Exorbital Lacrimal Gland Ablation and Regrafting Induce Inflammation but Not Regeneration or Dry Eye.

The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after lacrimal gland (LG) ablation. The LG of Wistar rats was submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n = 7-10/group). The eye wipe test, slit lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 3 groups showed corneal neovascularization. Histology revealed changes in the LG and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2, in RUNX-1 at M1 and M2 in G1, in RUNX-3 mRNA at M1 in G1, and at M2 in G2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1ß mRNA in the trigeminal ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation and grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.

Exploring tear viscosity with quartz crystal microbalance technology.

Tear viscosity is a critical property affecting tear distribution and ocular surface stability. While not widely established as a primary diagnostic marker, deviations from normal viscosity can impact ocular health, potentially contributing to conditions such as dry eye syndrome. Despite their importance, traditional viscometers require sample volumes that are not feasible to use with tear volume. This research introduces a novel Quartz Crystal Microbalance (QCM)-based method for tear viscosity measurement, offering a viscometer prototype that operates with minimal sample volumes. Human tear samples, solutions used in artificial eye drops, and various commercial eye drop brands were evaluated. Results show that the QCM method aligns with established viscosity ranges. The average viscosity of healthy human tears was found to be 1.73 ± 0.61 cP, aligning with the typical range of 1-10 cP. Variability in the viscosities of eye drop can be attributed to differences in their chemical compositions. The QCM method offers benefits such as reduced sample consumption and rapid results, enhancing understanding of tear dynamics for ocular health. Further research with larger sample sizes is needed to establish normative viscosity values in healthy individuals and those with dry eye syndrome, which is crucial for validating the device's clinical efficacy.

Effectiveness and safety of a novel crosslinked hyaluronate canalicular gel occlusive device for dry eye.

PURPOSE: To evaluate the effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared with a commercially available hydrogel canalicular plug (Form Fit). SETTING: 5 sites in the United States. DESIGN: Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). METHODS: Adults (≥22 years) with the Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was noninferiority of the mean within subject change from baseline to month 3 in Schirmer score for patients receiving filler compared with plugs. The key secondary effectiveness endpoint was noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety. RESULTS: 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was noninferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. CONCLUSIONS: Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

OphthalMimic: A new alternative apparatus without animal tissue for the evaluation of topical ophthalmic drug products.

The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical-chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min-1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.

Effect of upper eyelid blepharoplasty on the ocular surface, tear film, and corneal microstructure.

PURPOSE: This study aimed to investigate the effect of upper eyelid blepharoplasty with the removal of the skin and a strip of orbicularis oculi muscle on the ocular surface, tear film, and dry eye-related symptoms. METHODS: Twenty-two eyes of 22 consecutive patients operated by a single surgeon (21 females; mean age, 61 years; age range, 41-75 years) were included. All subjects completed the Ocular Surface Disease Index questionnaire, underwent in vivo confocal microscopy, tear film breakup time measurements, the Schirmer test with anesthesia, and fluorescein and lissamine green staining measurements before, 1 month, and 6 months after upper blepharoplasty alone with preseptal orbicularis excision. RESULTS: A significant increase in Ocular Surface Disease Index, and corneal fluorescein and lissamine green staining and a significant decrease in tear film breakup time were observed after 1 month (p=0.003, p=0.004, p=0.029, and p=0.024 respectively) and 6 months (p=0.001 for all findings). No significant difference in the Schirmer test score was observed during the follow-up. None of the in vivo confocal microscopy parameters showed significant changes during the study. CONCLUSIONS: An increase in dry eye symptoms and a decrease in tear film stability along with ocular surface staining were observed in patients undergoing upper eyelid blepharoplasty.

Impact of stress on the tear production of healthy cats.

OBJECTIVES: This study aimed to determine the impact of acute stress on tear production in companion cats to provide a basis for minimizing stress-inducing stimuli during ophthalmic evaluations. METHODS: A total of 24 healthy owned cats (12 males, 12 females) of mixed breed, aged 8 months to 7 years, with no history of ocular diseases, were selected for the study. The cats were housed in individual cages under controlled conditions for 6 days. The Schirmer tear test-1 (STT-1) was performed in the morning (between 9:00 am and 11:00 am) using test strips from the same batch. The first test (without stress) was conducted on the fifth day of acclimation, and the second test (with stress) on the sixth day. The stress stimulus consisted of recordings of barking dogs, cats fighting and the murmuring of people. For both tests, the heart rate was assessed with a stethoscope before, during and after the tests, and the environmental stress level was also evaluated. Results are presented as mean ± SD and 95% confidence interval (CI). RESULTS: The study found that STT-1 values were significantly higher (P = 0.009) with stress (22.2 ± 6.0 mm/min [95% CI 19.9-24.6]) than without stress (17.5 ± 6.9 mm/min [95% CI 14.8-20.2]). Similarly, the heart rate was significantly higher (P = 0.028) in stress vs non-stress conditions (213.4 ± 37.5 beats per minute [bpm] [95% CI 198.7-228.1] vs 171.5 ± 28.6 bpm [95% CI 160.3-182.7], respectively), and the environmental stress score was significantly higher (P <0.001) in stress vs non-stress conditions (3.3 ± 0.5 [95% CI 3.1-3.5] vs 1.2 ± 0.4 [95% CI 1.1-1.4], respectively). CONCLUSIONS AND RELEVANCE: Stress increased tear production in cats. Although the mean STT-1 value obtained under stress conditions was within the normal range, stress can influence the test results. The use of cat friendly handling techniques facilitates execution of the STT-1.

Immediate Impact on Tear Osmolarity Following the Application of Different Ocular Lubricants in Patients Experiencing Moderate Dry Eye Symptoms.

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy. METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface's tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED. RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance. CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

Two-Year Progression of Dry Eye Disease in Dry Eye Assessment and Management Study.

PURPOSE: The purpose of this study was to evaluate the progression of dry eye disease (DED) symptoms and signs over 2 years through a secondary analysis of data collected from the Dry Eye Assessment and Management study. METHODS: Participants who were assigned to omega-3 fatty acid in the first year were rerandomized in the second year to either continue with omega-3 fatty acid or switch to placebo. At baseline, 3, 6, 12, 18, and 24 months, DED symptoms were evaluated by using the Ocular Surface Disease Index and the Brief Ocular Discomfort Index (BODI). DED signs were assessed using conjunctival staining, corneal staining, tear break-up time, Schirmer testing, and keratography measures. Medication usage was documented at each visit. Because the treatment and placebo groups displayed no statistical differences in both signs and symptoms, data from the 43 participants were combined to assess longitudinal changes in symptoms and signs. RESULTS: At 3 months after omega-3 fatty acid treatment, there were significant improvements from baseline in Ocular Surface Disease Index and Brief Ocular Discomfort Index scores (all P ≤ 0.002) and less use of artificial tears or gel ( P = 0.02), but between 3 and 24 months, no significant changes in symptoms and treatments were observed ( P ≥ 0.06). Except for a significant improvement in conjunctival staining score over 2 years ( P = 0.001), there were no significant sign changes in corneal staining ( P = 0.32), tear break-up time ( P = 0.43), Schirmer test ( P = 0.09), and additional measures (all P ≥ 0.07). CONCLUSIONS: We did not observe a progression of DED signs or symptoms over a 2-year period, except for a probable placebo response in symptoms in the first 3 months and an improvement in conjunctival staining score.

Shih-Tzu dogs show alterations in ocular surface homeostasis despite adequate aqueous tear production.

BACKGROUND: Shih-Tzu dogs are frequently affected by ocular surface disorders such as corneal ulceration and dry eye disease (DED). The aim of this study was to evaluate ocular surface homeostasis in Shih-Tzu dogs that have adequate aqueous production. Twenty-eight dogs were subjected to eyelid blink counting, Schirmer tear test (STT-1), ophthalmic evaluation, tear film break-up time (TBUT), fluorescein test and Masmali tear ferning (TF) grading scale. RESULTS: Of the 28 animals evaluated, the median value of incomplete eyelid blinks/min (median = 15.0 blinks/min; Interquartil interval - IQR = 8.7 blinks/min - 19.5 blinks/min) was higher than the complete blinks/min (median = 2.5 blinks/min; IQR = 1.6 blinks/min - 4.3 blinks/min), with statistically significant difference. The Schirmer tear test had a median value of 25.0 mm/min (IQR = 22.7 mm/min - 27.5 mm/min), considered within the normal range for the species. On ophthalmic examination, all dogs had trichiasis of the caruncle and medial lower eyelid entropion. Lagophthalmos was the third most common alteration observed (71.4%; 20/28). The median of TBUT was 4.0 s; (IQR = 3.0 - 6.0 s). All the animals were negative to the fluorescein test and the TFT indicated that the majority of the eyes (51.8%; 29/56) were classified in abnormal grades 3 and 4 according to the Masmali tear ferning (TF) grading scale. CONCLUSIONS: Although the Shith-Tzu dogs had STT-1 values within the normal range for the species there was high prevalence of abnormal TFT grades and low TBUT in all dogs, showing that despite adequate aqueous production, these dogs have poor precorneal tear film quality. In addition, the dogs showed few complete eyelid blinks and ophthalmic alterations, promoting poor tear film diffusion. All these findings, isolated or together, can result in DED.

Prevalence of dry eye and Meibomian gland dysfunction in Central and South America: a systematic review and meta-analysis.

BACKGROUND: Dry eye is one of the most common ophthalmic conditions and can significantly impact quality of life. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye. We sought to conduct a systematic review and meta-analysis to estimate the prevalence and incidence of dry eye and MGD in Central and South America and to identify factors associated with disease burden. METHODS: Data sources Ovid MEDLINE and Embase. STUDY SELECTION: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded. DATA EXTRACTION AND SYNTHESIS: The review was based on a protocol registered on PROSPERO (CRD42021256934). Risk of bias was assessed in duplicate using a risk of bias tool designed for the purposes of descriptive epidemiological studies. Data were extracted by one investigator and verified by another for accuracy. Prevalence of dry eye and MGD were grouped based on study participant characteristics. MAIN OUTCOMES AND MEASURES: Prevalence and incidence of dry eye and MGD in Central and South America. Summary estimates from meta-analysis with 95% confidence intervals (CI). RESULTS: Fourteen studies (11,594 total participants) were included. The population prevalence of dry eye was 13% (95% CI, 12%-14%) in Brazil and 41% (95% CI, 39%-44%) in Mexico based on one study each. Meta-analyses suggested that dry eye prevalence was 70% among indoor workers (95% CI, 56%-80%; I2, 82%; 3 studies), 71% among students (95% CI, 65%-77%; I2, 92%; 3 studies), and 83% in general ophthalmology clinics (95% CI, 77%-88%; I2, 88%; 2 studies). MGD prevalence ranged from 23% among indoor workers (95% CI, 16%-31%; 1 study) to 68% in general ophthalmology clinics (95% CI, 62%-72%; 1 study). No studies reported incidence of dry eye or MGD. CONCLUSIONS: This systematic review and meta-analysis demonstrated considerable variation in the published prevalence of dry eye and MGD among the general population and subpopulations in Central and South America. Local and subpopulation estimates of dry eye disease burden may be valuable to assist needs assessments and implementation of measures to mitigate the condition.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Análise do filme lacrimal e dos sintomas de olho seco em pacientes submetidos à facoemulsificação / Analysis of the tear film and dry eye symptoms in patients undergoing phacoemulsification

RESUMO Objetivo: Avaliar o filme lacrimal e os sintomas de olho seco antes e após a realização da facoemulsificação. Métodos: Participaram deste estudo clínico 51 pacientes diagnosticados com catarata (55% mulheres; 78% brancos; 71,2 ± 6,5 anos de idade; sem uso de colírio lubrificante) que foram submetidos à facoemulsificação em um hospital na cidade de Aparecida (SP). A análise do filme lacrimal foi feita pelo teste de ruptura do filme lacrimal, e os sintomas de olho seco foram avaliados pelo Índice de Doença da Superfície Ocular, ambos antes da cirurgia e 30 e 60 dias de pós-operatório. Resultados: Na análise pré-operatória, 25,5% dos pacientes tinham olho seco pelo critério subjetivo (Índice de Doença da Superfície Ocular ≥ 25%), enquanto a proporção de pacientes com olho seco foi de 92,2% pelo critério objetivo (teste de ruptura do filme lacrimal < 10 segundos). Não houve correlação entre o teste de ruptura do filme lacrimal e o Índice de Doença da Superfície Ocular (r = −0,14; p = 0,33). Não foi observada redução dos sintomas de olho seco (15,9 ± 17,6 versus 12,2 ± 13,2 versus 7,8 ± 11,5; p < 0,001) e nem do tempo de ruptura do filme lacrimal (6,2 ± 2,2 vs. 4,3 ± 2,0 versus 6,9 ± 2,0 segundos; p < 0,001) no pré, 30 e 60 dias após a cirurgia. Conclusão: A facoemulsificação desencadeia sintomas de olho seco e altera os valores do teste de ruptura do filme lacrimal e do Índice de Doença da Superfície Ocular, havendo melhora depois da cirurgia, com o passar dos dias. Observou-se que, após os 60 dias, os sintomas de olho seco avaliados pelo Índice de Doença da Superfície Ocular apresentaram melhora. Em relação ao filme lacrimal, avaliado pelo teste de ruptura do filme lacrimal, observou-se que houve piora estatisticamente significativa aos 30 dias, seguida de melhora no pós-operatório de 60 dias. Os resultados sugerem que a análise clínica do olho seco deve ser realizada por diferentes métodos, preferencialmente objetivos.

ABSTRACT Objective: To evaluate the tear film and dry eye symptoms before and after phacoemulsification. Methods: Fifty-one patients diagnosed with cataracts participated in this clinical study (55% female; 78% white; 71.2 ± 6.5 years old; without the use of lubricating eye drops) and underwent phacoemulsification at a hospital in Aparecida (SP). Tear film analysis was performed by the tear film break-up test and dry eye symptoms were assessed by the Ocular Surface Disease Index, both before surgery and 30 and 60 days after surgery. Results: In the preoperative analysis, 25.5% of the patients had dry eye according to the subjective criterion (Ocular Surface Disease Index ≥ 25%), while the proportion of patients with dry eye was 92.2% according to the objective criterion (tear film break-up test < 10 seconds). There was no correlation between tear film break-up test and Ocular Surface Disease Index (r = −0.14; p = 0.33). There was no reduction in dry eye symptoms (15.9 ± 17.6 versus 12.2 ± 13.2 versus 7.8 ± 11.5; p<0.001) nor in tear film break-up time (6.2 ± 2.2 versus 4.3 ± 2.0 versus 6.9 ± 2.0 seconds; p < 0.001) before, 30 and 60 days after surgery. Conclusion: Phacoemulsification triggers dry eye symptoms and changes Ocular Surface Disease Index and tear film break-up test values, with improvement over the postoperative days. Sixty days after surgery, the symptoms of dry eye assessed according to the Ocular Surface Disease Index improved. Regarding the tear film, evaluated by tear film break-up test, it was observed that there was a statistically significant worsening at 30 days, followed by an improvement in the postoperative period of 60 days. The results suggest that the clinical analysis of dry eye should be performed using different methods, preferably objective ones.

Hemolacria or bloody tears in presumed lacrimal endometriosis: a case report / Hemolacria o lágrimas hemáticas en sospecha de endometriosis lacrimal: reporte de un caso

Background: Hemolacria or the presence of blood in tears is a rare condition, and there are only a few cases reported in the literature. Hemolacria is associated with multiple underlying diseases, including vicarious menstruation due to extragenital endometriosis. Case report: We present a 26-year-old woman with hemolacria and abdominal pain related to her menstrual cycle. The patient was diagnosed with bilateral ovarian endometriomas. After ruling out other possible causes of hemolacria, a progestin-only treatment was applied, with improvement of the abdominal pain and complete remission of hemolacria. Conclusions: When faced with hemolacria, a thorough anamnesis and physical examination must be performed, sometimes involving more than one specialist to reach a diagnosis. Considering hemolacria is a sign of a subjacent pathology, its treatment should be specific one for the disease in each case.

Antecedentes: La hemolacria o presencia de sangre en las lágrimas es una afección poco frecuente y sólo hay unos pocos casos descritos en la literatura. La hemolacria se asocia a múltiples enfermedades subyacentes, incluida la menstruación vicaria debida a endometriosis extragenital. Caso clínico: Presentamos a una mujer de 26 años con hemolacria y dolor abdominal relacionado con su ciclo menstrual. La paciente fue diagnosticada de endometriomas ováricos bilaterales. Tras descartar otras posibles causas de hemolacria, se aplicó un tratamiento sólo con progestágenos, con mejoría del dolor abdominal y remisión completa de la hemolacria. Conclusiones: Ante una hemolacria se debe realizar una anamnesis y exploración física minuciosa, en la que a veces interviene más de un especialista para llegar al diagnóstico. Teniendo en cuenta que la hemolacria es signo de una patología subyacente, su tratamiento debe ser el específico para la enfermedad en cada caso.

Ocular dryness in intensive care: proposal for a new nursing diagnosis.

OBJECTIVE: to analyze the concept associated with diagnostic proposition Ocular dryness in adult patients hospitalized in an Intensive Care Unit, identifying its attributes, antecedents and consequences. METHODS: a methodological study carried out through concept analysis, operationalized by scoping review. RESULTS: the analysis of 180 studies allowed the identification of two attributes, 32 antecedents and 12 consequences. The attributes were tear film deficiency and ocular signs and/or symptoms. The prevalent antecedents were incomplete eyelid closure (lagophthalmos) and blinking mechanism decrease. Major consequences included conjunctival hyperemia and decreased tear volume. CONCLUSIONS: this study allowed constructing nursing diagnosis Ocular dryness, part of domain 11, class 2, with 12 defining characteristics, 12 related factors, seven populations at risk and 13 associated conditions. This problem-focused proposal may provide targeted care by promoting early detection and implementing interventions that reduce the risk of ocular damage.

Distinct Inflammatory and Oxidative Effects of Diabetes Mellitus and Hypothyroidism in the Lacrimal Functional Unit.

Diabetes mellitus (DM) and hypothyroidism (HT) are prevalent diseases associated with dry eye (DE). Their impact on the lacrimal functional unit (LFU) is poorly known. This work evaluates the changes in the LFU in DM and HT. Adult male Wistar rats had the disease induced as follows: (a) DM: streptozotocin and (b) HT: methimazole. The tear film (TF) and blood osmolarity were measured. Cytokine mRNA was compared in the lacrimal gland (LG), trigeminal ganglion (TG), and cornea (CO). Oxidative enzymes were evaluated in the LG. The DM group showed lower tear secretion (p = 0.02) and higher blood osmolarity (p < 0.001). The DM group presented lower mRNA expression of TRPV1 in the cornea (p = 0.03), higher Il1b mRNA expression (p = 0.03), and higher catalase activity in the LG (p < 0.001). The DM group presented higher Il6 mRNA expression in the TG (p = 0.02). The HT group showed higher TF osmolarity (p < 0.001), lower expression of Mmp9 mRNA in the CO (p < 0.001), higher catalase activity in the LG (p = 0.002), and higher expression of Il1b mRNA in the TG (p = 0.004). The findings revealed that DM and HT induce distinct compromises to the LG and the entire LFU.

Validation of a Semiautomatic Optical Coherence Tomography Digital Image Processing Algorithm for Estimating the Tear Meniscus Height.

Purpose: To design and validate a high-sensitivity semiautomated algorithm, based on adaptive contrast image, able to identify and quantify tear meniscus height (TMH) from optical coherence tomography (OCT) images by using digital image processing (DIP) techniques. Methods: OCT images of the lacrimal meniscus of healthy patients and with dry eye are analyzed by our algorithm, which is composed of two stages: (1) the region of interest and (2) TMH detection and measurement. The algorithm performs an adaptive contrast sequence based on morphologic operations and derivative image intensities. Trueness, repeatability, and reproducibility for TMH measurements are computed and the algorithm performance is statistically compared against the corresponding negative obtained manually by using a commercial software. Results: The algorithm showed excellent repeatability supported by an intraclass correlation coefficient equal to 0.993, a within-subject standard deviation equal to 9.88, and a coefficient of variation equal to 2.96%, and for the reproducibility test, the results did not show a significant difference as the mean value was 244.4 ± 114.9 µm for an expert observer versus 242.4 ± 111.2 µm for the inexperienced observer (P = 0.999). The method strongly suggests the algorithm can predict measurements that are manually performed with commercial software. Conclusions: The presented algorithm possess high potential to identify and measure TMH from OCT images in a reproducible and repeatable way with minimal dependency on user. Translational Relevance: The presented work shows a methodology on how, by using DIP, it is possible to process OCT images to calculate TMH and aid ophthalmologists in the diagnosis of dry eye disease.

The development of the normal Schirmer tear test results during the dog's first year of life.

OBJECTIVE: To evaluate the relationship between lacrimation and age in a homogeneous group of healthy beagle dogs during the first year of life. MATERIALS AND METHODS: Schirmer tear test I (STT I) was performed at an interval of 12-15 days in both eyes of 16 clinically healthy beagle dogs (eight males and eight females) from 94 to 361 days of age. Three different quadratic polynomial regression equations were estimated for the variation in lacrimation: (1) for the entire period (19 observations), (2) for observations 1-4 (days 94-136), and (3) for observations 5-19 (days 150-361). RESULTS: By fitting quadratic regression equations to different phases of tear production during the dog's first year of life, it was possible to see that with each day of life, lacrimation increased 0.08 times (8%). From days 94 to 136, however, lacrimal production fell 1.1 times with each day of life. From day 150 to 361, production increased by 0.02 (2%) each day of life. In addition, there was a positive significant and moderate linear correlation between body weight and STT I values (p = .01). CONCLUSION: In dogs, during the first year of life, STT I data distribution is parabolic in shape. Age significantly affected tear production. STT I decreased at approximately 108-121 days of age and increased thereafter. Body weight was a significant factor for STT I in young dogs. The establishment of this normal pattern of lacrimation is important for both clinical practitioners and laboratory studies.

Tear levels of IL-7, IL-1α, and IL-1ß may differentiate between IgG4-related disease and Sjögren's syndrome.

We aim to assess and compare a cytokine and chemokine profile in tears from patients with IgG4-related disease (IgG4-RD) and Sjögren's syndrome (SS), and to see if this profile could aid in differentiating these two diseases. We included 10 patients with IgG4-RD who met the Comprehensive Diagnostic Criteria for IgG4-RD and 17 patients who met the AECG criteria for primary SS. The Schirmer-I test was carried out using two standardized sterile tear strips, which were then immediately frozen at - 86 °C until assayed. The tears were extracted from the strips after they had been defrosted using a buffer containing 0.5 M NaCl and 0.5% Tween-20. The amounts (pg/ml) of the following cytokines and chemokines were then measured using luminometry: IFN-γ, TNF-α, G-CSF, IL-1-α, IL-1ß, IL-4, IL-7, IL-12p40, IL-12p70, IL-13, IL-17A, CCL2, CCL3, CCL4, CCL11, and CXCL10. In the IgG4-RD group, seven patients had lacrimal gland involvement, five had dry eye symptoms, and six had a positive Schirmer-I test. In the SS group, 16 (94.1%) had dry eyes and all had a positive Schirmer-I test. We were able to differentiate between both diseases using levels of IL-7, IL-1α, and IL-1ß; in particular, the IL-7/IL-1α and IL-7/IL-1ß ratios had the best discriminatory potential, with cut-off values of 0.32 (AUC: 0.93, sensitivity: 94%, specificity: 80%, p = 0.0003) and 12.55 (AUC: 0.96, sensitivity: 94%, specificity: 90%, p = 0.0001), respectively. Our results suggest that IL-7, IL-1α, and IL-1ß tear levels could help differentiate IgG4-RD from SS. Key Points • The lacrimal gland is frequently involved in IgG4-RD and SS. This characteristic makes both diseases mimics of one another. • Patients with IgG4-RD and SS have different profiles of tear cytokines and chemokines. • Tear IL-7, IL-1α, and IL-1ß levels may serve as helpful biomarkers in separating IgG4-RD from SS.

Canine keratoconjunctivitis sicca therapeutics: literature review / Terapêutica da ceratoconjuntivite seca canina: revisão bibliográfica

Keratoconjunctivitis sicca (KCS) is a disease commonly seen in dogs that is characterized by the reduction or absence of lacrimal secretions. It can be classified as qualitative or quantitative, and both categories are able to elicit conjunctival and corneal inflammation, ocular pain, progressive corneal disease, and vision impairment. This disease's treatment is based on reestablishing and maintaining ocular surface homeostasis. Patients may benefit from different therapeutic protocols, such as the use of lacrimomimetics, that increase lacrimal stability, helping to retain ocular humidity; lacrimostimulants, that promote lacrimal secretion; fatty acids, which play a role on meibum synthesis and block pro-inflammatory cytokine genic expression; blood products, based on promotion of epithelial growth factors; and stem cells, due to their self-renewing capabilities. Stable cases may benefit from the use of steroidal or non-steroidal anti-inflammatory agents on the control of clinical signs. Refractory cases may eventually benefit from surgical therapies, which include techniques for parotid duct transposition, gland transplants, and lacrimal puncta occlusion.

A ceratoconjuntivite seca (CCS) é uma doença comumente observada em cães caracterizada pela ausência ou redução das secreções lacrimais. Pode ser classificada como qualitativa ou quantitativa, sendo que ambas as categorias são capazes de desencadear inflamação da conjuntiva e da córnea, dor ocular, doença corneana progressiva e redução da visão. O tratamento desta doença é contínuo e se baseia no restabelecimento e manutenção da homeostase do sistema da superfície ocular. Os pacientes podem se beneficiar de diferentes protocolos terapêuticos, tais como o uso de lacrimomiméticos, que aumentam a estabilidade lacrimal ajudando na retenção da umidade ocular; lacrimoestimulantes para a promoção de secreção de lágrimas; ácidos graxos, que desempenham papel na síntese de meibum e bloqueiam a expressão gênica de citocinas pró-inflamatórias; produtos derivados do sangue, baseando-se nos fatores de crescimento de promoção epitelial; e células tronco, devido à sua capacidade de auto renovação. Em casos estáveis, o uso de anti-inflamatórios esteroidais ou não esteroidais pode ser benéfico no controle de sinais clínicos. Casos refratários ao tratamento podem eventualmente se beneficiar de terapias cirúrgicas, que incluem as técnicas de transposição de ducto parotídeo, transplantes glandulares e oclusão da puncta lacrimal.

Analysis of ocular surface and quality of life in patients with corneal and conjunctival tumors.

PURPOSE: To evaluate the impact of corneal and conjunctival tumors on the ocular surface and quality of life of patients before and after surgical treatment. METHODS: This prospective study conducted a preoperative and 30- and 90-day postoperative assessment of patients diagnosed with conjunctival and corneal tumors. Demographic data were collected preoperatively. The 12-Item Short-Form Health Survey (SF-12) and Ocular Surface Disease Index (OSDI) questionnaires were applied to assess patients' quality of life and perception of their vision-related functions. The tear breakup time and Schirmer tests were performed for ocular surface evaluation. The tumor extensions were measured using ImageJ image analysis software. RESULTS: Twenty-three patients were enrolled. The mean age at examination was 52.8 ± 17.3 years (range: 27-9 years). The most common tumor type was squamous cell carcinoma (61.5%). The patients' visual acuity improved significantly at 1 month and 3 months (p=0.018 and p=0.036, respectively). No significant differences were found between tear breakup time and Schirmer tests preoperatively and at 3 months postoperatively (p=0.150 and p=0.490, respectively). The SF-12 scores demonstrated significant differences between the preoperative and 30- and 90-day postoperative mental components (p=0.008 and p=0.026, respectively). Tumor extension was 868.7 ± 344.9 pixels (range, 224.6-1481.6 pixels) and were significantly correlated with the preoperative (p=0.011), 30-day postoperative (p=0.017), and 90-day postoperative (p=0.012) SF-12 mental components, as well as the emotional component at the 30th postoperative day (p=0.016). CONCLUSION: Patients with corneal and conjunctival tumors improved their ocular symptoms, visual acuity, and the emotional component of their quality of life after surgical excision of the tumor.