Identification of Potential Biomarkers in Peripheral Blood Supernatants of South African Patients with Syphilitic and Herpetic Uveitis.

Purpose: To identify potential diagnostic biomarkers for herpetic and syphilitic uveitis.Methods: Blood samples were collected from 92 uveitis patients. Concentrations of 47 biomarkers were evaluated in unstimulated Quantiferon supernatants using the Luminex platform.Results: Results showed 11 patients (12%) had herpetic uveitis, 11 (12%) syphilis, 40 (43.5%) other infectious causes, 16 (17.4%) established noninfectious causes and 14 (15.2%) were idiopathic. Biomarker analysis revealed three proteins (Apo-A1, Apo-CIII, CRP) that differed between syphilis and other causes. A three-marker biosignature (CCL4/MIP-1ß, Apo-CIII and CRP) separated syphilis from other groups with AUC = 0.83 (95% CI: 0.68-0.98). Apo-CIII and CRP differed between herpetic cases and other groups (p < .05). A three-analyte biosignature (Apo-A1, SAP and CRP) separated the herpetic group from other groups with AUC = 0.79 (95% CI: 0.65-0.93).Conclusion: We have identified candidate biomarkers with potential to differentiate between herpetic, syphilitic and other causes of uveitis. These results warrant further investigation in larger future studies.

Bacterial infections as novel risk factors of severe diabetic retinopathy in individuals with type 1 diabetes.

BACKGROUND/AIMS: Diabetic retinopathy (DR) is associated and shares many risk factors with other diabetic complications, including inflammation. Bacterial infections, potent inducers of inflammation have been associated with the development of diabetic complications apart from DR. Our aim was to investigate the association between bacterial infections and DR. METHODS: Adult individuals with type 1 diabetes (n=1043) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. DR was defined as incident severe diabetic retinopathy (SDR), identified as first laser treatment. Data on DR were obtained through fundus photographs and medical records, data on bacterial infections from comprehensive national registries (1 January 1995 to 31 December 2015). Risk factors for DR and serum bacterial lipopolysaccharide (LPS) activity were determined at baseline. RESULTS: Individuals with incident SDR (n=413) had a higher mean number of antibiotic purchases/follow-up year compared with individuals without incident SDR (n=630) (0.92 [95% CI 0.82 to 1.02] vs 0.67 [0.62-0.73], p=0.02), as well as higher levels of LPS activity (0.61 [0.58-0.65] vs 0.56 [0.54-0.59] EU/mL, p=0.03). Individuals with on average ≥1 purchase per follow-up year (n=269) had 1.5 times higher cumulative incidence of SDR, compared with individuals with <1 purchase (n=774) per follow-up year (52% vs 35%, p<0.001). In multivariable Cox survival models, the mean number of antibiotic purchases per follow-up year as well as LPS activity were risk factors for SDR after adjusting for static confounders (HR 1.16 [1.05-1.27], p=0.002 and HR 2.77 [1.92-3.99], p<0.001, respectively). CONCLUSION: Bacterial infections are associated with an increased risk of incident SDR in type 1 diabetes.

Cytokine Profiles in Aqueous Humor and Plasma of HIV-infected Individuals with Ocular Syphilis or Cytomegalovirus Retinitis.

PURPOSE: To characterize the immunologic profile in aqueous humor (AqH) of HIV-infected individuals with cytomegalovirus retinitis (CMVr) or ocular syphilis and to assess if AqH and plasma represent independent cytokine compartments. METHODS: Concentrations of 27 cytokines in AqH and plasma of HIV-infected individuals with CMVr (n = 23) or ocular syphilis (n = 16) were measured by multiplex assay. Cytokine profiles of both groups were compared. RESULTS: Individuals with CMVr had higher plasma concentrations of interleukin (IL)-7, IL-8, IL-10, interferon (IFN)-γ, IFN-α2, G-CSF, IP-10 and IL-1α; as well as higher AqH concentrations of IL-1α, IP-10 and GM-CSF than those with ocular syphilis. AqH and plasma levels correlated only for IP-10 in both ocular infections. CONCLUSIONS: Individuals with CMVr had higher plasma cytokine levels than those with ocular syphilis. The immunologic profiles in AqH and plasma are independent. Therefore, AqH cytokine concentrations cannot be inferred from plasma cytokine concentrations in the population studied.

Time to development of ocular syphilis after syphilis infection.

To provide an estimate of the incubation period of ocular syphilis based on serology using both clinical data and stored serum samples, we retrospectively reviewed patients with HIV-1 infection who presented with ocular syphilis between August 1997 and July 2015 in a tertiary hospital in Japan. The incubation period of ocular syphilis was defined as the time from syphilis infection to the development of ocular symptoms due to ocular syphilis. During the study period, 20 patients were diagnosed with ocular syphilis and 8 patients were enrolled in the present study. All patients were Japanese men who have sex with men with a median age of 46 years (IQR 41.5-53.5). The median CD4 count was 668.5/µL (IQR 567.8-734.3) and 5 of the 8 patients had HIV-1 viral load of less than 50 copies/mL. All study patients presented to our clinic because of the development of ocular symptoms, and they did not have any other symptoms compatible with primary, secondary, or tertiary syphilis. The median time between syphilis infection and development of ocular symptoms was 11 months (IQR 4-19, range 2.5-45). Seven out of eight (87.5%) cases developed ocular syphilis within 2 years of syphilis infection. Ocular syphilis should be suspected even in patients with early syphilis who present with ocular symptoms. Moreover, routine serologic screening for syphilis among patients with HIV-1 infection is critical for prevention of irreversible visual loss in ocular syphilis cases.

[Lues - Ocular syphilis]. / Lues ­ Okuläre Syphilis.

Ocular syphilis is not a new issue but due to increasing rates of new cases is now a contemporary issue. The clinical features are unspecific and can be manifested as all forms of ocular inflammation. Unspecific anterior uveitis is the most frequent ocular involvement; however, typical distinctive patterns are superficial white preretinal precipitates within a panuveitis and acute syphilitic posterior placoid chorioretinitis. The diagnosis should be confirmed by serological tests. Treatment is based on parenteral administration of penicillin.

C-Reactive Protein As a Marker for Initiating Steroid Treatment in Children With Orbital Cellulitis.

PURPOSE: To determine both the benefit of systemic steroids in pediatric patients with orbital cellulitis and to assess the usefulness of C-reactive protein (CRP) levels as a marker for starting steroids. METHODS: Prospective, comparative interventional study. Pediatric patients aged 1 to 18 years admitted to a tertiary care children's hospital with a diagnosis of orbital cellulitis from October 2012 to March 2014 were included in the study. All patients were treated with intravenous antibiotics, and patients with subperiosteal abscess who met previously published criteria for surgical decompression underwent combined transorbital drainage and/or endoscopic sinus surgery. CRP was measured daily as a biomarker of inflammation, and when below 4 mg/dl, patients were started on oral prednisone 1 mg/kg per day for 7 days. Patients whose families did not consent to steroid treatment served as the control group. Patients were followed after discharge until symptoms resolved and all medications were discontinued. RESULTS: Thirty-one children were diagnosed with orbital cellulitis during the study period. Of these 31 children, 24 received oral steroids (77%) and 7 did not (23%). There were 19 males and 5 females in the steroid group with an average age of 8.1 years, and 6 males and 1 female in the nonsteroid group with an average age of 7.1 years (p = 0.618). Thirteen patients (54%) in the steroid group and 2 patients (29%) in the nonsteroid group underwent sinus surgery with or without orbitotomy (p = 0.394). The average CRP at the onset of steroid treatment was 2.8 mg/dl (range: 0.5-4). Patients who received oral steroids were admitted for an average of 3.96 days. In comparison, patients who did not receive steroids were admitted for an average of 7.17 days (p < 0.05). Once CRP was ≤4 mg/dl, patients treated with steroids remained in the hospital for another 1.1 days, while patients who did not receive steroids remained hospitalized for another 4.9 days (p < 0.01). In the steroid group, 2 families reported increased hyperactivity in their children while on steroids. There was 1 case in each group of recurrence of symptoms after discharge from the hospital. Average follow-up time was 2.4 months in the steroid group and 2 months in the nonsteroid group (p = 0.996). At last visit, all patients returned to their baseline ophthalmic examination. There were no cases of vision loss or permanent ocular disability in either group. CONCLUSIONS: Our results give further evidence of the safety and benefit of systemic steroids in children with orbital cellulitis. Futhermore, this is the first study to suggest a standardized starting point (CRP ≤ 4 mg/dl) and dosing schedule (oral prednisone 1 mg/kg for 7 days) for children with orbital cellulitis. Patients who received systemic steroids after CRP dropped below 4 mg/dl were discharged from the hospital earlier than patients who did not receive systemic steroids.

Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis.

PURPOSE: Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs). METHODS: Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-ß1, TGF-ß2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation. RESULTS: The concentrations of TGF-ß1, TGF-ß2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS. CONCLUSIONS: The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

Chlamydia pneumoniae seropositivity and the risk of nonarteritic ischemic optic neuropathy.

OBJECTIVE: To determine whether IgG antibodies to Chlamydia pneumoniae are associated with nonarteritic ischemic optic neuropathy (NAION). DESIGN: Retrospective case-control study. PARTICIPANTS: The study cohort consisted of 71 consecutive patients with NAION and 71 controls matched for age and gender. MAIN OUTCOME MEASURES: Serum immunoglobulin G (IgG) antibody titers to Chlamydia pneumoniae. RESULTS: Patients with NAION had significantly higher IgG antibody titers to C. pneumoniae compared with control subjects (IgG titer > or =1:128: 29 patients versus 15 controls, P = 0.017). The odds ratio for patients with an IgG titer > or =1:128 was 2.56 (95% confidence interval [CI], 1.2-5.5). Adjustment for arterial hypertension, diabetes mellitus, and myocardial infarction resulted in an odds ratio of 3.48 (95% CI, 1.3-9.6). CONCLUSIONS: Our results suggest that elevated titers of IgG antibodies to C. pneumoniae are associated with NAION.

An ocular cat-scratch disease patient positive for cytoplasmic anti-neutrophil cytoplasmic antibody.

BACKGROUND: We report a case of ocular cat-scratch disease with permanent vision reduction in a patient who was cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) positive. METHODS: Case report and review of the literature. RESULTS: While taking steroids and antibiotics, a 52-year-old man with uveitis associated with cat-scratch disease developed retinal vein occlusion and a macular exudate. His final visual acuity was poor because of residual macular degeneration and optic atrophy. Serum C-ANCA increased and decreased in parallel with ocular inflammatory activity. CONCLUSION: C-ANCA is an indicator of vasculitis and may be useful as an indicator of severe cat-scratch disease.

The laboratory diagnosis of ocular Lyme borreliosis.

BACKGROUND: A study was carried out to evaluate indirect enzyme-linked immunosorbent assay (ELISA), immunoblot analysis, and polymerase chain reaction (PCR) in the diagnostic work-up of ocular Lyme borreliosis. METHODS: Twenty patients with ocular Lyme borreliosis were examined. IgG and IgM antibodies to Borrelia burgdorferi were measured by ELISA in serum, and in cerebrospinal fluid (CSF) when indicated, and immunoblot analysis of B. burgdorferi IgG antibodies in serum was performed. A nested PCR was used to detect a segment of a gene coding for B. burgdorferi endoflagellin. The samples used in PCR testing were serum and CSF and in isolated cases conjunctiva and vitreous. RESULTS: Seventeen patients had elevated Borrelia antibodies in serum or CSF by ELISA. Seven patients, including two with negative ELISA, had a positive immunoblot. Seven of the 13 patients in whom PCR was examined during clinically active disease had a positive PCR result. Immunoblot analysis gave a negative result from the sera of five PCR-positive patients. CONCLUSIONS: For efficient diagnosis of ocular Lyme borreliosis, immunoblot analysis and PCR should be used in addition to ELISA. A positive PCR seems to be associated with a negative immunoblot.

Frequency of ocular chlamydial infection among young adults.

Young adults are at particular risk for Chlamydia trachomatis infection. To determine whether there is a high rate of asymptomatic ocular chlamydial infection in this population, 131 eyes from 72 patients aged 18 to 30 years with no symptoms of conjunctivitis were tested for C. trachomatis by means of McCoy cell culture and a direct enzyme immunoassay. In addition, 51 of the patients underwent serologic testing to detect systemic chlamydial disease. Ocular chlamydial infection was not found in any of the patients, including the 26 with a positive result of serologic testing. We conclude that routine screening of young adults for ocular chlamydial infection would be of no benefit in detecting systemic chlamydial infection and its sequelae.