Management of Intraocular Infections in HIV.

Purpose: Overview of treatment options for the most common intraocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), including ocular syphilis, ocular tuberculosis, toxoplasmic chorioretinitis, and viral retinitis. Method: Narrative Review. Results: Despite the huge advances in the development of combined antiretroviral therapy (cART) for the management of patients with human immunodeficiency virus (HIV) infection, opportunistic infections still represent a significant diagnostic dilemma and cause of ocular morbidity in patients with HIV. Conclusion: Although the treatment of intraocular infections in patients with AIDS may be challenging, prompt assessment of the clinical features and appropriate aggressive management of the underlying etiology are critical to avoid life and vision threatening.

Onchocerca jakutensis ocular infection in Poland: a new vector-borne human health risk?

BACKGROUND: Zoonotic onchocerciasis is a vector-borne disease, which involves many animal species, including large ungulates, boars, dogs, and sporadically, humans. So far, 39 cases of zoonotic onchocerciasis have been reported worldwide, 30 of which have been found in the last 20 years. Onchocerca nematodes are transmitted to humans by blood-sucking vectors during a blood meal. The following species have been responsible for zoonotic infections: Onchocerca cervicalis, O. dewittei japonica, O. gutturosa, O. jakutensis and O. lupi. In humans, the worms have usually been found in the subcutaneous tissues where they form subcutaneous nodules, induce inflammation of musculature, or penetrate the eye. Thirteen ocular zoonotic onchocerciasis cases have been reported so far. In the eye, nematodes were localized in the subconjunctival space, anterior chamber and within the vitreous body. METHODS: In a 39-year-old male patient, a writhing worm in the vitreous body of the left eye was detected and surgically removed. Laboratory identification of the worm was based on macroscopic and molecular identification, based on sequencing of the cytochrome c oxidase subunit 1 gene (cox1). Phylogenetic analysis of the first 250 nucleotide sequences showing the highest levels of similarity with the present isolate in a BLAST analysis was performed. RESULTS: Here, we report the first case worldwide of human ocular infection with O. jakutensis, a natural parasite of red deer. By exploiting a PCR assay, we detected the sequence almost identical to O. jakutensis (GenBank: KT001213.1; positions 1-650) with a single mismatch G/A at position 622. The sequence reported in this paper was deposited in the GenBank database under the accession number MK491767. CONCLUSIONS: Our case together with the previous case reports indicate that zoonotic Onchocerca worms exhibit no tissue specificity and an eye infection has been described in over one third of human zoonotic onchocerciasis cases. In terms of the growing number of cases of zoonotic onchocerciasis in Europe, the USA and Japan, attention should be paid to the diagnosis of subcutaneous nodules and eye infestations.

Understanding the Role of Pro-resolving Lipid Mediators in Infectious Keratitis.

Keratitis is a sight-threatening inflammatory condition of the cornea that can be caused by both infectious and non-infectious agents. Physical or chemical trauma are typically related to non-infectious keratitis, which may then become secondarily infected or remain non-infected. Etiology of infectious keratitis is most often associated with bacteria; but viruses, fungi, and parasites are common causative pathogens as well. As a global concern, common risk factors include: systemic immunosuppression (secondary to malnutrition, alcoholism, diabetes, steroid use), previous corneal surgery (refractive corneal surgery, penetrating keratoplasty), extended wear contact lens use, pre-existing ocular surface diseases (dry eye, epithelial defect) and ocular trauma (agriculture- or farm-related) [1-8]. Annual rates of incidence include nearly one million clinical visits due to keratitis in the United States, while it has been reported that roughly two million people develop corneal ulcers in India. Clinically, patients may show signs of eye pain (ranging from mild to severe), blurred vision, photophobia, chemosis and redness. Pathogenesis is generally characterized by rapid progression, focal white infiltrates with underlying stromal inflammation, corneal thinning, stromal edema, mucopurulent discharge and hypopyon, which can lead to corneal scarring, endophthalmitis, and perforation. In fact, corneal opacity is not only a complication of keratitis, but among the leading causes of legal blindness worldwide. Despite that empirical treatment effectively controls most of the pathogens implicated in infectious keratitis, improved clinical outcomes are not guaranteed. Further, if treatment is not initiated in a timely manner, good visual outcome is reduced to approximately 50% of keratitis patients [9]. Moreover, resultant structural alterations, loss of tissue and an unresolved host response remain unaddressed through current clinical management of this condition.

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

PURPOSE: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis. DESIGN: Consecutive interventional case series. METHODS: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). RESULTS: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm2 and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 µm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months. CONCLUSION: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.

Real-Time Multiplex PCR Analysis in Infectious Uveitis.

Introduction: Infectious uveitis is a serious inflammatory condition that often causes grave ocular morbidity including permanent vision loss and damage to the structures of the eye. The most common causes of infectious uveitis include herpesviruses and Toxoplasma gondii. Traditionally, these infections have been identified and differentiated based on characteristic clinical examination findings; however, there is often overlap between these presentations and the unique cause of a given patient's infection is not always clear. Therefore, a reliable and fast method for definitively diagnosing infectious uveitis would be helpful and potentially sight-saving. Several groups have recently found experimental success with real-time multiplex polymerase chain reaction (PCR) techniques. Methods: A comprehensive review of the literature was undertaken to further understand the current state of real-time multiplex PCR and its clinical use. Search terms including "real time multiplex PCR", "infectious uveitis", and "uveitis diagnosis" were used. Appropriate English-language articles were included in this review. Results: Publications from four main groups (two from the United States, one from Japan, and one from India) citing success with real-time multiplex PCR were compared and contrasted. All four groups used the same technique to develop a highly sensitive and specific multiplex PCR analysis and found that their tests maintained high sensitivity and specificity during validation testing. These tests confirmed clinical suspicions in the majority of cases of infectious uveitis, but there were also cases of clinical misdiagnosis that were corrected based on molecular pathogen detection. These patients were then initiated on appropriate antimicrobial therapy with subsequent clinical improvement. Discussion: Real-time multiplex PCR is a highly sensitive and specific laboratory assay that allows for rapid and reliable molecular diagnosis of causative agents in infectious uveitis. This in turn facilitates swift initiation of effective therapy and prevents long-term ocular damage and vision loss.

An outbreak of philophthalmosis in Larus michahellis and Larus fuscus gulls in Iberian Peninsula.

Trematodes of the genus Philophthalmus Loos, 1899 are the eye parasites of birds and mammals, which use freshwater snails as their first intermediate hosts. Here we examined the presence of philophthalmids in a total of 1515 gulls (589 Larus fuscus and 926 Larus michahellis) admitted between January 2010 and October 2016 for rehabilitation at Olhão (Portugal), by the use of combined morphological and molecular analysis. We recorded the first infected L. fuscus and L. michahellis in July and November 2015, respectively. The philophthalmids were located in the conjunctival sac or under the nictitating membrane. Gulls infected with Philophthalmus lucipetus Rudolphi, 1819 presented no clinical signs, while those infected with Philophthalmus lacrymosus Braun, 1902 presented serious eye damage in the same host species. The prevalence of P. lucipetus reached 3.6% in L. fuscus and 0.8% in L. michahellis; the prevalence of P. lacrymosus reached 0.3% and 0.0%, respectively. The outbreak of P. lucipetus likely started in a narrowly defined area, since the first six cases, found between July and October 2015, originated from a single municipality, and only later more cases started to be retrieved from other municipalities of Portugal. These findings represent the first records of both philophthalmids in the Iberian Peninsula, their first records in L. michahellis and the first record of P. lacrymosus in L. fuscus. Further follow-up of the outbreak and the identification of intermediate hosts are needed.

Candidatus Dirofilaria hongkongensis as Causative Agent of Human Ocular Filariosis after Travel to India.

We report a human case of ocular Dirofilaria infection in a traveler returning to Austria from India. Analysis of mitochondrial sequences identified the worm as Candidatus Dirofilaria hongkongensis, a close relative of Dirofilaria repens, which was only recently described in Hong Kong and proposed as a new species.

Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis: A Longitudinal In Vivo Confocal Microscopy Study.

PURPOSE: To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, case-control, single-center study. PARTICIPANTS: Fifty-six eyes of 56 patients with the diagnosis of bacterial (n=28), fungal (n=15), or Acanthamoeba (n=13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. METHODS: Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection. MAIN OUTCOME MEASURES: Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period. RESULTS: Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47±0.69 mm/mm2 versus 20.59±1.06 mm/mm2 (P<0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49±0.94 mm/mm2; P=0.02) and nerve branch length (4.80±0.37 mm/mm2; P=0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13±1.97 mm/mm2; P=0.005), main nerve trunk length (5.80±1.00 mm/mm2; P=0.01), and nerve branch length (6.33±0.76 mm/mm2; P=0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P<0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r=0.47; P=0.0009). CONCLUSIONS: Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning.

The value of routine polymerase chain reaction analysis of intraocular fluid specimens in the diagnosis of infectious posterior uveitis.

OBJECTIVE: To assess the value of routine polymerase chain reaction (PCR) analysis on intraocular fluid from patients presenting with a first episode of suspected active infectious posterior uveitis in a population with a high prevalence of human immunodeficiency virus infection. DESIGN: Retrospective, interventional case series. Participants. 159 consecutive patients presenting at a tertiary care hospital over a five-year period. METHODS: PCR analysis was performed for cytomegalovirus, varicella zoster virus, herpes simplex virus types 1 and 2, Toxoplasma gondii, and Mycobacterium tuberculosis. RESULTS: PCR analysis confirmed the initial clinical diagnosis in 55 patients (35%) and altered the initial clinical diagnosis in 36 patients (23%). The clinical diagnosis prior to PCR testing was nonspecific (uncertain) in 51 patients (32%), with PCR providing a definitive final diagnosis in 20 of these patients (39%); necrotizing herpetic retinopathy and ocular toxoplasmosis were particularly difficult to diagnose correctly without the use of PCR analysis. CONCLUSION: The clinical phenotype alone was unreliable in diagnosing the underlying infectious cause in a quarter of patients in this study. Since the outcome of incorrectly treated infective uveitis can be blinding, PCR analysis of ocular fluids is recommended early in the disease even in resource poor settings.

Use of a comprehensive polymerase chain reaction system for diagnosis of ocular infectious diseases.

PURPOSE: To measure the genomic DNA of ocular infectious pathogens in ocular fluids and to analyze the clinical relevance of these pathogens in uveitis and endophthalmitis. DESIGN: Prospective clinical case series. PARTICIPANTS: A total of 500 patients with infectious uveitis and endophthalmitis were examined at Tokyo Medical and Dental University, Tokyo Medical University, Kyushu University, Osaka University, and Kyoto Prefectural University, all in Japan. METHODS: Genomic DNA of bacteria, fungi, parasites, and viruses in collected intraocular samples were examined by comprehensive polymerase chain reaction (PCR). Samples were analyzed first by multiplex PCR and quantitative real-time PCR for human herpes viruses (HHVs) 1 through 8 and toxoplasma. Subsequently, samples were examined by broad-range real-time PCR for bacterial 16S and fungal 18S/28S ribosomal DNA (rDNA). MAIN OUTCOME MEASURES: Infectious uveitis and endophthalmitis diagnoses were obtained when using the PCR system. Calculations of the positivity and the diagnostic parameters such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) also were evaluated. RESULTS: In all of the tested infectious uveitis and endophthalmitis patients, either herpes simplex virus type 1 (n = 18), herpes simplex virus type 2 (n = 4), varicella-zoster virus (n = 55), Epstein-Barr virus (n = 17), cytomegalovirus (n = 68), HHV type 6 (n = 2), toxoplasma (n = 6), bacterial 16S (n = 33), or fungal 18S/28S (n = 11) genome was detected. Neither HHV type 7 nor HHV type 8 DNA was detected in any of the samples. Of the 21 false-negative results found during the PCR analyses, 12 cases were negative for patients clinically suspected of having bacterial endophthalmitis. Conversely, false-positive results for the comprehensive PCR examinations occurred in only 3 cases that subsequently were found to have bacterial 16S rDNA. Diagnostic parameters for the sensitivity, specificity, PPV, and NPV of our PCR examinations were 91.3%, 98.8%, 98.6%, and 92.4%, respectively. CONCLUSIONS: Use of our comprehensive PCR assay to examine ocular samples in patients with endophthalmitis and uveitis seems to be clinically useful for detecting infectious antigen DNA. Thus, this PCR method is a reliable tool for both diagnosing ocular disorders and further screening of patients for intraocular infections. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Pharmacological treatment for infectious corneal ulcers.

INTRODUCTION: Cornea ulceration and infectious keratitis are leading causes of corneal morbidity and blindness. Infectious causes are among the most frequent and most severe. Management strategies for bacterial corneal ulcers have changed significantly over the last decades, however with a more limited progress in the treatment and management of nonbacterial, infectious ulcers. AREAS COVERED: This paper provides an overview of the current principles, strategies and treatment choices for infectious corneal ulcers in adults. EXPERT OPINION: Topical application with a broad-spectrum antimicrobial remains the preferred method for the pharmacological management of infectious corneal ulcers. Increasing reports of clinical failures and in vitro resistance to antibiotics to treat the most common infectious (bacterial) corneal ulcers are increasing concerns. New approaches for improvement in the pharmacological management of corneal ulcers should focus on strategies for a more rational and evidence-based use of current antimicrobials and development of products to modulate the host immune response and to neutralize microbial toxins and other immune modulators.

A systematic analysis of Acanthamoeba genotype frequency correlated with source and pathogenicity: T4 is confirmed as a pathogen-rich genotype.

Acanthamoeba is a genus of facultative human parasites that is currently classified into 17 genotypes (T1-T17) each of which arguably represents a species. These amoebae cause Acanthamoeba Keratitis (AK) a disease of the eye, and a rare but usually fatal Granulatomous Acanthamoeba Encephalitis (GAE). A database of strains derived from the literature and a number of fresh isolates has been constructed to detect trends of pathogenic and other associations with these genotypes. One genotype in particular, T4, was found to be over represented in human disease. The prevalence of this genotype has been commented upon previously, however T4 is also the most common type isolated from the environment. Our statistical analysis of the database allows us to claim that T4 is in fact the genotype most often associated with human disease, even after its abundance in the general environment is taken into account. T3 and T11 are closest relatives to T4 and they are the second and third most often associated with AK. A number of other more subtle correlations also emerge from this analysis.

Photoactivated riboflavin treatment of infectious keratitis using collagen cross-linking technology.

PURPOSE: To evaluate riboflavin/ultraviolet-A (UVA) as an adjunct treatment for infectious keratitis. METHODS: This prospective, dual-center, interventional case series included cases of infectious keratitis that were treated by instilling riboflavin 0.1% solution for 30 minutes to saturate the cornea, followed by exposure to 365-nm UVA light (3 mW/cm(2)) for 15 to 45 minutes, with continued instillation of riboflavin. Eyes continued on standard antibiotic treatment. The primary outcome measures were the times to resolution of the infiltrate and the epithelial defect. RESULTS: Forty patients aged 14 to 86 years were enrolled. Seven (18%) eyes had a previous keratoplasty. Bacterial species were identified in 24 eyes, fungal in 7, protozoan in 2, viral in 1, and no organism in 6. The maximum infiltrate diameter ranged from 1 to 12 mm and the epithelial defect diameter was 0 to 8 mm before treatment. In 6 cases (2 bacterial, 3 fungal, and 1 without growth), the keratitis did not resolve successfully and the eye received a penetrating keratoplasty (PK). In 1 eye with prior PK, the infection resolved following treatment, but a regraft was required to address perforation of the PK incision. CONCLUSIONS: Riboflavin/UVA should be avoided in eyes with prior herpes simplex but otherwise posed no obvious safety risk in this series and appeared to be most effective when the infection depth was limited. The success rate was higher for bacterial infections than fungal infections. Randomized studies against antibiotics alone are needed to further evaluate efficacy.

Photo-activated riboflavin therapy of refractory corneal ulcers.

PURPOSE: To evaluate the therapeutic effect of photo-activated riboflavin (PAR) for treating refractory corneal ulcers. METHODS: Seven eyes with infectious keratitis, presented with a gradually deteriorating, vision-threatening, corneal ulcer, despite intense antimicrobial therapy, were treated with PAR. The surgical procedure was deepithelialization of the affected corneas followed by UV-A riboflavin (B2) cross-linking. Local antimicrobial therapy was continued after the procedure. RESULTS: In all cases, the progression of corneal melting was halted after PAR treatment. Emergency keratoplasty was not necessary in any of the 7 eyes presented. More importantly, all the ulcers were healed without significant vascularization. CONCLUSION: PAR is a promising option for treating patients with therapy-refractory infectious keratitis to avoid emergency keratoplasty and should be considered as a potential adjuvant therapeutic tool in such eyes.

Two cases of human thelaziasis and brief review of Korean cases.

The present study was performed to describe 2 cases of human thelaziasis (HT) which occurred in Gyeongsangnam- do and to briefly review the previously reported Korean cases. A 58-year old woman, residing in Hadong-gun, Gyeongsangnam-do, came to Gyeongsang National University Hospital (GNUH) complaining of foreign body sensation and itching of the right eye in March 2000. Total 6 adult nematodes of Thelazia callipaeda (2 males and 4 females) were detected in her right eye. A 80-year old man, residing in Jinju-si, Gyeongsangnam-do, came to GNUH complaining of foreign body sensation, itching, and pain of the right eye in December 2007. A total of 5 worms (4 females and 1 degenerated) were removed from his right eye. We analyzed characteristics of the total 39 Korean HT cases reported to date, including the present 2 cases. Most of the cases (71.8%) occurred in Seoul and Gyeonggi-do before 2000, and 21 cases (53.8%) were males and 18 (46.2%) were females. The prevalence was higher in younger ages below 30 years (48.7%) than 31-60 years (41.0%) and over 61 years (10.3%). The seasonal prevalence showed a higher incidence in autumn (43.6%) than in other seasons. Most of the cases (94.9%) were conjunctival sac infections and only 2 (5.1%) were intraocular cases. The present 2 HT cases are the first reported cases in Gyeongsangnam-do. Some characteristics of Korean HT cases were analyzed.