Monitoring the transition from corneal ulceration to healed scar using a Scheimpflug tomography-based densitometry.

PURPOSE: To compare corneal haze between active ulcer and healed scarring using a Scheimpflug densitometry. MATERIALS AND METHODS: A prospective longitudinal study enrolled 30 patients (30 eyes) with ulcerative keratitis (UK). Each subject's corneal optical density (COD) was measured with a Scheimpflug corneal densitometry, Pentacam® AXL (Oculus GmbH, Wetzlar, Germany), at the active ulcerative and complete scarring stage. The COD data were analyzed through distinct methods (inbuilt, sorted annular partitions, and ulcer-matching densitometric maps). We compared different CODs to select the better index for clinically monitoring the transition from corneal ulceration to healed scar. RESULTS: The CODs of the periphery (P = 0.0024) and outside of the active ulcer (P = 0.0002) significantly decreased after scarring. Partitioning the cornea into different depths and annular zones, the anterior layer, center layer, and the 2-6 mm annular zone had a more remarkable COD decrease after scar formation. The 3rd-sorted COD in the anterior layer revealed the highest area under the receiver-operating characteristic curves (0.709), in which 90% of subjects had COD reduction during the ulcer-to-scar transition. CONCLUSIONS: Aside from subjective judgment based on clinical signs, the Scheimpflug tomography-based densitometry could provide objective and efficient monitoring of the corneal opacity evolution in UK patients. Because the 3rd-sorted annular COD is a better index than the inbuilt or mapping CODs in differentiating active ulcers from healed scars, this COD could be a clinically promising parameter to monitor the progression of UK patients.

Monitoring the Progression of Clinically Suspected Microbial Keratitis Using Convolutional Neural Networks.

Purpose: For this study, we aimed to determine whether a convolutional neural network (CNN)-based method (based on a feature extractor and an identifier) can be applied to monitor the progression of keratitis while managing suspected microbial keratitis (MK). Methods: This multicenter longitudinal cohort study included patients with suspected MK undergoing serial external eye photography at the 5 branches of Chang Gung Memorial Hospital from August 20, 2000, to August 19, 2020. Data were primarily analyzed from January 1 to March 25, 2022. The CNN-based model was evaluated via F1 score and accuracy. The area under the receiver operating characteristic curve (AUROC) was used to measure the precision-recall trade-off. Results: The model was trained using 1456 image pairs from 468 patients. In comparing models via only training the identifier, statistically significant higher accuracy (P < 0.05) in models via training both the identifier and feature extractor (full training) was verified, with 408 image pairs from 117 patients. The full training EfficientNet b3-based model showed 90.2% (getting better) and 82.1% (becoming worse) F1 scores, 87.3% accuracy, and 94.2% AUROC for 505 getting better and 272 becoming worse test image pairs from 452 patients. Conclusions: A CNN-based approach via deep learning applied in suspected MK can monitor the progress/regress during treatment by comparing external eye image pairs. Translational Relevance: The study bridges the gap between the investigation of the state-of-the-art CNN-based deep learning algorithm applied in ocular image analysis and the clinical care of suspected patients with MK.

Comparing Tear Film Viscosity between Sjögren and Non-Sjögren Dry Eye Disease.

This study aimed to compare tear film viscosity (TFV) in Sjögren and non-Sjögren dry eye diseases (DEDs). This was a cross-sectional observational study. A total of 68 DED patients were enrolled, including 32 patients with Sjögren syndrome (SS) and 36 without SS. TFV was assessed by a tear film analyzer and determined by the momentary moving speed (MMS; MMS (t) = α × t-ß, t = time (s)) with its power-law fitting-derived parameters (α and ß). Among the four indices of TFV (MMS (0.1 s), MMS (2.0 s), α, and ß), the SS-DED patients had significantly lower MMS (0.1 s) (p = 2.01 × 10-5), α (p = 0.0375), and ß (p = 0.0076). The SS-DED group also had significantly higher OSDI, lower central and nasal tear meniscus height (TMH), and higher OSS. MMS (0.1 s) was significantly correlated with nasal TMH and OSS (ρ = 0.2520, p = 0.0381 in nasal TMH; ρ = -0.3487, p = 0.0036 in OSS). Index ß was not correlated with any non-TFV tests. In conclusion, MMS (0.1 s), α, and ß are promising TFV indices in distinguishing SS-DED from non-SS-DED patients early. Among these TFV indices, lower MMS is the best alternative clue for detecting SS-DED.

Deep Learning Approach in Image Diagnosis of Pseudomonas Keratitis.

This investigation aimed to explore deep learning (DL) models' potential for diagnosing Pseudomonas keratitis using external eye images. In the retrospective research, the images of bacterial keratitis (BK, n = 929), classified as Pseudomonas (n = 618) and non-Pseudomonas (n = 311) keratitis, were collected. Eight DL algorithms, including ResNet50, DenseNet121, ResNeXt50, SE-ResNet50, and EfficientNets B0 to B3, were adopted as backbone models to train and obtain the best ensemble 2-, 3-, 4-, and 5-DL models. Five-fold cross-validation was used to determine the ability of single and ensemble models to diagnose Pseudomonas keratitis. The EfficientNet B2 model had the highest accuracy (71.2%) of the eight single-DL models, while the best ensemble 4-DL model showed the highest accuracy (72.1%) among the ensemble models. However, no statistical difference was shown in the area under the receiver operating characteristic curve and diagnostic accuracy among these single-DL models and among the four best ensemble models. As a proof of concept, the DL approach, via external eye photos, could assist in identifying Pseudomonas keratitis from BK patients. All the best ensemble models can enhance the performance of constituent DL models in diagnosing Pseudomonas keratitis, but the enhancement effect appears to be limited.

Tear Proteomics Approach to Distinguishing Primary from Secondary Sjögren's Syndrome for Dry Eye Patients with Long-Term Instillation of Eyedrops.

The diagnosis and monitoring of Sjögren syndrome (SS) is often difficult, requiring a multidisciplinary approach with invasive procedures. Our aim is to elucidate the tear protein alterations of dry eye disease (DED) with primary SS (pSS) and secondary SS (sSS) with the long-term instillation of eyedrops. We collected clinical demographics and tear fluid (TF) samples from DED patients with no autoimmune diseases (non-SS-DED), pSS-DED, and sSS-DED patients, followed by TF screening with tandem mass tagging-labeling gel-free proteomics assay. Bioinformatic analysis via Ingenuity Pathway Analysis was used to identify functional pathways and interacting networks. Validation of candidate proteins with enzyme-linked immunosorbent assay on the tear samples was done. The top functional pathways of the two comparisons (sSS-DED vs. pSS-DED and sSS-DED vs. non-SS-DED) were both associated with inflammation and stress-related signaling. After constructing an interaction network model with the selected candidate proteins, five proteins were identified. A Disintegrin and Metalloproteinase domain-containing protein 10 (ADAM10) was found to be an important candidate biomarker in all groups, followed by epidermal growth factor (EGF) in TF. This study revealed novel DED markers, ADAM10 and EGF, in differentiating between primary and secondary SS patients from tears by in-depth proteomic analysis.

Steroid-Induced Ocular Hypertension in a Pediatric Patient with Acute Lymphoblastic Leukemia: A Case Report.

Glucocorticoids play a pivotal role in therapeutic protocols in acute lymphoblastic leukemia (ALL) treatment. Systemic steroids are known to be less likely to elevate the intraocular pressure when compared to topical administration, and reports addressing hypertensive ocular response in the Asian pediatric ALL population are currently limited. We report a case of a nine-year-old girl with acute lymphoblastic leukemia (ALL) who was found to have highly elevated intraocular pressure (IOP) during maintenance treatment when taking oral dexamethasone (6 mg/m2/day). Her IOP increased on day 5 after taking dexamethasone, reached a peak on day 7 or 8, and returned back to baseline on day 13 before anti-glaucoma medications were used. Thus, we prescribed IOP-lowering agents for 10 consecutive days starting on the day oral dexamethasone was administered, and observed that not only did the peak levels lower remarkably, but the IOP levels returned to baseline more rapidly as well.

Diagnosing Fungal Keratitis and Simultaneously Identifying Fusarium and Aspergillus Keratitis with a Dot Hybridization Array.

Fungal keratitis (FK) is one of the most common microbial keratitis, which often leads to poor prognosis as a result of delayed diagnosis. Several studies implied that early differentiation of the two major FK, Fusarium and Aspergillus keratitis, could be helpful in selecting effective anti-fungal regimens. Therefore, a novel dot hybridization array (DHA) was developed to diagnose FK and differentiate Fusarium and Aspergillus keratitis in this study. One hundred forty-six corneal scrapes obtained from one hundred forty-six subjects impressed with clinically suspected FK were used to evaluate the performance of the DHA. Among these patients, 107 (73.3%) patients had actual FK confirmed by culture and DNA sequencing. We found that the DHA had 93.5% sensitivity and 97.4% specificity in diagnosing FK. In addition, this array had 93.2% sensitivity and 93.8% specificity in diagnosing Fusarium keratitis, as well as 83.3% sensitivity and 100% specificity in diagnosing Aspergillus keratitis. Furthermore, it had 83.9% sensitivity and 100% specificity in identifying Fusarium solani keratitis. Thus, this newly developed DHA will be beneficial to earlier diagnosis, more precise treatment, and improve prognosis of FK, by minimizing medical refractory events and surgical needs.

Comparisons of deep learning algorithms for diagnosing bacterial keratitis via external eye photographs.

Bacterial keratitis (BK), a painful and fulminant bacterial infection of the cornea, is the most common type of vision-threatening infectious keratitis (IK). A rapid clinical diagnosis by an ophthalmologist may often help prevent BK patients from progression to corneal melting or even perforation, but many rural areas cannot afford an ophthalmologist. Thanks to the rapid development of deep learning (DL) algorithms, artificial intelligence via image could provide an immediate screening and recommendation for patients with red and painful eyes. Therefore, this study aims to elucidate the potentials of different DL algorithms for diagnosing BK via external eye photos. External eye photos of clinically suspected IK were consecutively collected from five referral centers. The candidate DL frameworks, including ResNet50, ResNeXt50, DenseNet121, SE-ResNet50, EfficientNets B0, B1, B2, and B3, were trained to recognize BK from the photo toward the target with the greatest area under the receiver operating characteristic curve (AUROC). Via five-cross validation, EfficientNet B3 showed the most excellent average AUROC, in which the average percentage of sensitivity, specificity, positive predictive value, and negative predictive value was 74, 64, 77, and 61. There was no statistical difference in diagnostic accuracy and AUROC between any two of these DL frameworks. The diagnostic accuracy of these models (ranged from 69 to 72%) is comparable to that of the ophthalmologist (66% to 74%). Therefore, all these models are promising tools for diagnosing BK in first-line medical care units without ophthalmologists.

Simultaneously Monitoring Whole Corneal Injury with Corneal Optical Density and Thickness in Patients Undergoing Cataract Surgery.

To pursue the least corneal implication during cataract surgery, this study aimed to monitor corneal wound injury after cataract surgery with a novel method. The prospective cohort study involved thirty-two patients, who were assessed by a Scheimpflug tomography AxL® (Oculus GmbH, Wetzlar, Germany) via the following two kinds of indices: whole corneal optical density (COD) and corneal thickness (CT), two weeks before and one month after cataract surgery. The results of the COD revealed that corneal annuli 0.0-2.0 mm and 2.0-6.0 mm, and the average and maximal values at the incisional site significantly increased postoperatively. Also, the anterior and central stroma of 0.0-2.0 mm, and all three depths of 2.0-6.0 mm, increased remarkably after the operation. For the CT, all ranges of diameters plus incisional sites showed significant increases postoperatively. Furthermore, we analyzed the differences (delta) of COD and CT between pre- and post-operation, and found significant correlations between the delta of COD and the delta of CT, regarding annuli 0.0-2.0 mm, 2.0-6.0 mm, and 6.0-10.0 mm, but no correlation at the incisional site, with either average density or maximal density, was detected. We concluded that whole COD and CT, especially at the central zones of the cornea (annulus < 6 mm), are both valuable parameters in the assessment of corneal damage post-cataract surgery, and are independent indices at the incisional site.

Stepwise low concentration atropine for myopic control: a 10-year cohort study.

The aim of this study was to analyze changes in refraction and evaluate the variables in school children who received atropine as myopic control for 10 years. Low-concentration atropine (0.05%) was prescribed initially, and the dose was increased in a stepwise manner if rapid myopic progression (≥ 0.5D per half year) was noted during the regular follow-up visit. 23 children with a mean age of 6.96 ± 1.07 years were included. The initial spherical equivalent was - 1.25 ± 0.84 D. The overall mean myopic progression was - 0.30 ± 0.27 D/year. Younger initial age, female, higher initial spherical equivalent and the need of higher concentration of atropine were found to be risk factors for myopic progression in multivariate mixed-effect analysis (p = 0.013, 0.017, 0.024 and 0.014). Children who kept using a lower concentration of atropine (≤ 0.1%) tended to have slower myopic progression throughout the 10-year course than those who shifted to higher concentrations (> 0.1%) (p ≤ 0.001). Stepwise low concentration of atropine might be effective for long-term myopic control in school students. Those who had poor response to lower concentration of atropine may have the risk of faster progression, even with high concentration of atropine. Additional or alternative treatment might be considered.

Grading reliability of the tear film viscosity examination.

PURPOSE: To assess the reliability of a tear film (TF) viscosity video grading system. METHODS: Thirty-four dynamic TF viscosity videos were obtained by a clinically available TF analyzer and objectively sorted according to the movement speed of three arbitrary reflective light particles. A 4-grade system was constructed on a specially designed window for simultaneous comparison with the three standard videos. Two masked graders were invited to grade these videos under a randomized procedure. Observer reliabilities were determined by Spearman's correlation analysis and Bland-Altman agreement analysis. RESULTS: For this four-grade system, the intra-observer correlation was very strong in the two graders (ρ = 0.96 and 0.82; both P < 0.0001). However, the inter-observer correlation showed moderate strength in normal playback speed (ρ = 0.53, P = 0.002 and ρ = 0.52, P = 0.003 for 1st and 2nd gradings, respectively). In slower playback videos, the inter-observer correlation of the two graders was higher (ρ = 0.70 and P < 0.0001) when reduced to 0.8-times playback speed. Moreover, the 0.8-times mode was also significantly better than normal playback mode (P = 0.0204) in terms of inter-observer agreement. CONCLUSIONS: The dynamic 4-grade system has an excellent intra-observer reliability and a good inter-observer reliability under 0.8-times playback speed. The grading system established in this study provides a promising solution for rapidly determining the level of TF viscosity.

Axial length of cataract eyes: a comparison of two cohorts over a span of 10 years apart.

BACKGROUND: To assess the associations of axial length with age-related cataract within a span of 10 years in an Asian population in southern Taiwan. METHODS: A retrospective cohort study examined 960 adults who underwent cataract surgery at the Kaohsiung Chang Gung Memorial Hospital in year 2008 and year 2018. Axial length was assessed with the ultrasound biometry and/or the Zeiss IOLMaster. Eyes with prior blunt eye trauma or had underwent vitrectomy operations were excluded. The significance of the changes in axial length between the two cohorts was determined after performing age-matched analyses. Due to utilization of ultrasound biometry and/or Zeiss IOLMaster, axial length corrections with our mean difference in measurement results, which were similar to previous studies on comparison between the two measurement tools, were carried out. RESULTS: Axial length showed an age-related elongation in 10-year cross-sectional data, from a mean of 23.65 ± 1.80 mm in year 2008 to a mean of 24.30 ± 1.90 in year 2018 (p = 0.003). Patients with high myopia (axial length > 26 mm) increased significantly over the 10-year period from 8.1 to 16 % (p < 0.001). A birth cohort effect on axial length was evident as the axial lengths of year 2008 cohort were shorter than the 2018 cohort when they were in the same operation age group. In particular, persons born after the 1960s demonstrated a predominant increase in axial length in both cohorts. CONCLUSIONS: Our study confirms a trend in increase of axial myopia, especially high myopias, over the 10-year period. A novel finding of this study was discovering a birth cohort effect on axial length, especially in persons born after the 1960s in southern Taiwan.

Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt as the Representative Eye for the Study?

Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye's performance cannot represent that of the other eye or both eyes. Therefore, in studies for elucidating tear film homeostasis of DED, we may lose some important messages hidden in the fellow eye if we collected clinical and proteomic data only from a unilateral eye. For mechanistic studies, it is recommended that researchers collect tear samples from the eye with more severe DED under sensitive criteria for identifying the more severe eye and evaluating the tear biochemical and proteomic markers with binocular concordance drawn in prior binocular studies.

Analysis of tear film spatial instability for pediatric myopia under treatment.

In Taiwan, the prevalence of myopia in children between 6 and 18 years old is over 80%, and high myopia accounts for over 20%, which turned out to be in the leading place worldwide. Orthokeratology and low-dose atropine are proven treatments to reduce myopia progression, though the potential corneal disturbances remain an issue in young populations. The alteration of the tear film is widely discussed but there is no consensus to date, so we aim to investigate the tear film spatial instability in children with myopia control using atropine or orthokeratology. Thirty-eight treatment-naïve participants and 126 myopic children under treatments were enrolled. The ocular surface homeostasis, spatial distribution of tear break-up, and high-order aberrations (HOAs) of the corneal surface were assessed. We found out that myopic children treated with either atropine or orthokeratology showed ocular surface homeostasis similar to that in treatment-naïve children. Nevertheless, children treated with orthokeratology presented higher HOAs (p < 0.00001) and a tendency of the first tear break-up zone at the inner half of the cornea (p = 0.04). This unique spatial instability of the tear film associated with myopia treatment might provide a more focused way of monitoring the pediatric tear film instability.

A deep learning approach in diagnosing fungal keratitis based on corneal photographs.

Fungal keratitis (FK) is the most devastating and vision-threatening microbial keratitis, but clinical diagnosis a great challenge. This study aimed to develop and verify a deep learning (DL)-based corneal photograph model for diagnosing FK. Corneal photos of laboratory-confirmed microbial keratitis were consecutively collected from a single referral center. A DL framework with DenseNet architecture was used to automatically recognize FK from the photo. The diagnoses of FK via corneal photograph for comparing DL-based models were made in the Expert and NCS-Oph group through a majority decision of three non-corneal specialty ophthalmologist and three corneal specialists, respectively. The average percentage of sensitivity, specificity, positive predictive value, and negative predictive value was approximately 71, 68, 60, and 78. The sensitivity was higher than that of the NCS-Oph (52%, P < .01), whereas the specificity was lower than that of the NCS-Oph (83%, P < .01). The average accuracy of around 70% was comparable with that of the NCS-Oph. Therefore, the sensitive DL-based diagnostic model is a promising tool for improving first-line medical care at rural area in early identification of FK.

Determination of Tear Lipid Film Thickness Based on a Reflected Placido Disk Tear Film Analyzer.

This study aims at determining the thickness of the tear lipid layer (LL) observed from a placido-disc-based tear film analyzer. We prospectively collected reflections of placido-disk LL images using a tear film analyzer (Keratograph® 5M, Oculus) from subjects with dry eye symptoms. The LL thickness (LLT) over the inferior half of the cornea was estimated with the use of interference color analysis and the preprocessing of images with and without ring segmentation were obtained and analyzed. Moreover, LLTs before and after 1 h of applying topical ointment (Duratears, Alcon) were compared to validate the estimation of LLT. Our results suggested that the tear LLT can be assessed using a placido-disk-based tear film analyzer and interference color analysis. We verified a high correlation between non-segmented and segmented LL images and estimated LLT increase after applying ointment. In addition, we concluded that LLT can be evaluated by direct interference analysis without segmentation preprocessing.

Comparison of fungal and bacterial keratitis between tropical and subtropical Taiwan: a prospective cohort study.

BACKGROUND: Fungal keratitis (FK) has been shown to be a climate-sensitive disease. The differentiation between FK from bacterial keratitis (BK) was difficult. The purpose of this study was to compare the bacteriology and mycology between tropical and subtropical Taiwan and to investigate the independent risk factors for identification of fungi from bacteria. METHODS: Two hundred ninety-seven patients with clinical suspected microbial keratitis were prospectively enrolled. A fungal to bacteria rate (FBR), the number of fungi divided by bacteria identified, was determined to estimate the prevalence of fungi and bacteria. Clinical presentation, profiles of microorganisms, and predisposing risk factors were determined. Univariate and multivariate logistic regression analysis were used to investigate the independent risk factors. RESULTS: A total of 82 fungi and 143 bacteria were laboratory confirmed. The identification rate of fungus was higher in tropical Taiwan (p = 0.010). Among the fungi and bacteria confirmed, the FBR was 0.29 (22.4% vs. 77.6%) in subtropical Taiwan, and 0.70 (41.3% vs. 58.7%) in tropical Taiwan. Samples obtained in tropical area (p = 0.019), ocular trauma (p = 0.019), and plant exposure (p = 0.003) were independent risk factors for identification of fungus from bacteria. The predominant fungus isolated from corneal scraping were Fusarium solani (25%) and Trichosporon faecale (25%) in subtropical Taiwan; in tropical Taiwan was Fusarium spp. (50%). CONCLUSIONS: The identification rate of fungus was higher in tropical Taiwan than subtropical Taiwan. Awareness of the local epidemiology is crucial for early diagnosis of fungal keratitis in tropical area.

Tracking the Reflective Light Particles Spreading on the Cornea: An Emerging Assessment for Tear Film Homeostasis.

PURPOSE: To implement an emerging noninvasive approach for assessing the dynamic tear film (TF) homeostasis. METHODS: The video records of dynamic TF from 12 healthy orthokeratology lens wearers were obtained by a clinically available TF analyzer and decomposed as image sequences. The trajectories of TF particles were analyzed by two tracking models, the full-span model (FSM) and the fixed-duration model (FDM). FSM tracked a particle for a complete opening blink cycle, while FDM tracked 1 second of the same cycle. A power-law fitting operation [Formula: see text] was used to extract homeostasis markers based on the tracking model for each subject. RESULTS: Comparing two tracking models (N = 6), only one subject had statistical difference in averaged momentary moving speed (MMS; P = 0.0488), while none had significant difference in averaged momentary moving direction (MMD). However, both models showed good correlations in average MMS (ρ = 0.94, P = 0.0048) and MMD (ρ = 1.00, P < 0.0001) and all extracted homeostasis markers [α, ß, MMS(0.1), and MMS(2.0)]. Assessing interblink reliability in these markers under FDM tracking (N = 12), only one subject in the MMS (0.1) and another subject in the MMS (2.0) were outside 95% limits of agreement, respectively. CONCLUSIONS: FDM is a good alternative to FSM and has tracking properties of higher efficiency and easier implementation. The homeostasis markers under FDM tracking showed a good interblink consistence; therefore this approach will be a promising method for analyzing dynamic TF homeostasis in future practice. TRANSLATIONAL RELEVANCE: FDM analytical architecture can practice the past experimental platform on a TF analyzer to obtain homeostasis markers of TF.

Tear Proteomics Approach to Monitoring Sjögren Syndrome or Dry Eye Disease.

Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis.

A Review of Periocular Botulinum Neurotoxin on the Tear Film Homeostasis and the Ocular Surface Change.

Clinical usage of botulinum neurotoxin (BoNT) in ophthalmology has dramatically increased since the 1980s and has become one of the most widely used agents for treating facial movement disorders, autonomic dysfunction and aesthetic wrinkles. Despite its high efficacy, there are some complications with periocular BoNT injections due to its chemodenervation effect. Among these, there is still controversy over the BoNT effect on tear film homeostasis and the ocular surface. A periocular BoNT injection could dry the eye by reducing tear production of the lacrimal gland and increase tear evaporation due to potential eyelid malposition and abnormal blinks. On the contrary, the injection of BoNT in the medial eyelids could treat dry eye disease by impairing lacrimal drainage. Regarding the ocular surface change, corneal astigmatism and high-order aberrations may decrease due to less eyelid tension. In conclusion, the entire awareness of the effect of BoNT and the patients' ocular condition is crucial for successful and safe results.