Semi-MsST-GAN: A Semi-Supervised Segmentation Method for Corneal Ulcer Segmentation in Slit-Lamp Images

Corneal ulcer is a common leading cause of corneal blindness. It is difficult to accurately segment corneal ulcers due to the following problems: large differences in the pathological shapes between point-flaky and flaky corneal ulcers, blurred boundary, noise interference, and the lack of sufficient slit-lamp images with ground truth. To address these problems, in this paper, we proposed a novel semi-supervised multi-scale self-transformer generative adversarial network (Semi-MsST-GAN) that can leverage unlabeled images to improve the performance of corneal ulcer segmentation in fluorescein staining of slit-lamp images. Firstly, to improve the performance of segmenting the corneal ulcer regions with complex pathological features, we proposed a novel multi-scale self-transformer network (MsSTNet) as the MsST-GAN generator, which can guide the model to aggregate the low-level weak semantic features with the high-level strong semantic information and adaptively learn the spatial correlation in feature maps. Then, to further improve the segmentation performance by leveraging unlabeled data, the semi-supervised approach based on the proposed MsST-GAN was explored to solve the problem of the lack of slit-lamp images with corresponding ground truth. The proposed Semi-MsST-GAN was comprehensively evaluated on the public SUSTech-SYSU dataset, which contains 354 labeled and 358 unlabeled fluorescein staining slit-lamp images. The results showed that, compared with other state-of-the-art methods, our proposed method achieves better performance with comparable efficiency.

Analysis of the first tear film break-up point in Sjögren’s syndrome and non-Sjögren’s syndrome dry eye patients

Background Tear film instability plays an important role in the course of Sjögren’s Syndrome dry eye (SSDE) even though it is generally classified as aqueous-deficient dry eye. The measurement of the first tear film break-up point (FTBUP) helps to evaluate the most unstable position of the tear film on ocular surface. We aim to investigate FTBUP in Sjögren’s Syndrome dry eye (SSDE) and non-Sjögren’s Syndrome dry eye (NSSDE) patients, and explore its correlation with dry eye indices. Methods Twenty-two SSDE patients (44 eyes) and 22 NSSDE patients (44 eyes) were enrolled in the study. Oculus Keratograph K5M was used to measure FTBUP, the first and average non-invasive keratographic breakup time (f-NIKBUT and av-NIKBUT), the tear meniscus height, and meibomian gland dropout. Other tests of tear film were also performed including Ocular Surface Dryness Index (OSDI), Schirmer I test, fluorescein break-up time and corneal fluorescein staining. Dry eye indices and the locations of the FTBUP were compared between SSDE and NSSDE patients. Generalized estimating equation (GEE) was used to ajusted the correlations between right and left eyes. The correlations between the FTBUP and ocular symptoms and signs were investigated using Pearson’s correlation coefficient test. Results The FTBUP occurred at the supranasal quadrant in 12/88 eyes, supratemporal quadrant in 8/88 eyes, inferonasal quadrant in 34/88 eyes, and inferotemporal quadrant in 34/88 eyes. The percentage eyes with inferior FTBUP was significantly higher in the SSDE than in the NSSDE subjects (86.3% vs 68.1%, P = .049). Moreover, in SSDE subjects, temporal breakup point was seen more often in those who presented corneal fluorescein staining in any location, while nasal breakup point was more frequent in those who did not present any corneal fluorescein staining (P = .045). Conclusion The location of the FTBUP in SSDE patients had specific characteristics. However, the diagnostic potential of FTBUP in early recognition of SSDE needs further validation.

Ocular surface conditions in Asian glaucoma patients with existing corneal disorders switching from preserved prostaglandin analogue monotherapy to preservative-free tafluprost

Introduction: Glaucoma medications are often preserved with agents such as benzalkonium chloride, which commonly lead to ocular surface diseases.Purpose: To investigate the effect of switching to a preservative-free prostaglandin analogue, tafluprost 0.0015% on treatment tolerability and ocular surface diseases.Study design: This was a prospective, open-label, non-randomised, observational study performed in a single hospital.Materials and methods: This study involved patients of Asian descent diagnosed with primary open-angle glaucoma and ocular hypertension (n = 28), who received preserved prostaglandin monotherapy for longer than 3 months and had a National Eye Institute ocular surface staining scale score higher than 1. Patients were switched from preserved prostaglandin monotherapy to preservative-free tafluprost 0.0015%. Patients were analysed at baseline (Visit 0), 1 month (Visit 1), and 3 months (Visit 2). The main parameter measured is the change in the fluorescein staining score at Visit 2.Results: There was a significant improvement in the fluorescein staining score, with a mean reduction score of 1.96 (standard deviation, SD = 1.53; p < 0.0001), and significant reductions in conjunctival hyperaemia (bulbar, p < 0.0001; palpebral, p < 0.05) from baseline to Visit 2. The Ocular Surface Disease Index questionnaire also showed a mean reduction of 4.14 from baseline to visit 2 (SD = 8.20; p < 0.05). The intraocular pressure and tear breakup time were maintained from baseline to Visit 2.Conclusion: Switching patients to preservative-free tafluprost 0.0015% showed significant improvements in ocular surface disease with minimal side effects and similar intraocular pressure reduction rates.

Alternation of Lipidomic in the Meibomian Gland After Exposure to Intense Pulsed Light in Patients With Meibomian Gland Dysfunction and Suggestions for Applications of 3PM Medicine

Importance: Aside from the clinical index, there is no established criterion for assessing the effectiveness of intense pulsed light (IPL) in treating meibomian gland disease.Objective：To determine if there is an association between changes in the meibum lipidomic profiles and alleviation of clinical signs in patients with meibomian gland dysfunction (MGD) who are treated with IPL. To provide predictive, preventive and and personalized medical programs for MGD patients. Design: This is an observational Study. Patients were followed for up for 6 months from January 1, 2019.Setting: This is a single center, human-oriented clinical and basic research study.Participants: Adult patients, who were diagnosed with MGD and had not received any alternative treatments for at least 3 months, were enrolled in the study. Exposures: Each patient received a series of three treatments at 3-week intervals. The meibum was collected before the first treatment (T0) and the third treatment (T2). All enrolled patients completed the whole examination and treatment. The meibum of randomly assigned 26 patients and 10 healthy volunteers was chosen for performing the lipid analysis using LC-MS/MS. Main Measures: The following information from each patient was recorded: tear break-up time (BUT), average tear BUT, tear meniscus height, assessment of the lid margin, bulbar redness, meibomian gland opening position, corneal fluorescein staining, meibomian gland drop, meibomian gland expressibility, and meibum quality.Results: A total of 191 patients’ right eyes were enrolled in the study, including 95 females (49.7%) and 96 males (50.3%), with a median age of 53 years (range: 28–85 years). IPL increased the BUT (P<0.0001, t=7.9, df=380), average tear BUT (P<0.01, t=2.774, df=374.5), and tear meniscus height (P<0.01, t=2.642, df=367.1). At the same time, IPL improved bulbar redness (P<0.0001, t=12.95, df=380) and corneal fluorescein staining (P<0.0001, t=4.147, df=380). Furthermore, following IPL treatment, the meibomian gland expressibility (MGE) and meibum quality were significantly improved (from 1.342±0.05815 to 0.9354±0.03922, P<0.0001, t=5.798, df=380 and from 1.266±0.04969 to 0.8639±0.03318, P<0.0001, t=6.733, df=380, respectively). Lipidomic analysis of the meibum characterized the changes in lipid profiles induced by IPL. Conclusion: IPL treatment offers a novel approach to markedly improve the treatment of patients with MGD due to correction of altered lipid profiles. The changes in lipid expression profiles are potential indexes to evaluate the therapeutic effectiveness of IPL treatment or other treatments on MGD. The lipid changes that are pertinent include: LPC(18:2)+HCOO, OAHFA(18:1/34:1)-H, TG(16:0/18:2/20:5)+H, and etc.. Therefore, accurate evaluation of the changes of lipid expression profile in patients with MGD can be used as a predictive, preventive, and personalized medical method.

Comparative Evaluation of Tear Film Parameters Following Cataract Surgery in Diabetic Patients.

Purpose: To compare the propensity of manual small incision and phacoemulsification cataract surgery in causing tear film dysfunction and dry eye syndrome in diabetic patients. Methods: Diabetic patients in group A underwent manual small Incision Cataract surgery whereas in group B underwent phacoemulsification with similar post-operative regimes. The primary outcome measures were the Ocular Surface Disease Index (OSDI), a Subjective questionnaire. The secondary outcome measures were the Subjective Dry Eye (DE) questionnaire, Corneal Fluorescein staining, Tear meniscus height, Schirmer’s II test, and Tear film break-up time. All parameters were measured pre and then postoperatively. Result: 126 patients were divided into group A (undergoing small incision cataract surgery) and group B (undergoing phacoemulsification). The OSDI and subjective DE scores continued to be worse for Group A until the first month after which they became similar to group B with no statistically significant difference (p-value of 0.726 and 0.347 respectively). The OSDI and subjective DES at 3 months were better in both groups as compared to baseline (p <0.0001). The objective tear film parameters (Schirmer’s, TBUT, TMH, and fluorescein staining scores) showed statistically significant changes from the baseline in both groups but the scores remained in the normal range clinically. Schirmer’s test scores were different between the two groups at three months (p=0.007) in SICS group being higher. Conclusion: Manual Small Incision Cataract Surgery (SICS) causes subjective dry eye symptoms more than phacoemulsification until 1 month of surgery in diabetic patients after which the subjective symptoms become similar to phacoemulsification at 3 months.

CLINICAL AND HISTOPATHOLOGICAL FEATURES OF SCOPOLAMINE HYDROBROMIDE INDUCED DRY EYE SYNDROME IN SPRAGUE-DAWLEY RATS

Dry eye syndrome (DES), is one of the most common and irritating ocular diseases in humans and animals due to deficits in quantities or/and quality of tear film. In this study, a rat model of experimental DES has been developed using the cholinergic inhibitor, scopolamine hydrobromide (SCOP), at the dose of 25[Formula: see text]mg/rat/day via subcutaneous injection, for a consecutive 21 days without low humidity environment. Clinical ophthalmic evaluations were performed by tear volume assessment using endodontic paper point, slit-lamp biomicroscope, and fluorescein staining at day 0, 7, 14, and 21 post-inductions. The results of ophthalmic examination showed that rats with SCOP treatment reduced about 40% of tear secretion. Half of the SCOP-treated rats exhibited diffuse corneal fluorescein staining involving 80% of the corneal surface, minimal keratoconjunctivitis, roughened corneal surface and thin corneal epithelium under histopathological examination. About 30% of the rats showed variable infiltration of lymphocytes in between the tubular acinar glands. This animal model with significant reduction of tear production and diffuse corneal fluorescein staining in rats could be used for the preclinical assessment of therapeutic interventions.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM: To compare the short-term impacts of femtosecond lenticule extraction (FLEx) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) on ocular surface measures and tear inflammatory mediators. METHODS: This prospective comparative nonrandomized clinical study comprised 75 eyes (75 patients). Totally 20 male and 15 female patients (age 21.62±3.25y) with 35 eyes underwent FLEx, and 26 male and 14 female patients (age 20.18±3.59y) with 40 eyes underwent FS-LASIK. Central corneal sensitivity, noninvasive tear breakup time, corneal fluorescein staining, Schirmer I test, tear meniscus height, and ocular surface disease index were evaluated in all patients. Tear concentrations of nerve growth factor (NGF), interleukin-1α (IL-1α), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and matrix metalloproteinase-9 (MMP-9) were assessed by multiplex antibody microarray. All measurements were performed preoperatively, and 1d, 1wk, and 1mo postoperatively. RESULTS: Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1wk after the procedure (P<0.01). NGF was significantly higher 1d and 1wk after surgery in the FS-LASIK group than in the FLEx group (P<0.01). By contrast, compared to those in the FLEx group, higher postoperative values and slower recovery of tear TGF-β1, IL-1α, and TNF-α concentrations were observed in the FS-LASIK group (P<0.01). Tear concentrations of NGF, TGF-β1, TNF-α, and IL-1α were correlated with ocular surface changes after FLEx or FS-LASIK surgery. CONCLUSION: There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK. NGF, TGF-β1, TNF-α, and IL-1α may contribute to the process of ocular surface recovery.

Sodium Fluorescein for Spinal Intradural Tumors

Technological innovations in spinal intradural tumor surgery simplify treatment. Surgical treatment of cranial benign and malignant pathologies under microscope with sodium (Na)-fluorescein guidance has often been reported, but few studies have focused on spinal intradural tumors. We aimed to investigate the usefulness of Na-fluorescein under yellow filter in intradural spinal tumor surgery by retrospectively reviewing cases involving intramedullary and extramedullary tumors operated under the guidance of Na-fluorescein. Forty-nine adult patients with a diagnosis of spinal intradural tumor operated under a yellow filter (560 nm) microscope using Na-fluorescein dye were included in the study. Demographic data, such as age and sex, neurological status, extent of tumor resection, histopathological diagnosis, Na-fluorescein staining pattern, and its usefulness during surgery were noted and statistically analyzed. Of all recruited patients, 26 women (53.1%) and 23 men (46.9%), were included for analysis. The age range of the patients was 18–64 years, with a mean age of 41.6 ± 13.9. An intradural intramedullary mass was found in 30.6% (n = 15) of the patients, and an intradural extramedullary mass in 69.4% (n: 34). While Na-fluorescein staining was homogeneous in all intradural extramedullary tumors, 73.3% (n: 11) of intradural intramedullary tumors were homogeneous, and 13.3% (n: 2) moderately heterogeneous. In the whole study group, the Na-fluorescein staining pattern was helpful in surgical resection in 47 cases (95.9%). While 34/34 (100%) found it helpful for extramedullary tumors, 13/15 (86.7%) did in intramedullary tumors, and for 2/15 (13.3%) it was not. In conclusion, Na-fluorescein helps in distinguishing tumor from healthy tissue in intradural extramedullary and intramedullary tumor surgery under a yellow filter microscope in most cases, thus providing convenient assistance to surgeons.

Large diameter scleral lens benefits for Asians with intractable ocular surface diseases: a prospective, single-arm clinical trial

To report the efficacy and safety of large diameter scleral lenses and determine their suitability in Asian subjects with intractable ocular surface diseases. This prospective study enrolled intractable ocular surface diseases subjects with uncorrected visual acuity > counting finger but ≥ 0.3 logMAR and best-corrected visual acuity (BCVA) ≥ 0.3 logMAR, to fit large diameter scleral lenses for 12 weeks. 21 eyes (13 subjects) consisting ten eyes (47.6%) with persistent epithelial defects, 6 (28.6%) with graft-versus-host disease, 4 (19.0%) with Stevens–Johnson syndrome and one (4.8%) with severe dry eye were ultimately enrolled. Primary outcome measures were the visual acuity, corneal and conjunctival fluorescein staining, Ocular Surface Disease Index (OSDI), and National Eye Institute 25-Item Visual Function Questionnaire (NEI-VFQ-25). At week 12 with large diameter scleral lenses, BCVA improved from 0.77 logMAR to 0.27 logMAR (P < 0.001). High-grade corneal and conjunctival fluorescein staining proportion decreased from 61.90 to 14.29% and 52.38 to 9.52%, respectively (P = 0.0036 and 0.0063, respectively). OSDI and NEI-VFQ-25 improved from 67.89 to 34.69 and 51.40 to 64.48, respectively (P < 0.001). No adverse effects were observed. In Asians with intractable ocular surface diseases, large diameter scleral lens improves visual acuity and alleviates signs and symptoms of ocular surface diseases without any significant complications.Trial registration Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No. HI12C0015 (A120018)). Clinical Trials.gov, NCT04535388. Registered 18 August 2020—Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT04535388.