is a severe and recurrent allergic conjunctivitis, the mechanism of which is not well understood. In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of VKC, with a focus on tissue remodeling. STUDY DESIGN: Clinical and experimental. PATIENTS AND METHODS: The OSM concentrations in tear fluid samples obtained from VKC patients and healthy controls were measured using ELISA, and the expression of OSM mRNA and protein in giant papillae resected from VKC patients was investigated using RT-PCR and immunohistochemistry, respectively. In cultured human conjunctival epithelial cells (HconEpiCs), expression of OSM receptor ß (OSMRß) was detected using immunocytochemical and FACS analyses. Finally, we investigated whether recombinant OSM activated STAT1 and STAT3 to induce the expression of various genes related to tissue remodeling in HconEpiCs, by using Western blot analysis, microarray analysis, and RT-PCR. RESULTS: The OSM concentration was higher in the tear fluid of VKC patients than in that of the healthy controls, and strong expression of OSM mRNA was found in the giant papillae. We also detected T cells expressing OSM in the giant papillae. In addition, HconEpiCs showed surface expression of OSMRß. Recombinant human OSM strongly activated both STAT1 and STAT3 in HconEpiCs and induced various tissue remodeling-related genes, including MMP-1, MMP-3, IL-24, IL-20, serpinB3, S100A7, tenascin C, and SOCS3. CONCLUSION: Our results suggest that OSM is one of the key molecules involved in remodeling of giant papillae in VKC.

Fusobacterium necrophorum Endocarditis with Liver Abscesses: A Case Report and Review of the Literature.

Fusobacterium necrophorum is a very rare cause of endocarditis. We herein report a case of F. necrophorum endocarditis with liver abscesses in a 51-year-old woman. This is the first reported case of monomicrobial F. necrophorum endocarditis to present in a patient over 50 years old. We also reviewed 10 reported cases, including the present case. Our review indicated that anaerobic bacteria, including Gram-negative anaerobic bacilli such as F. necrophorum, should be considered in the differential diagnosis of infective endocarditis, especially in patients without preexisting organic heart disease.

Comparison of ocular surface squamous neoplasia and pterygium using anterior segment optical coherence tomography angiography.

PURPOSE: To compare ocular surface squamous neoplasia (OSSN) and pterygium using anterior segment optical coherence tomography angiography (AS-OCTA). OBSERVATIONS: Flow patterns of conjunctival vessels in patients with OSSN and pterygium were investigated using AS-OCTA. In case 1, slit-lamp examination of a 72-year-old woman revealed an elevated lesion with increased permeability of fluorescein in the inferior nasal conjunctiva of her left eye. AS-OCTA showed markedly meandering large blood vessels in both the superficial and deep layers. Histopathological evaluation of the conjunctival biopsy indicated conjunctival intraepithelial neoplasia. Case 2 was that of a 79-year-old man with a history of three conjunctival tumor excisions. Slit-lamp examination showed an elevated lesion with hyperpermeability of fluorescein in the nasal conjunctiva of his left eye. AS-OCTA revealed increased meandering vasculature in both the superficial and deep layers. Histopathological investigation concluded that the diagnosis was squamous cell carcinoma. Case 3 involved a 61-year-old man with a pterygium. Slit-lamp examination showed typical findings of an elevated nasal lesion accompanied by a head that appeared triangular with a blunt apex. AS-OCTA revealed increased straight vasculature in the superficial layer and an avascular area in the deep layer of the pterygium head. CONCLUSIONS AND IMPORTANCE: AS-OCTA revealed abnormal "zigzag vessel patterns" in both the superficial and deep layers denoting meandering vessels in the patients with OSSN. In the patient with the pterygium, it showed "straight vessel patterns" signifying unbending stretched vessels in the superficial layer and an avascular zone in the deep layer of the pterygium head. These findings may be useful for the differential diagnosis of OSSN and pterygium.

Correlation Between Angle Parameters and Central Corneal Thickness in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To evaluate the correlation between anterior chamber parameters and central corneal thickness (CCT) or peripheral corneal thickness (PCT) in patients with Fuchs endothelial corneal dystrophy (FECD) using anterior segment optical coherence tomography. METHODS: This case-control study included 20 eyes from 20 patients with FECD and 31 eyes from 31 patients with healthy corneas. CCT was measured as an indicator of FECD severity. Anterior chamber angle parameters, including trabecular-iris angle (TIA500) and angle opening distance (AOD500), were measured as an indicator of peripheral anterior chamber morphology. We also analyzed PCT and lens vault (LV). The relationships between CCT or PCT and anterior chamber parameters were also analyzed in patients with FECD. RESULTS: Patients with FECD had a larger CCT (593.9 ± 54.6 µm vs. 533.0 ± 25.4 µm, P < 0.001), smaller TIA500 (21.8 ± 9.9 vs. 32.5 ± 11.2 degrees, P = 0.002), smaller AOD500 (0.21 ± 0.11 vs. 0.34 ± 0.18 mm, P = 0.002), and greater LV (0.60 ± 0.27 vs. 0.40 ± 0.29 mm, P = 0.02) than control subjects. In patients with FECD, CCT was negatively correlated with the angle parameters TIA500 (R = 0.29, P = 0.009) and AOD500 (R = 0.19, P = 0.03). There were no significant correlations between PCT and TIA500 (R = 0.008, P = 0.29) or AOD500 (R = 0.007, P = 0.29). There were also no significant correlations between CCT and LV (R = 0.02, P = 0.55). CONCLUSIONS: Larger CCT was significantly associated with narrower anterior chamber angle width, but not with LV. We showed that the severity of FECD is associated with angle chamber morphology.

Efficacy of therapeutic soft contact lens in the management of gelatinous drop-like corneal dystrophy.

BACKGROUND/AIMS: To investigate the efficacy of therapeutic soft contact lenses (SCLs) in gelatinous drop-like corneal dystrophy (GDLD) management. METHODS: This was a retrospective, consecutive, observational case series, including 20 patients (40 eyes) with GDLD treated in Osaka University Hospital within the last 15 years. We tested the effects of therapeutic SCL on clinical features, visual acuity and surgical interventions. Examinations for clinical features and visual acuity were done on patients who had no surgical intervention for 3 years. Scoring and evaluation of changes in three main clinical GDLD features and visual acuity (logMAR units) were performed using Fisher's exact test and Mann-Whitney U test. Surgery-free survival time was compared by Kaplan-Meier analyses in all patients. RESULTS: We found a significantly lower rate of progression in GDLD nodular lesions in patients wearing SCLs compared with those who did not (p=0.0179). No suppressant effects were observed regarding opacity and neovascularisation, and no significant improvements were found in visual acuity (in logMAR values, SCL-on: mean=- 0.036, median=0; SCL-off: mean=0.149, median=+ 0.088; p=0.14). The surgery-free survival time for all 16 SCL-on eyes was 2770 ± 1918 days, significantly longer than that for 22 SCL-off eyes, 1342 ± 1323 days (Kaplan-Meier analysis, p=0.0007), suggesting that therapeutic SCL extends the period until surgical intervention and reduces their necessity in patients with GDLD. CONCLUSION: Wearing therapeutic SCLs in GDLD slows the progression of nodular lesions and decreases the need for surgical interventions.