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.

Association between genetic variants of microRNA-21 and microRNA-155 and systemic lupus erythematosus: A case-control study from a Chinese population.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis remains unclear. The alteration of genetic materials is believed to play a role in SLE development. This study evaluated the association between the genetic variants of microRNA-21 (miR-21) and microRNA-155 (miR-155) and SLE. METHODS: The SNaPshot genotyping method was used to detect the genotypes of selected SNPs in patients and controls. The expression of miR-21 and miR-155 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The functional annotation and the biological effects of SNPs were assessed by HaploReg V4.1 and Regulome DB V2.0 software. The Hardy-Weinberg equilibrium test was used to gather statistics, and odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression. RESULTS: The distribution difference of TA genotype in rs767649 was observed (TA vs. T/T: OR = 0.68, 95%CI, 0.48-0.95, p = 0.026). There was a significant difference in the T/A + A/A (T/A + A/A vs. T/T: OR = 0.68, 95%CI, 0.49-0.94, p = 0.020). A significant difference in T allele distribution was found in the depressed complement of SLE (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026). There were significant differences in genetic variants of rs13137 between the positive and the negative SSB antibodies (Anti-SSB) (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026; T/A + T/T vs. AA: OR = 2.23, 1.18-4.49, p = 0.013). The expression levels of miR-21 and miR-155 were significantly higher in patients than in controls (p < 0.001). CONCLUSIONS: This study provides novel insight that genetic variants of rs767649 and rs13137 are associated with susceptibility to SLE.

Evaluation of corneal cross-linking as adjuvant therapy for the management of fungal keratitis.

PURPOSE: To evaluate the efficacy of corneal cross-linking (CXL) as adjuvant therapy for the treatment of fungal ulcerative keratitis. METHODS: Forty-one patients with fungal ulcerative keratitis were recruited and assigned into two randomized controlled groups. These groups were treated with CXL combined with antifungal medications (CXL-M) or antifungal medications alone (M). The ulcers were assessed by slit-lamp biomicroscopy, slit-lamp images, in vivo confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT). The patients were followed up before surgery/first visit (FV), 1 day after surgery, 1 and 2 weeks, and 1, 2, 3, 4, 5, and 6 months after surgery/FV. RESULTS: In the cured patients, the area of corneal ulcers, the duration of ulcer healing, the time to non-observed fungal hyphae by IVCM, the number of antifungal medications, the frequency of administered medications, and the maximum ulcer depth decreased significantly after CXL (all P < 0.05) compared with the M group. There were no significant differences in either corneal thickness or epithelial thickness of ulcers after healing between 5 and 6 months after surgery in the CXL-M group, while these were increased significantly at 6 months compared with 5 months after FV in the M group (both P < 0.05). CONCLUSIONS: In our study, CXL accelerated healing of the fungal ulcers, shortened the treatment duration, and minimized the need for medications and surgery. It appears that CXL is an effective procedure and adjuvant therapy for managing fungal keratitis.

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.

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.

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.

[The study of corneal epithelial change in keratoconic eyes with Fourier-domain optical coherence tomographic pachymetry].

OBJECTIVE: To compare the corneal epithelial thickness profile in keratoconic and normal eyes with advanced Fourier-domain optical coherence tomography (OCT) and to evaluate the diagnostic efficiency of pachymetry parameters. METHODS: Cross-sectional observational study. Twenty-five consecutive keratoconus patients (34 eyes) and 41 normal volunteers (41 eyes) in Eye & ENT Hospital of Fudan University between June 1 and July 31, 2013 were enrolled.Observations of corneal epithelial thickness and corneal thickness profiles were taken from all subjects. The epithelial pachymetry parameters were superior, inferior, inferior-superior (I-S), minimum (Min), maximum (Max), Min-Max, and central. The corneal pachymetry parameters were inferotemporal-superonasal (IT-SN), I-S, Min, Min-median, Min-Max, and central.Statistical analysis methods included Chi-square test, independent two-sample t-test, and Wilcoxon rank sum test. The diagnostic efficiency of all parameters were analyzed by receiver operating characteristic (ROC) curves and Youden index. RESULTS: The inferior, I-S, Min, Min-Max, and central epithelial thickness averages were (50.5 ± 4.8) µm, (-2.7 ± 7.5) µm, (35.9 ± 10.7) µm, (-33.6 ± 18.9) µm, and (50.1 ± 6.8) µm in keratoconic eyes.In normal eyes, they were (54.8 ± 2.5) µm, (0.9 ± 1.3) µm, (51.4 ± 2.6) µm, (-5.7 ± 1.8) µm, and (54.7 ± 2.2) µm. Among the epithelial pachymetry parameters, Min-Max and Min showed high diagnostic efficiency for keratoconus (AUC = 0.967, 0.968; Youden index = 0.882, 0.829); inferior, I-S, and central parameters showed moderate efficiency (AUC = 0.794, 0.728, 0.715; Youden index = 0.461, 0.564, 0.565). The IT-SN, I-S, Min, Min-median, Min-Max, and central corneal thickness averages were (-82.8 ± 65.2) µm, (-72.5 ± 55.6) µm, (401.2 ± 83.8) µm, (-83.4 ± 48.2) µm, (-169.7 ± 99.4) µm, and (453.4 ± 58.6) µm in keratoconic eyes.In normal eyes, these parameters were respectively (-23.7 ± 18.5) µm, (-20.5 ± 19.8) µm, (525.4 ± 28.1) µm, (-23.1 ± 4.8) µm, (-59.2 ± 23.3) µm, and (533.4 ± 28.8) µm. Min, Min-median, and Min-Max had preferable diagnostic efficiency (AUC = 0.952, 0.938, 0.924; Youden index = 0.784, 0.829, 0.721); central, IT-SN, and I-S parameters showed moderate efficiency (AUC = 0.891, 0.877, 0.862; Youden index = 0.643, 0.707, 0.580). CONCLUSIONS: In observation with Fourier-domain OCT, keratoconus was characterized by central and inferior epithelial thinning, increased epithelial thickness variation, central cornea thinning, increase in asymmetry, and gaps between corneal IT-SN and I-S thickness.Fourier-domain OCT was confirmed to have high speed, high resolution, and noninvasion. The pachymetry parameters showed specific strengths in diagnosis of keratoconus, especially epithelial pachymetry parameters of Min and Min-Max, and corneal pachymetry parameters of Min, Min-median and Min-Max.

Spectral-domain optical coherence tomographic assessment of Schlemm's canal in Chinese subjects with primary open-angle glaucoma.

PURPOSE: To evaluate in vivo features of Schlemm's canal (SC) in patients with primary open-angle glaucoma (POAG) with spectral-domain optical coherence tomography (SD-OCT) and to investigate the relationship of SC size with intraocular pressure (IOP) and glaucoma severity. DESIGN: Prospective, comparative study. PARTICIPANTS: Fifty Chinese patients with newly diagnosed POAG who had not undergone surgery and 50 normal Chinese subjects from a population-based, cross-sectional study in Shanghai. METHODS: All participants underwent SD-OCT. The diameter and area of SC were examined in the temporal and nasal sections and measured with customized software. MAIN OUTCOME MEASURES: Patient demographics, repeatability and reproducibility assessed with the coefficient of variation (CV) and the intraclass correlation coefficient (ICC), SC parameters and their correlation with IOP, and the mean deviation (MD) of the visual field were analyzed. RESULTS: The percentage of sections in which SC was observable was similar between eyes with POAG and normal eyes, and ranged from 78% to 86%. For intraobserver repeatability, the CV and ICC values were 7.9% and 0.97 for diameter, and 13.8% and 0.83 for area, respectively. For interobserver repeatability, the CV and ICC values were 13.6% and 0.89 for diameter, and 13.4% and 0.80 for area, respectively. Significant differences between the 2 groups were found for the average SC area (11332 ± 2015 µm(2) vs. 13991 ± 1357 µm(2); P<0.001), but not for the SC diameter (40.2 ± 7.1 µm vs. 45.2 ± 4.0 µm; P = 0.195). In addition, the mean IOP values correlated well only with the SC area (ρ = -0.674, P<0.001), not with the SC diameter (ρ = -0.103, P = 248). No significant correlations were found between the MD values and the SC parameters. CONCLUSIONS: Eyes with POAG have a decreased SC area compared with normal eyes. A correlation between the SC area and the IOP also was observed. However, the degree of glaucoma damage was not consistently associated with the SC area. Spectral-domain OCT could be used for investigating SC changes in patients with glaucoma.

Clinical Investigation of the Safety and Efficacy of Low-temperature Plasma as an Adjuvant Treatment for Mild to Moderate Fungal Keratitis: A Pilot Study.

PURPOSE: This pilot study assessed the safety and efficacy of low-temperature plasma (LTP) as an adjuvant treatment for mild to moderate fungal keratitis (FK). METHODS: Thirty FK patients were randomized into LTP (n = 15) and control (n = 15) groups. Patients were followed up for 3 months. The best-corrected visual acuity (BCVA), ulcer size, and hypopyon height were measured; healing time or complications were documented and compared. RESULTS: More patients in the LTP group healed completely (11/15 in 48 days) compared with the control group (4/15 in 59.5 days), and those patients had a deeper initial ulcer depth and exhibited better BCVA improvements. Four patients failed after LTP treatment due to perforation, increased inflammatory infiltration, or hypopyon; those with more hypopyon were more likely to fail. CONCLUSIONS: LTP could be a promising adjuvant therapy to topical antifungal drugs for mild to moderate FK.

Effect of eye rubbing on corneal biomechanical properties in myopia and emmetropia.

Purpose: To investigate short-term changes in corneal biomechanical properties caused by eye rubbing in myopia and emmetropia and compare the different responses between the two groups. Methods: This was a prospective observational study of 57 eyes of 57 healthy subjects aged 45 years and younger. The participants were divided into myopia and emmetropia groups. All the subjects underwent eye rubbing by the same investigator using the same technique. Biomechanical parameters were recorded using the Corvis ST device before and after 1 min of eye rubbing. One week later, all the participants underwent the test again. Statistical methods were employed to compare the differences between the data from before and after the 1 min of eye rubbing and demonstrate the different responses of the two groups. Results: After 1 min of eye rubbing, smaller SP-A1 (p < 0.001), higher deformation and deflection amplitudes (p < 0.001, p = 0.012), higher peak distances (p < 0.001), earlier A1 times (p < 0.001), faster velocities (p < 0.001), and lower maximum inverse radii (p = 0.004) were observed. According to the automatic linear modeling analysis, the refractive states (B = -5.236, p = 0.010) and biomechanically corrected intraocular pressure (bIOP) (B = 0.196, p = 0.016) had influenced a decrease in the stiffness parameter at the first applanation (SP-A1). The central corneal thickness (CCT) had decreased only in the myopia group (p = 0.039). The change of SP-A1 in amplitude was larger in the myopia group than in the emmetropia group (p < 0.001). All the parameters returned to the baseline level 1 week later. Conclusion: Eye rubbing appears to alter corneal biomechanical properties temporarily and make the cornea softer, especially for myopic young patients.

Comparison of Accelerated and Standard Corneal Collagen Cross-Linking Treatments in Experimental Fungal Keratitis for Aspergillus fumigatus.

Introduction: To compare accelerated and standard corneal collagen cross-linking (CXL) treatments in experimental Aspergillus keratitis models. Methods: Twenty-six New Zealand rabbits were divided into two groups: a 1% voriconazole combined with standard CXL group, and a 1% voriconazole combined with accelerated CXL group. The ulcer area, corneal opacity, and corneal neovascularization score were measured via slit-lamp imaging, and the corneal and corneal epithelial thickness and ulcer depth were measured via anterior segment optical coherence tomography (AS-OCT). The duration of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling (day 0) and at 1, 4, 7, 14, 21, and 28 days after the intervention. Results: The area and depth of the ulcer decreased in both groups after CXL (all P < 0.05). Interestingly, the ulcer area in the accelerated CXL group still tended to increase on the first day after CXL although the difference was not statistically significant (P=0.6649). On the 21st and 28th days after CXL, the ulcer area and depth of the standard CXL group were larger and deeper than those of the accelerated CXL group (all P < 0.05). The ulcer healing time in the accelerated CXL group was 18.67 ± 6.21 days, while that in the standard CXL group was 23.55 ± 4.72 days, and the difference was statistically significant (P=0.0475). Conclusions: Both accelerated and standard CXL can significantly inhibit the progression of Aspergillus keratitis corneal ulcers and promote ulcer healing. The accelerated CXL was superior to the standard CXL, which could control infection faster and promote ulcer healing. However, it is important to note that there may be a risk of early deterioration of the ulcer with accelerated CXL.

Application of Keratograph and Fourier-Domain Optical Coherence Tomography in Measurements of Tear Meniscus Height.

To compare the interoperator repeatability of tear meniscus height (TMH) measurements obtained with a keratograph and Fourier-domain optical coherence tomography (FD-OCT) and to assess the agreement between the methods.Forty-seven eyes with DED and 41 healthy eyes were analyzed using the Schirmer test I and tear breakup time test (TBUT). The TMH was measured three times with each device. The repeatability of measurements was assessed by within-subject standard deviation (Sw), repeatability (2.77 Sw), coefficient of variation (CoV) and intraclass correlation coefficient (ICC). Efficacy in detecting DED was evaluated in terms of the area under the curve (AUC). The TMHs obtained with the keratograph were 0.03 mm lower than those obtained with FD-OCT in both groups (p < 0.001 for the DED group and p = 0.0143 for the control group, respectively). The intraexaminerICCs of the keratographic TMH were 0.789 and 0.817 for the DED and control groups, respectively, and those of the FD-OCT TMH were 0.859 and 0.845, respectively. Although a close correlation was found between the TMHs measured with the keratograph and FD-OCT by the Spearman analysis in both groups (both p < 0.001), poor agreement between the devices was shown in both groups using a Bland−Altman plot. The AUCs of the keratography and FD-OCT results were 0.971 (p < 0.001) and 0.923 (p < 0.001), respectively. Both devices had excellent diagnostic accuracy in differentiating normal patients from DED patients. FD-OCT TMH measurements were more reliable than the keratograph data in the DED group. Agreement between the devices was poor in both groups.

Combination Therapy of 0.1% Fluorometholone and 0.05% Azelastine in Eyes with Severe Allergic Conjunctival Diseases: A Randomized Controlled Trial.

This study sought to evaluate the efficacy of the isolated use of fluorometholone compared with the combined use of azelastine and fluorometholone for the treatment of severe allergic conjunctival disease (ACD). One hundred and eleven patients with severe ACD were randomized into two groups: one treated with topical 0.1% fluorometholone combined with 0.05% azelastine and the other with 0.1% fluorometholone alone. The Ocular Surface Disease Index (OSDI) and the signs of keratopathy, palpebral conjunctiva papillae and conjunctival congestion were scored before and at one, two and six weeks after treatment and compared between the groups. The intra-ocular pressure (IOP) was also monitored. There were no significant differences between the groups in the baseline mean scores of signs and OSDI scores, which gradually improved at all visits after therapy in both groups. Although the time effect was significant for all the parameters (all p < 0.001), the reduction in corneal involvement scores from week 2 to week 6 was insignificant in both groups (p = 0.460 for the steroids group and p = 0.074 for the combination group). All signs and symptoms were significantly more improved in the combination group than in the isolated group at each control visit. IOP remained stable at all visits (all p < 0.001), except one patient in each group had elevated IOP over 21 mmHg. While both the isolated use of fluorometholone and combined use of azelastine and fluorometholone are effective in alleviating the signs and symptoms of severe ACD, optimal response can be achieved with adjunctive treatment including azelastine.

Combination of 0.05% Azelastine and 0.1% Tacrolimus Eye Drops in Children With Vernal Keratoconjunctivitis: A Prospective Study.

Aims: To compare the efficacy of the combination of 0. 05% azelastine and 0.1% tacrolimus eye drops with 0.1% tacrolimus monotherapy in pediatric patients with vernal keratoconjunctivitis (VKC). Methods: Prospective study. Seventy-six patients with VKC were randomized 1:1 into monotherapy group with 0.1% tacrolimus or combination therapy group with 0.1% tacrolimus and 0.05% azelastine. The Ocular Surface Disease Index (OSDI) scores and the signs of conjunctival hyperemia, corneal involvement, and palpebral conjunctiva papillae were assessed at baseline and at 1, 2, and 6 weeks after treatment. Results: Two groups were comparable in age, sex, duration of VKC, OSDI, and clinical signs of VKC at baseline. Significant improvements in OSDI score and clinical signs were observed in both groups at all follow-up visits (all p < 0.001), compared with baseline. The combination therapy group showed a larger decrease in OSDI score from baseline (10.30 ± 0.9) compared with monotherapy group (7.30 ± 0.7, p =0.0085) at 1 week. Greater improvements in conjunctival hyperemia and conjunctival papillae were identified in the combination therapy group, compared with in the monotherapy group, at all follow-up visits (all p < 0.05). The corneal involvement scores in the combination group is significantly lower than the monotherapy group at 2 weeks after the treatment (p = 0.0488). No severe adverse effect was found in either group during the study. Conclusions: Compared with a monotherapy of 0.1% tacrolimus, the combination of 0.05% azelastine and 0.1% tacrolimus eye drops lead to faster and greater improvements in clinical signs and symptoms of vernal keratoconjunctivitis in pediatric patients.

[Advances in penetrating keratoplasty technique].

Rejection after corneal transplantation is currently the lead of the main reasons for corneal graft failure. Penetrating keratoplasty (PK) is still one of the gold standard surgeries for these patients. In recent years, improving the surgical techniques to reduce the incidence of corneal allograft rejection has been the way to more and more attention to the majority of ophthalmologists. To generalize and analyze the recent research of new technologies of femtosecond laser shaped penetrating keratoplasty of top-hat configuration (FS-TH-PKP), manual top-hat wound configuration for penetrating keratoplasty (M-TH-PKP), and half-top-hat penetrating keratoplasty (HTH-PKP) surgeries.

Comparison of the Meibomian Gland Openings by Optical Coherence Tomography in Obstructive Meibomian Gland Dysfunction and Normal Patients.

PURPOSE: The aim of this study was to use swept-source anterior segment optical coherence tomography (OCT) to explore imaging the meibomian gland openings and to identify their in vivo characteristics in patients with obstructive meibomian gland dysfunction (MGD) and healthy participants. METHODS: We enrolled 49 patients with MGD and 54 health controls in this case-control study. Each participant underwent slit-lamp examination, meibography, and OCT scanning. Sixteen patients with MGD underwent a repeat OCT examination after eyelid massage. The outcome measures included determinations of meibomian gland openings (orifices and terminal ducts) from OCT images and comparisons of the meibomian openings between patients with MGD and normal controls before and after meibomian gland massage. RESULTS: Using the same OCT scanning model, the number of visible orifices of the meibomian glands was similar between eyes with MGD and normal eyes (9.2 ± 2.3 vs. 9.7 ± 2.4). The mean diameter of the terminal ducts in patients with MGD was larger (120.22 ± 27.92 µm vs. 100.96 ± 20.30 µm) than in the normal controls, and had a larger coefficient of variation. Significant differences were observed in the mean diameter of the terminal ducts of patients with MGD before and after meibum gland massage (133.73 ± 27.81 µm vs. 102.26 ± 24.30 µm, p < 0.001). CONCLUSIONS: Patients with MGD have more diversified orifices and larger meibomian gland terminal duct diameters than normal subjects. In addition, meibomian gland terminal duct diameters seem to decrease in patients with MGD after meibum gland massage.

Deep learning for identifying corneal diseases from ocular surface slit-lamp photographs.

To demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm's performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis.

Vitamin A Palmitate and Carbomer Gel Protects the Conjunctiva of Patients With Long-term Prostaglandin Analogs Application.

PURPOSE: To investigate the protective effects of vitamin A palmitate and carbomer gel on the morphology of conjunctival epithelium and density of goblet cells (GCs) in patients on long-term prostaglandin analogs (PGAs) application. METHODS: In this prospective cohort study, 23 primary open-angle glaucoma patients and 7 normal-tension glaucoma patients prescribed PGAs for >1 year were enrolled into 3 identical clinical trials and randomized into 3 groups (10 per group). Patients were treated twice daily with vitamin A palmitate eye gel 0.1%, or carbomer eye gel 0.2%, or no additional application of these 2 drugs. Ocular surface disease index questionnaires, Schirmer 1 test without anesthesia, tear break-up time test, and GCs density assessment by in vivo confocal microscopy and conjunctival impression cytology analysis were performed at baseline and at months 1, 3, and 6 of the study. RESULTS: Both vitamin A palmitate and carbomer gel led to a significant improvement in ocular surface disease index questionnaires score and prevented the gradual decline in tear break-up time. Vitamin A palmitate significantly increased the GC density after treatment. The GC density assessed by in vivo confocal microscopy positively correlated with that measured by conjunctival impression cytology. CONCLUSIONS: Vitamin A palmitate and carbomer eye gel can effectively relieve dry eye symptom caused by long-term application of PGAs by increasing the GCs density and thereby reducing the toxicity to the conjunctiva. Vitamin A palmitate and carbomer eye gel may be valuable alternatives for glaucoma patients who prescribed long-term PGAs.

Nasolacrimal recanalization as an alternative to external dacryocystorhinostomy for treating failed nasolacrimal duct intubation.

To compare the surgical duration and clinical outcomes of nasolacrimal recanalization versus external dacryocystorhinostomy (DCR) in the treatment of failed nasolacrimal duct intubation.This is a retrospective, comparative, and interventional study. We evaluated the outcomes of 66 consecutive patients undergoing either nasolacrimal recanalization (n = 32) or DCR (n = 34) in a tertiary lacrimal disease referral center. Length of surgical duration, clinical outcomes, and rate of recurrence at 18 months postoperatively were compared.The mean surgical duration was 18.5 minutes (range, 15-25 minutes) for nasolacrimal recanalization and 48.2 minutes (range, 45-61 minutes) for DCR, respectively (P < 0.001). The rate of success was 84.4% in the recanalization group and 85.3% in the DCR group, respectively (P = 0.91). The time to recurrence was 2.6 ±â€Š1.1 months in the recanalization group and 5.6 ±â€Š2.1 months in the DCR group (P < 0.001). Five failed cases in each group received a secondary DCR surgery with the same resolution rate (40%). The absence of ocular discharge at baseline was a significant predictor for a successful outcome in the recanalization group (P = 0.04) but not in the DCR group (P = 0.63).Nasolacrimal recanalization is an effective, safe, and time-saving alternative to DCR for the treatment of failed nasolacrimal duct intubation. Clinicians should be cautious in patients with discharge.

Optical Coherence Tomography Assessment of Angle Anatomy Changes After Trabeculectomy in Primary Angle-Closure Glaucoma.

PURPOSE: Using anterior chamber optical coherence tomography to evaluate changes in angle anatomy in patients with primary angle-closure glaucoma (PACG) before and after trabeculectomy. METHODS: This is a prospective observational study in 38 eyes of 38 patients with PACG, who underwent trabeculectomy. We used customized software to analyze optical coherence tomography images (Visante) of all participants before and after the surgical treatment. Multivariate linear regression analysis was performed for predictors of percentage change in mean angle parameters, including scleral spur angle, angle opening distance, angle recess area, and trabecular-iris surface area. The main outcome measures were changes in angle parameters and their relationship with age, sex, refraction, MD, visual outcomes, central corneal thickness, axial length of eye, number of glaucoma bottles, baseline intraocular pressure (IOP), and percentage changes in IOP (ΔIOP). RESULTS: There was a significant increase in all angle parameters at the follow-up examination compared with the baseline value (all P<0.001). After multivariate analysis, the only variable related to changes in all angle parameters was ΔIOP. CONCLUSIONS: Trabeculectomy results in a significant increase in the angle width in PACG. The increase in angle parameters was significantly related to the IOP changes.