A case report of long-delayed diagnosis of pseudorabies virus encephalitis with endophthalmitis: lessons from metagenomic next generation sequencing.

BACKGROUND: Pseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human. CASE PRESENTATION: We report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss. CONCLUSIONS: This case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability.

Severe Intraocular Inflammation following Hydrophilic Acrylic Phakic Intraocular Lens Implantation in A Case with Concealed History of COVID-19: A Case Report and Literature Review.

Purpose: To firstly present management of toxic anterior segment syndrome (TASS) and possible postoperative endophthalmitis (POE) after implantation of a new hydrophilic-acrylic posterior chamber (PC) phakic intraocular lens (pIOL) in a case with undeclared history of COVID-19.Methods: A 21-year-old male without known disease represented severe anterior chamber inflammation (hypopyon), poor vision and corneal edema without vitreous involvement (TASS) at 24-hours after PC-pIOL implantation for unilateral high myopia (amblyopic).Results: Preoperative best-corrected visual acuity (BCVA) was 0.2 OS (-13 diopters). At 56-hours, vitreous was involved with visual loss indicating POE. The patient confessed that he had COVID-19 1-month ago. COVID-19 immunoglobulin M/G tests were positive, while other markers were negative. Intracameral/intravitreal antibiotics were applied. BCVA was 0.15 without hypopyon at 24-hours. Cultures were negative. Final BCVA was 0.6 with normal examination.Conclusion: TASS/POE etiology could not be demonstrated in this case, whereas COVID-19-related proinflammatory systemic background could have effect on triggering/aggravating this scenario.].

Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India.

Human anelloviruses (Torque Teno Virus (TTV) and TTV Like Mini Virus (TLMV)) are now being reported at a high prevalence across the world, with a controversial disease-inducing potential. The aim of this study was to investigate the role of these anellovirus in vitreous of patients with presumed infectious endophthalmitis. After informed consent, vitreous fluid from patients with endophthalmitis (n = 103) and non-infectious pathologies (n = 102) were analyzed for the presence of TTV and TLMV DNA by qPCR with the limit of quantification defined as 100 copies per reaction. Among the patients clinically diagnosed with endophthalmitis, 29 of the 40 culture proven samples (72.5%) and 42 out of 63 (66.6%) of culture-negative samples were positive for presence of TTV/TLMV. Interestingly, 51 of the 102 (50%) samples in the control group were also positive for TTV/TLMV. Comparing the clinical outcome among patients diagnosed with endophthalmitis, we observed no significant association in the final visual acuity of patients who were positive for presence of TTV/TLMV, however, these patients had significantly higher repeat antibiotic injections (p = 0.03). Further evidence is however needed to correlate TTV / TLMV with a particular pathology or group of pathologies in the eye.

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis.

Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

Platelet Transfusion Related Panophthalmitis and Endophthalmitis in Patients with Dengue Hemorrhagic Fever.

Dengue is a vector-borne viral illness of major public health importance. It is endemic in many parts of India and also causes frequent epidemics. Platelet transfusions are given in severe cases of dengue fever to treat and prevent hemorrhagic complications. Here, we report three patients in North India with development of panophthalmitis and endophthalmitis shortly after receiving platelet transfusion.

Human Endophthalmitis Caused By Pseudorabies Virus Infection, China, 2017.

We report human endophthalmitis caused by pseudorabies virus infection after exposure to sewage on a hog farm in China. High-throughput sequencing and real-time PCR of vitreous humor showed pseudorabies virus sequences. This case showed that pseudorabies virus might infect humans after direct contact with contaminants.

Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing.

PURPOSE: To test the hypothesis that uncultured organisms may be present in cases of culture-negative endophthalmitis by use of deep DNA sequencing of vitreous biopsies. DESIGN: Single-center, consecutive, prospective, observational study. PARTICIPANTS: Aqueous or vitreous biopsies from 21 consecutive patients presenting with presumed infectious endophthalmitis and 7 vitreous samples from patients undergoing surgery for noninfectious retinal disorders. METHODS: Traditional bacterial and fungal culture, 16S quantitative polymerase chain reaction (qPCR), and a representational deep-sequencing method (biome representational in silico karyotyping [BRiSK]) were applied in parallel to samples to identify DNA sequences corresponding to potential pathogens. MAIN OUTCOME MEASURES: Presence of potential pathogen DNA in ocular samples. RESULTS: Zero of 7 control eyes undergoing routine vitreous surgery yielded positive results for bacteria or virus by culture or 16S polymerase chain reaction (PCR). A total of 14 of the 21 samples (66.7%) from eyes harboring suspected infectious endophthalmitis were culture-positive, the most common being Staphylococcal and Streptococcal species. There was good agreement among culture, 16S bacterial PCR, and BRiSK methodologies for culture-positive cases (Fleiss' kappa of 0.621). 16S PCR did not yield a recognizable pathogen sequence in any culture-negative sample, whereas BRiSK suggested the presence of Streptococcus in 1 culture-negative sample. With the use of BRiSK, 57.1% of culture-positive and 100% of culture-negative samples demonstrated the presence of torque teno virus (TTV) sequences, compared with none in the controls (P=0.0005, Fisher exact test). The presence of TTV viral DNA was confirmed in 7 cases by qPCR. No other known viruses or potential pathogens were identified in these samples. CONCLUSIONS: Culture, 16S qPCR, and BRiSK provide complementary information in presumed infectious endophthalmitis. The majority of culture-negative endophthalmitis samples did not contain significant levels of bacterial DNA. "Culture negativity" does not seem to be due to failure of growth of fastidious bacteria. The small DNA virus TTV was unexpectedly found in all culture-negative samples and some culture-positive samples. This study cannot distinguish whether TTV is a direct intraocular pathogen, an adjuvant for inflammation, a general marker of inflammation, or a commensal virus but provides a testable hypothesis for a pathogenic mechanism in culture-negative endophthalmitis.

Herpes simplex keratitis-induced endophthalmitis in a patient with AIDS with disseminated tuberculosis.

We present the case of a 42-year-old man with AIDS who had lost complete vision of his left eye for the past 15 days. MRI and brightness scan ultrasonography were performed on his eyes that suggested of endophthalmitis with dendritic involvement in the left eye. Viral DNA PCR was performed in aqueous humour sample that confirmed the presence of herpes simplex virus and showed a negative result for cytomegalovirus. The patient was treated with a high dose of oral acyclovir for 10 days and long-term topical acyclovir. Neodymium-doped yttrium aluminum garnet procedure was performed to clear up the cornea, and intraocular pressure was controlled with brimonidine and timolol maleate. The patient was diagnosed to have disseminated tuberculosis (tuberculoma of the brain) and was started with antituberculosis therapy. His condition improved significantly after the treatment, and keratitis in cornea started to clean up.

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.

Virological analysis in patients with human herpes virus 6-associated ocular inflammatory disorders.

PURPOSE: To determine whether human herpes virus 6 (HHV-6) genomic DNA and mRNA can be detected in ocular samples from patients with inflammatory disorders, and whether viral replication is involved in the development of inflammation in the eye. METHODS: After informed consent was obtained, ocular fluid samples (aqueous humor and vitreous fluids) were collected from 350 patients with uveitis or endophthalmitis. Corneal samples were also collected from 65 patients with corneal infections. Multiplex PCR was performed to screen ocular samples from the patients for HHV-1 to HHV-8. Samples were also assayed for HHV-6 DNA using quantitative real-time PCR. Primers for nested RT-PCR were designed to detect amplification of mRNA (HHV-6 A IE1 U90). RESULTS: PCR results indicated a total of seven patients with uveitis or endophthalmitis (7/350, 2% +) and a single patient with corneal inflammatory disease were positive for HHV-6 DNA (1/65, 1.5% +). These eight patients had high copy numbers of HHV-6 DNA, with values ranging from 4.0 × 10(3) to 5.1 × 10(6) copies/mL. Real-time PCR analysis indicated that two of these cases were HHV-6 variant A and six cases were variant B. In addition, HHV-6 mRNA was clearly detected in vitreous cells collected from one of the patients, suggesting that viral replication may occur in the eye. CONCLUSIONS: Our results indicate that HHV-6 infection/reactivation is implicated in ocular inflammatory diseases.

[Herpetic endotheliitis and trabeculitis with delayed corneal involvement]. / Endotelitis y trabeculitis herpética con afectación corneal tardía.

CASE REPORT: A 62-year-old man with previous renal transplant and immunosuppressive treatment presented with decreased visual acuity (20/100) in his left eye, corneal oedema and intraocular pressure of 46 mmHg. One month later an inferior marginal dendritic keratitis appeared. Corneal scraping and real-time polymerase chain reaction showed herpes simplex virus (HSV). DISCUSSION: The autoimmune corneal endotheliopathy or acute idiopathic corneal endotheliitis is characterised by corneal stromal oedema and keratic precipitates. HSV might be secreted from the trabeculum, innervated by the trigeminal nerve. This hypothesis is supported by the clinical observation that the corneal stromal oedema usually starts from the periphery.

Highly active antiretroviral therapy-induced immune recovery in an HIV-positive patient with a history of herpes zoster ophthalmicus.

BACKGROUND: With the introduction of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections in human immunodeficiency virus (HIV)-positive patients has dramatically decreased; however, clinicians should be made aware of the clinical presentation of immune recovery-mediated HAART-induced ocular inflammation. This case report discusses the correlation of HAART induction with immune recovery and ocular inflammation in an HIV-positive patient with a history of herpes zoster ophthalmicus (HZO). CASE REPORT: An HIV-positive man presented with a chief complaint of headache, severe facial pain, swollen eyelid, and light sensitivity in the right eye. The patient indicated the ocular discomfort was similar to his HZO outbreak treated successfully 3 months prior. He recently was initiated on HAART by his infectious disease specialist. The patient's diagnosis was immune recovery-mediated HAART-induced ocular inflammation associated with HZO. CONCLUSION: HAART has significantly reduced HIV-related morbidity and mortality, but new complications have emerged. Recognition of immune reconstitution inflammatory syndrome and the correlation with ocular inflammation is critical because treatment is based on protecting the patient against the effects of the inflammatory response without compromising antimicrobial or antiviral therapy.

[Phenotypic characterization of Staphylococcus epidermidis isolated from patients with endophthalmitis]. / Caracterización fenotípica de Staphylococcus epidermidis aislado de pacientes con endoftalmitis.

OBJECTIVE: To carry out the phenotypic characterization of Staphylococcus epidermidis isolated from endophthalmitis developed after cataract extraction and implantation of an intraocular lens. This bacteria produces a biofilm, adheres to polystyrene and host proteins such as collagen and fibronectine, significant virulence factors. METHODS: Five S. epidermidis strains were isolated from cases of endophthalmitis, they developed after crystalline extraction and implantation of an intraocular lens. We assessed if these strains adhere to polystyrene, to Type I collagen and to fibronectine and if bacteria produced biofilm. Finally, the bacterial surface proteins were obtained and analyzed using polyacrylamide gel electrophoresis. RESULTS: All five bacterial strains adhered to polystyrene, with a maximum adherence time of 105 min; they also displayed adherence to fibronectine but only two to collagen. Only two strains were weak biofilm producers. We identified proteins that by molecular weight are similar to those identified in the literature as proteins binding to biomaterials. CONCLUSIONS: As the strains that we studied were not biofilm-forming they should be considered as non-pathogenic. Nevertheless, they meet the initial criteria of pathogenicity and adherence, aside from being isolated from an intraocular infectious process and being able to provoke endophtalmitis when inoculated in rabbit eyes.

Early vitrectomy and diagnostic testing in severe infectious posterior uveitis and endophthalmitis.

BACKGROUND: To determine the therapeutic and diagnostic value of vitreoretinal surgery in various types of severe viral retinitis and endogenous endophthalmitis. MATERIAL/METHODS: Pars plana vitrectomy with silicon-oil tamponade was performed on 12 eyes (12 patients) with severe viral retinitis and endogenous endophthalmitis. The mean age of the patients was 35.2 years (range, 18-56 years). Investigations consisted of chest radiography, RT 23, serology (for toxoplasmosis, cytomegalovirus, herpes simplex virus, and human immunodeficiency virus), and routine blood tests and urinalysis. Examination of vitreous samples consisted of polymerase chain reaction for cytomegalovirus, herpes simplex virus, and Mycobacterium tuberculosis, and cultures for fungi and bacteria. The results were analyzed 7 days and 6 months after surgery. RESULTS: Analysis of vitreous samples showed cytomegalovirus in 3 patients, herpes simplex virus in 2, tuberculosis in 2, and Candida albicans in 5. All patients had improvement in visual acuity and severity of clinical signs seven days after surgery and in 10 cases after long-term follow-up. Final visual acuity was compromised by chronic macular edema, postinflammatory macular scarring, optic atrophy, subcapsular cataract formation, and capsular opacification after cataract surgery. CONCLUSIONS: Modern laboratory tests are useful for quick and accurate diagnosis of atypical cases of severe infectious posterior uveitis. Early pars plana vitrectomy with silicon oil tamponade is valuable in diagnosing and treating severe infectious posterior uveitis and endophthalmitis.

Caracterización fenotípica de Staphylococcus epidermidis aislado de pacientes con endoftalmitis / Phenotypic characterization of Staphylococcus epidermidis isolated from patients with endophthalmitis

Objetivo: Conocer las características fenotípicas de Staphylococcus epidermidis aislado de endoftalmitis relacionadas con el implante de lente intraocular de metilmetacrilato, su capacidad para formar biofilm y adherencia a proteínas de matriz extracelular y poliestireno. Métodos: Se estudiaron cinco cepas de Staphylococcus epidermidis aisladas de enfermos con endoftalmitis posterior la extracción del cristalino con implante de lente intraocular. Se investigó si estas cepas se adhieren a poliestireno, a colágena tipo I y a fibronectina, así como si las bacterias eran formadoras de biofilm. Al final se extrajeron las proteínas de superficie de las bacterias y se analizaron por electroforesis en gel de poliacrilamida. Resultados: Se encontró que las cinco cepas se unieron al poliestireno y que lo hicieron con mayor eficacia en la fase de crecimiento exponencial, con máxima adherencia a los 105 minutos; las cinco cepas se adhirieron a fibronectina y solo dos (CV y EN) a colágena. Dos cepas (CV y EN) fueron débiles formadoras de biofilm. Se identificaron proteínas que por peso molecular corresponden con las informadas en la literatura como proteínas de unión a biomateriales. Conclusiones: Las cepas estudiadas al no ser formadoras de biofilm tendrían que ser consideradas no patógenas, pero cumplen con el paso inicial de la patogenicidad, la adherencia, además de que fueron aisladas de un proceso infeccioso intraocular y produjeron endoftalmitis cuando fueron inoculadas en ojos de conejo.

OBJECTIVE: To carry out the phenotypic characterization of Staphylococcus epidermidis isolated from endophthalmitis developed after cataract extraction and implantation of an intraocular lens. This bacteria produces a biofilm, adheres to polystyrene and host proteins such as collagen and fibronectine, significant virulence factors. METHODS: Five S. epidermidis strains were isolated from cases of endophthalmitis, they developed after crystalline extraction and implantation of an intraocular lens. We assessed if these strains adhere to polystyrene, to Type I collagen and to fibronectine and if bacteria produced biofilm. Finally, the bacterial surface proteins were obtained and analyzed using polyacrylamide gel electrophoresis. RESULTS: All five bacterial strains adhered to polystyrene, with a maximum adherence time of 105 min; they also displayed adherence to fibronectine but only two to collagen. Only two strains were weak biofilm producers. We identified proteins that by molecular weight are similar to those identified in the literature as proteins binding to biomaterials. CONCLUSIONS: As the strains that we studied were not biofilm-forming they should be considered as non-pathogenic. Nevertheless, they meet the initial criteria of pathogenicity and adherence, aside from being isolated from an intraocular infectious process and being able to provoke endophtalmitis when inoculated in rabbit eyes.

Effect of an herbal formula containing Ganoderma lucidum on reduction of herpes zoster pain: a pilot clinical trial.

Administration of hot water extracts of a herbal formula containing Ganoderma lucidum, WTMCGEPP (Wisteria floribunda 0.38, Trapa natans 0.38, Miristica agrans 0.38, Coix lachryma-jobi 0.75, cultivated Ganoderma lucidum 0.75, Elfuinga applanata 0.38, tissue cultured Panax ginseng 0.3, and Punica granatum 0.38: numerals designate dry weight gram/dose), decreased herpes zoster pain for five Japanese patients suffering from shingles. Pain relief started within a few days of intake and was almost complete within 10 days. Two acute herpes zoster with manifestations including trigeminal nerve ophthalmia (both 74 years old), lower body zoster (70 years old), herpes zoster oticus (17 years old), and leg herpes (28 years old), responded quickly to treatment and no patient developed post-herpetic neuralgia (PHN) after more than one year of follow-up.

Pathologic findings in red-tailed hawks (Buteo jamaicensis) and Cooper's hawks (Accipiter cooper) naturally infected with West Nile virus.

Carcasses of 13 red-tailed hawks (RTHAs) and 11 Cooper's hawks (COHAs) were tested for West Nile virus (WNV) using WNV-specific reverse transcriptase-polymerase chain reaction (RT-PCR) on fresh brain tissue and WNV-specific immunohistochemistry (IHC) on various organs. Ten COHAs (91%) and 11 RTHAs (85%) were positive for WNV RNA by RT-PCR. All 11 COHAs (100%) and 10 RTHAs (77%) were positive for WNV antigen by IHC. A triad of inflammatory lesions, including chronic lymphoplasmacytic and histiocytic encephalitis, endophthalmitis, and myocarditis, was common in both species. In COHAs, the heart (54%), cerebrum (50%), and eye (45%) were the organs that most commonly contained WNV antigen. The amount of WNV antigen was usually small. In RTHAs, the kidney (38%), cerebrum (38%), cerebellum (38%), and eye (36%) were the organs most commonly containing WNV antigen. Unlike COHAs, larger amounts of WNV antigen were present in the cerebrum of RTHAs. WNV antigen was detected in similar cell populations in both species, including neurons of brain, spinal cord, and retina, pigmented epithelial cells of the retina, epithelial cells of renal medullary tubules, cardiomyocytes, endothelial cells and smooth muscle cells of arteries, dendritic cells of splenic lymph follicles, exocrine pancreatic cells, adrenal cells, and keratinocytes of the skin. The study presents strong evidence that WNV can cause a chronic fatal disease in RTHAs and COHAs. The lesion distribution of WNV infection in both species is variable, but inflammatory lesions are common, and a triad of lesions including encephalitis, myocarditis, and endophthalmitis is indicative of WNV infection in both species.