Infectious Keratitis Associated with Contact Lenses

The use of contact lenses for correcting refraction, suppressing myopia progression, and cosmetic purposes is increasing steadily. Contact lenses have various effects on the corneal surface and corneal infection can occur following obstruction of tear flow, micro-damage to corneal epithelial cells, corneal hypoxia, changes in corneal immunity, and exposure to contaminants. When a patient who used to wear contact lenses presents with keratitis, it is important to distinguish whether it is an infection; if it is an infection, it is important to find the causative strain and promptly treat it appropriately. Since improper lens care is related to infection, appropriate patient education is necessary, and the risk of contact lens infection should be reduced through regular ophthalmic examinations.

Diagnostic biomarkers in tear fluid: from sampling to preanalytical processing

Tear fluid is receiving growing attention as a source for novel diagnostic biomarkers. Multiple techniques are available for its collection and impact the composition of acquired samples. We sought to provide a direct comparison of two collection methods with regard to implementation, acceptance, and impact on sample composition. Tear fluid was collected from fifteen healthy volunteers with capillary tubes and Schirmer strips and analyzed for total protein and IgG concentrations. Sampling parameters and perception by test persons were compared. The use of capillary tubes was more convenient for the participants while causing more effort for the collector. Tear flow rates as well as the relative and absolute amount of IgG were higher when Schirmer strips were used. Consecutive collections with Schirmer strips significantly influenced tear flow rates, IgG, and protein concentrations. A moderate correlation was observed between tear flow rates and IgG concentrations for both methods. Samples collected with both methods can be analyzed by isoelectric focusing, a potential diagnostic application in the field of neurology. The specific advantages and limitations of tear fluid sampling with either capillary tubes or Schirmer strips demonstrate the need for a thorough investigation of collection methods with regard to the application of interest.

Tear secretion from the lacrimal gland: variations in normal versus dry eyes

PurposeTo investigate the secretory status of the main lacrimal gland in healthy and dry eye disease (DED) via fluorescein-assisted direct assessment of tear secretion from the palpebral lobes.MethodsIncluded were 25 healthy subjects (50 lobes) and 75 subjects with DED (cicatrising conjunctivitis (CC, n=27), evaporative dry eyes (EDE, n=25) and Sjogren’s syndrome (SS, n=23)). Analysed parameters included number and location of ductular openings, tear flow rate per gland and per ductule, and the time lag for the initiation of secretion.ResultsDuctular openings could be observed in all patients with EDE and healthy subjects whereas only 33% (18/54) glands of CC patients and 67% glands (31/46) patients with SS revealed ductules. The median number of ductules per lobe was 4 in normal (range 3–5), 3 in EDE (3–6), 1 in SS (0–3) and 0 in CC group (0–3) (p<0.000001). The median tear flow rate per lobe in CC (0.00 μL/min) and SS (0.21 μL/min) was significantly lesser than normal lobes (1.05 μL/min, and EDE (0.99 μL/min eyes. The tear flow rate differed significantly between SS and CC group (p<0.0001). The maximum time lag occurred in the CC group (median, 20 s), followed by the SS group (median, 1.5 s) whereas the EDE group had similar time lag (<1 s) as of normal glands (p<0.0001).ConclusionDirect assessment of tear secretion from the palpebral lobe demonstrates significant differences between EDE, aqueous deficient dry eye and dry eye in CC.

Role of Eyes and Eyes Protection Amidst SARS-CoV-2 Infection

Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has infected millions of people. Theconjunctival epithelium is easily exposed to infectious droplets and body fluids making eyes apotential route and reservoir of the infection. The CD147 and ACE2 receptor has been demonstratedin ocular surface cells, which implies that these cells may facilitate as a portal of entry for transmissionof Severe Acute Respiratory Syndrome Coronavirus 2. Despite low viral load in tears and conjunctivalswab, the negative RT-PCR results cannot exclude the possibility of the presence of Severe AcuteRespiratory Syndrome Coronavirus 2 in ocular secretions. Pathogens might be transported byconstant tear flow through the lacrimal duct system to the respiratory tract causing infection. Eyesare unlikely to be the main transmission route, however, their role in the transmission of SevereAcute Respiratory Syndrome Coronavirus 2 cannot be overlooked. Therefore, proper eye protectionshould be instituted while attending Severe Acute Respiratory Syndrome Coronavirus 2 positiveindividuals, especially by health professionals.

Effect of Different Doses of Atipamezole on Reversal of Medetomidine-Induced Tear-Flow Decrease in Rats

It has been reported that α2-adrenoceptor agonists such as medetomidine decrease tear flow in many species, including rats. Few studies have investigated the involvement of α2-adrenoceptor in decreased tear flow; the issue has not been illustrated sufficiently. Therefore, we aimed to investigate the effect of different doses of atipamezole on the reversal of medetomidine-induced tear-flow decrease to reveal the specific involvement of α2-adrenoceptor. Treatment with 400, 800, or 1600 µg/kg atipamezole (or saline as the control) was intramuscularly administered to rats 15 min following intramuscular administration of 200 µg/kg medetomidine. After medetomidine administration, tear flow was measured using a phenol red thread test (PRTT). PRTT values decreased significantly after 200 µg/kg medetomidine administration. The PRTT values after 800 (optimal dose to reverse) and 1600 µg/kg atipamezole administration reached baseline, but never exceeded it significantly. Treatment with 400 µg/kg atipamezole also reversed the decrease in PRTT value but the PRTT remained lower than baseline. The optimal dose and the higher dose of atipamezole fully reversed the medetomidine-induced decrease in tear flow to the baseline level in rats, while the lower dose of atipamezole partially recovered tear flow.

Ontogenesis of the tear drainage system requires Prickle1-driven polarized basement membrane deposition

ABSTRACTIn terrestrial animals, the lacrimal drainage apparatus evolved to serve as conduits for tear flow; however, little is known about the ontogenesis of this system. Here, we define the anatomy of the fully formed tear duct in mice, characterize crucial morphogenetic events for the development of tear duct components and identify the site for primordial tear duct (PTD) initiation. We report that the PTD originates from the orbital lacrimal lamina, a junction formed by the epithelia of the maxillary and lateral nasal processes. We demonstrate that Prickle1, a key component of planar cell polarity signaling, is expressed in progenitors of the PTD and throughout tear duct morphogenesis. Disruption of Prickle1 stalls tear duct elongation; in particular, the loss of basement membrane deposition and aberrant cytoplasmic accumulation of laminin are salient. Altered cell adhesion, cytoskeletal transport systems, vesicular transport systems and cell axis orientation in Prickle1 mutants support the role of Prickle1 in planar cell polarity. Taken together, our results highlight a crucial role of Prickle1-mediated polarized basement membrane secretion and deposition in PTD elongation.

Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling

The tear drainage apparatus evolved in terrestrial animals serving as conduits for tear flow. Obstruction of tear drainage causes a range of ocular surface disorders. Hitherto, genetics of tear duct development and obstruction has been scarcely explored. Here we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to blockage of the tear drainage by the incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (CL). Further analysis revealed that the precocious eyelid opening, previously observed in the same type of Prickle 1 mutants, is also caused by tear duct dysplasia. A comparison of wild type, the Prickle 1 hypomorph and null mutants revealed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. As a key component of a set of six Wnt/PCP core proteins, Prickle 1 usually works together with other PCP components. An investigation of expression of Wnt/PCP core genes demonstrated three of the six PCP components in tear duct, supporting the notion of context-dependent organization of PCP protein complexes. Furthermore, expression of Fgfr2/Fgf10 and p63 genes, mutations of which are associated with NLD and CL hypoplasia in human, were not altered in Prickle 1 mutant mice. Lastly, we showed that Prickle 1 expression in developing tear drainage system is conserved between mouse and human despite anatomical differences. Altogether, the study uncovered how obstruction of the tear drainage could lead to a complex ocular surface disorder, which may have genetic implications in human ocular health.

Effect of Intramuscular Medetomidine Administration on Tear Flow in Rats

Medetomidine has been reported to decrease tear flow significantly in dogs, cats, and pigs when used as a sedative or analgesic; however, there are no such reports when it comes to rats. The present study aimed to investigate the effect of medetomidine on tear flow in rats. Medetomidine in doses of 50, 100, or 200 µg/kg or a physiological saline solution as the control, were administered intramuscularly to male Slc:Wistar/ST rats. After the administration of medetomidine, tear flow in both eyes was measured using a phenol red thread tear test. The area under the curve (AUC) of phenol red thread test values from baseline to 8 h was calculated. Data were plotted against the dose of medetomidine and simple linear regression analysis was performed. The effect of the drug on phenol red thread test values was considered dose-related when linear analysis yielded a significant relationship. In all medetomidine-treated groups, tear flow decreased significantly in both eyes after administration, while no significant changes were observed in either eye in the control group. The AUC values from baseline to 8 h after administration in groups treated with 100 and 200 µg/kg of medetomidine were significantly lower in both the left and right eyes compared to the control group. The linear regression of the AUC values was significant for both eyes. Our results indicated that the intramuscular administration of medetomidine in rats decreased tear flow significantly in a dose-dependent manner.

Ontogenesis of the tear drainage system requires Prickle 1-controlled polarized basement membrane (BM) deposition

In terrestrial animals, lacrimal drainage apparatus evolved to serve as conduits for tear flow. Little is known about the ontogenesis of this system. Here, we investigated tear duct origin, developmental course, genetic and cellular determinants in mouse. We report that primordial tear duct (PTD) originates from junction epithelium of the joining maxillary and lateral nasal processes, which reshapes into future tear duct branches. We identified Prickle 1 as a hallmark for tear duct outgrowth, ablation of which stalled duct elongation. In particular, the disruption of basement membrane (BM) with cytoplasmic accumulation of laminin suggests aberrant protein trafficking. Mutant embryoid bodies (EBs) derived from iPSCs recapitulate BM phenotype of the PTD exhibiting defective visceral endoderm (VE), which normally expresses high level of Prickle 1. Furthermore, replenishing mutant VE with Prickle 1 completely rescued BM but not cell polarity. Taken together, our results reveal a distinct role of Prickle 1 in regulating polarized BM secretion and deposition in precedently uncharacterized tear drainage system and VE, which is independent of apicobasal polarity establishment.

Tears – more to them than meets the eye: why tears are a good source of biomarkers in Parkinson's disease

Tears are a known source of biomarkers for both ocular and systemic diseases with particular advantages; specifically, the noninvasiveness of sample collection and a unique and increasingly better-defined protein composition. Here, we discuss our rationale for use of tears for discovery of biomarkers for Parkinson's disease (PD). These reasons include literature supporting changes in tear flow and composition in PD, and the interconnections between the ocular surface system and neurons affected in PD. We highlight recent data on the identification of tear biomarkers including oligomeric α-synuclein, associated with neuronal degeneration in PD, in tears of PD patients and discuss possible sources for its release into tears. Challenges and next steps for advancing such biomarkers to clinical usage are highlighted.