Cannabis and the Cornea.

Purpose: While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption.Methods: Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted.Results: Five studies examined corneal dysfunctions caused by cannabis consumption (opacification, decreased endothelial cell density). Twelve studies observed a reduction in corneal pain and inflammation (less lymphocytes, decreased corneal neovascularization, increased cell proliferation and migration).Conclusion: More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.

Investigação oftalmológica pré-clínica do óleo essencial de Origanum vulgare L. Lamiaceae / Ophthalmological pre-clinical research about essential oil from the Origanum vulgare L. Lamiaceae

RESUMO Objetivo: Avaliar a irritação ocular aguda em coelhos, após a administração tópica de óleo essencial. Métodos: Para tanto, os animais foram divididos em três grupos, cada um com três coelhos, totalizando 6 olhos por grupo, e a diferença entre eles foi a concentração utilizada ( 1, 3 e 9%). Aplicou-se no saco conjuntival, de um dos olhos do animal, uma dose única de 0,1 ml do produto e o olho contralateral foi usado como controle. Analisou-se os efeitos causados pelo óleo essencial na conjuntiva, íris e córnea após 1, 24, 48, 72 horas e no final do sétimo dia após a aplicação tópica. As avaliações oftalmológicas foram feitas com o auxílio de um oftalmoscópio binocular indireto com e sem fluoresceína. As reações observadas foram graduadas segundo a escala de Draize. Foram realizados exames anatomopatológicos em todos os olhos estudados no final do experimento. Resultados: No grupo de animais submetidos à instilação ocular do óleo essencial a 1%, não se observou alterações. O tratamento com o óleo a 3% provocou alteração conjuntival no exame feito em 1 hora, o que foi reduzindo. A administração do óleo essencial a 9% induziu hiperemia conjuntival, não havendo qualquer alteração nos outros tempos de avaliação oftalmológica. Conclusão: A avaliação contribuiu para conhecer as alterações clínicas na superfície ocular. Desta forma, foi possível classificar o óleo a 1% como não irritante e nas concentrações de 3 e 9% como pouco irritante, tornando possível estudos clínicos, a fim de estabelecer o óleo como alternativa terapêutica em conjuntivites bacterianas.

ABSTRACT Objective: To evaluate acute eye irritation in rabbits following topical administration of essential oil. Methods: animals were divided into three groups, each containing three rabbits, with a total of 6 eyes per group. The difference between them was the concentration used (1, 3 and 9%). A single dose of 0.1 ml of the product was applied into the conjunctival sac of one eye of the animal, and the contralateral eye was used as control. The effects caused by the essential oil in the conjunctiva, iris and cornea were analyzed after 1, 24, 48 and 72 hours and at the end of the seventh day after topical application. Ophthalmologic evaluations were performed with the aid of a binocular indirect ophthalmoscope fluorescein and with and without the observed responses, before being graded according to the Draize scale. Pathological examinations were performed on all eyes studied at the end of the experiment. Results: in the group of animals subjected to the ocular instillation of 1% essential oil, there was no change. For treatment with 3% oil, conjunctival changes were found to be decreasing during the examination after 1 hour. Administration of the 9%essential oil induced conjunctival injection, without any change in the other ophthalmologic evaluation times. Conclusion: the evaluation contributed to meet the clinical changes in the ocular surface. Thus, it was possible to classify the oil at 1% as non-irritating and the concentration of 3% and 9 as mildly irritating, making it possible for clinical studies to establish the oil as an alternative therapy in bacterial conjunctivitis.

Acute calcific band keratopathy: case report and literature review.

UNLABELLED: An 86-year-old patient developed a significant intraocular inflammatory reaction after having phacoemulsification. Topical therapy did not eliminate the inflammation, and tissue plasminogen activator (tPA) was injected into the anterior chamber. A white corneal plaque appeared in the previously clear cornea within days of the injection. The lesion was diagnosed as calcific band keratopathy and successfully treated with ethylenediaminetetraacetic acid chelation. Electron microscopy and elemental analysis of a corneal scraping from the lesion established its composition to be mainly calcium and phosphate, validating the diagnosis. This is the seventh reported case of rapid formation of calcific band keratopathy after tPA injection. The pathogenesis of this rare complication involves multiple factors, including alkalinization of the intraocular pH, increased phosphate concentration, and endothelial dysfunction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Effects of the folk medicinal plant extract Ankaferd Blood Stopper® on the ocular surface.

PURPOSE: To investigate the effects of Ankaferd Blood Stopper(®) (ABS) on the ocular surface. METHODS: Twenty adult male Wistar albino rats, weighing 390-530 g, were used in this prospective, controlled trial. One drop of ABS and one drop of balanced salt solution (BSS) were instilled into the lower conjunctival sac of the right and left eyes, respectively. After the rats were anesthetized, the ocular surface was evaluated based on the Draize criteria, and fluorescein tests were performed at 1, 2, 4, 18, 24, and 48 h. Subsequently, the rats were killed and all eyes were enucleated for histopathological examination. RESULTS: The outcome of the Draize and fluorescein tests revealed that ABS caused more irritation of the ocular surface than BSS (P < 0.001). The highest mean ABS score was 4.9 for the Draize test and 0.4 for the fluorescein test, and ABS was considered to be a slight irritant. Histopathological examinations of the cornea and the conjunctiva revealed no significant difference between the eyes instilled with BSS and those instilled with ABS. CONCLUSIONS: ABS is a hemostatic drug that exerts a slight toxic effect on the ocular surface. Given its ease of use and antibacterial activity, as well as its efficiency in stopping bleeding, the use of ABS during ocular surgery should be further investigated in experimental and clinical studies.

Coumarin embryopathy in an extremely low birth weight infant associated with neonatal hepatitis and ocular malformations.

Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to vitamin K antagonists. We report on a female premature infant (25 weeks' gestation) born to a mother who had received phenprocoumon during pregnancy following mechanical heart valve replacement. The infant presented with impaired coagulation, intraventricular and minor parenchymal cerebral haemorrhages and midface hypoplasia typical of CE. In addition, there was hepatopathy with conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of hypoglycemia upon attempts to discontinue glucose supplementation, all lasting for 4 months. There was corneal opacity with anterior segment dygenesis in the left eye, and persistent pupillary membrane, cataract and persistent hyperplastic primary vitreous in the right eye. While liver disease is an uncommon but serious side effect of vitamin K antagonists, this is the first report describing neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with mechanical heart valves, vitamin K antagonists should be used with utmost restraint.

Corneal endothelial toxicity of topical anesthesia.

PURPOSE: To determine the relative corneal endothelial toxicities of the following topical anesthetic agents: bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, proparacaine HCl 0.5%, and tetracaine HCl 0.5%. METHODS: The experiment was conducted using pigmented rabbits. Approximately nine animals each were randomly assigned to eight groups. Right eyes received injections of 0.2 ml of one of the four anesthetic agents at one of two concentrations and left eyes received injections of 0.2 ml of balanced salt solution. Corneal thickness and clarity were measured before surgery and on postoperative days 1, 3, and 7. RESULTS: A statistically significant increase (P < 0.05) in corneal thickness and opacification over preoperative measurements was noted with injections of bupivacaine, lidocaine, and proparacaine, controlling for changes occurring in control eyes from surgery alone. Proparacaine was statistically more toxic than were the others. The toxicity of tetracaine was statistically indistinguishable from balanced salt solution, although mild toxicity was evident clinically. Injection of 1:10 dilutions of the same anesthetic agents failed to produce a statistically significant increase in corneal thickness or opacification on any postoperative examination. CONCLUSIONS: Anterior chamber injection of bupivacaine HCl 0.75%, unpreserved lidocaine HCl 4%, and proparacaine HCl 0.5% produces corneal thickening and opacification that is clinically and statistically significant. Tetracaine HCl 0.5% injection produces corneal thickening and opacification that is clinically apparent in some eyes but statistically insignificant. Ophthalmic surgeons should be aware of the potential for endothelial cell injury if anesthetic agents enter or are injected into the eye during cataract surgery in the concentrations supplied commercially.

[Band-like keratopathy after treatment of postoperative fibrin reaction with tissue plasminogen activator]. / Bandförmige Keratopathie nach Behandlung der postoperativen Fibrinreaktion mit Gewebeplasminogenaktivator.

BACKGROUND: In recent years TPA (tissue-plasminogen activator) has been increasingly and successfully used for the treatment of severe, postoperative fibrin reaction in the anterior chamber. So far no serious side effects of this treatment have been reported. PATIENTS AND METHODS: Altogether, 32 patients received 0.2 ml solution with 20 micrograms TPA intracamerally. In 2 cases a dense corneal opacity was observed 12-24 hours after the injection of TPA which was resistant to treatment with local dexamethasone and lubricants. Therefore it was removed by superficial keratectomy. In one case the keratectomy specimen could be examined by light- and electronmicroscopy. RESULTS: In the keratectomy specimen a selective, fine-granular calcification of Bowman's membrane could be demonstrated. CONCLUSIONS: The intracameral TPA treatment for postoperative fibrin reaction can cause a rapid band keratopathy. Therefore the application of TPA should be restricted to severe therapy-resistant cases of intracameral fibrin reaction. In cases with the development of a band keratopathy EDTA-treatment is recommended.

[A 4-week repeated percutaneous dose toxicity study of calcipotriol (MC903) followed by a 4-week recovery test in rats].

A 4-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 4 weeks was studied in Slc:SD rats at doses of 4, 20 and 100 micrograms/kg/day as low, mid and high dose levels. 1. One male and female at high dose died probably due to stress and circulatory failure. One female at mid dose died with clonic convulsion considered to be results in attached error of a neck collar. Survival of rats showed reddish tear, reddening and desquamation of the skin at application site, and vocalization at all groups including control. Furthermore, abnormal gait, dirty hair, emaciation and opacity of the eyeball surface in both sexes were observed at high dose. 2. A decreased body weight and a slight increased water consumption in both sexes, and a decreased food consumption in males were observed at high dose. 3. An increased incidence of corneal opacity was noted significantly in both sexes as compared with control at high dose. Urinalysis revealed an increased Ca excretion in both sexes at more than mid dose, and lower pH in females at mid dose and in both sexes at high dose, and a decreased urinary volume in males at high dose. The increases of neutrophil and serum beta-globulin ratios in females, and serum Ca level in both sexes were observed at high dose. The increased mineralization of the cornea in males at mid dose and in both sexes at high dose, and of the Kidney in males at high dose were observed. At the skin of application site, cellular infiltration in the epidermis and dermis in both sexes at more than mid dose was observed. Furthermore, hyperplasia of the squamous cell in females, and hyperkeratosis in the epidermis and hypertrophy of the sebaceous gland in both sexes were observed at high dose. 4. After a 4-week recovery period, the changes related with application disappeared except for opacity of the eyeball surface and cornea, and mineralization of organs. 5. On the basis of results obtained in the present study, it is considered that 4 micrograms/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

[A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903) followed by a 5-week recovery test in rats].

A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No mortality during the experimental period was observed in both sexes of all groups including control. An increased incidence of opacity of the eyeball surface in males was noted at high dose. There were no difference in body weight and food consumption between control. An increased water consumption in both sexes was observed at high dose. 2. An increased incidence of the corneal opacity was noted significantly at high dose in both sexes compared with that observed in control. Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na, Cl and IP in males at high dose, and an decreased urinary volume in females and lower pH in both sexes at high dose. An increased serum Ca level in males at mid dose and in both sexes at high dose, and an elevated ALP activity in males at high dose were observed. The increased weights of the kidney in males at more than mid dose and adrenal gland in both sexes at high dose were observed. The increased incidence of mineralization of the cornea and kidney was noted significantly in males at more than mid dose as compared with control. Dilatation of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was observed at high dose on electron microscopic examination. 3. After a 5-week recovery period, the changes related with the treatment of MC903 almost disappeared except for mineralizations of the cornea and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in both sexes of rats.

[A 26-week repeated percutaneous dose toxicity study of calcipotriol (MC903) in rats].

A 26-week repeated percutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, was studied in Slc:SD rats at doses of 0.8, 4 and 20 micrograms/kg/day as low, mid and high dose levels. 1. No mortality were observed in both sexes of all groups including control. An increased water consumption was observed in females at mid dose and in both sexes at high dose. 2. An increased incidence of the corneal opacity in males at mid dose and in both sexes at high dose was noted significantly as compared with that observed in control. Urinalysis revealed a slight increased urinary volume, increased excretions of Ca and IP, and lower pH in both sexes at more than mid dose. Levels of the serum IP in females and Ca in both sexes were elevated at high dose. 3. The increased weights of the kidney in males and adrenal gland in females were observed at high dose. The kidney in females at mid dose and in both sexes at high dose showed a higher incidence of mineralization than in control. Furthermore, osteosclerosis of the sternum and femur in both sexes, and hyperkeratosis of the skin at application site in females at high dose were observed. Electron microscopic examination revealed no abnormality in the liver and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.8 microgram/kg/day is the no-toxic dose of MC903 applied percutaneously in both sexes of rats.

The chicken enucleated eye test (CEET): a practical (pre)screen for the assessment of eye irritation/corrosion potential of test materials.

The enucleated eye test with chicken eyes (CEET) obtained from an abattoir proved to be a valuable and practical alternative for the 'traditional' enucleated eye test with eyes of laboratory rabbits. Since 1992, the CEET has been incorporated in standard contract toxicity testing at the Toxicology Division of the TNO Nutrition and Food Research Institute as a (pre)screen for the Draize eye test with rabbits. The results of the first 44 compounds tested showed excellent correlation with the in vivo results. The CEET identified non-irritating or severely irritating compounds, and predicted (slightly to moderately) irritating compounds. Statistical analysis of the CEET and the rabbit in vivo scores showed high linear correlations between the critical values of both tests and confirmed the relevance of this assay with respect to ocular effects. In general, tiered in vitro/in vivo testing was considered a meaningful approach for further validation of alternative methods and for reducing the use of suffering of laboratory animals to a minimum. Tiered testing of compounds in cases of eye irritation hazard assessment should be incorporated in the legislation of the European Community.

Ocular effects of treatment with various psoralen derivatives and ultraviolet-A (UVA) radiation in HRA/Skh hairless mice.

Hairless (HRA/Skh) mice were administered one of four dietary concentrations (50, 100, 625 or 1250 ppm) of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP), or molar equivalent concentrations of 5-methylisopsoralen (5-MIP) or 3-carbethoxypsoralen (3-CPS) by 'pulse feeding' technique, 3 days per week for 13 weeks. For the final 11 weeks psoralen derivative administration was followed by exposure to 0.2 or 48 J/cm2 of unfiltered ultraviolet-A (UVA) radiant energy from FR74T12PUVA lamps. At 0 and 13 weeks eyes were dilated with 0.2% atropine solution and were examined using a binocular indirect ophthalmoscope with a +20.0 D condensing lens. The lids, cornea, anterior chamber and the lens were evaluated for pathological changes. Ocular damage consisting of dense central corneal opacification was seen at significant levels in animals given 8-MOP or 5-MOP and exposed to UVA. In addition, opacities in the area of the posterior lens were seen in all experimental groups and appeared to be related to drug treatment, independent of light exposure, and therefore appeared not to be related to drug-light interaction. Some corneal and lenticular opacification was seen at non-significant levels in all experimental and control groups.

8-methoxypsoralen and long ultraviolet effects on the rat lens: experiments with high dosage.

The effect of systemic 8-methoxypsoralen (8-MOP; 100 mg/kg daily) and subsequent long ultraviolet irradiation (UVA; 300 mJ/cm2; peak: 365 nm) on albino and pigmented rat eyes was studied in a 3-dimensional experimental set-up. While 8-MOP and UVA did not cause any ocular pathology when administered alone, a combined application of the two factors caused reversible corneal opacities, and irreversible iris devascularisation and cataracts. The irreversible changes were seen only in the albinos and accompanied by a significant decrease in lens wet weight. Phosphorescence and EPR spectroscopy demonstrated the formation of an 8-MOP-protein photoadduct in the animals treated with both 8-MOP and UVA. The results of this study emphasize the necessity of shielding the eyes of patients on photochemotherapy with protective spectacles.

Treatment of Vaccinial keratitis with trifluorothymidine.

The efficacy of trifluorothymidine was compared with idoxuridine on a blind basis by noting the effect of topical administration of the drugs on the severity of vaccinial keratitis induced in rabbits. Trifluorothymidine was found to be substantially more effective, and was well tolerated. In addition, positive viral cultures after the treatment period were substantially reduced in the trifluorothymidine groups when compared with the idoxuridine or control groups.