Detection of Coronavirus in Tear Samples of Hospitalized Patients With Confirmed SARS-CoV-2 From Oropharyngeal Swabs.

PURPOSE: This study was designed to detect CoV-RNA in the tears of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 positive patients. METHODS: We performed a prospective case series study of hospitalized patients who have been confirmed SARS-CoV-2 positive by oropharyngeal swab within the previous 5 days. Tear samples obtained with a laboratory capillary and oropharyngeal swabs were analyzed by real-time PCR using the Altona SARS-CoV-2 Assay or the Roche SARS-CoV-2 LightMix PCR, depending on the availability. Patient history was documented, and ophthalmoscopy was used to assess for ocular surface disease. RESULTS: Of all 18 patients recruited in April 2020, 5 suffered from respiratory failure and were submitted to an intensive care unit. None of our patients had signs of viral conjunctivitis although all patients in intensive care showed chemosis and conjunctival hyperemia because of third-spacing or fluid overload. The presence of coronavirus RNA was confirmed by PCR in 5 of 18 patients (28%) in tears and 72% for oropharyngeal swabs. CONCLUSIONS: Using a tear fluid sampling technique similar to oropharyngeal lavage presents a higher percentage of SARS-CoV-2 positive tears in contrast to earlier reports that used a conjunctival swab. This does not automatically indicate viral shedding in ocular tissue or contagiousness of tear fluid.

Comparison of the effects of various lubricant eye drops on the in vitro rabbit corneal healing and toxicity.

Ingredients of lubricant eye drops are potentially harmful to the ocular surface. The products Optive, Optive Fusion, Neopt were tested regarding corneal irritability versus Vismed Multi and 0.01% benzalkonium chloride as negative and positive control, respectively. Formulas (30-40µl per hour) were applied hourly in-vitro for six days on rabbit corneas (n=5, per product) cultured in artificial anterior chambers (EVEIT system). Initially, four corneal abrasions (2.4-4.6mm2) were induced. All defects were monitored during drop application by fluorescein stains and photographs. To ensure corneal vitality, glucose and lactate concentrations in artificial anterior chamber fluids were determined photometrically. All products showed a complete corneal healing on day 2. Thereafter, all five Optive-treated corneas developed progressive fluorescein-positive epithelial lesions until day six (24.96µm, ±21.45µm, p<0.01). For Optive Fusion three corneas showed corneal erosions on day six (23.11µm, ±37.02µm, p>0.5) while Vismed Multi did not adversely affect the corneal integrity. Glucose/lactate concentrations remained unchanged while lubricants were applied. Histology revealed epithelial loss and severe alterations of the superficial stroma for Optive. Optive Fusion displayed a comparable pathology. Neopt did not significantly affect the corneal healing and integrity. This study suggested a cumulative corneal toxicity of Optive and, to a lesser extent, Optive Fusion most likely caused by its oxidative preservative, SOC. Clinical data are needed to clarify the application frequency at which corneal toxicity might occur. Neopt and Vismed Multi did not affect the corneal integrity.

The Impact of Glaucoma Medications on Corneal Wound Healing.

PURPOSE: To evaluate the impact of antiglaucoma drugs on the corneal healing process and corneal toxicity. MATERIALS AND METHODS: Four eye drops to treat glaucoma--Xalatan (latanoprost 50 µg/mL; Pfizer), Monoprost (latanoprost 50 µg/mL; Théa Pharma), Taflotan Sine (tafluprost 15 µg/mL; Santen Pharmaceutical Co.), Travatan (travoprost 40 µg/mL; Alcon), and 0.02% benzalkonium chloride (BAC) solution and HyloComod (1 mg/mL sodium hyaluronate; Ursapharm) as positive and negative control were tested regarding corneal irritability and effect on corneal healing. Formulas were tested over 3 days and administered 6 times daily on rabbit corneas cultured on an artificial anterior chamber (the Ex Vivo Eye Irritation Test system). Initially, 4 corneal abrasions (2.5 to 5.7 mm2) were applied. All defects were monitored during drug application by fluorescein stains and photographs. Glucose/lactate concentrations were monitored for corneal metabolic activity evaluation. RESULTS: For Xalatan and BAC, the corneal erosion size increased from 14.65 to 66.57 mm2 and 14.80 to 87.26 mm2. Travatan and Taflotan Sine did not interfere with corneal healing. Monoprost delayed corneal healing. For Xalatan and BAC, histology showed severe alteration of the superficial cornea. An increase in anterior chamber lactate concentration indicates corneal toxicity for Xalatan, BAC, and Monoprost. CONCLUSIONS: Corneal toxicity of Xalatan is most probably caused by BAC. Monoprost delays corneal healing, which is not well understood. The Monoprost effects could be caused by its additive, macrogolglycerolhydroxystearate 40. This excipient is a known skin irritant, and its concentration is relatively elevated in Monoprost, 50 mg/mL, compared with its active ingredient, latanoprost (0.05 mg/mL).

Amyloid precursor protein processing and retinal pathology in mouse models of Alzheimer's disease.

BACKGROUND: Retinal ganglion cell loss is considered to be a cause of visual impairment in Alzheimer;s patients. Alterations in amyloid precursor protein (APP) processing and amyloid-beta (Abeta) accumulation, key molecules associated with Alzheimer;s disease pathogenesis, may therefore contribute to retinal damage. We therefore investigated retinal APP processing and eye morphology in Alzheimer;s transgenic mouse models. METHODS: Eyes and brain samples of 2- to 18-month-old transgenic mice expressing human APP with the double Swedish mutation (APPswe) (APP K595N/M596L)(Tg2576) were compared with eyes and brain tissue from wild-type background C57BL6xSJL controls. In addition, 6- to 12-month-old double transgenic mice over-expressing human APPswe and mutant presenilin 1 with exon 9 deletion (APPswe/PS1-dE9) were compared with background controls of C57BL6xC3H strain. Tissue samples were fixed in formalin for immunohistochemistry, and dissected retinal and cerebellar extracts were frozen for Western blotting and enzyme-linked immunosorbent assay (ELISA). Monoclonal antibodies 1E8 and WO2 were used for immunohistochemical detection of APP and Abeta, whereas Abeta 42/40 levels were assayed by ELISA. APP and processed fragments were detected biochemically by Western blotting with domain-specific antibodies, using antibody WO2 (Abeta) and rabbit antibody 369 to the C-terminal domain of APP. RESULTS: Immunocytochemistry revealed strong cytoplasmic expression of APP and possibly Abeta in retinal ganglion cells and inner nuclear layer cells, and in lens and corneal epithelia for APP transgenic mice. Retinas from the APP transgenic mouse strains contained 18 to 70 kDa APP proteolytic products that were not detected in the cerebellum. We found a higher proportion of APP alpha-secretase generated C-terminal fragments in transgenic retinal tissues than beta-secretase-generated C-terminal fragments. Very low level Abeta was detected in transgenic retinas by ELISA; retinal Abeta 42 was 75 times less than for transgenic brain. Abeta was not detected in mouse retina by Western blotting in our study, indicating much less generation of Abeta in retina than brain tissue. CONCLUSIONS: Alzheimer's mouse model retinas present with different APP proteolytic products and have a significantly lower production of amyloidogenic Abeta than found in brain.