Infectious Keratitis: An Update on Role of Epigenetics.

Epigenetic mechanisms modulate gene expression and function without altering the base sequence of DNA. These reversible, heritable, and environment-influenced mechanisms generate various cell types during development and orchestrate the cellular responses to external stimuli by regulating the expression of genome. Also, the epigenetic modifications influence common pathological and physiological responses including inflammation, ischemia, neoplasia, aging and neurodegeneration etc. In recent past, the field of epigenetics has gained momentum and become an increasingly important area of biomedical research As far as eye is concerned, epigenetic mechanisms may play an important role in many complex diseases such as corneal dystrophy, cataract, glaucoma, diabetic retinopathy, ocular neoplasia, uveitis, and age-related macular degeneration. Focusing on the epigenetic mechanisms in ocular diseases may provide new understanding and insights into the pathogenesis of complex eye diseases and thus can aid in the development of novel treatments for these diseases. In the present review, we summarize the clinical perspective of infectious keratitis, role of epigenetics in infectious keratitis, therapeutic potential of epigenetic modifiers and the future perspective.

Abscesos de córnea bilaterales en una paciente con SIDA. Presentación de un caso y revisión de la literatura / Corneal Abscess in a patient with aids: case report and literature review

El epitelio corneal es una importante barrera de defensa que impide el ingreso de una gran variedad de microorganismos. Cualquier alteración de la superficie ocular facilita la invasión bacteriana de la córnea. El germen más frecuentemente identificado es Staphylococcus aureus. Se presenta una paciente con enfermedad debida al virus de la inmunodeficiencia humana (VIH) con diagnóstico de sida, absceso corneal bilateral y lesiones cutáneas. S.aureus meticilino resistente se aisló en hemocultivos y en material obtenido por raspado de la córnea. El absceso corneal es una entidad poco frecuente en pacientes con infección por VIH y síndrome de inmunodeficiencia adquirida.

The corneal epithelium is an important defense barrier that prevents the entry of great variety of microorganisms. Any alteration of the ocular surface facilitates bacterial invasion of the cornea. The most frequently reported germ is Staphylococcus aureus. Here, we present a patient with a diagnosis of HIV/ AIDS disease, who developed bilateral corneal abscess and skin lesions. Methicillin-resistant Staphylococcus aureus was isolated from blood cultures and corneal scrapings. Corneal abscess is a rare entity in patients with HIV and acquired immunodeficiency syndrome

Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection.

The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long-term storage studies, and they successfully impede the growth of gram-negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.

Gene editing and elimination of latent herpes simplex virus in vivo.

We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.

[Ocular foreign bodies: Epidemiological, clinical and therapeutic aspects in Lubumbashi: About 98 cases]. / Corps étrangers oculaires : aspects épidémiologiques, clinique et thérapeutique à Lubumbashi : à propos de 98 cas.

PURPOSE: The purpose of this study was to determine the epidemiological, clinical and therapeutic features of ocular foreign bodies in our practice setting. METHODS: We conducted a cross-sectional descriptive study with retrospective data collection at the Sainte Ivonne ophthalmology center in Lubumbashi. We studied 98 medical records of patients seen from January through December 2016 for an ocular foreign body. The parameters used for this study were: age, gender, profession, circumstances of the injury, nature of the foreign body, complications, location, entry site, management and prognosis. RESULTS: The frequency of ocular foreign bodies was 2.4%. We saw predominantly young subjects; the mean age was 33.18±17.98 years. Males predominated, with a frequency of 78.57% of the cases, for a gender ratio of 3.7 men to women. The circumstances of the injuries were primarily work-related (36.46% of cases). The type of foreign body was most commonly wood (41.8% of cases). The FB was corneal in 81.7% of cases, conjunctival (bulbar and tarsal) in 13.3% of cases, and limbal in 5% of cases. Treatment consisted of either simple removal (86.61% of cases) or removal with suturing for deeper foreign bodies (13.27% of cases). The functional results obtained were encouraging; 90.82% of patients recovered well with preservation of visual acuity. The majority of the complications consisted of superficial punctate keratopathy in 27.53% of cases and corneal ulcer in 26.53% of cases. The results of our study are consistent with those in the literature in terms of the frequent corneal location of FB's. CONCLUSION: Ocular foreign bodies represent a situation of non-negligable severity and thus require proper early management in order to prevent progression to visual loss or blindness.

Ocular infection by a psychrophile: Pseudomonas fluorescens.

Accurate identification of infectious pathogens is essential for appropriate management of ocular infections. Routine laboratory protocols typically support bacterial growth at 37°C. We report a case, wherein we serendipitously isolated Pseudomonas fluorescens - an organism that prefers lower temperatures for optimal growth (psychrophilic) in the environment - from eviscerated contents of an eye with total corneal melt. This case highlights the need for being vigilant for organisms with different temperature sensitivities in culture media than that found in routine protocols.

[Efforts to improve the level of clinical diagnosis and treatment of infectious fundus diseases].

In recent years, the incidence of tuberculosis, HIV, syphilis and other infectious diseases has a "rising" trend. The incidence of infectious fundus diseases is also increasing, and missed diagnosis and misdiagnosis are becoming more common. How to diagnose infectious fundus diseases accurately, avoid missed diagnosis and misdiagnosis, carry out standardized treatment in time, carry out research on infectious fundus diseases related to systemic infectious diseases, and save the visual function of patients are the problems we are facing. This article discusses the related issues. (Chin J Ophthalmol, 2019, 55: 241-245).

Orbital infections: a complete cycle 7-year audit and a management guideline.

OBJECTIVES: Orbital infections are regularly encountered and are managed by various healthcare disciplines. Sepsis of the orbit and adjacent tissues can be associated with considerable acute complication and long-term sequelae. Therefore, prompt recognition and management of this condition are crucial. This article presents the outcomes of a 7-year complete cycle audit project and describes the development of the new local guideline on the management of orbital infections in our tertiary centre. METHODS: (1) A retrospective 5-year audit cycle on patients with orbital infections. (2) A review of available evidence on the management of orbital infections. (3) A new local multidisciplinary guideline on the management of orbital infections. (4) A retrospective 2-year second audit cycle to assess the clinical outcomes. RESULTS: Various disciplines intersect in the management of orbital infections. Standardising the management of this condition proved to be achievable through the developed guideline. However, room for improvement in practice exists in areas such as the promptness in referring patients to specialist care, the multidisciplinary assessment of patients on admission, and the improvement of scanning requests of patients.

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

Infectious uveitis: An enigma.

Infectious uveitis accounts for majority of the cases of uveitis in developing countries. It also encompasses an array of various microorganisms and their clinical presentations. Some of these infectious uveitic entities are familiar, while others are newly emerging in the global ophthalmic world. Many of these entities are also a major cause of morbidity and mortality, and appropriate, timely management is required to save not the eye, but life of the patient. This review highlights the ocular manifestations of various infectious uveitic entities, relevant to the ophthalmologist.

[Alternative Methods of Local Therapy for Complicated Periocular Infections - Two Case Reports]. / Alternative Methoden der Lokaltherapie bei komplizierten periokulären Infektionen ­ 2 Fallberichte.

Background Wounds of the eyelid can usually be cured with common surgical measures and the use of local antibiotics. Here we present two cases to demonstrate that biological debridement and negative pressure vacuum therapy (NPWT), two second line therapies, are effective and possibly superior alternatives to conventional, antibiotic-based approaches. Methodology and Result A persistent infectious wound of the upper eyelid after surgical debridement of necrotising fasciitis and an upper eyelid abscess with multiple purulent entry points, which was refractory to a five-week antibiotic regimen, were treated with biological debridement and NPWT. The combination of these two therapies leads to an optimal outcome. Conclusion Our cases demonstrate that, in ophthalmology, uncommon methods such as biological debridement and NPWT are quite practicable and are valuable therapeutic options.

[Diagnostic and therapeutic contribution of microbiological analysis in severe microbial keratitis at Reims University Hospital between 2012 and 2014]. / Apport diagnostique et thérapeutique des prélèvements microbiologiques des abcès de cornées avec critères de gravité au CHU de Reims entre 2012 et 2014.

PURPOSE: To investigate the contribution of microbial analysis in the diagnosis and management of severe microbial keratitis. MATERIAL AND METHOD: This is a monocentric retrospective study at the University Hospital of Reims from January 2012 to December 2014. Corneal scrapings with infectious keratitis were subjected to routine bacterial and fungal culture. PCR was also performed to detect various viral DNA (VZV, CMV, EBV, HSV 1 & 2, adenovirus) and Acanthamoeba sp. DNA. All contact lens cases were analyzed if available. RESULTS: One hundred and six patients were hospitalized, including 30 contact lens wearers (28.3%). Sixty-four bacterial cultures were positive (68%). Twenty-five different bacterial species were identified with a majority of gram-positive bacteria (67.92%). Among contact lens wearers, the initial VA was better than non-wearers (P=0.0004) and 37% of bacteria identified (a plurality) were gram positive. Of 11 contact lens case analyzed, in only one case (3.3%) did the result correlate with the corneal culture. Only 9 samples from the 323 viral DNA extractions and real time PCR were positive (2.8%); 7 were HSV1. No prior antiviral therapy had been started. Fungal culture was positive in 2 of the 97 corneal samples taken and 63.6% of the contact lens cases (7/11 cases). Only one of the 40 Acanthamoeba sp. PCR's was positive. CONCLUSION: The systematic performance of microbiological investigations is a good diagnostic approach given the polymorphism of clinical presentations of corneal ulcers, which can sometimes be extremely misleading. Culture of contact lens cases appears ineffective for the detection and determination of the causative microorganism. The high incidence of Staphylococcus in bacterial keratitis and the prevalence of infections with gram-positive bacteria in contact lens wearers were noted.

[Corneal collagen cross-linking in the treatment of infectious keratitis and corneal ulcers]. / Krosslinking rogovichnogo kollagena v lechenii infektsionnykh keratitov i gnoinykh iazv rogovitsy.

In recent years, collagen cross-linking (CXL) of the cornea has acquired a new usage - in the treatment of infectious keratitis and corneal ulcers. This review was aimed at compiling the previously published data and assessing the effectiveness of the method.

Infections after refractive surgery.

PURPOSE OF REVIEW: The purpose of the review is to provide a summary of the recent literature concerning infections after refractive surgery pertinent to each procedure category. RECENT FINDINGS: New data from a large retrospective study suggest that the incidence of post-laser assisted in-situ keratomileusis infectious keratitis is declining. Additionally, recent case studies have reported viral, fungal, and Acanthamoeba pathogens. Corneal collagen cross-linking is emerging as an alternative therapeutic option for early stage post-LASIK infectious keratitis. Postoperative bandage contact lens used in patients undergoing surface ablation procedures may confer a higher risk of infection because of greater colonization rates in those individuals, such as healthcare providers, with relatively high risk of exposure to potential pathogens. In the setting of post-penetrating keratoplasty astigmatism, femtosecond laser astigmatic keratotomy procedures pose a risk of infectious keratitis and even endophthalmitis. Lastly, recent case reports of endophthalmitis after refractive lens procedures highlight the importance of postoperative monitoring for this sight threatening, albeit rare, complication. SUMMARY: The risks and management of infections after surgical refractive procedures vary widely depending on the specific technique employed. As technology and treatment options continue to evolve with further research, we anticipate continued success in the management of postoperative infections after refractive surgery.

[Congenital dacryocystocele: Surgical treatment or routine follow-up?]. / Dacryocystocèles congénitales : traitement chirurgical ou simple surveillance ?

INTRODUCTION: Congenital dacryocystoceles are rare and often misunderstood pathologies. Their treatment varies and consists in simple follow-up, lacrimal catheterization or endoscopic surgical drainage, depending on medical teams. The aim of our study was to discuss the place of endoscopic drainage in the treatment of congenital dacryocystocele. METHODS: We conducted a retrospective review on 18 cases of congenital dacryocystoceles taken in charge in a tertiary care center between 2009 and 2012. RESULTS: Thirteen newborns, including five bilateral cases, were taken in charge. The average age was 14.6 days. Six newborns presented with an acute dacryocystitis at the time of diagnosis. No respiratory complications were observed. Spontaneous drainage of the dacryocystocele was observed in 38.8% of the cases, occurring at 22 days of life on average. Endonasal endoscopic drainage was performed in 66.6% of the cases. No recurrence or complication was observed after surgery. After spontaneous drainage, one recurrence was observed. The mean follow-up period of these patients was 8.8 months. DISCUSSION: Spontaneous drainage is common. Conservative management may therefore be considered in absence of infection. In case of infection and/or persistence of dacryocystocele after 4 weeks of life, endonasal surgical drainage should be considered. Imaging of the facial structure should be performed before any surgical treatment.

[Management of uveomeningitis in internal medicine: Proposal for a diagnostic work-up]. / Prise en charge diagnostique des uvéoméningites en médecine interne.

Uveomeningitis relates to an inflammatory state extending from iris and ciliary bodies to the choroid behind the eye. Because of a close contact between eye and brain, and barrier disruption, the inflammation can spread into the central nervous system (CNS). We review the clinical manifestations of uveitis, which are known to provide helpful clues to the diagnosis and describe the infectious, inflammatory, and neoplastic conditions classically associated with the uveomeningitis. Inflammatory or auto-immune diseases are probably the most common clinically recognized causes of uveomeningitis associated with a significant pleiocytosis. These entities often cause inflammation of various tissues in the body, including ocular structures and the meninges (i.e., sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada syndrome). The association of an infectious uveitis with an acute or a chronic meningo-encephalitis is unusual but occasionally the eye examination may suggest an infectious etiology or even a specific organism responsible for an uveomeningitis. One should consider the diagnosis of primary ocular-CNS lymphoma in patients of 40 years of age or older with bilateral uveitis, especially with prominent vitritis, showing poor response to corticosteroid therapy. Finally, an algorithm for the diagnostic approach of uveomeningitis is proposed.

[Tropical ophthalmology : Intraocular inflammation caused by "new" infectious pathogens and travel-related infections]. / Tropenophthalmologie : Intraokulare Entzündungen bei "neuen" Infektionserregern und Reiseinfektionen.

A number of "new" (emerging) infections that can also cause inflammatory eye changes are appearing and becoming increasingly important. In the past, diseases such as chikungunya, dengue fever or West Nile virus infections were endemic in tropical regions, but are now expanding worldwide and causing significant morbidity and even mortality. "Globalization" and human migration are important factors leading to the import of these infections. Climate changes are probably even more important. Increasing temperatures provide suitable conditions for new vectors, and may lead to autochthonous transmission of infectious pathogens. Diagnosis of these diseases requires not only careful assessment of medical and travel history, but also the application of specific laboratory diagnostic tests. A broad spectrum of ocular involvement has been reported, with frequent posterior segment involvement. Emerging infections should therefore be considered in the differential diagnosis of retinitis, chorioretinitis, retinal vasculitis and optic neuropathy in a patient living in or traveling back from an endemic area. Since these infections are often vector (insect) borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and initiation of supportive care. Here, we focus on Chikungunya, Dengue fever, Ebola fever, the West Nile virus and Rickettsioses, which frequently demonstrate ocular involvement.