Abstract Almost half the patients who undergo laser in situ keratomileusis (LASIK) experience dry eye following the procedure. However, the etiology of LASIK-induced dry eye is unclear. The purpose ...of this review is to examine and summarize the current evidence for the etiology of LASIK-induced dry eye, with a focus on ocular surface sensitivity and corneal innervation. Evidence suggests that the alteration of corneal nerves after LASIK is the most likely cause of the subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and the clinical indicators of dry eye return to apparently normal values within a year due to the partial recovery of the corneal nerve plexus. The hypothesis is explored that dry eye symptoms following LASIK may result from abnormal sensation due to LASIK-induced corneal neuropathy. Other factors, such as alterations in conjunctival goblet cell density, might also contribute to the symptoms and signs of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear neuropeptide levels and dry eye require further investigation. A better understanding of this phenomenon may result in improved management of post-LASIK dry eye.
Meibomian gland (MG) dysfunction is the leading cause of evaporative dry eye and it leads to inflammation of the ocular surface. Eicosanoids may be involved in inflammation of dry eye. This study ...aimed to profile tear eicosanoid levels in healthy individuals and those with MG dysfunction, and to examine if these levels are associated with clinical factors and expressibility of MG. Forty participants with MG dysfunction and 30 healthy controls were recruited in this study. Clinical signs of MG dysfunction were assessed, and tear lactoferrin concentration was evaluated. Tear eicosanoids were extracted from Schirmer's strips and analyzed using mass spectrometry. We were able to quantify 38 tear eicosanoids and levels were increased in older individuals. In participants with MG dysfunction, higher 5-HETE, LTB
, 18-HEPE, 12-HEPE and 14-HDoHE were associated with poorer MG expressibility. The eicosanoids PGF
, 18-HEPE, 20-HDoHE and 17-HDoHE were elevated with increased corneal staining; higher 5-HETE, LTB
were associated with lower tear lactoferrin levels. The receiver-operating-characteristics analysis shows higher levels of 5-HETE, LTB
and 18-HEPE were able to predict poor expressibility of MGs. In conclusion, tear eicosanoid levels are age-dependent and specific eicosanoids may be indicators of clinical obstruction of MG or the severity of ocular surface damage.
Dry eye disease (DED) is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis and ocular symptoms, in which neurosensory abnormalities have recently been ...shown to play an etiological role. Although the role of inflammation has been widely studied in DED, the kinetics of immune cells of the ocular surface in this complex disease are hereto unclear. Herein, we utilized intravital multiphoton imaging on transgenic mice to investigate the 3D morphology and kinetics of conventional dendritic cells (cDCs) and the role of ocular surface sensory nerves in regulating them in both the naïve state and experimental DED. Mice with DED had significantly lower tear secretion (
< 0.01), greater corneal fluorescein staining (
< 0.001), and higher cDC density in the ocular surface (
< 0.05), compared to naïve mice. cDCs in DED mice showed morphological alterations in the limbus, exhibiting smaller surface area (
< 0.001) and volume (
< 0.001) compared to naïve mice. Furthermore, corneal cDCs showed greater sphericity in DED mice compared to naïve mice (
< 0.01). In addition, limbal cDCs displayed significantly increased migratory kinetics in DED, including mean track speed, 3D instantaneous velocity, track length, and displacement, compared to naïve mice (all
< 0.05). In mice with DED, cDCs showed a higher meandering index in the limbus compared to central cornea (
< 0.05). In DED, cDCs were less frequently found in contact with nerves in the limbus, peripheral, and central cornea (
< 0.05). cDCs in contact with nerves demonstrated a larger surface area (
< 0.001) and volume (
< 0.001), however, they exhibited less sphericity (
< 0.05) as compared to cDCs not in contact with nerves in naïve mice. Importantly, cDCs in contact with nerves during DED had a decreased track length, displacement, mean track speed, and 3D instantaneous velocity compared to those not in contact with nerves (all
< 0.05). Taken together, we present
evidence of altered cDC kinetics and 3D morphology in DED. Furthermore, apparent neuronal contact significantly alters cDC kinetics and morphological characteristics, suggesting that ocular surface nerves may play a direct role in mediating immune responses in DED.
US adults visit eye care providers more often than primary healthcare providers, placing these doctors in a prime position to help identify and manage patients with prediabetes and diabetes. ...Currently, diabetes is identified in eye clinics in an advanced stage, only after visible signs of diabetic retinopathy. Recent ophthalmic research has identified multiple subclinical and clinical changes that occur in the anterior segment of the eye with metabolic disease. The corneal epithelium exhibits increased defects and poor healing, including an increased risk of neurotrophic keratitis. Increased thickness and stiffness of the cornea artificially alters intraocular pressure. There is damage to the endothelial cells and changes to the bacterial species on the ocular surface, both of which can increase risk of complications with surgery. Decreased corneal sensitivity due to a loss of nerve density predispose patients with metabolic disease to further neurotrophic complications. Patients with diabetes have increased Meibomian gland dysfunction, blepharitis and reduced tear production, resulting in increased rates of dry eye disease and discomfort. Early detection of metabolic disease may allow eye care providers to be more proactive in recommending referral and intervention in order to reduce the risk of blindness and other diabetes-related morbidity. Continued research is needed to better understand the time course of changes to the anterior segment and what can be done to better detect and diagnose patients with prediabetes or undiagnosed diabetes and provide improved care for these patients.
The lacrimal gland (LG) is the main source of the tear film aqueous layer and its dysfunction results in dry eye disease (DED), a chronic immune-mediated disorder of the ocular surface. The ...desiccating stress (DS) murine model that mimics human DED, results in LG dysfunction, immune cell infiltration, and consequently insufficient tear production. To date, the immune cell kinetics in DED are poorly understood. The purpose of this study was to develop a murine model of intravital multi-photon microscopy (IV-MPM) for the LG, and to investigate the migratory kinetics and 3D morphological properties of conventional dendritic cells (cDCs), the professional antigen presenting cells of the ocular surface, in DED. Mice were placed in a controlled environmental chamber with low humidity and increased airflow rate for 2 and 4 weeks to induce DED, while control naïve transgenic mice were housed under standard conditions. DED mice had significantly decreased tear secretion and increased fluorescein staining (
< 0.01) compared to naïve controls. Histological analysis of the LG exhibited infiltrating mononuclear and polymorphonuclear cells (
< 0.05), as well as increased LG swelling (
< 0.001) in DED mice compared to controls. Immunofluorescence staining revealed increased density of cDCs in DED mice (
< 0.001). IV-MPM of the LG demonstrated increased density of cDCs in the LGs of DED mice, compared with controls (
< 0.001). cDCs were more spherical in DED at both time points compared to controls (
< 0.001); however, differences in surface area were found at 2 weeks in DED compared with naïve controls (
< 0.001). Similarly, 3D cell volume was significantly lower at 2 weeks in DED vs. the naïve controls (
< 0.001). 3D instantaneous velocity and mean track speed were significantly higher in DED compared to naïve mice (
< 0.001). Finally, the meandering index, an index for directionality, was significant increased at 4 weeks after DED compared with controls and 2 weeks of DED (
< 0.001). Our IV-MPM study sheds light into the 3D morphological alterations and cDC kinetics in the LG during DED. While in naïve LGs, cDCs exhibit a more dendritic morphology and are less motile, they became more spherical with enhanced motility during DED. This study shows that IV-MPM represents a robust tool to study immune cell trafficking and kinetics in the LG, which might elucidate cellular alterations in immunological diseases, such as DED.
•Density, distribution and morphology of corneal epithelial dendritic cells (CEDC) do not differ in established contact lens wearers.•Reduced CEDC density in the corneal centre observed in ...orthokeratology lens wear requires confirmation in a larger group.•CEDC in the central cornea were similar in density and morphology to CEDC cells in the mid-peripheral cornea.•A lower ratio of central relative to mid-peripheral density of CEDC occurs with younger age.•A relatively lower density of CEDC in the corneal centre vs mid-periphery in younger patients may reflect a more naive immune status.
Contact lens wearers aged 15–25 years are at higher risk of corneal inflammation, yet little is known about corneal inflammatory state in this group. Previous investigations show density of corneal epithelial dendritic cells (CEDC) may increase with contact lens wear. However, it is not known how corneal distribution or morphology of CEDC alters with lens wear or whether these markers are affected by age. This study characterised CEDC in adolescent and young adult contact lens wearers to determine effects of contact lens wear and age on CEDC density, distribution and morphology.
Forty participants (20 contact lens wearers, 20 healthy non-wearers; age 16–36 years; 16M:24F) completed this pilot study. Corneal images were captured using in vivo confocal microscopy (HRTII, Rostock). CEDC were manually counted in a 1 mm2 area of the central and mid-peripheral cornea, and ratio of central to midperipheral density was calculated. CEDC morphology and dendrite length were graded. Differences between groups and between regions, and associations with age were examined. Significance was determined at P < 0.05.
A lower ratio of central to mid-peripheral CEDC density was found with younger age (ρ = 0.42, P = 0.01). CEDC morphology was not associated with age or contact lens wear. CEDC density in the mid-peripheral cornea was higher in soft lens wearers than non-wearers (P = 0.04), but central density did not differ. CEDC density and morphology were not significantly different between centre (median density 11 cells/mm2, range 0–120) and mid-periphery (10 cells/mm2, 0–58).
Density, distribution and morphology of CEDC do not differ in established contact lens wearers. A relatively lower density of CEDC in the central cornea of younger patients may allude to a more naive immune status in this group and warrants further study. Decreased central CEDC density identified in orthokeratology lens wear requires confirmation in a larger group.
Introducción: la hipertensión arterial pulmonar (HAP) es una condición clínica que conduce al fallo ventricular derecho y la muerte. Se caracterizó la epidemiología de pacientes con HAP en un centro ...de referencia de Uruguay. Métodos: se incluyeron 52 pacientes adultos con diagnóstico invasivo de HAP (enero 2006-diciembre 2016). Se estimó el riesgo mediante un modelo de cuatro variables (clase funcional CF, distancia recorrida de 6 minutos DR6M, presión auricular derecha e índice cardíaco). Se le asignó un valor de 1, 2 y 3 (bajo, intermedio y alto riesgo, respectivamente) a cada variable (Sociedad Europea de Cardiología y European Respiratory Society 2015 ESC/ERS 2015). Se categorizó el riesgo mediante el redondeo al valor entero más cercano del promedio de la suma de los valores asignados para cada variable. Resultados: edad 46±2 años, 85% femenino. Predominaron la HAP idiopática, HAP asociada a cardiopatía congénita (HAP-CPC) e HAP asociada a enfermedades del tejido conectivo (HAP-ETC). Los pacientes con HAP-CPC presentaron la mayor DR6M y la menor proporción de CF III/IV (p < 0,05). La sobrevida fue menor en HAP-ETC (p = 0,069). La mortalidad al año observada fue de 0%, 6% y 20% para pacientes con bajo (n=17), intermedio (RI, n=28) y alto (RA, n=7) riesgo, respectivamente, independientemente de la edad, sexo y subgrupo de HAP. El 51% de los pacientes con RI/RA recibieron tratamiento combinado. Conclusiones: se analizaron las características y sobrevida de pacientes con HAP de un centro de referencia uruguayo. El modelo de riesgo permitió discriminar la mortalidad de los pacientes. El 51% de los pacientes con RI/RA recibieron tratamiento combinado.
Introducción: en Uruguay funciona desde el año 2003 un programa de trasplante pulmonar (TP) mediante un convenio binacional con la República Argentina, con Fundación Favaloro, centro regional de ...referencia. Objetivos: describir los resultados del programa y herramientas en curso para mejorar la procuración pulmonar en Uruguay. Material y método: estudio descriptivo, retrospectivo, entre 2003 y 2017. Recopilación de datos del registro electrónico y análisis mediante SPSS. Resultados: ingresaron a lista 70 pacientes, 27 fueron trasplantados, 95% se reinsertaron a actividades sociales o laborales. Las etiologías fueron enfisema (33%), fibrosis quística (26%) y fibrosis pulmonar idiopática (11%). Las complicaciones más frecuentes fueron infecciones respiratorias y alteraciones de la vía aérea. La mortalidad postrasplante es 34% y la supervivencia mediana condicional supera los ocho años. La elevada mortalidad en lista (32%) impulsó el establecimiento de nuevas estrategias de procuración pulmonar. Destacamos: seguimiento longitudinal de pacientes, modificación de umbral de convocatoria, realización de maniobras de reclutamiento alveolar, realización sistemática de fibrobroncoscopía; minimización de tiempos de traslado y entrenamiento de equipo quirúrgico uruguayo para ablación. La procuración pulmonar pasó de 0 por millón de población (pmp) en 2014 y 2015 a 1,8 pmp en 2017 Conclusiones: el Programa Uruguayo de Trasplante Pulmonar ha tenido importantes avances. Los últimos dos años han sido claves para el crecimiento de la procuración pulmonar. Los resultados, la sobrevida y la morbimortalidad son comparables a los descritos internacionalmente. Las perspectivas a futuro serán consolidar el programa en un centro de referencia y realización de ablación e implante en nuestro territorio
To determine tear neuropeptide levels in contact lens wearers and non-wearers, and to examine relationships with indices of corneal innervation, tear function, and ocular discomfort.
A ...cross-sectional, single-visit, investigator-masked pilot study. Assessments included Ocular Comfort Index (OCI), central and mid-peripheral corneal nerve density and morphology (HRT-Rostock), corneal sensitivity (Cochet-Bonnet aesthesiometer), tear Substance P and calcitonin gene-related peptide (CGRP) concentration (ELISA), in situ tear osmolarity (TearLab), tear secretion (Phenol Red Thread), and noninvasive tear break-up time (NITBUT; Keeler Tearscope). Groups were compared using independent t-test or Mann-Whitney U test, and regional differences assessed using paired t-tests. Associations were analyzed using Pearson or Spearman correlation. Significance was determined at P < .05.
Twenty contact lens wearers (7M:13F, 32 ± 5 years) and 20 non-wearers (7M:13F, 31 ± 5 years) completed the study. OCI score was numerically higher in lens wearers (32.27 ± 5.33) than non-wearers (27.66 ± 9.94). Tear osmolarity was higher 298.0 (IQR 291.0-309.8) vs. 288.5 (282.3-298.3) mOsmol/L; P = .01 whereas NITBUT was lower (9.8 ± 3.4 vs. 13.8 ± 5.6 s; P = .01) in lens wearers compared with non-wearers. Tear neuropeptide concentrations were not different between groups Substance P 4.29 ng/ml (IQR 1.57-6.05), CGRP 14.89 ng/ml (5.08-59.26), and there were no differences in nerve morphology or ocular surface sensitivity. Higher nerve density, interconnections, and tortuosity were observed in the central cornea than mid-peripherally (P < .05). OCI score was moderately associated with nerve tortuosity (r = 0.42, P = .01). CGRP was associated with central nerve density (ρ = 0.38, P = .02), as was tear secretion (r = -0.37, P = .02). Nerve interconnections were strongly associated with corneal sensitivity (ρ = 0.64, P < .001).
Relationships were demonstrated between nerve density, tear CGRP, and corneal sensitivity. Markers of corneal neurobiology and sensory function do not appear to be altered in contact lens wear despite worse tear function (osmolarity and stability) in lens wearers. This suggests that mechanisms other than overt changes in corneal innervation regulate tear function during lens wear. The relationship between nerve tortuosity and ocular discomfort requires elucidation.
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