CRISPR-free, programmable RNA pseudouridylation to suppress premature termination codons.

Nonsense mutations, accounting for >20% of disease-associated mutations, lead to premature translation termination. Replacing uridine with pseudouridine in stop codons suppresses translation termination, which could be harnessed to mediate readthrough of premature termination codons (PTCs). Here, we present RESTART, a programmable RNA base editor, to revert PTC-induced translation termination in mammalian cells. RESTART utilizes an engineered guide snoRNA (gsnoRNA) and the endogenous H/ACA box snoRNP machinery to achieve precise pseudouridylation. We also identified and optimized gsnoRNA scaffolds to increase the editing efficiency. Unexpectedly, we found that a minor isoform of pseudouridine synthase DKC1, lacking a C-terminal nuclear localization signal, greatly improved the PTC-readthrough efficiency. Although RESTART induced restricted off-target pseudouridylation, they did not change the coding information nor the expression level of off-targets. Finally, RESTART enables robust pseudouridylation in primary cells and achieves functional PTC readthrough in disease-relevant contexts. Collectively, RESTART is a promising RNA-editing tool for research and therapeutics.

Reversible Assembly of Proteins and Phenolic Polymers for Intracellular Protein Delivery with Serum Stability.

The design of intracellular delivery systems for protein drugs remains a challenge due to limited delivery efficacy and serum stability. Herein, we propose a reversible assembly strategy to assemble cargo proteins and phenolic polymers into stable nanoparticles for this purpose using a heterobifunctional adaptor (2-formylbenzeneboronic acid). The adaptor is easily decorated on cargo proteins via iminoboronate chemistry and further conjugates with catechol-bearing polymers to form nanoparticles via boronate diester linkages. The nanoparticles exhibit excellent serum stability in culture media but rapidly release the cargo proteins triggered by lysosomal acidity and GSH after endocytosis. In a proof-of-concept animal model, the strategy successfully transports superoxide dismutase to retina via intravitreal injection and efficiently ameliorates the oxidative stress and cellular damage in the retina induced by ischemia-reperfusion (I/R) with minimal adverse effects. The reversible assembly strategy represents a robust and efficient method to develop serum-stable systems for the intracellular delivery of biomacromolecules.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

Factors affecting long-term changes of meibomian gland in MGD patients.

PURPOSE: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout. METHODS: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening. RESULTS: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG. CONCLUSION: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.

The relationship between corneal biomechanical parameters and treatment outcomes of orthokeratology lenses.

BACKGROUND: To evaluate changes in corneal biomechanical properties after long-term orthokeratology (OK) treatment and the factors affecting treatment outcomes. METHODS: Twenty-four myopic teenagers who wore OK lenses for more than 1 year were included. Twenty-three individuals of the same age and with the same spherical equivalent wearing single-vision spectacles (SVS) were enrolled as controls. After routine eye examinations, corneal biomechanical properties and axial length were measured. Parameters were compared between groups. RESULTS: Less axial elongation (AE) occurred in the OK group (P = 0.021). The OK group experienced a statistically significant decrease in the A1 deformation amplitude (P = 0.02), whole eye movement maximum (P = 0.026), and Ambrósio's relational thickness to the horizontal profile (ARTh) (P < 0.001), and a statistically significant increase in the pachyslope (P < 0.001) and Corvis biomechanical index (P < 0.001). Smaller ARTh and a larger highest concavity deflection area resulted in a better refractive state. The inhibitory effect of AE was better for older patients with smaller ARTh. CONCLUSIONS: Long-term OK treatment slowed myopia progression by reshaping the cornea. Smaller ARTh after OK lens wear indicated a better refractive state and slower AE and could predict OK lens treatment outcomes.

Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase.

Schnyder corneal dystrophy (SCD) is a rare genetic eye disease characterized by corneal opacification resulted from deposition of excess free cholesterol. UbiA prenyltransferase domain-containing protein-1 (UBIAD1) is an enzyme catalyzing biosynthesis of coenzyme Q10 and vitamin K2. More than 20 UBIAD1 mutations have been found to associate with human SCD. How these mutants contribute to SCD development is not fully understood. Here, we identified HMGCR as a binding partner of UBIAD1 using mass spectrometry. In contrast to the Golgi localization of wild-type UBIAD1, SCD-associated mutants mainly resided in the endoplasmic reticulum (ER) and competed with Insig-1 for HMGCR binding, thereby preventing HMGCR from degradation and increasing cholesterol biosynthesis. The heterozygous Ubiad1 G184R knock-in (Ubiad1G184R/+) mice expressed elevated levels of HMGCR protein in various tissues. The aged Ubiad1G184R/+ mice exhibited corneal opacification and free cholesterol accumulation, phenocopying clinical manifestations of SCD patients. In summary, these results demonstrate that SCD-associated mutations of UBIAD1 impair its ER-to-Golgi transportation and enhance its interaction with HMGCR. The stabilization of HMGCR by UBIAD1 increases cholesterol biosynthesis and eventually causes cholesterol accumulation in the cornea.

Therapeutic Nanoparticles from Grape Seed for Modulating Oxidative Stress.

The therapeutic potential of nanomaterials toward oxidative damage relevant diseases has attracted great attentions by offering promising advantages compared with conventional antioxidants. Although different kinds of nanoantioxidants have been well developed, the facile fabrication of robust and efficient nanoscavengers is still met with challenges like the use of toxic and high-cost subunits, the involvement of multistep synthetic process, and redundant purification work. Herein, a direct fabrication strategy toward polyphenol nanoparticles with tunable size, excellent biocompatibility, and reactive oxygen species (ROS) scavenging capacities from grape seed via an enzymatic polymerization method is reported. The resulting nanoparticles can efficiently prevent cell damage from ROS and exert promising in vivo antioxidant therapeutic effects on several oxidative stress-related diseases, including accelerating wound healing, inhibiting ulcerative colitis, and regulating the oxidative stress in dry eye disease. This study can stimulate the development of more kinds of low-cost, safe, and efficient biomass-based antioxidative nanomaterials via similar fabrication methodologies.

IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters.

BACKGROUND: Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. METHODS: To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. RESULTS: We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. CONCLUSIONS: Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.

Lipidomic profiling of virus infection identifies mediators that resolve herpes simplex virus-induced corneal inflammatory lesions.

Lipid mediators (LMs) play a pivotal role in the induction and resolution of inflammation. To identify and elucidate their involvement during virus infection, multiple reaction monitoring (MRM) based liquid chromatography-tandem mass spectrometry lipidomic profiling of 62 lipid species was performed in this study. Results show that RAW264.7 macrophages differentially produce specific LMs signals depending on difference in virus pathogenicity. Integration of large-scale lipidomics with targeted gene expression data revealed mediators, such as RVD3, 18-HEPE, 11(12)-EET etc. correlated with the pathogenic phase of the infection. The herpes simplex virus (HSV)-induced keratitis model demonstrates that 11(12)-EET treatment represents a novel alternative for treating viral infection.

Malapposition of graft-host interface after penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK): an optical coherence tomography study.

BACKGROUD: Previous studies of internal graft-host malappositions have not dealt with the precise ways in which each malapposition affected post-penetrating keratoplasty (post-PK) visual outcomes. In this study, we reviewed our post-PK and post-deep anterior lamellar keratoplasty (post-DALK) keratoconic patients and used anterior segment optical coherence tomography (AS-OCT) to evaluate the associations between graft-host interface (GHI) characteristics and visual outcomes. METHODS: Novel GHI metrics included: mean graft-host touch (GHT), total prevalence of malapposition proportion (Pm), frequency of apposition (F), size of malapposition (Sm), junctional graft thickness (Tg), junctional host thickness (Th) and the absolute value of difference between Tg and Th (|Tg-Th|). We connected the external and internal junction points of GHI (GHT) and drew a straight line through the central point, perpendicular to both sides of the cornea. Tg and Th were the thicknesses at cross-points 1 mm away from the meeting point on the external side of the graft and host, respectively. Linear regression analysis was used to describe associations between GHI metrics and postsurgical visual outcomes [logarithm of minimum angle of resolution best-corrected visual acuity (logMAR BCVA), spherical equivalent diopter (SE), diopter of spherical power (DS), diopter of cylindrical power (DC) and keratometric astigmatism (Astig value)]. RESULTS: We enrolled 22 post-PK and 23 post-DALK keratoconic patients. Compared with the regular-apposition results, GHT was decreased in step and gape patterns, and increased in hill and tag patterns. SE increased averagely by 6.851, 5.428 and 5.164 diopter per 1% increase in: F (step) [ß = 6.851; 95% Confidence interval (CI) = 2.975-10.727; P = 0.001]; F (graft step) [ß = 5.428; 95% CI = 1.685-9.171; P = 0.005]; and Pm [ß = 5.164; 95%CI = 0.913-9.146; P = 0.018], respectively. SE increased averagely by 0.31 diopter per 10-µm increment in |Tg-Th| [ß = 0.031; 95% CI = 0.009-0.054; P = 0.007]. LogMAR BCVA increased (on average) by 0.01 per 10-µm increment in both GHT [ß = 0.001; 95% CI = 0-0.002; P = 0.030]. and Tg [ß = 0.001; 95% CI = 0.001-0.002; P = 0.001]. Astig value increased on average by 0.17 diopter per 10-µm increment in Sm [ß = 0.017; 95% CI = 0-0.033; P = 0.047]. CONCLUSION: This investigation of GHI characteristics suggests explanations for varied ametropia in keratoconic eyes and has potential significance as a reference for promoting pre-surgical planning and technology for corneal transplantation.

Femtosecond laser-assisted Descemet's stripping endothelial keratoplasty: a prospective study of 6-month visual outcomes, corneal thickness and endothelial cell loss.

PURPOSE: To report 6-month outcomes of visual acuity, the corneal thickness and endothelial cell density (ECD) in patients undergoing femtosecond laser-assisted Descemet's stripping endothelial keratoplasty (FS-DSEK). METHODS: This prospective, consecutive, interventional series examined 25 eyes of 25 patients who underwent FS-DSEK for Fuchs endothelial dystrophy and bullous keratopathy. The pre-cut corneal endothelial graft thickness (CET) was 150 µm. Best-corrected visual acuity (BCVA), central corneal thickness (CCT), donor CET, recipient corneal stromal thickness (CST) and ECD were assessed at 1 week and 1, 2, 3 and 6 months postoperatively. RESULTS: The mean BCVA at 6 months was 0.76 ± 0.35 logMAR units, improving from 1.54 ± 0.52 logMAR. CCT decreased significantly, from 759.8 ± 152.4 µm at 1 week to 631.7 ± 79.7 µm at 6 months (P = 0.001) postoperatively. CET recovered to 153.4 ± 33.7 µm (P = 0.076) at 6 months as pre-cut status. The CST decreased from 561.5 ± 96.3 µm at 1 week to 479.7 ± 57.9 µm at 6 months (P < 0.001). Preoperatively, the donor ECD was 2747.6 ± 255.4 cells/mm2, and the ECD decreased to 1729.1 ± 562.9 cells/mm2 at 6 months, for a peak ECD loss of 36.86%. A greater decrease in CST observed from 1 week to 6 months postoperatively correlated with a lower ECD loss (P = 0.019) and a lower preoperative ECD (P = 0.012). However, a thinner CET correlated with a higher preoperative ECD (P = 0.028). CONCLUSIONS: FS-DSEK is a safe and effective surgical alternative for corneal endothelial decompensation. The donor ECD and its changes could be used as predictive factors for the improvement of CST and CET.

Comparison of human corneal cell density by age and corneal location: an in vivo confocal microscopy study.

BACKGROUND: Peripheral and central regions of the cornea are optically different and have different repair capacity and pathology. For this reason, we characterized the cellular morphology and quantified the cell density of the central and peripheral regions of the cornea with age. METHODS: Eighty healthy subjects were enrolled in the study and divided into four groups according to age: A (0-19 years), B (20-39 years), C (40-59 years), and D (>60 years). In vivo confocal microscopy was used to measure the following parameters for the central and peripheral regions of the cornea: average cellular density and area of the superficial and basal epithelium; average density of the anterior and posterior keratocytes; average endothelial cell density and cellular area; percentage of hexagonal endothelial cells. RESULTS: Statistically significant differences between the central and peripheral cornea were observed for the cellular density of basal epithelial cells in group A. The density of keratocytes in the anterior stroma was significantly greater in the central region compared with the peripheral region in group B and group C. The percentage of hexagonal cells in the endothelial layer was significantly greater in the central region compared with the peripheral region. Age-related changes were found in peripheral basal epithelial cell density, central and peripheral endothelial cell density, and the percentage of hexagonal endothelial cells. CONCLUSION: Both similarities and differences in morphology of the central and peripheral regions of the transparent cornea were observed. These observations would provide a histological basis for further studies to define its regional pathological mechanisms.

Assessment of Lower Tear Meniscus.

PURPOSE: To evaluate the applicability of the fourth-generation OCULUS keratograph in measuring lower tear meniscus height. METHODS: Seventy cases (140 eyes) with dry eye disease and 37 controls (74 eyes) were enrolled. Tear breakup time (TBUT), Schirmer test I, and corneal fluorescein staining were examined. The images of lower tear meniscus were obtained by OCULUS keratograph. The tear meniscus height was measured and its correlation with traditional tear film diagnostic tests were analyzed. RESULTS: Using the hyper-reflective lines, the height of the tear meniscus was measured using the images of the OCULUS keratograph. For the inter-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.914 and 16.4%, respectively. For the intra-individual variation, the intraclass correlation coefficients and coefficient of variation values were 0.939 and 15.9%, respectively. The interobserver reproducibility and the intraobserver repeatability were for the control only. The average tear meniscus height value in dry eye disease group was 0.22 (0.19-0.24) mm, being significantly lower compared with 0.29 (0.26-0.34) mm in the control group (p<0.001). Tear meniscus height value had significantly correlation with TBUT and Schirmer test I (r=0.619 and 0.626, both p<0.001). The measurement of lower tear meniscus by OCULUS had lower individual variability and better repeatability. CONCLUSIONS: OCULUS keratograph is a quick, noninvasive, and reliable method to measure lower tear meniscus, whose value has a significant correlation with traditional dry eye disease diagnostic tests.

Assessment of Bulbar Redness with a Newly Developed Keratograph.

PURPOSE: To determine the validity and reliability of the clinical assessment of bulbar redness (BR) using a newly developed corneal topographer. METHODS: This is a cross-sectional diagnostic evaluation study. The BR scores [Oculus Index (OI)] from 30 eyes of 26 patients with different degrees of conjunctival hyperemia were assessed and scored automatically using a new method: a keratograph equipped with scanning and scoring software. The values obtained via this system were correlated with three image-based comparative subjective scales: the Institute for Eye Research (IER), the Efron, and the Validated Bulbar Redness (VBR) grading scales. The IER and Efron scores were interpolated to 0.1 unit, and the VBR scores were interpolated to 1 unit. We also evaluated the repeatability of each method and the level of agreement between the OI score and the scores achieved using the three other image-based methods. RESULTS: There was a significant correlation between the OI score and the scores obtained with the IER (r = 0.921, p < 0.001), Efron (r = 0.958, p < 0.001), and VBR (r = 0.965, p < 0.001) scales. The intraobserver intraclass correlation coefficients were 0.947, 0.874, 0.810, and 0.920 for the OI, IER, Efron, and VBR, respectively, and the intraobserver coefficients of repeatability were 13.924, 16.111, 17.684, and 16.900, respectively. Furthermore, the interobserver intraclass correlation coefficients were 0.889, 0.880, 0.884, and 0.881 for the OI, IER, Efron, and VBR, respectively, and the interobserver coefficients of repeatability were 15.934, 16.366, 22.059, and 21.373, respectively. CONCLUSIONS: The OI is an objective and reliable method for scoring BR. Its reproducibility was the highest of all the four modalities. The keratograph is recommended, therefore, as a suitable alternative for BR assessment.

Corvis ST Tonometer for Measuring Postoperative IOP in LASIK Patients.

PURPOSE: To compare the postoperative measurements of intraocular pressure (IOP) using the Corvis ST Tonometer (CST), ocular response analyzer (ORA), and Goldmann applanation tonometry (GAT) in eyes undergoing laser in situ keratomileusis (LASIK), as well as to analyze the relationship between the corneal biomechanical parameters of the CST and the ORA. METHODS: Fifty participants who had undergone LASIK to treat myopia in the previous 3 months were enrolled. Postoperative IOP measurements of these participants were obtained using the CST, ORA (corneal-compensated IOP [IOPcc], Goldmann-correlated IOP [IOPg]), and GAT. Device agreement was calculated by Bland-Altman analysis. The metrics of corneal biomechanical properties were recorded using the ORA and the CST. Corneal biomechanical parameters were compared. RESULTS: The Bland-Altman analysis revealed a significant bias between CST and GAT, between CST and IOPcc, and between CST and IOPg of 3.4, 1.0, and 3.8, mm Hg, respectively, with 95% limits of agreement of -0.7 to 7.5 mm Hg, -2.1 to 4.2 mm Hg, and -0.4 to 8.0 mm Hg. The ORA-derived IOP measurements, CST-derived IOP, and GAT IOP values showed good correlation with each other. The CST IOP and IOPcc were higher than the GAT IOP (all p < 0.05), whereas IOPg did not differ from the GAT IOP readings. Ocular response analyzer-derived corneal biomechanical parameters (corneal hysteresis and the corneal resistance factor) showed significant correlations with CST-derived parameters, including the maximum deformation amplitude at the corneal apex and the time from start until the first applanation. CONCLUSIONS: The CST offers an alternative method for measuring postoperative IOP in LASIK patients, and it appears to obtain higher IOP values than other tonometry techniques. The technique may facilitate the investigation of corneal biomechanical property changes in LASIK-treated eyes.

Corneal epithelial thickness map in long-term soft contact lenses wearers.

PURPOSE: To map the corneal epithelial thickness in vivo with Fourier-domain optical coherence tomography in long-term soft contact lens (SCL) wearers. METHODS: This is a cross-sectional observational study. Forty eyes from 40 normal subjects who had never worn SCL and 40 eyes from 40 SCL wearers who had worn lenses for more than 2 years were enrolled. Corneal epithelium over the entire cornea was topographically imaged using a novel optical coherence tomography system. An epithelial thickness map was automatically generated. Epithelial thicknesses of the central 2-mm, paracentral 2- to 5-mm (P1), and midperipheral 5- to 6-mm (P2) zones were obtained. In addition, the epithelial map variability in P1 and P2 zones, including maximum - minimum (MAX - MIN), map SD, and coefficient of variation (CV), was measured and analyzed. RESULTS: The average epithelial thickness of the central, P1, and P2 zones was 54.4 ± 1.1 µm, 53.2 ± 2.2 µm, and 52.3 ± 2.0 µm, respectively, in normal eyes and 49.2 ± 1.9 µm, 48.8 ± 2.2 µm, and 48.7 ± 2.8 µm, respectively, in eyes wearing SCL. Compared with normal control subjects, eyes with long-term SCL had significantly thinner epithelial thickness in all three zones (p < 0.05). However, there was no difference in MAX - MIN, SD, and CV of P1 and P2 zones between two groups. In both groups, there was significant difference in the epithelial thickness among different sectors in the paracentral and midperipheral zones. CONCLUSIONS: There is a decrease in epithelial thickness in subjects who wear SCL long term. Clinicians should take note of the nonuniformity of the paracentral and midperipheral corneal epithelium thicknesses. This method may be useful for detecting early changes in corneal epithelial thickness caused by long-term SCL wear.

Evaluation of age-related changes in noninvasive tear breakup time.

PURPOSE: To establish normal noninvasive tear film breakup time (NI-BUT) values in the Chinese population and investigate age-related changes in NI-BUT using a newly developed Keratograph. METHODS: Forty normal volunteers with a mean age of 32.8 ± 16.7 years were recruited for this study. Clinical and demographic data, including age, gender, fluorescein tear film breakup time (FBUT), and Schirmer I test values were collected from the subjects. Noninvasive tear film breakup time was measured using a new method based on a corneal topographer equipped with a modified scan software. The correlations between the NI-BUT, age, and gender were determined. RESULTS: In total, a significant difference between the NI-BUT and the FBUT was found (4.9 ± 2.4 seconds vs. 9.0 ± 3.0 seconds; p < 0.001). No statistically significant difference in the NI-BUT was observed between the male and female subjects (5.5 ± 2.0 seconds vs. 4.5 ± 2.5 seconds; p = 0.137). In addition, no significant correlation was detected between the NI-BUT and age (0.143, p = 0.321). CONCLUSIONS: The NI-BUT values found in this study are much lower than those of previous reports. Our results show no significant differences in tear film stability with age. The tear physiology of the Chinese population may not be the same as in Western populations.

Assessment of corneal epithelial thickness in dry eye patients.

PURPOSE: To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients. METHODS: In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated. RESULTS: The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) µm, 52.00 (±3.39) µm, and 53.03 (±3.67) µm in normal eyes and 52.71 (±2.83) µm, 50.58 (±3.44) µm, and 52.53 (±3.36) µm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017). CONCLUSIONS: Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Vision-related quality of life in patients with infectious keratitis.

PURPOSE: To determine the vision-related quality of life (VR-QOL) in patients with infectious keratitis using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). METHODS: Sixty-five patients with infectious keratitis (IK) were enrolled in the study. The NEI VFQ-25 scores and clinical and demographic data, including age, gender, pathogen, best corrected visual acuity (BCVA), and duration of the disease, were collected from the subjects. The subscale and composite scores were calculated and analyzed. Correlations between the VFQ-25 scores and the clinical and demographic features were also explored. RESULTS: The mean age of enrolled subjects was 48.4 years (SD, 16.2), with 44 males (67.7%). The microbial pathogens were viruses (n = 48, 73.8%), fungi (n = 13, 20.0%), and bacteria (n = 4, 6.2%). The mean scores of each VFQ-25 subscale ranged from 31.9 (SD, 28.6) for role difficulties to 92.7 (SD, 13.1) for color vision; the mean composite score was 58.1 (SD, 19.2). Significant differences in scores were observed only in the subscale of dependency among educational levels and in the mental health subscale and the composite among the three pathogen groups. Multivariate regression analysis revealed that VFQ-25 composite score correlated significantly with the BCVA of the worse-seeing eye, duration of the disease, history of operation (for IK treatment), and gender. CONCLUSIONS: Infectious keratitis has extensive impacts on patients and VR-QOL. The BCVA of worse-seeing eye, duration, history of operation for IK treatment, and gender contributed independently to VR-QOL. Early treatment should be encouraged to obtain better visual prognosis and VR-QOL for patients with IK.

[Efficacies of continuous positive airway pressure on mixed sleep respiratory events in patients with sleep apnea].

OBJECTIVE: To explore the efficacies of continuous positive airway pressure (CPAP) for mixed sleep apnea (MSA) events in patients with sleep apnea. METHODS: A total of 21 patients with sleep apnea whose MSA events >10 events/h on overnight polysomnography (PSG) were studied. They were selected from the Sleep Center, Guangzhou Institute of Respiratory Disease. Ten of them were diagnosed only by conventional polysomnography (PSG group) while the diagnosis of another 11 patients was further confirmed by diaphragm electromyogram (EMG) (EMG group). All of them were treated by CPAP titrated manually on PSG. RESULTS: Manual CPAP titrating pressure in PSG group was (8.1 ± 2.2) cmH2O (1 cmH2O = 0.098 kPa) and it was similar to that in EMG group ((8.9 ± 1.5) cmH2O). Apnea-hypopnea index (AHI) decreased significantly after CPAP in both PSG group (6.9 (3.5, 10.2) vs 62.2 (54.7, 71.4) events/h) and EMG group (1.5 (0.5, 5.5) vs 71.3 (59.5, 79.5) events/h) (both P < 0.01). CPAP could eliminate MSA diagnosed either by conventional PSG (0.1 (0.0, 0.4) vs 29.6 (19.6, 32.4) events/h) or by diaphragm EMG (0.0 (0.0, 0.2) vs 18.1 (9.1, 19.3) events/h) (both P < 0.01). CONCLUSION: CPAP can effectively treat MSA events in patients with sleep apnea.