Reflex Tearing Research Articles

Weak association between total alpha‐synuclein reflex tear levels and non‐motor symptoms burden in Parkinson's disease

AbstractBackgroundAlpha‐synuclein (αSyn) is critical to the pathogenesis of Parkinson's disease (PD). Recognition of non‐motor symptoms as clinical manifestations of PD suggests aggregation of αSyn in extranigral areas.AimThis study aimed to evaluate the association between total αSyn levels in reflex tears with non‐motor symptoms.MethodsThis cross‐sectional study included 25 people living with PD (PwP) and 38 age‐matched healthy controls (HC). Total αSyn reflex tear levels were measured using an enzyme‐linked immunosorbent assay. PwP were evaluated using the Non‐Motor Symptoms Scale (NMSS), the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), Hoehn and Yahr Stage (HY), and Montreal Cognitive Assessment (MoCA).ResultsTotal αSyn reflex tear levels were significantly higher in PwP when compared with HC (1.77 pg/mL [IQR 1.75–1.79] vs. 1.73 pg/mL [IQR 1.70–1.75], p < 0.001). The urinary domain was negatively correlated with total αSyn levels in tears (r = −0.416, p = 0.048). No correlation was observed between total αSyn levels in reflex tears with MDS‐UPDRS, HY, or MoCA.ConclusionsTotal αSyn levels in reflex tears can differentiate PD from HC. In addition, total αSyn reflex tear levels were associated with the urinary domain of NMSS but are not associated with motor and cognitive symptoms, nor HY. Therefore, our findings suggest that it does not reflect ongoing dopaminergic neurodegeneration.

Comparison of tear Matrix Metalloproteinase 9 (MMP-9) estimation with Schirmer's test in Ocular Surface Disorders.

Ocular surface disorder (OSD) is a vexed eye problem and a diagnostic conundrum. Diagnosis has traditionally depended upon symptoms and tests like Schirmer's, TBUT, staining with dyes, and tear meniscus height. Schirmer's test is the most popular. However, the test strips irritate with reflex tearing - producing false high results. Matrix Metalloproteinase 9 (MMP) in the tear is believed to be expressed by stressed epithelial cells of the corneal surface - a key pathology in dry eye disease. This study attempts to compare the results of Schirmer's test and MMP-9 so that the test can individually or severally add to a more definite diagnosis of dry eye disease. 100 eyes of 50 symptomatic patients underwent MMP-9 estimation and were divided into two groups (MMP-9+ve and MMP-9-ve). They were then sub-grouped as per DEWS-2007 based on Schirmer test levels and Ocular Symptomatology Score (OSS). The two groups were compared for severity of dry eye based on Schirmer's test and OSS. Mean Schirmer's value was 12.85 (SD 7.07) for MMP-9+ve and 19.18 (SD 8.94) for MMP-9-ve patients. 80% of patients with severe dry eye and 55.6% of moderate dry eye patients were positive for MMP-9. 85% of the MMP-9 patients had OSS values of 2 or 3. A higher OSDI and positive MMP-9 were shown to be correlated in a statistically remarkable way (p<0.001). The OSDI values of 0-12 for 3/44 (6.8%) positive results, 13-22 for 2/8 (25%) positive results, 23-32 for 4/14 (28.6%) positive results, and 33-100 for 13/35 (37.1%) positive results all showed an increase in MMP-9 positivity along with a rise in the subjective severity of the illness. MMP-9 compares well with Schirmer's values and DED categories based on Schirmer's. The result pointed towards the usefulness of this test in diagnosing patients who may have not yet manifested symptoms.

Schirmer tear test-1 with open or closed eyelids: An evaluation in brachycephalic and nonbrachycephalic dogs.

Assess aqueous tear production when measured with the dogs' eyelids open or closed. Thirty healthy dogs (15 Shih Tzus, 15 Labrador retrievers) were recruited. With the order of testing randomized for each dog, two sessions (separated by 30 min) of STT-1 testing were performed with the dogs' eyelids closed or open. Schirmer strip wetness (every 10 s for 60 s) and number of time(s) the strip dislodged during testing were recorded in each eye. Preferred STT-1 method was surveyed via a global Listserv of the veterinary ophthalmology community. STT-1 values were significantly higher in closed versus open eyes in Shih Tzus (18.6 ± 2.7 mm/min vs. 16.3 ± 2.5 mm/min; p = .002) and Labrador retrievers (21.6 ± 2.9 mm/min vs. 17.8 ± 3.2 mm/min, p < .001), findings that were also significant at times <60 s for either breed (p ≤ .004). Schirmer strips dislodged from six dogs with open eyelids and no dogs with closed eyelids. Maximal STT-1 difference with closed versusopen eyelids was 13 mm/min in Labrador retrievers and 7 mm/min in Shih Tzus. Survey results from 275 veterinarians showed STT-1 performed with "closed eyelids" (38.5%), "open eyelids" (26.9%), or "never paid attention, sometimes closed, sometimes open" (34.6%). Eyelids status (closed or open) during STT-1 testing had a significant impact on aqueous tear secretion in brachycephalic and nonbrachycephalic dogs, highlighting the importance of consistency when repeating STT-1 in a canine patient. STT-1 differences are likely due to sustained reflex tearing throughout the test duration when the dogs' eyelids are closed.

In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called ‘personalized lag time’. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Evaluating the Effectiveness of Lacrimal Gland Botulinum Toxin Using the TEARS Score.

Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.

CORRELATION OF THE DURATION OF DOCETAXEL ADMINISTRATION IN BREAST CANCER PATIENTS WITH EPIPHORA DEGREES

Abstract&#x0D; Introduction &amp; Objectives : Epiphora is caused by excessive secretion and/or obstruction of lacrimal drainage system, malposition or weakness of the eyelids, failure of the nasolacrimal duct, and reflex tearing. Obstruction of the lacrimal drainage system can be caused by inflammatory processes in the palpebra, the use of certain medications or congenital abnormalities. Some drugs that are at risk of causing epiphora are chemotherapy drugs, especially 5-FU and docetaxel. Most epiphora were foundin weekly therapy than every 3 weeks therapy. Docetaxel causes epiphora, induces obstruction of the lacrimal drainage system and fibrosis of the stroma in the mucous layer of the lacrimal drainage system. According to Erkan et al, cases of recurrent or persistent and symptomatic epiphora had a Munk score of 2 to 4. This study interested in conducting research on the Correlation of the Duration of Docetaxel Administration in Breast Cancer Patients with Epiphora Degrees at RSUP Dr. Mohammad Hoesin Palembang.&#x0D; Methods : Cross sectional study with 25 samples suffering from breast cancer and experiencing epiphora at RSUP Dr. Mohammad Hoesin Palembang. The epiphora degree assessment is carried out using the Munk Score.&#x0D; Results : The sample was predominantly ≤50 years old as many as 21(84%) samples with a median 45 (23-64) years. The most dose of docetaxel was 70 mg in 20(80%) samples. Somer's D test showed that there was a significant correlation (p=0.021) between the duration of docetaxel administration to epiphora degrees and the strength of the strong correlation (r=0.645).&#x0D; Conclusion : The length of the docetaxel cycle is strongly correlated to having an epiphora

Role of corneal sensory nerves in tearing and blinking

The cornea is innervated trigeminal neurons classified in three different functional types: polymodal nociceptor, mechano‐nociceptor and cold thermoreceptor neurons. Corneal sensory nerves are responsible of the conscious sensations evoked by corneal stimulation, and are also involved in the trophic maintenance of the tissue. Besides, corneal nerve activity is also involved in the regulation of the protective functions of the ocular surface such as tearing and blinking.Regulation of reflex and basal tearing is integrated at the brainstem and, in both cases, under the influence of the sensory inflow provided by several types of corneal sensory nerves. While reflex tearing is induced selectively by the stimulation of corneal polymodal nociceptors, basal tearing rate depends on the spontaneous activity of cold thermoreceptors. Thus, when cold thermoreceptors are silenced by environmental warming, basal tearing is compromised.Voluntary, reflex and spontaneous (basal) blinking present differences in their characteristics and regulation mechanisms. Voluntary blinking depends on the direct instructions generated at the brain cortex, acting over the motor neurons located at the facial nucleus. Reflex blinking is integrated at the brainstem, being induced by the stimulation of the cornea and periocular skin, and even by loud sounds. Spontaneous blinking is claimed to be controlled by a CNS centre that established a blinking pattern. This pattern is modified under different conditions such as cognitive activity, being for example reduced during visual attentional tasks in order not to lose relevant visual information. When the activity of corneal cold thermoreceptors is abolished or reduced by ocular instillation of local anaesthetics, the frequency and characteristics of the spontaneous blinking is not modified. However, when the activity of cold thermoreceptors is increased for prolonged periods (for instance after topical instillation of F6H8 drops, which reduces the ocular surface temperature), blinking pattern become more regular and an increased number of blinks of larger the amplitude and shorter duration are induced. This increased blinking frequency produced when the activity of cold thermoreceptors is increased is sufficient to even counteract the reduction of blinking frequency induced during visual tasks performance. The increase in blink frequency driven by corneal cold thermoreceptors' activation may constitute a protective mechanism to prevent excessive desiccation of the ocular surface.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

The role of exocytotic proteins in the (dys)regulation of human reflex tearing and aqueous‐deficient dry eye syndrome

Aims/Purpose: Reflex tears triggered by various external and internal stimuli play vital functions in the protection of the ocular surface and visual acuity. The impairment of the molecular processes involved in reflex tearing is conjectured to be associated with the progression of dry eye syndrome (DES). Therefore, this study was undertaken to unravel the intricate proteome changes in the reflex and DES tears.Methods: Thirty six subjects underwent basic secretory test (BST) via Schirmer I (without anaesthetics) to determine the secretory rate of the lacrimal gland due to the irritating nature of the strip and were divided into reflex (RF, n = 12, BST = 35.0 ± 0.0), normal (NR, n = 12, BST = 15.3 ± 3.0) and severe aqueous‐deficient DES (DRY, n = 12, BST = 3.4 ± 1.4). The individual tear samples were analysed employing the state‐of‐the‐art mass spectrometry‐based proteomics strategy, followed by bioinformatics analyses to elucidate the underlying molecular processes.Results: A total of 293 and 237 proteins were found to be significantly (p &lt; 0.05) differentially regulated in the RFL vs. NR (up‐regulated, UR = 12; down‐regulated, DR = 281) and DRY vs. NR (UR = 197; DR = 40), respectively. The hallmark of this study was the identification of 10 lacrimal gland‐specific proteins (e.g., LYZ, LCN1, LTF, PRR4, ZG16B) secreted mainly via the exocytotic pathway, which were significantly up‐regulated in the RFL vs. NR but down‐regulated in the DRY vs. NR. Antibacterial response was also significantly activated in RFL (p = 1.9 × 10−2) compared to DRY (p &gt; 0.05). The activated inflammatory response (e.g. S100A8/A9, ANXA1) associated with DRY (p = 2.7 × 10−8, z = 4.0) was found to be inhibited in the RFL (p = 2.7 × 10−9, z = −3.5). Likewise, proteins involved in glycolysis (z = −2.8), acute phase response (z = −2.7) and actin cytoskeleton signalling (z = −2.1) were also inhibited in the RFL compared to DRY.Conclusions: In summary, this study has demonstrated that protein markers involved in the exocytotic pathway play major roles in the production of reflex tears and their regulation is impaired in the DES. Importantly, the abrogation of the vicious cycle of pathways involved in the progression of DES, especially inflammation, was observed in the reflex tears, which may be the key for the protection and maintenance of dynamic balance of the ocular surface.

Conscious sensations and protective reflexes driven by eye surface nerves in health and disease

The trigeminal primary sensory neurons that innervate the ocular surface, especially the cornea, have been classified in three functional types: polymodal nociceptors, mechano‐nociceptors and cold thermoreceptors. These sensory nerves are responsible for the conscious sensations evoked in response to ocular surface stimulation as well as for the regulation of tearing and blinking, and they are also involved in the trophic maintenance of the ocular tissues.Depending on the transducing channels they express in their membrane, sensory nerves from the ocular surface respond to different types of stimulus and, after this information is processed by the CNS, different conscious sensations are evoked: corneal mechano‐nociceptors' activation led to pricking pain; polymodal nociceptors evoke burning irritation, and cold thermoreceptors' activation may evoke freshness/cold/dryness/pain depending on the subtype of cold thermoreceptor neuron activated by the stimulus. While reflex blinking and tearing are driven by the activation of polymodal nociceptors as the afferent arm of the reflex, basal blinking and tearing rate are under the control of cold thermoreceptors' activity.During inflammation and after injury (such as UV‐induced keratitis, allergic keratoconjunctivitis, corneal surgery, tear‐deficient dry eye) the activity of corneal sensory nerves is modified in both eyes, even when inflammation or damage affects only one eye. The abnormal corneal sensory nerve activity constitutes the basis for the discomfort, dryness and pain sensations experienced under these conditions. Also, protective mechanisms depending on ocular nerve activity such as blinking and tearing become altered.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

Biomarkers for Parkinson’s Disease with Reflex Tears Stratified by Disease Duration

Biomarkers for Parkinson’s Disease with Reflex Tears Stratified by Disease Duration

Non-targeted Metabolomics Analysis Reveals Distinct Metabolic Profiles Between Positive and Negative Emotional Tears of Humans: A Preliminary Study.

Background Basal, reflex, and emotional tears differ in chemical components. It is not yet known whether chemical differences exist in tears of different emotions. We investigated the biochemical basis of emotional tears by performing non-targeted metabolomics analyses of positive and negative emotional tears of humans. Methods Samples of reflex, negative, and positive emotional tears were obtained from 12 healthy college participants (11 females and one male). Untargeted metabolomics was performed to identify metabolites in different types of tears. The differentially altered metabolites were screened and assessed using univariate and multivariate analyses. Results The orthogonal partial least squares discriminant analysis model showed that reflex, negative, and positive emotional tears were clearly separated. A total of 133 significantly differentially expressed metabolites of electrospray ionization source (ESI-) mode were identified between negative and positive emotional tears. The top 50 differentially expressed metabolites between negative and positive emotional tears were highly correlated. Pathway analysis revealed that secretion of negative emotional tears was associated with some synapses in the brain, regulation of a series of endocrine hormones, including the estrogen signaling pathway, and inflammation activities, while secretion of positive emotional tears was correlated with biotin and caffeine metabolism. Conclusions It is indicated that metabolic profiles of reflex, positive, and negative emotional tears of humans are distinct, and secretion of the tears involves distinct biological activities. Therefore, we present a chemical method for detecting human emotions, which may become a powerful tool for the diagnosis of mental diseases and the identification of fake tears.

Состояние системы глазной поверхности у детей с аномалиями рефракции

Purpose. To evaluate subjective signs and objective clinical symptoms of disorders of the ocular surface system in children with refractive errors. Material and methods. 76 children (152 eyes) with ametropia aged 8 to 18 years were examined. All patients were divided into 2 groups: group 1 – 30 patients aged 8 to 11 years, group 2 – 46 patients aged 12 to 18 years. The severity of the subjective signs of the "dry eye" syndrome and the state of visual comfort were assessed using an online survey developed by the authors. Objectively, the state of the ocular surface system was examined by invasive methods (Schirmer I test, Schirmer II test, Norn test), as well as non-invasive methods using a keratograph (non-invasive tear breakup time, tear meniscus height, meibography, assessment of the severity of hyperemia of the bulbar conjunctiva). In 20 patients (40 eyes) osmometry of the lower lacrimal meniscus was performed. Results. According to a survey of 76 patients, 34 patients (44.7%) had minor disorders of the ocular surface system, 25 patients (32.9%) had moderate disorders, 7 patients (9.2%) had severe disorders, and 10 patients (13.2%) – significantly severe disorders. The indicators of the main tear secretion in the younger age group differ slightly from the standards, while in the older age group they exceed them by 2 mm, the total tear production in both groups of the study was slightly lower than the age standards. The obtained values of reflex tear production are sharply reduced in both study groups, at the age of 12–18 years the deviation is more significant. The average tear film osmolarity in the group of 20 patients aged 12–18 years was 302.75 mOsm/l, which corresponds with adult standards, however, in 6 patients from this group, the values exceeded the standards up to 332 mOsm/l, which is typical for moderate severity dry eye syndrome. It has been established that the indicators of tear film stability measured by both invasive and non-contact methods have similar values. In the group of children from 12 to 18 years old, the indicators are at the lower limit of the norm, however, the spread of the results indicates that there were patients with reduced indicators in the group. The number of eyes with loss of meibomian glands ducts of the 1st degree in the group of children aged 12–18 years was 31.5%, while in the younger group it was 26.7%. A mixed injection of the conjunctiva in the form of hyperemia of the 2nddegree was observed in 10.8% of the eyes in the older group, while in the other group only in 3.4% of the eyes. If more significant subjective chnges were detected, in combination with a deviation from the norms in clinical trials, it was advisable to prescribe age-appropriate drug therapy to patients to correct these conditions. Conclusion. When evaluating the subjective signs of a disorder of the state of the ocular surface system in children, special attention should be paid to the procedure for collecting an anamnesis and quantitative assessment of symptoms. Even in the absence of complaints, it is necessary to conduct an objective, preferably non-invasive study of the stability of the tear film, the state of the meibomian glands, and, if necessary, tear production. When a complex of subjective signs of moderate severity is detected, it is necessary to conduct an explanatory conversation with patients and their parents, paying attention to the aspects of eliminating risk factors for the development of disorders of the ocular surface system. Key words: ocular surface system, tear secretion, tear film stability, meibography

Improvement in Epiphora Using TEARS Grading Following Surgical Treatment of Meibomian Gland Inversion in Patients With Facial Nerve Palsy.

To assess epiphora outcomes using the TEARS grading score in patients with concomitant meibomian gland inversion (MGI) and facial nerve palsy (FNP) undergoing correction of MGI. Retrospective, 5-year, noncomparative, single-center study of patients with MGI and FNP, treated with MGI correction, under the supervision of a single surgeon. A validated "TEAR" score was used to assess changes in epiphora. Ten patients with FNP, MGI, and epiphora were analyzed from a group of 160 patients with FNP who underwent MGI surgery between 2017 and 2022. The mean age at surgery was 50 years (range, 13-76 years). T, E, and A scores significantly improved (p < 0.05). Eighty percent of patients saw a reduction in tearing frequency (T), with 60% gaining ≥ 2-grade improvement. Improvements in clinical effects (E) and activity limitation (A) were seen in 80% of patients, with 40% and 50% gaining ≥ 2-grade improvement, respectively. R scores (related to reflex tearing) improved by 60%, with 40% seeing ≥ 2-grade improvement. Nine patients (90%) improved symptomatically with an average improvement "S" score of 65% over a mean follow-up period of 30 months. All patients demonstrated restoration of the normal anatomical position of the meibomian glands. MGI can cause epiphora in patients with FNP and may explain cases where symptoms persist despite standard surgical intervention. This study provides proof of concept that MGI correction can improve epiphora and that identifying MGI may be considered a critical step in the treatment algorithm for epiphora in patients with FNP.

Comparison of Each Eye According to the Order of Noninvasive Keratographic Tear Film Evaluation.

To investigate the effect of order of examination on the results of noninvasive keratograph tear film evaluation using Keratograph5M in dry eye patients. One hundred and four patients with dry eye symptoms were analyzed retrospectively. All patients underwent bilateral noninvasive tear film evaluation using measurements of tear meniscus height (TMH) and noninvasive keratograph break-up time (NIKBUT) obtained using Keratograph5M. Measurements were performed sequentially in the order of right TMH, left TMH, right NIKBUT, and left NIKBUT. There was no statistically significant difference in TMH values between the right and left eyes (0.24 ± 0.08 and 0.23 ± 0.08 mm, respectively). Mean NIKBUT-first (time at first tear film break-up) and mean NIKBUT-average (the mean of all tear film break-up time over the entire cornea) were 6.17 ± 3.28 and 10.00 ± 3.97 seconds, respectively, for right, and 7.43 ± 3.86 and 11.57 ± 4.34 seconds, respectively, for left eyes. In addition, mean NIKBUT-first between right and left eyes, and mean NIKBUT-average between them were statistically significant (p = 0.013 and p = 0.007, respectively). Mean NIKBUT and mean TMH differences were not significantly influenced by right or left eyes, age, or sex (all p > 0.050). Spearman correlation analyses of TMH, NIKBUT-first, and NIKBUT-average results showed moderate positive correlations between right and left eyes (r = 0.470, r = 0.322, and r = 0.576, respectively; p < 0.001). TMH evaluation was not affected by test order; however, NIKBUT measurement was affected by test order, because of reflex tearing due to forced eye opening during the examination. Therefore, TMH should be evaluated before NIKBUT, and sufficient time interval and caution should be needed between NIKBUT measurements on both eyes.

Is there any correlation between alpha-synuclein levels in tears and retinal layer thickness in Parkinson's disease?

To determine the total alpha-synuclein (αSyn) reflex tears and its association with retinal layers thickness in Parkinson's disease (PD). Fifty-two eyes of 26 PD subjects and 52 eyes of age-and sex-matched healthy controls were included. Total αSyn in reflex tears was quantified using a human total αSyn enzyme-linked immunosorbent assay (ELISA) kit. The retinal thickness was evaluated with spectral-domain optical coherence tomography. The Movement Disorder Society-Unified Parkinsońs Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), and Montreal Cognitive Assessment (MoCA) were used to assess motor, non-motor, and cognition. In PD, total αSyn levels were increased compared to control subjects [1.76pg/mL (IQR 1.74-1.80) vs 1.73pg/mL (IQR 1.70-1.77), p < 0.004]. The nerve fiber layer, ganglion cell layer, internal plexiform layer, inner nuclear layer, and outer nuclear layer were thinner in PD in comparison with controls (p < 0.05). The outer plexiform layer and retinal pigment epithelium were thicker in PD (p < 0.05). The total αSyn levels positively correlated with the central volume of the inner nuclear layer (r = 0.357, p = 0.009). Total αSyn reflex tear levels were increased in subjects with PD compared to controls. PD patients showed significant thinning of the inner retinal layers and thickening of outer retinal layers in comparison with controls. Total αSyn levels positively correlate with the central volume of the inner nuclear layer in PD. The combination of these biomarkers might have a possible role as a diagnostic tool in PD subjects.

Dependence of radioactive iodine-131 capture by the lacrimal ducts on the tear production level.

Secondary acquired lacrimal duct obstruction (SALDO) is one of the complications of radioiodine therapy. SALDO is formed a few months after therapy if there is a sufficient uptake of radioactive iodine by the nasolacrimal duct. To date, risk factors leading to SALDO are unclear. The objective was to determine the correlation between the tear production level and radioactive iodine-131 uptake in the lacrimal ducts. Basal and reflex tear production was studied in 64 eyes prior to the therapy with radioactive iodine-131 after drug-induced hypothyroidism. The condition of the ocular surface was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Seventy-two hours after the radioactive iodine therapy, scintigraphy was performed, which determined the presence or absence of iodine-131 in the lacrimal ducts. T-statistics and the Mann-Whitney criterion were used to identify the differences between the groups. The differences were considered significant at P ≤ 0.05. The current tear production level in patients receiving radioiodine therapy was determined using a mathematical model. A statistically significant difference between the basal (p = 0.044) and reflex (p = 0.015) tear production levels was found in cases with and without iodine-131 uptake by the lacrimal ducts. The probable current tear production level corresponds to the sum of basal and 10-20% of reflex tear production. The uptake of iodine-131 was found regardless of the OSDI results. The probability of iodine-131 uptake by the lacrimal ducts rises as the tear production level increases.

Changes in the oculas surface after hypotensive surgery

BACKGROUND: Hundreds of studies are dedicated to the negative effects of glaucoma therapy on the ocular surface. At the same time, the state of the eye surface after successful hypotensive surgery, which resulted in the cessation or significant reduction of medical therapy, has not been studied.&#x0D; AIM: To identify ocular surface changes after glaucoma surgery.&#x0D; MATERIALS AND METHODS: The study group consisted of 475 consecutively enrolled patients who were operated during 20162020 in Saint Petersburg Multidisciplinary City Hospital No. 2 for primary open-angle unstable glaucoma, and then observed for 6 to 24 months. Trabeculectomy (TE) was used as the first hypotensive procedure (418 patients), as re-operation TE (25 patients) or Ahmed valve implantation (32 patients) were chosen. Using statistical methods, the dynamics of symptoms (OSDI) and signs [tear film break-up time (TBUT) and reflex tear production defined by Schirmer I test] depending on outcome (complete or partial success and total failure) were analyzed.&#x0D; RESULTS: The cessation of the pharmacological load due to the complete success of the surgery was accompanied by pronounced (two-fold) and long (for at least two years) decrease of OSDI scores. The obliged, even partial, return to instillations by patients, who were included into the subgroup of partial success, within six months, transformed the achieved differences into insignificant ones. TBUT at complete and partial success significantly increased at all end-points of the study, significantly differing from the similar indicator in the subgroup total failure. The results of the Schirmer I test against the background of complete success of the operation showed a statistically significant increase, compared to the baseline , delayed for six months, throughout the whole further follow-up period. Patients entering the partial success subgroup in 24 months after surgery, also showed a significant increase in tear secretion. The failure of glaucoma surgery was accompanied by a brief and insignificant improvement in all scores.&#x0D; CONCLUSIONS: The hypotensive surgery, which lead to complete success, was accompanied by a significant improvement of the ocular surface state. Restart of local therapy reduces achieved results. Failure of surgical treatment is associated with minimal fluctuations of the studied parameters.

Optimization and evaluation of tear protein elution from Schirmer's strips in dry eye disease.

Extraction of tear protein from Schirmer's strip is a prerequisite for the proper identification and screening of biomarkers in dry eye disease. The study compares different methods of extraction of tear proteins from the Schirmer's strip. Reflex tear was collected from healthy controls (HC; n = 12), Stevens-Johnson syndrome (SJS; n = 3) and dry eye disease (DED; n = 3) patients using capillary tube. This tear was used to measure the volume absorbed by Schirmer's strip per microliter. Different buffers (6) were used to compare the protein yield from the Schirmer's strip in four different conditions. The tear proteins extracted using the highest protein yield buffer were analyzed by mass spectrometry. A linear relationship between the tear volume and wetting length was observed (r = 0.0.997, n = 6). The highest yield was observed after incubation of the Schirmer's strip in 100 mM ammonium bicarbonate (ABC) with 0.25% Nonidet P-40(NP-40) at 4°C for an hour (P < 0.00005). The in-solution digestion of tear eluted in the above condition 100 Mm ABC + 0.25% NP-40 with one-hour incubation yielded a total of 2119 proteins in HC, SJS, and DED. The unique protein observed in SJS and DED was 0.6% and 17.9%, respectively. The significantly expressed proteins are associated with innate immune response, proteolysis, wound healing, and defense response. A method for extraction of protein from Schirmer's strip was optimized for increase in protein yield from the tear sample. SJS and DED tear samples have unique protein signature. The study will aid in better design of tear protein-based experimental study.

Causes of Tearing in Patients With Chemotherapy: Meibomian Gland Dysfunction Versus Lacrimal Drainage Obstruction.

Numerous ocular toxicities that have been associated with the use of chemotherapeutic agents present as problems with the ocular surface, ocular adnexa, and lacrimal system, and many chemotherapeutic agents have tearing as a side effect. In this study, 34 eyes from 17 patients with a mean age of 62.4±14.8 years were analyzed. Chemotherapy was administered for a mean of 13.8±7.6 months. Chemotherapeutic agents of the following types were included: titanium silicate-1 (58.8%), Docetaxel (23.5%), Paclitaxel (11.8%), and 5-fluorouracil (5.9%). Tearing began 9.1 to 10.9 months after chemotherapy treatment. Within 3 months of beginning chemotherapy, tearing occurred in 9 patients (52.9%), and within 6 months, it occurred in 11 patients (64.7%). Mean tear break-up time was 5.4±2.6 sec. Ten eyes (29.4%) had normal fluorescein dye disappearance test findings (within grade 1), and the mean fluorescein dye disappearance test was 1.91±0.87. Among the 34 eyes, 24 (70.6%) had normal puncta and 9 (26.5%) and 1 (2.9%) had stenosis and blockage, respectively. Ten eyes (29.4%) showed total regurgitation, 19 eyes (55.9%) showed partial regurgitation, and 5 eyes (14.7%) showed no regurgitation upon syringing. Four eyes (11.8%) and 30 eyes (88.2%), respectively, showed soft and hard stops upon probing. Dacryoscintigraphy confirmed that 6 eyes (17.6%) were normal, 8 eyes (23.5%) showed post-sac delay or obstruction, and 20 eyes (58.8%) showed pre-sac delay or obstruction. The mean meiboscores for the upper and lower eyelids on LipiView were 2.15±0.86 and 2.53±0.79, respectively. The difference in meiboscores between the upper and lower eyelids was significant ( P=0.004 ). Obstruction of the lacrimal drainage system is a significant contributing factor to tearing in chemotherapy patients. However, reflex tearing because of meibomian gland dysfunction should also be fully considered to effectively manage the tearing because of the high incidence of accompanying meibomian glands loss when the lacrimal drainage system is obstructed.

Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects.

To measure, the tear flow changes evoked in healthy subjects and dry eye disease (DED) patients by controlled sensory stimulation of the eye surface with i-Onion™, a new stimulation device. Sensory corneal nerves were stimulated with an instrument (i-Onion™) that ejects puffs of CO2 gas (99.9%) at 200 ml.min-1 for 3s, delivered 5 mm from the cornea. Using Schirmer test strips, tear volumes were measured over 3 min in the cornea of one eye before (basal tear volume -BTV) and in the other eye after stimulation of the sensory nerves with CO2 (stimulated tear volume -STV). These measurements were obtained from a control group of adults of either sex (17 students aged 20-30 and 29 subjects without signs of dry eye aged 25-61), a cohort of DED patients (aged 34-75) that included 12 asymptomatic, suspected DED subjects (Schirmer <7 mm and/or TBUT <10s), and 30 Sjögren's syndrome (SS) patients. CO2 stimulation significantly increased the tear volume (BTV = 14.6 ± 1.0 mm, STV = 19.0 ± 1.1 mm: n = 46) in 78% of control subjects, reflecting a mean tear reserve volume (TRV = STV-BTV) of 4.4 ± 0.8 mm. Individual differences were wide, and while no increase in reflex tearing was evoked in 30% of subjects with a BTV >10 mm, the remaining 70% responded vigorously to stimulation, even those with a BTV >18 mm. Asymptomatic DED subjects displayed weaker responses to CO2 stimulation, with lower STVs. Both the BTV and STV of SS patients were low, significantly below those of the healthy controls. Measuring the rise in reflex tearing volume evoked by controlled corneal stimulation provides objective information about the tear glands' secretory capacity in health and disease.