Corneal subbasal nerve analysis in patients with primary Sjogren's syndrome: a novel objective grading method and clinical correlations.

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.

Change patterns in the corneal sub-basal nerve and corneal aberrations in patients with dry eye disease: An artificial intelligence analysis.

We aimed to investigate the change patterns in corneal sub-basal nerve morphology and corneal intrinsic aberrations in dry eye disease (DED). Our study included 229 eyes of 155 patients with DED and 40 eyes of 20 healthy control. We used the Oculus keratograph and the ocular surface disease index questionnaire to assess their signs and symptoms. In vivo confocal microscopy was used to observe the corneal sub-basal nerves, corneal endothelial cells, and Langerhans cells (LCs). An artificial intelligence (AI) technique run by the deep learning model generated the sub-basal nerve fibre parameters. Furthermore, we used the Pentacam HR system to measure the corneal intrinsic aberrations and corneal surface regularity indices. DED patients more frequently had increased anterior and total corneal aberrations than controls (P < 0.05). In addition, DED had decreased average density and maximum length of corneal nerve. (Both P < 0.01) The LC number was significantly correlated with maximum length (CC = -0.19, P = 0.01) of the sub-basal nerve fibre. Furthermore, the corneal nerve average density was negatively correlated with IHD, and anterior, posterior, and total corneal aberrations (All P < 0.05) especially the higher-order aberrations. Significant correlations were seen between corneal nerve morphology changes, analysed by AI and corneal intrinsic aberrations, particularly higher-order aberrations.

Analysis of lens epithelium telomere length in age-related cataract.

We aimed to investigate the associations among lens epithelium telomere length (LETL), cataract types, and systemic pro-senescence factors in patients with age-related cataract. In this prospective study, the general demographic factors, body mass index, smoking history, depression, hypertension, diabetes, various psychological measures, and uncorrected distant visual acuity of patients with age-related cataract were recorded. Lens Opacities Classification System III (LOCS III) scores and lens density measured by Scheimpflug imaging were used to evaluate the cataracts. LETL was measured by real-time polymerase chain reaction. Correlations among these parameters were analyzed. The LOCS III nuclear opalescence (NO) score was associated with age (ß = 0.053, P < 0.001) and Patient Health Questionnaire-9 score (ß = -0.042, P = 0.004). Smoking was identified as a risk factor affecting LOCS III NO score (odds ratio = 1.546, 95% confidence interval, 1.128-2.119), but not the LOCS III cortical or posterior subcapsular scores. LETLs showed a weak association with systemic factors and LOCS III scores, and a significantly moderate correlation with the average objective lens densities of different regions measured by Scheimpflug imaging (r values ranged from -0.278 to -0.523, P < 0.05). However, there was no correlation between the LETLs and the maximum lens densities. The groups with a relatively low lens density had longer LETLs. In Conclusion, being an age-related disease, cortical cataract was also associated with "aging of the lens epithelium." Notably, lens epithelium activity rarely showed systemic effects. Thus, future studies should emphasize the importance of the telomeric system in cataractous process and aging.

Evaluation of objective visual quality in dry eye disease and corneal nerve changes.

PURPOSE: To explore objective visual quality in dry eye diseases (DED) and the correlation between corneal nerves and objective visual quality. METHODS: Ninety-eight eyes of 49 patients with DED were included. Each patient was evaluated with the ocular surface disease index (OSDI), eyelid margin signs and meibomian gland assessments; corneal staining; tear film breakup time (TBUT); tear meniscus height (TMH); in vivo confocal microscopic (IVCM); objective visual quality including the objective scatter index (OSI), mean objective scattering index (mOSI), modulation transfer function (MTF) cutoff value and Strehl ratio. RESULTS: A significant correlation was found between the OSDI and mOSI (r = 0.422, p = 0.005), MTF cutoff value (r = - 0.355, p = 0.020), and Strehl ratio (r = - 0.446, p = 0.003). The OSI was significantly correlated with TBUTf (r = - 0.213, p = 0.042). The mOSI, MTF cutoff value, Strehl ratio were correlated with eyelid margin signs and meibomian assessments. Additionally, there was a statistically significant correlation between corneal nerve length and the mOSI (r = - 0.239, p = 0.037), OSI (r = - 0.294, p = 0.028), MTF cutoff value(r = 0.282, p = 0.012), and Strehl ratio (r = 0.299, p = 0.008). CONCLUSIONS: Our study explored that objective visual quality was correlated with clinical symptoms and signs in DED patients. Furthermore, for the first time, our study explored the relationship between corneal nerves and objective visual quality and discovered that longer and wider corneal nerves were associated with better objective visual quality, which suggested that nerve changes may be a factor that related to poor visual quality in DED patients.

Analysis of Globular Cells in Corneal Nerve Vortex.

Purpose: Less was known about globular cells which were a type of dendritic cells (DCs) in cornea. We aimed to investigate the morphological and distribution characteristics of globular cells in corneal vortex and their clinical correlations with ocular surface. Methods: Case records of patients who underwent in vivo confocal microscopy (IVCM) were evaluated retrospectively. The morphology and distribution features of globular cells in cornea nerve vortex and their co-existence status with Langerhans cells (LCs) were analyzed. Data of ocular surface symptoms and signs were collected and their correlations with globular cells distribution patterns and dendritic forms were performed. Dry eye patients without LCs were treated with preservative-free artificial tears, while patients with LCs were treated with artificial tears and fluoromethalone until the activated LCs disappeared. Results: A total of 836 eyes from 451 individuals were included. Three distribution patterns of globular cells in vortex were investigated, type 1 scattered globular cells (57.66%), type 2 large amounts of globular cells (≥50 cells) gathering in vortex and along some fixed vortex direction horizontally (13.52%) and type 3 no globular cells (28.83%). Their location and cell count altered slightly in the follow-ups but would not disappear. LCs could co-exist with globular cells and could fade after treatment. The type 2 distribution pattern was associated with older age (p = 0.000) and higher upper eyelid Meiboscore (p = 0.006). Dendritic globular cells had higher Meiboscore than Non-dendritic forms. Conclusions: Globular cells had characteristic distribution patterns and biological features different from LCs. They were associated with long-term irritation of the meibomian gland dysfunction.

Impression Cytology and In Vivo Confocal Microscopy of Lip Mucosa Compared With Labial Gland Biopsy and Classification Criteria In Patients With Clinically Suspected Primary Sjögren's Syndrome.

Purpose: The study assessed the validity of impression cytology (IC) and in vivo confocal microscopy (IVCM) of lip mucosa compared with labial gland biopsy, anti-Sjögren's syndrome A (SSA)/Ro antibody status, and classification criteria in suspected primary Sjögren's syndrome (pSS) patients. Methods: Clinically suspected pSS patients (n = 201) were enrolled consecutively and were divided into pSS (n = 56) and control (n = 145, only with dryness) groups according to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. All patients underwent lip mucosa IC (inflammatory cell density) and IVCM (epithelium/intrinsic layer thickness and labial gland density/diameter) analyses. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed. Results: The absolute agreement between positive lip mucosal IC (≥50 cells/4 mm2) and the ACR-EULAR criteria (94.5%)/labial gland biopsy (95.5%) was good, with sensitivities of 82.1 and 85.2%, respectively, and a specificity of 99.3%. Compared with controls, IVCM revealed significant lip mucosal atrophy and glandular decreases in the pSS group (all P = 0.000). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤128 µm and a gland diameter ≤114 µm were 85.7 and 89.3%; the specificities were 90.3 and 95.9%, respectively. A combination of positive IC/IVCM and anti-SSA/Ro antibody results showed a high predictive value for diagnosing pSS. Conclusions: IC and IVCM could detect distinctive cellular and morphological changes in the lip mucosa of patients with pSS. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsy for diagnosing pSS.

In vivo Confocal Microscopic Evaluation of Previously Neglected Oval Cells in Corneal Nerve Vortex: An Inflammatory Indicator of Dry Eye Disease.

This study aimed to investigate the association of between previously neglected oval cells located in the corneal vortex and dry eye disease (DED). This was an observational, prospective study involving 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal subbasal nerves and Langerhans cells (LCs) in the corneal vortex and periphery. Bright and oval cells were also observed in the corneal vortex. An artificial intelligence technique was used to generate subbasal nerve fiber parameters. The patients were divided into the three groups based on the presence of inflammatory cells. Group 2 patients showed a significant increase in the corneal peripheral nerve maximum length and average corneal peripheral nerve density. Patients in group 3 had more LCs than other patients. A bright and oval cell was identified in the corneal vortex, which might be a type of immature LC related to the disease severity of DED.

Change Patterns in Corneal Intrinsic Aberrations and Nerve Density after Cataract Surgery in Patients with Dry Eye Disease.

This study aimed to evaluate the change patterns in corneal intrinsic aberrations and nerve density after cataract surgery in dry eye disease. The preoperative, 1- and 3-month postoperative dry eye-related parameters were obtained by the Oculus keratograph and the ocular surface disease index questionnaire. The corneal intrinsic aberrations were measured using the Pentacam HR system. In vivo confocal microscopy was performed to observe the vortical and peripheral corneal nerves. An artificial intelligence technique run by the deep learning model generated the corneal nerve parameters. Corneal aberrations on the anterior and total corneal surfaces were significantly increased at 1 month compared with the baseline (p < 0.05) but gradually returned to the baseline by 3 months (p > 0.05). However, the change in posterior corneal aberration lasted up to 3 months (p < 0.05). There was a significant decrease in the corneal vortical nerve maximum length and average density after the operation (p < 0.05), and this damage lasted approximately 3 months. The corneal vortical nerve maximum length and average density were negatively correlated with the anterior corneal surface aberrations before and 1 month after the operation (correlation coefficients, CC = −0.26, −0.25, −0.28; all p < 0.05). Corneal vortex provided a unique site to observe long-term corneal nerve injury related to eye dryness. The continuous damage to the corneal vortical nerve may be due to the continuous dry eye state.

The Efficacy and Safety of New-Generation Intense Pulsed Light in the Treatment of Meibomian Gland Dysfunction-Related Dry Eye: A Multicenter, Randomized, Patients-Blind, Parallel-Control, Non-Inferiority Clinical Trial.

INTRODUCTION: This study aimed to evaluate the efficacy and safety of a new-generation intense pulsed light (IPL) device in improving the symptoms and signs of meibomian gland dysfunction (MGD)-related dry eye, and compare it with a traditional IPL device. METHODS: This multicenter randomized controlled trial enrolled 132 patients with MGD-related dry eye from two centers. Patients were randomly assigned into the new-generation IPL (Eyesis) group or traditional IPL (E-Eye) group, and then blinded to receive treatment on days 0 and 7. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer test, and meibomian gland signs were evaluated on days 0, 7, and 14. The primary outcome was defined as the effective rate of treating MGD at day 14. Any adverse events were recorded for safety assessment. Intergroup comparisons and non-inferiority analysis were performed. p values less than 0.05 were considered statistically significant. RESULTS: Basic information showed no significant difference between treatment groups. The intergroup difference of the effective rate was - 1.7% in the left eye and 1.6% in right eye, verifying the non-inferiority of the Eyesis device (p = 0.927). Significant improvements in OSDI, TBUT, Schirmer test, TMH, CFS, and meibomian gland signs were observed in Eyesis group on days 7 and 14 (all p < 0.05). Compared to the E-Eye group, the Eyesis group achieved more significant improvements in OSDI, TBUT, Schirmer test, TMH, and meibum quality (all p < 0.05). There was no significant difference in the incidences of adverse events between groups (p = 1.000). CONCLUSIONS: The new-generation IPL was effective and safe in relieving the symptoms and signs of MGD-related dry eye, exhibiting a non-inferior effective rate compared to the traditional IPL. Additionally, Eyesis showed more clinical benefits over E-Eye in alleviating symptoms, increasing tear film stability and improving meibomian gland function.

The Utility of Oral Vitamin B1 and Mecobalamin to Improve Corneal Nerves in Dry Eye Disease: An In Vivo Confocal Microscopy Study.

Our purpose is to demonstrate the changes in cornea nerve parameters and symptoms and signs in dry eye disease (DED) patients after oral vitamin B1 and mecobalamin treatment. In this randomized double-blind controlled trial, DED patients were randomly assigned to either the treatment group (oral vitamin B1 and mecobalamin, artificial tears) or the control group (artificial tears). Corneal nerve parameters via in vivo confocal microscopy (IVCM), DED symptoms, and signs were assessed at baseline and 1 and 3 months post-treatment. In total, 398 eyes from 199 patients were included. In the treatment group, there were significant improvements in corneal nerve length, width, and neuromas, the sign of conjunctival congestion score (CCS), symptoms of dryness, pain, photophobia, blurred vision, total symptom score, and OSDI (OSDI) at 1/3 months post-treatment (all p < 0.05). Patients who received vitamin B1 and mecobalamin showed greater improvement in CCS, dryness scores at 1 month (p < 0.05), corneal fluorescein staining (CFS) (p = 0.012), photophobia (p = 0.032), total symptom scores (p = 0.041), and OSDI (p = 0.029) at 3 months. Greater continuous improvement in CFS (p = 0.045), dryness (p = 0.033), blurred vision (p = 0.031) and total symptom scores (p = 0.023) was demonstrated at 3 months than at 1 month post-treatment in the treatment group. We found that oral vitamin B1 and mecobalamin can improve corneal nerve length, width, reflectivity and the number of neuromas in IVCM, thereby repairing epithelial cells and alleviating some ocular symptoms. Thus, vitamin B1 and mecobalamin are potential treatment options for patients with DED.

Adaptive metabolic responses in a thermostabilized environment: Transgenerational trade-off implications from tropical tilapia.

Relatively warm environments caused by global warming enhance the productivity of aquaculture activities in tropical/subtropical regions; however, the intermittent cold stress (ICS) caused by negative Arctic Oscillation can still result in major economic losses. In contrast to endotherms, ectothermic fishes experience ambient temperature as an abiotic factor that is central to performance and survival. Therefore, the occurrence of extreme temperatures caused by climate change has ignited a surge of scientific interest from ecologists, economists and physiologists. In this study, we test the transgenerational effects of rearing cold-experienced (CE) and cold-naïve (CN) strains of tropical tilapia. Our results show that compared to CN tilapia, the CE strain preferentially converts carbohydrates into lipids in liver at a regular temperature of 27 °C. Besides, at a low temperature of 22 °C, the CE strain exhibits a broader aerobic scope than CN fish, and their metabolite profile suggests a metabolic shift towards the utilization of glutamate derivatives. Therefore, in response to thermal perturbations, this transgenerational metabolic adjustment provides evidence into the adaptive trade-off mechanisms in tropical fish. Nevertheless, global warming may result in less thermal variation each year, and the stabilized ambient temperature may cause tropical tilapia to gradually exhibit lower energy deposits in liver. In addition to those habitants in cold and temperate regions, a lack of cold exposure to multiple generations of fish may decrease the native cold-tolerance traits of subtropical/tropical organisms; this notion has not been previously explored in terms of the biological effects under anthropogenic climate change.

Patient satisfaction with the ocular surface individualized medical program.

PURPOSE: To improve the medical management system and the quality of medical treatment, this study aimed to assess patient satisfaction related to an ocular surface individualized medical program for dry eye, and identified patient needs that should be addressed in future. METHODS: We enrolled 166 patients from the dry eye clinic at the Peking University Third Hospital from December 2017 to May 2019. An investigator followed up with all patients by telephone 2 months after the first assessment of overall patient satisfaction, expectations, and experiences. We determined patient satisfaction using a questionnaire and analyzed the results. Multivariate linear regression analysis was used to assess the predictors of overall patient satisfaction. RESULTS: The overall patient satisfaction with the ocular surface individualized medical program skewed toward a positive assessment. Ten variables were significantly associated with overall patient satisfaction: two involving fulfilment of expectations, seven involving patient-reported experiences, and one involving socio-demographics. The most important predictor of overall patient satisfaction was patient-reported experiences with the treatment outcome (ß = 0.281, p < 0.001), followed by experiences with medical staff services (ß = 0.240, p = 0.002), examination services (ß = 0.198, p = 0.002), and interpretation and professionalism (ß = 0.168, p = 0.04), expectations fulfilment (ß = 0.147, p = 0.025), as well as age (ß = -0.13, p = 0.014). Free response-style negative patient feedback suggested that examination wait time and environment needed improvement. CONCLUSION: Overall, the ocular surface individualized medical program is effective and is able to achieve satisfaction for most patients. The examination procedures and environment require improvements, and treatment must be made more patient-centric to improve satisfaction.

Comparison of intense pulsed light and near-infrared light in the treatment of dry eye disease: a prospective randomized study.

PURPOSE: To compare the efficacy of intense pulsed light (IPL) and near-infrared light (NIL) treatments in alleviating symptoms and signs of dry eye disease (DED). METHODS: Patients diagnosed with DED at the Peking University Third Hospital Eye Center from January 2019 to October 2019 were randomized to undergo either NIL therapy combined with meibomian gland expression (MGX; NIL Group) or IPL combined with MGX (IPL Group). Treatments were performed three times at 1-month intervals. DED signs and symptoms were evaluated before every treatment. We compared the clinical improvement within and between the groups. Additional comparisons were made according to the meibomian gland (MG) dropout grade. RESULTS: A total of 260 eyes of 130 patients (mean age, 49.68 ± 18.01 years) were included. The dryness and total symptom scores and the MG expressibility and secretion quality (upper and lower eyelids) significantly improved after the three treatments in both groups (p < 0.05). However, IPL had superior efficacy in improving blurred vision, photophobia, burning, increased secretions and the total symptom score at 2 months in patients with more severe MG dropout. CONCLUSIONS: Both IPL and NIL treatments were effective in the treatment of DED, but IPL provided greater symptom improvement, particularly in patients with severe MG dropout. NIL can be a new therapeutic option for the treatment of DED.

Pendulum test in chronic hemiplegic stroke population: additional ambulatory information beyond spasticity.

Spasticity measured by manual tests, such as modified Ashworth scale (MAS), may not sufficiently reflect mobility function in stroke survivors. This study aims to identify additional ambulatory information provided by the pendulum test. Clinical assessments including Brünnstrom recovery stage, manual muscle test, MAS, Tinetti test (TT), Timed up and go test, 10-m walk test (10-MWT), and Barthel index were applied to 40 ambulant chronic stroke patients. The pendular parameters, first swing excursion (FSE) and relaxation index (RI), were extracted by an electrogoniometer. The correlations among these variables were analyzed by the Spearman and Pearson partial correlation tests. After controlling the factor of motor recovery (Brünnstrom recovery stage), the MAS of paretic knee extensor was negatively correlated with the gait score of TT (r = - 0.355, p = 0.027), while the FSE revealed positive correlations to the balance score of TT (r = 0.378, p = 0.018). RI were associated with the comfortable speed of 10-MWT (r = 0.367, p = 0.022). These results suggest a decrease of knee extensor spasticity links to a better gait and balance in chronic stroke patients. The pendular parameters can provide additional ambulatory information, as complementary to the MAS. The pendulum test can be a potential tool for patient selection and outcome assessment after spasticity treatments in chronic stroke population.

Comparative Evaluation of Bandage Contact Lenses and Eye Patching after Bilateral Cataract Surgery.

PURPOSE: To comparatively evaluate the safety and satisfaction of bandage contact lens (BCL) and eye patching in patients after cataract surgery. METHODS: Sixteen (32 eyes) patients who planned to undergo bilateral cataract surgery were recruited. The two eyes of each patient were randomly divided into 2 groups. Group A and Group B were instructed to wear BCLs immediately at the end of the surgery until one week and eye patch immediately after surgery until one day, respectively. Visual analog scales of ten specific symptoms, Visual Function Index (VF-14) questionnaire, and best-corrected visual acuity (BCVA) were conducted on the first day before the surgery and Day 1 and Day 7 after surgery. Oculus keratography was conducted on the first day before surgery and on Day 7. Patient satisfaction was determined on Day 1. Moreover, bacterial species in the conjunctival sac, meibomian gland secretions, and BCLs were subsequently identified using 16S rRNA gene sequencing. RESULTS: The patient satisfaction scores of Group A were higher than Group B. Group A were more motivated to choose the same treatment and were more likely to recommend BCLs to others. No statistically significant differences were found in bacterial culture positivity between the groups. The differences in ocular signs and symptoms between the two groups were not statistically significant. There were no significant differences in the BCVA and VF-14 between the groups at any time point. CONCLUSIONS: BCLs could be safely and effectively used in patients after cataract surgery.

Therapeutic Effect of Intense Pulsed Light (IPL) Combined with Meibomian Gland Expression (MGX) on Meibomian Gland Dysfunction (MGD).

PURPOSE: Our study aimed to evaluate the efficiency of intense pulsed light (IPL) combined with meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD). METHODS: This study was a prospective interventional study. A total of 53 patients were included in the study and received a series of three treatments at an interval of 3-4 weeks. Follow-up examinations were completed 4 weeks after the last treatment. The Ocular Surface Disease Index (OSDI) questionnaire, tear meniscus height (TMH), tear break-up time (TBUT), slit-lamp examinations, and in vivo confocal microscopy (IVCM) were recorded before and after treatment. Additionally, an artificial intelligence automated software program was applied in our study for corneal nerve analysis. RESULTS: The OSDI score was significantly reduced after the IPL treatment compared with baseline (P < 0.001). Meibomian gland assessment scores, including meibum quality and expressibility, eyelid margin abnormalities, and corneal staining, significantly decreased after treatment (P < 0.05). Moreover, the corneal nerve fiber length (CNFL) significantly increased after the treatment (P < 0.001). CONCLUSION: Intense pulsed light (IPL) combined with MGX is an effective treatment for MGD, and neurotrophism could be one of the mechanisms of IPL.

A Deep Learning Model for Automated Sub-Basal Corneal Nerve Segmentation and Evaluation Using In Vivo Confocal Microscopy.

Purpose: The purpose of this study was to establish a deep learning model for automated sub-basal corneal nerve fiber (CNF) segmentation and evaluation with in vivo confocal microscopy (IVCM). Methods: A corneal nerve segmentation network (CNS-Net) was established with convolutional neural networks based on a deep learning algorithm for sub-basal corneal nerve segmentation and evaluation. CNS-Net was trained with 552 and tested on 139 labeled IVCM images as supervision information collected from July 2017 to December 2018 in Peking University Third Hospital. These images were labeled by three senior ophthalmologists with ImageJ software and then considered ground truth. The areas under the receiver operating characteristic curves (AUCs), mean average precision (mAP), sensitivity, and specificity were applied to evaluate the efficiency of corneal nerve segmentation. The relative deviation ratio (RDR) was leveraged to evaluate the accuracy of the corneal nerve fiber length (CNFL) evaluation task. Results: The model achieved an AUC of 0.96 (95% confidence interval [CI] = 0.935-0.983) and an mAP of 94% with minimum dice coefficient loss at 0.12. For our dataset, the sensitivity was 96% and specificity was 75% in the CNF segmentation task, and an RDR of 16% was reported in the CNFL evaluation task. Moreover, the model was able to segment and evaluate as many as 32 images per second, much faster than skilled ophthalmologists. Conclusions: We established a deep learning model, CNS-Net, which demonstrated a high accuracy and fast speed in sub-basal corneal nerve segmentation with IVCM. The results highlight the potential of the system in assisting clinical practice for corneal nerves segmentation and evaluation. Translational Relevance: The deep learning model for IVCM images may enable rapid segmentation and evaluation of the corneal nerve and may provide the basis for the diagnosis and treatment of ocular surface diseases associated with corneal nerves.

Effects of Oral Vitamin B1 and Mecobalamin on Dry Eye Disease.

PURPOSE: To assess the effects of oral vitamin B1 and mecobalamin on dry eye disease (DED) and patient satisfaction with treatment. METHODS: In this randomized controlled study, DED patients were divided into 4 groups based on treatment: group 1, only artificial tears; group 2, corticosteroid eye drops and artificial tears; group 3, oral vitamin B1, mecobalamin, and artificial tears; and group 4, oral vitamin B1, mecobalamin, corticosteroid eye drops, and artificial tears. DED symptoms, signs, and patient satisfaction with treatment were assessed at baseline and at 1 and 2 months after treatment. RESULTS: In total, 152 eyes from 76 patients (age, 55.25 ± 18.16 years) were included. In group 3, there were significant differences in dryness, foreign body sensation, burning, and tear film breakup time first (TBUTF) between 1 and 2 months after treatment and in satisfaction scores before and after treatment (P < 0.05). In group 3, there were also significant differences in dryness, foreign body sensation, photophobia, and TBUTA and between baseline and 2 months after treatment (P < 0.05). There was a significant difference in foreign body sensation between 1 and 2 months after treatment in groups 3 and 4 (P < 0.05). Furthermore, we also find obvious improvement in corneal nerve fiber density (CNFD) between baseline and 1 and 2 months after treatment in groups 3 and 4 (P < 0.05). CONCLUSIONS: Oral vitamin B1 and mecobalamin can relieve some dry eye symptoms such as dryness, pain, and photophobia and improve DED signs and patient satisfaction. Thus, vitamin B1 and mecobalamin are potential treatment options for patients with DED.

Corneal Subbasal Nerve Analysis Using In Vivo Confocal Microscopy in Patients With Dry Eye: Analysis and Clinical Correlations.

PURPOSE: This study aimed to observe corneal subbasal nerves and Langerhans cells (LCs) using in vivo confocal microscopy (IVCM) in patients with dry eye, a tool for the evaluation of disease stage and severity and for treatment monitoring at the microstructural level. METHODS: A total of 107 eyes from 62 patients were included. The Ocular Surface Disease Index (OSDI) questionnaire and other examinations were used to assess dry eye symptoms and signs. IVCM was performed to observe subbasal corneal nerves and LCs. Corneal nerves were graded using both objective and subjective methods. The correlations between dry eye symptoms and corneal nerve parameters, corneal nerve grading, and LC number were analyzed. RESULTS: Corneal nerve length was negatively correlated with sensitivity to light [correlation coefficient (CC)= -0.24, P < 0.05]; nerve width was positively correlated with the OSDI score, painful eyes, and blurred vision (CC = 0.41, 0.23, and 0.46, respectively, all P < 0.05); and nerve tortuosity was positively correlated with sensitivity to light (CC = 0.23, P < 0.05). Moreover, both total objective and subjective grading scores were positively correlated with OSDI scores (CC = 0.48 and 0.27, respectively, both P < 0.05). LC number was found not to be significantly correlated with dry eye symptoms (P > 0.05). CONCLUSIONS: IVCM is a useful tool to evaluate corneal subbasal nerve changes in patients with dry eye. Detailed nerve grading could help to understand and evaluate the pathophysiologic conditions of the disease and could be used for further treatment follow-up in the future.

Evaluation of ocular surface impairment in meibomian gland dysfunction of varying severity using a comprehensive grading scale.

This study aimed to propose a comprehensive grading scale to evaluate different clinical manifestations in patients with varying severity of meibomian gland dysfunction (MGD) and analyze the correlations between the parameters of ocular surface impairment in MGD.A total of 63 patients with MGD were enrolled. Ten specific symptoms were evaluated each with a subjective score and total score was applied to grade the severity of MGD. Thirty-seven patients were diagnosed with mild, 19 with moderate, and 7 with severe MGD. Slit-lamp and keratography were used to assess the signs of ocular surface and meibomian gland (MG). In vivo confocal microscopy (IVCM) was performed to evaluate the corneal nerves and dendritic cells. The differences and correlations between symptoms, signs, and IVCM parameters were analyzed.Dryness, foreign body sensation, asthenopia, and photophobia were the most common and severe symptoms in our patients. The severe MGD group showed worse MG expressibility, Meibum score, Meiboscore, MG score, and higher nerve reflectivity (P < .05). The mild MGD group showed higher nerve density (P < .05). Total symptom score was negatively correlated with nerve density (r = -0.374, P < .05), while positively correlated with nerve reflectivity and dendritic cell density (r = 0.332 and 0.288, respectively, P < .05). MG score was correlated with nerve reflectivity (r = 0.265, P < .05).The comprehensive grading scale was suitable for evaluating clinical manifestations in MGD of varying severity. The relationship between the specific symptoms, signs, and IVCM results concerning whole ocular surface impairment could help elucidate MGD pathophysiology and benefit evaluation or treatment in the future.