Infectious Eye Diseases Research Articles

Features of Diseases of the Anterior Part of the Eye in Patients after COVID-19

There are quite systematic data of the ophthalmic manifestations in SARS-CoV-2, on the presence of conjunctivitis in patients with COVID-19, as well as on the detection of viruses in the lacrimal fluid and eye tissues. And, although ophthalmic manifestations are considered rather rare for COVID-19 and are not included in the list of important for diagnosis, there is not enough reliable data on the inflammatory processes of the eye’s anterior part and their connection with COVID-19, as well as those arising against the background of the treatment.Purpose. To study the development of inflammatory diseases of the anterior part of the eye in patients who have undergone the new coronavirus infection COVID-19.resu. In the Department of Infectious and Allergic Eye Diseases of the Helmholts National Medical Research Center of Eye Diseases, 88 patients with confirmed transferred new coronavirus infection COVID-19 of varying severity were observed. The main method of laboratory diagnostics is the detection of SARS-CoV-2 RNA in swabs from the nasopharynx, the patient’s sputum. Serodiagnostics of COVID-19 includes the determination of IgG-, IgM-antibodies to SARS-CoV-2 in the blood in an enzyme-linked immunosorbent assay.Results. Acute conjunctivitis associated with COVID-19 is quite rare and is an early sign of the disease. In the complex nonspecific topical therapy of viral conjunctivitis in COVID-19, along with etiopathogenetic systemic treatment, local eye medications with immunomodulatory and antiviral activity should be used. Conjunctivitis during a pandemic may be the only sign of COVID-19. The development of allergic conjunctivitis in COVID-19 is possibly associated not only with the effect of a viral agent, but also depends on the toxic effect of drugs used in the complex treatment of this disease. The increase in the number of patients with episcleritis after the postponed coronavirus infection needs further detailed study, with the analysis of laboratory data from this group of patients and the accumulation of clinical material.Conclusion. Ophthalmic manifestations in COVID-19 are very different, affecting various structures of the eye, occur at different periods — both during the course of the disease and after clinical recovery, and, of course, need further consideration, study and structuring.

Местная антибиотикотерапия бактериальных инфекционно-воспалительных заболеваний переднего отрезка глаза

Inflammatory eye diseases are one of the most important problems of ophthalmology. They can be caused by various pathogens of the infection, which is still more often bacterial. Therapy of bacterial inflammatory diseases of the eye involves the use of antibacterial drugs (sulfonamides, antiseptics, nitrofurans, etc.), among which antibiotics are of primary importance. Of this group of drugs, in this review article, special attention is paid to quinolones, mainly synthetic fluoroquinolones, which are distinguished by a wide range of bactericidal action, fairly high efficiency, low level of resistance of microorganisms to it and the frequency of side effects, as well as good tolerability by patients, i.e. they best meet the requirements for modern topical antimicrobial agents. In certain clinical situations and indications, it is advisable to use ophthalmic antiseptics and combined preparations containing several antibiotics of different effects at once, or an antibiotic and a corticosteroid. Key words: infectious and inflammatory eye diseases, antibacterial agents, antibiotics, combined preparations, antiseptics.

Clinical Application and Efficacy of Silver Drug in Ophthalmology: A Literature Review and New Formulation of EYE Drops with Drug Silver (I) Complex of Metronidazole with Improved Dosage Form.

The use of silver preparations in medicine is becoming increasingly popular. The basic aim of this evaluation was to review the literature on the clinical (in vivo) and antibacterial potential of silver preparations in ophthalmic diseases. The second goal was to summarize the results of experimental research on the use of silver preparations in ophthalmology. The third objective was to present a method for stabilizing eye drops containing silver (I) complex. Analysis of the pH stability of the silver (I) complex with metronidazole in the prepared dosage form (eye drops) was carried out. Most silver preparations are clinically used for topical application. Few experimental results indicate the usefulness of intraocular or systemic administration of silver (I) preparations as an alternative or additional therapy in infectious and angiogenic eye diseases. The development of a new formulation increases the stability of the dosage form. New forms of silver (I) products will certainly find application in the treatment of many ophthalmic diseases. One of the most important features of the silver (I) complex is its capacity to break down bacterial resistance. The new eye drops formula can significantly improve comfort of use. Due to their chemical nature, silver (I) compounds are difficult to stabilize, especially in the finished dosage form.

Fluoroquinolone resistance of Staphylococcus epidermidis isolated from healthy conjunctiva and analysis of their mutations in quinolone-resistance determining region

BackgroundStaphylococcus epidermidis is the most common pathogen in postoperative endophthalmitis and causes various infectious eye diseases. However, there is very little information on fluoroquinolone antibiotic resistance to S. epidermidis identified in conjunctival microbe and analysis of related genes. Here, the authors investigated the rate of resistance to fluoroquinolones of Staphylococcus epidermidis isolated from normal conjunctival microbes and mutations in the quinolone-resistance determining region (QRDR).Methods377 eye samples from 187 patients who underwent intravitreal injection and cataract surgery were included. Specimens were taken from the bilateral lower conjunctival sacs using a cotton swab and cultured. The cultures were identified using MALDI-TOP MS and gyrA, gyrB, parC, and parE gene mutations of QRDR were confirmed by DNA extraction from resistant strains of S. epidermidis with a micro-dilution method using ciprofloxacin, levofloxacin, and moxifloxacin.ResultsThe culture positive rate was 61.8% (231) for 374 eye samples. Of the 303 total strains cultured, S. epidermidis was the most common with 33.7% (102). Ten types of gene mutations were observed in the resistant S. epidermidis of 21 strains. One-point mutation was observed mainly in gyrA and parC, and a small number of mutations were observed in parE in the form of a double point mutations. When there were multiple point mutations in both gyrA and parC, the highest minimum inhibitory concentration was observed.ConclusionsThe quinolone resistance rate of S. epidermidis increased in comparison with previous studies, and resistant S. epidermidis showed mostly QRDR mutations, which were mainly found in gyrA and parC, and showed strong resistance when mutated in both genes.

Paying attention to adopting modern epidemiological methods for the prevention and treatment of infectious eye diseases

Carrying out research on infectious epidemics is an important work contents stipulated in the Law on the Prevention and Control of Infectious Diseases in China. Nowadays, Based on the recent Chinese prevention and treatment system of infectious eye diseases, it is difficult to meet the needs of data collection, etiology determination, and spatiotemporal analysis. The present article explores how to use modern social epidemiology methods to clarify the role of individual factors, social factors, and structural factors in the three links of eye disease epidemic, how to use spatial epidemiology methods to describe, quantify, and explain the spatial distribution characteristics of eye diseases in the population, and how to use infodemiology and digital epidemiology methods to promptly and efficiently mine and process massive amounts of electronic data of eye diseases. These may be used to improve the scientific nature of Chinese eye disease epidemiology research, and strengthen the China's infectious eye disease prevention and control system.(Chin J Ophthalmol, 2020, 56:567-570).

Visual Impairment and Eye Diseases in HIV-infected People in the Antiretroviral Therapy (ART) Era in Rakai, Uganda

ABSTRACT Purpose Antiretroviral therapy reduced infectious eye diseases (EDs) in HIV-infected people. There is limited data on age-related EDs and visual impairment (VI) in people living with HIV. We report prevalence of VI and spectrum of EDs in HIV-infected people in an ART era in Rakai, Uganda. Methods A philanthropic campaign during 2009–2012 provided ophthalmic services to HIV+ patients in care. Unilateral presenting visual acuity (VA) was assessed by a trained staff in HIV clinics using a 6-m Snellen chart. A slit-lamp examination by an ophthalmologist evaluated eyes with impaired acuity. A retrospective chart review was later conducted retrieving data of patients participating the ophthalmic service. VI was defined referencing WHO’s ICD-11. Ophthalmic diagnosis was summarized by VI level. Logistic regressions estimated demographic associations with cataract diagnosis. Results 688 HIV+ patients were evaluated, median age was 44 (IQR: 37–50) years, 69% were female. Fifty-one percent were on ART (median duration 4, IQR: 2–5 years). Crude prevalence of moderate/severe VI and blindness were both 2%. The main diagnoses were refractive error (55%), conjunctivitis (18%), cataract (15%), and pterygium (11%). Cataract prevalences were 10%, 12%, and 26% among age groups of 19–34, 35–49, and ≥50 years, respectively. Cataract was found in 73% of the HIV+s with blindness and in 63% of those with moderate/severe VI. Older age and male sex were significantly associated with higher cataract prevalence. Conclusion VI in HIV+ patients in Rakai was mainly due to refractive error and cataract. Cataract was common in all age groups.

Infectious and inflammatory processes leading to the eye damage. Principles of diagnosis and treatment

Infectious and inflammatory eye diseases are a fairly common pathology among ophthalmic diseases. The reason for the development of the infectious process can be noncompliance with personal hygiene rules, traumatic eye damage, contact with a person who has a similar pathology. In some cases development of an infectious and inflammatory process is observed against the background of a decrease in the general body resistance to the action of viral and bacterial agents. Most often infection affects eye against the background of diabetes mellitus, long-term use of hormonal drugs, and alcohol abuse. Symptoms of diseases are diverse and depend on the type of pathogen and what particular structural part of the eye is affected. Viruses (adenoviruses, herpes simplex virus), bacteria (Staphylococcus aureus, gonococcus), chlamydia and even fungi can act as infecting agent. Conjunctivitis, keratitis, blepharitis, uveitis, dacryocystitis, etc. are distinguished depending on what part of the eye is affected. Diagnosis of infectious and inflammatory processes affecting the organs of vision is carried out by visual inspection, using a slit lamp, if necessary, as well as taking sample for the microbiological test in order to determine the type of pathogen. Ultrasound or computed tomography is indicated in some cases.

Strengthening basic and clinical research on ocular infection caused by coronavirus

This article was published ahead of print on the official website of Chinese Jounal of Ophthalmology on February 19, 2020. The prevention and treatment of coronavirus disease 2019 (COVID-2019) has reached the critical stage in China. Ocular surface represents a possible route for infection. Based on the previous studies and our own research, we summarize the potential transmission route and clinical symptoms of COVID-2019 in the eye, as well as the further prevention and research, with the expectation of contributing to the development in the field of infectious eye disease in China. (Chin J Ophthalmol, 2020, 56:250-252).

Useful Medicinal Plants for Vision Impairment in Traditional Iranian Medicine

Vision impairment is an important general health issue that imposes many costs on governments and the health system every year. Despite the decline in infectious eye diseases, which has reduced the vision impairment and blindness over the past two decades, vision impairment is still a major health problem in some parts of the world. In traditional medicine books, visual weakness is referred to as “any disturbance in the act of seeing”. Many medicinal herbs have been mentioned in books of Traditional Iranian medicine (TIM) for the management of vision impairment. The aim of this study is to review the medicinal plants mentioned in TIM, which are considered effective for the treatment of vision impairment or its enhancement. In this library-based study, medicinal plants effective in the treatment of vision impairment were searched using 6 valid sources of traditional medicine, including Makhzan ol-Adawiya, The Canon of Medicine, Tuhfat al-Momenin, Al-Abniyah An Haqaiq al-adwiya, Al-Shamil Fi al-Sana’at al-tebiyah, and Ekhtiarate Badiee. This was done in 10 steps (finding keywords, searching for resources, preparing a single list, finding synonyms, classifying, reviewing, extracting plants from compositions, summarizing, scoring and sorting based on the obtained score). A total of 89 medicinal plants were extracted, most of which had a hot and dry temperament. Based on the obtained score, 12 plants got the highest scores (10 and above). The extracted plants can be the basis for further clinical studies to make new effective drugs for the prevention and treatment of vision impairment.[GMJ.2019;8:e1285]

Useful Medicinal Plants for Vision Impairment in Traditional Iranian Medicine.

Vision impairment is an important general health issue that imposes many costs on governments and the health system every year. Despite the decline in infectious eye diseases, which has reduced the vision impairment and blindness over the past two decades, vision impairment is still a major health problem in some parts of the world. In traditional medicine books, visual weakness is referred to as "any disturbance in the act of seeing ". Many medicinal herbs have been mentioned in books of Traditional Iranian medicine (TIM) for the management of vision impairment. The aim of this study is to review the medicinal plants mentioned in TIM, which are considered effective for the treatment of vision impairment or its enhancement. In this library-based study, medicinal plants effective in the treatment of vision impairment were searched using 6 valid sources of traditional medicine, including Makhzan ol-Adawiya, The Canon of Medicine, Tuhfat al-Momenin, Al-Abniyah An Haqaiq al-adwiya, Al-Shamil Fi al-Sana’at al-tebiyah, and Ekhtiarate Badiee. This was done in 10 steps (finding keywords, searching for resources, preparing a single list, finding synonyms, classifying, reviewing, extracting plants from compositions, summarizing, scoring and sorting based on the obtained score). A total of 89 medicinal plants were extracted, most of which had a hot and dry temperament. Based on the obtained score, 12 plants got the highest scores (10 and above). The extracted plants can be the basis for further clinical studies to make new effective drugs for the prevention and treatment of vision impairment.

Pathogens distribution and drug resistance of preschool children with infectious eye diseases in Nanyang Area

Pathogens distribution and drug resistance of preschool children with infectious eye diseases in Nanyang Area

Pharmaceutical challenges and perspectives in developing ophthalmic drug formulations

Ocular drug delivery has been widely recognized as an attractive route for drug administration for cures of ocular diseases. Overall, designing an effective therapy to cure ocular diseases has been considered as a formidable task. Even though some infectious or inflammatory eye diseases could be alleviated by eye drops or ointments, achieving the required therapeutic efficacy along with ocular bioavailability remains a challenge due to the numerous anatomical and physiological barriers prevailing in the eye. Drug delivery to the posterior segment of the eye is yet a more challenging task. In this context, a better understanding of physiologic natures of the eyes and ocular pharmacokinetics would facilitate the development of new drug delivery systems to treat various vision-threatening disorders. For the effective drug delivery to target sites and to enhance the ocular bioavailability, recent progress in formulation strategies using nanotechnologies holds promises in terms of devising improved ophthalmic medicines. Hence, this review presents an overview of various aspects of ocular drug delivery, with a specific emphasis on nanocarrier-based strategies, including physiological barriers in eyes and conventional drug formulations. Recent research on sustained, controlled, and targeted systems for ocular drug delivery was updated as well.

Prevalence and determinants of active trachoma among preschool-aged children in Dembia District, Northwest Ethiopia

BackgroundTrachoma is an infectious eye disease caused by Chlamydia trachomatis, which is the leading infectious cause of blindness worldwide. In areas where trachoma is endemic, active trachoma is common among preschool-aged children, with varying magnitude. This study aimed to estimate the prevalence of active trachoma and associated risk factors among preschool-aged children in Dembia District, northwest Ethiopia.MethodsA community-based cross-sectional survey was conducted among preschool-aged children of northwest Ethiopia. Multistage systematic random sampling was used to select 695 subjects. Trained clinical optometrists subjected each child to an ocular examination and assessed the presence of active trachoma. Face to face interview using pretested and structured questionnaire were conducted to collect data on possible risk factors. Trachoma cases were graded following a World Health Organization simplified grading scheme. All statistical analysis was carried out using the SPSS software version 20. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were used to identify factors associated with active trachoma.ResultsOf the 681 preschool-aged children studied, 18% (95% CI: 15.4% – 21.1%) had a prevalence of active trachoma. Children who had clean faces (absence of nasal and ocular discharges) had a lower chance of having active trachoma [aOR = 0.55, 95% CI: 0.37 – 0.82]. The odds of having active trachoma decreased with an increase in the distance to a water point [aOR = 0.51, 95% CI: 0.33 – 0.78]. Similarly, no or poor utilization of liquid waste disposal in the child’s household was associated with an increased chance of having active trachoma [aOR = 3.83, 95% CI: 1.26 – 11.61].ConclusionThe prevalence of active trachoma in these preschool-aged children was found to be high and needs special interventions that focus on educating families about proper face washing, liquid waste disposal, and improving safe water supply near the households.

Perfil clínico y epidemiológico de las enfermedades oculares no infecciosas en comunidades indígenas de Chocó, Colombia.

Objetivo: determinar el perfil clínico y epidemiológico de las enfermedades oculares no infecciosas en población indígena del departamento de Chocó, Colombia. Materiales y Métodos: estudio descriptivo transversal, en comunidades indígenas de la Asociación de Cabildos Indígenas Embera, Wounaan, Katío, Chami y Tule en 2015. No se realizó muestreo, se evaluaron líderes indígenas mayores de 18 años, sin enfermedades oftalmológicas infecciosas y que decidieron participar voluntariamente mediante consentimiento informado. Se diseñó un cuestionario para registrar variables sociodemográficas y oftalmológicas. Resultados: se evaluaron 46 indígenas, con un promedio de edad de 34,2 ± 9,5, 69,6% eran hombres, 21,7% eran Embera Dobida, 56,5% habían completado los estudios de secundaria y 23,9% se desempeñaban en el área de educación. El 82,6% de los participantes presentaron agudeza visual normal, 15,2% presentaron déficit visual y ninguno presentó déficit visual severo o ceguera. Se encontraron alteraciones conjuntivales en el 56,5% y alteraciones al Cover test en 58,6%, siendo la endotropia y endoforia los hallazgos más frecuentes. No se encontraron alteraciones en la evaluación de la movilidad ocular, tonometría, campimetría, ni fondo de ojo. Conclusiones: se encontraron niveles aceptables de visión y salud oftalmológica entre la población evaluada, que no representan limitaciones considerables para su quehacer diario, pero que potencialmente las podrían ocasionar. La endotropia y las alteraciones conjuntivales corresponden a los hallazgos más frecuentes.

Getting to 2020: A Clinical Review of the Diagnosis, Treatment and Prevention of Trachoma

Objectives: 1) to undertake a review of the literature to provide information to clinicians and trainees about the epidemiology, treatment and most importantly, prevention, of trachoma - the leading infectious cause of blindness worldwide. 2) To highlight the diagnosis and treatment of this preventable infectious eye disease for trainees and to evaluate the efficacy of the SAFE treatment and prevention strategy endorsed by the WHO as the target trachoma elimination year of 2020 nears.
 Methods: A review of the literature was undertaken. PubMED, Clinical Key, UpToDate and Google Scholar databases were searched using the following MeSH terms and keywords: trachoma, infectious eye disease, chlamydia trachomatis, SAFE, community prevention.
 Results: The diagnosis of trachoma is typically clinical and is made by identifying the signs of conjunctival inflammation and scarring, trichiasis and corneal opacification in the context of a trachoma-endemic region. Randomized controlled trials have demonstrated the efficacy of the WHO’s SAFE (Surgery, Antibiotics, Facial Cleanliness, Environmental change) treatment and prevention strategy, the implementation of which has been associated with declining rates of trachoma worldwide.

History and development of ophthalmology in Taiwan.

Western medicine was first introduced to Taiwan by medical missionaries in the mid-19th century. Modernization of medicine was systematically transplanted to Taiwan in the Japanese colonial period, and ophthalmology was established third among hospital departments, following internal medicine and surgery. Dr Hidetaka Yamaguchi, an ophthalmologist, was the first head of the Taihoku Hospital, later known as National Taiwan University Hospital (NTUH; Taipei, Taiwan). Ophthalmologists during the colonial period conducted studies on tropical and infectious eye diseases. After World War II, ophthalmologists at NTUH played an important role in medical education, residency training, studies, and teaching. Dr Yan-Fei Yang established the Taiwan Ophthalmological Society in 1960 and instituted its official journal in 1962. Dr Ho-Ming Lin established the Department of Ophthalmology at the Tri-Service General Hospital in the 1950s and the Veterans General Hospital in the 1960s. Taiwan ophthalmologists eradicated trachoma by 1971. Cataract surgery and penetrating keratoplasty were initially performed in the 1960s. Currently, there are about 1600 ophthalmologists in Taiwan conducting an estimated 120,000 cataract surgeries and 600 corneal transplantations annually. Many subspecialty societies have been established recently that serve to educate Taiwanese ophthalmologists and to connect with international ophthalmic societies. Taiwan ophthalmologists continue to contribute to the advancement of ophthalmic knowledge globally.

Surveillance Tools Emerging From Search Engines and Social Media Data for Determining Eye Disease Patterns.

Internet-based search engine and social media data may provide a novel complementary source for better understanding the epidemiologic factors of infectious eye diseases, which could better inform eye health care and disease prevention. To assess whether data from internet-based social media and search engines are associated with objective clinic-based diagnoses of conjunctivitis. Data from encounters of 4143 patients diagnosed with conjunctivitis from June 3, 2012, to April 26, 2014, at the University of California San Francisco (UCSF) Medical Center, were analyzed using Spearman rank correlation of each weekly observation to compare demographics and seasonality of nonallergic conjunctivitis with allergic conjunctivitis. Data for patient encounters with diagnoses for glaucoma and influenza were also obtained for the same period and compared with conjunctivitis. Temporal patterns of Twitter and Google web search data, geolocated to the United States and associated with these clinical diagnoses, were compared with the clinical encounters. The a priori hypothesis was that weekly internet-based searches and social media posts about conjunctivitis may reflect the true weekly clinical occurrence of conjunctivitis. Weekly total clinical diagnoses at UCSF of nonallergic conjunctivitis, allergic conjunctivitis, glaucoma, and influenza were compared using Spearman rank correlation with equivalent weekly data on Tweets related to disease or disease-related keyword searches obtained from Google Trends. Seasonality of clinical diagnoses of nonallergic conjunctivitis among the 4143 patients (2364 females [57.1%] and 1776 males [42.9%]) with 5816 conjunctivitis encounters at UCSF correlated strongly with results of Google searches in the United States for the term pink eye (ρ, 0.68 [95% CI, 0.52 to 0.78]; P < .001) and correlated moderately with Twitter results about pink eye (ρ, 0.38 [95% CI, 0.16 to 0.56]; P < .001) and with clinical diagnosis of influenza (ρ, 0.33 [95% CI, 0.12 to 0.49]; P < .001), but did not significantly correlate with seasonality of clinical diagnoses of allergic conjunctivitis diagnosis at UCSF (ρ, 0.21 [95% CI, -0.02 to 0.42]; P = .06) or with results of Google searches in the United States for the term eye allergy (ρ, 0.13 [95% CI, -0.06 to 0.32]; P = .19). Seasonality of clinical diagnoses of allergic conjunctivitis at UCSF correlated strongly with results of Google searches in the United States for the term eye allergy (ρ, 0.44 [95% CI, 0.24 to 0.60]; P < .001) and eye drops (ρ, 0.47 [95% CI, 0.27 to 0.62]; P < .001). Internet-based search engine and social media data may reflect the occurrence of clinically diagnosed conjunctivitis, suggesting that these data sources can be leveraged to better understand the epidemiologic factors of conjunctivitis.

Instrument-Free Synthesizable Fabrication of Label-Free Optical Biosensing Paper Strips for the Early Detection of Infectious Keratoconjunctivitides.

We introduce a surface-enhanced Raman scattering (SERS)-functionalized, gold nanoparticle (GNP)-deposited paper strip capable of label-free biofluid sensing for the early detection of infectious eye diseases. The GNP biosensing paper strip was fabricated by the direct synthesis and deposition of GNPs on wax-divided hydrophilic areas of a permeable porous substrate through a facile, power-free synthesizable, and highly reproducible successive ionic layer absorption and reaction (SILAR) technique. To maximize localized surface plasmon resonance-generated SERS activity, the concentration of the reactive solution and number of SILAR cycles were optimized by controlling the size and gap distance of GNPs and verified by computational modeling with geometrical hypotheses of Gaussian-estimated metallic nanoparticles. The responses of our SERS-functionalized GNP paper strip to Raman intensities exhibited an enhancement factor of 7.8 × 10(8), high reproducibility (relative standard deviation of 7.5%), and 1 pM 2-naphthalenethiol highly sensitive detection limit with a correlation coefficient of 0.99, achieved by optimized SILAR conditions including a 10/10 mM/mM HAuCl4/NaBH4 concentration and six SILAR cycles. The SERS-functionalized GNP paper is supported by a multivariate statistics-preprocessed machine learning-judged bioclassification system to provide excellent label-free chemical structure sensitivity for identifying infectious keratoconjunctivitis. The power-free synthesizable fabrication, label-free, rapid analysis, and high sensitivity feature of the SILAR-fabricated SERS-functionalized GNP biosensing paper strip makes it an excellent alternative in point-of-care applications for the early detection of various infectious diseases.

Pathogenesis and treatment of overwhelming inflammation induced by Pseudomonas aeruginosa keratitis in rabbit

Background Infectious keratitis is common blinding eye disease in China. Inflammatory runaway reaction often occurs in infectious keratitis, and its mechanism and treating approach are worthy of research. Objective This study was to investigate the clinical manifestation, mechanism and treatment outcome of doxycycline in overwhelming inflammation induced by Pseudomonas aeruginosa keratitis. Methods Pseudomonas aeruginosa suspension was intrastromal injected in 60 right eyes of 60 New Zealand white rabbits, and gatifloxacin eye drops was frequent instilled for consecutive 3 days to establish corneal inflammatory runaway reaction models, and 42 eyes with worse keratitis were defined as overwhelming inflammation. Then the models were randomly divided into gatifloxacin treatment group (15 rabbits), combined treatment group (gatifloxacin with doxycycline treatment, 15 rabbits) and balance salt solution (BSS) control group (12 rabbits), and corresponding eye drops was topically administered in the rabbits 8 times per day for 14 days. The symptoms of the models were observed under the slit lamp microscope on day 1, 3, 7 and 14 after treatment, and the corneal infiltration area was calculated. The corneal morphology was examined by using hematoxylin-eosin staining. The expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the corneal tissue were examined by immunohistochemistry. The contents of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in corneal homogenate were detected by ELISA. The use and care of the animals complied with the ARVO Statement. Results The inflammatory scores were lower and infiltration area of cornea was smaller 7 days after treatment than those before treatment in the combined treatment group and gatifloxacin treatment group (both at P<0.05). Hematoxylin-eosin staining result showed that the inflammation response of cornea subsided 14 days in comparison with 5 days after treatment in the combined treatment group, with the proliferation and rearrangement of fiberal tissue. The MMP-2 and MMP-9 were strongly expressed in corneal tissue with overwhelming inflammation in day 5 after treatment, however, the expression intensity weakened in 14 days after treatment in the combined treatment, showing significant differences in the absorbance between them (all at P<0.05). ELISA assay showed that the contents of TNF-α and IL-1β in corneal tissue were significantly lower in the combined treatment group than those in the BSS group (P=0.00, 0.03). In addition, contents of TNF-α and IL-1β in corneal tissue were significantly declined at day 14 in comparison with day 5 and day 7 after treatment in the combined treatment group (all at P<0.05). Conclusions Overwhelming inflammatory keratitis models can be successfully established by corneal intrastromal injection of Pseudomonas aeruginosa suspension and immediately frequent 3-day instillation of gatifloxacin eye drops in rabbits. The topical application of doxycycline plays treating effect on overwhelming inflammatory keratitis by inhibiting the release of pro-inflammatory cytokines and MMPs. Key words: [Key words] Infectious eye disease, corneal; Bacteria; Pseudomonas aeruginosa; Antibacterial agents; Overwhelming inflammation; Keratitis/drug therapy; Doxycycline; Disease models, animal; Rabbits

Liposomal voriconazole (VOR) formulation for improved ocular delivery

Treating infectious eye diseases topically requires a drug delivery system capable of overcoming the eye's defense mechanisms, which efficiently reduce the drug residence time right after its administration, therefore reducing absorption. In order to try to surpass such administration issues and improve life quality for patients with fungal keratitis, liposomal voriconazol (VOR) formulations were prepared. Formulations were composed of soy phosphatidylcholine (PC) containing or not 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and cholesterol. Liposomes were characterized by their drug entrapment efficiency (EE), drug recovery (DR), average diameter (size) and polydispersivity index (PdI). In vitro mucosal interaction and irritancy levels, ex vivo permeation, as well as the short-term stability were also assessed. Liposomal VOR formulation produced with 7.2:40mM VOR:PC showed to be the most promising formulation: mean size of 116.6±5.9nm, narrow PdI (0.17±0.06), negative zeta potential (∼−7mV) and over 80% of EE and yield, remaining stable for at least 30 days in solution and 90 days after lyophilization. This formulation was classified as ‘non-irritant’ after HET-CAM's test and was able to deliver about 47.85±5.72μg/cm2 of VOR into porcine cornea after 30min of permeation test. Such drug levels are higher than the minimal inhibitory concentrations (MIC) of several fungi species isolated from clinical cases of corneal keratitis. Overall results suggest VOR can be effectively incorporated in liposomes for potential topical treatment of fungal keratitis.