Immune Cell Status and Cytokines Profiles in Patients with Acute Retinal Necrosis.

Purpose: To assess the immune status of acute retinal necrosis (ARN) patients and to investigate the immune cell types involved in the immunopathogenesis.Methods: Peripheral blood and intraocular fluid were collected from 17 ARN patients and 9 control subjects. The Percentage of immune cells was measured using flow cytometry, levels of complement and antibodies were determined by rate nephelometry, and cytokine levels in the serum and aqueous humor (AH) were detected using cytokine quantitative chips. Data were analyzed using SPSS 23.0. p < .05 was considered statistically significant.Results: Proportion of T-helper 17 cells (p = .034) in serum and concentrations of multiple cytokines associated with Th17 cells (IL-6, IL-17, IL-17 F, IL-21, IL-22) in AH and serum were elevated of ARN patients.Conclusion: Th17 cells appeared to participate in the development of ARN. We found inflammatory cytokines and cells were elevated in the serum and AH of ARN patients.

Study of ocular manifestations in tuberculosis and its association with HIV AIDS in a tertiary care hospital.

OBJECTIVE: To assess and understand the prevalence and clinical presentation of ocular morbidity in patients suffering from tuberculosis and compare it with ocular involvement in patients coinfected with tuberculosis and HIV AIDS. MATERIALS AND METHODS: This was a non-comparative, observational, cross sectional study done on 580 patients, who were diagnosed cases of tuberculosis, pulmonary or extrapulmonary, on or off treatment, visiting the Ophthalmology OPD, Tuberculosis OPD and ART Centre of the institute in the period from March 2015 to March 2018, screened for ocular morbidity. RESULTS: Out of 580, 408 patients had only tuberculosis and 172 had tuberculosis with HIV AIDS. 108 patients were found to have ocular involvement (18.6%) out of which 63 were males and 45 were females. The prevalence of ocular morbidity in patients with only tuberculosis was found to be 16.4% and in those having both tuberculosis and HIV AIDS was found to be 23.8%. CONCLUSION: Our study concludes that posterior uveitis, pan uveitis, periphlebitis and vitritis are the most common ocular manifestations in tuberculosis. In patients with both tuberculosis and HIV most common ocular findings included vitritis and herpes zoster ophthalmicus. Our study also concludes that lower CD4 counts (less than 200) in HIV AIDS patient is significantly associated with ocular involvement.

Headache and vision changes in an elderly man with rheumatoid arthritis.

We present a case of an elderly, immunosuppressed patient with rheumatoid arthritis who was not appropriately vaccinated, and subsequently developed herpes zoster ophthalmicus, which initially presented similar to giant cell arteritis. Evidence-based vaccinations are integral in decreasing the incidence of preventable diseases and promoting optimal health at the individual and population level. Although the patient ultimately did not suffer any long-term adverse sequelae, this case highlights the importance of vaccination in the rheumatology setting, and to consider both inflammatory and infectious causes of headache and vision changes in the elderly.

Immunopathology of Virus-Induced Anterior Uveitis.

Herpes simplex virus, varicella zoster virus, human cytomegalovirus, and rubella virus are the most common causes of virus-induced anterior uveitis. They can present in a variety of entities not only with typical but also overlapping clinical characteristics. These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response. The infections differ in that the herpes viruses cause an acute lytic infection and inflammation, whereas rubella virus is a chronic low-grade infection with slowly progressing immunopathological responses. The outcome of an intraocular viral infection may largely be guided by the characteristics of the virus, which subsequently dictates the severity and type of the immune response, and the host immune status.

Valacyclovir versus acyclovir for the treatment of herpes zoster ophthalmicus in immunocompetent patients.

BACKGROUND: Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications. OBJECTIVES: To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach. MAIN RESULTS: One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir. AUTHORS' CONCLUSIONS: This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.

Ophthalmic manifestations of herpes zoster virus in patients with multiple myeloma following bone marrow transplantation.

We report three patients with ophthalmic herpes zoster (HZ) manifestations on the background diagnosis of multiple myeloma (MM). It seems that immunocompromised status has caused reactivation of the varicella zoster virus (VZV) producing a well-characterised neurological syndrome and subsequent postherpetic neuralgia in two patients. One patient experienced lymphocytic leptomeningitis resulting in unilateral optic neuritis. All patients received similar myeloma disease-specific treatment prior to HZ reactivation. All patients were treated with thalidomide and steroids, and they thereafter underwent autologous stem cell transplantation. Prior to HZ reactivation they received new immunomodulatory drugs in the form of thalidomide in addition to bortezomib (2 patients) and lenalidomide (1 patient). Immediate specific antiviral therapy was successfully applied with intravenous acyclovir for 10 days, followed by long-term oral famciclovir maintenance. Two patients progressed to have chronic HZ ophthalmicus and postherpetic neuralgia requiring ongoing antiviral therapy and neuroepileptic medications for the neuropathic pain.

Hutchinson's sign as a marker of ocular involvement in HIV-positive patients with herpes zoster ophthalmicus.

BACKGROUND: A positive Hutchinson's sign indicates an increased risk of ocular involvement in herpes zoster ophthalmicus (HZO). We examined the sensitivity of Hutchinson's sign as an indicator of ocular involvement in a consecutive series of patients presenting with HZO. METHODS: We conducted a descriptive observational prospective study of patients > or =18 years old presenting with HZO and consenting to pre-and post-test counselling and HIV and CD4 testing. A full ophthalmological examination focused on the extent of ocular involvement, and the presence of Hutchinson's sign was confirmed by two clinicians. RESULTS: Thirty-three patients were enrolled; 29 were HIV positive, of whom 18 (62%) had not been diagnosed with HIV prior to enrollment. Of the 29 HIV-positive patients, 21 (72%) were Hutchinson's sign positive (HSP), all of whom had intra-ocular involvement (95% confidence interval 88 - 100%). Of the 8 HIV-positive, Hutchinson's sign-negative (HSN) patients, 4 did and 4 did not display intra-ocular involvement. Neither the mean CD4 count nor the average age in the HSP group differed significantly from the HSN group. CONCLUSION: We confirmed that a Hutchinson's sign- and HIV-positive patient with HZO has a very high positive predictive value for intra-ocular involvement. Neither age nor CD4 count had predictive value for ocular involvement. Young adults presenting with HZO should be suspected of having HIV, and HIV-positive patients with HZO but HSN may still have ocular involvement. All patients with HZO should be seen by an ophthalmologist.

Course and complications of varicella zoster ophthalmicus in a high HIV seroprevalence population (Cape Town, South Africa).

AIM: To describe the course and complications of varicella zoster ophthalmicus (VZO) in patients attending an eye clinic in a community with a high HIV seroprevalence. STUDY DESIGN: Prospective cohort study of consecutive patients presenting to a tertiary hospital eye clinic with VZO. METHOD: Patients recruited in 2001 and 2002 received standardized initial topical and systemic management, which was then modified according to complications. Information on the course and complications of the disease was entered in a database prior to statistical analysis. RESULTS: Information on 102 patients who had 250 visits to the eye clinic was collected. HIV serology was positive, negative, and unknown in 66, 22, and 14 patients, respectively. The most common complication was uveitis (40/102). Median delay from onset of rash to starting acyclovir was 5 days. Complications were present in 33 patients at the first visit. Complications were commoner in patients with positive Hutchinson's sign and were less common at CD4 counts <200. At CD4 counts, > or =200 HIV infection had little effect on the course and complications of VZO. Timing of commencement of Acyclovir therapy within or after 72 h had no demonstrable effect on the incidence of new complications. CONCLUSION: In a resource-limited setting, patients with the following characteristics should have immediate ophthalmic assessment: symptoms suggesting ocular complications or the presence of Hutchinson's sign. All VZO patients should receive antiviral therapy at the first doctor's visit even if they present >72 h after onset of the rash.

Human ocular-derived virus-specific CD4+ T cells control varicella zoster virus replication in human retinal pigment epithelial cells.

PURPOSE: Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4(+) T cells to control VZV infection in RPE cells in vitro is addressed. METHODS: Human primary RPE cell cultures (n=2) were infected with a VZV strain expressing green fluorescent protein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-gamma (IFN-gamma), were infected with VZV and subsequently cultured with VZV-specific CD4(+) T-cell clones (TCCs; n=3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry. RESULTS: Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4(+) TCCs only if the RPE cells were pretreated with IFN-gamma and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells. CONCLUSIONS: The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis.

Ring corneal infiltrate and progressive ring thinning following primary varicella infection.

Unilateral stromal keratitis is a known rare sequela of primary varicella infection. The authors describe a unique case of immunological (Wessely) ring formation and progressive ring thinning following primary varicella infection in a 6-year-old girl.

[Atypical ocular toxoplasmosis with concomitant ocular reactivation of varicella-zoster virus and cytomegalovirus in an immunocompromised host]. / Atypische Toxoplasmose-Chorioretinitis mit begleitender Varizella-Zoster-Virus und Zytomegalovirus-Reaktivierung bei einem immunsupprimierten Patienten.

BACKGROUND: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical. HISTORY AND SIGNS: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia. THERAPY AND OUTCOME: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy. CONCLUSIONS: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Immune deviation and ocular infections with varicella zoster virus.

Since experimental, herpes simplex virus-induced acute retinal necrosis (ARN) develops in mice only if the mice fail to acquire virus-specific delayed hypersensitivity (DH) and despite their production of anti-viral antibodies (i.e. ACAID), I investigated whether a similar situation exists for patients with either varicella zoster virus (VZV)-induced ARN or anterior uveitis caused by VZV. Patients with either acute VZV-induced ARN, anterior uveitis with dermatitis (herpes zoster ophthalmicus, ZO-AU), or anterior uveitis without dermatitis (zoster sine herpete, ZSH-AU) were skin-tested with VZV to evaluate DH. The formal diagnoses of ARN associated with VZV, ZO-AU, and ZSH-AU were established by PCR analysis of the ocular samples and/or by the Goldmann-Witmer coefficient to determine levels of local antibody production. ARN, ZO-AU, and ZSH-AU activity were assessed clinically, and DH skin tests were repeated three months after onset when ocular recovery had taken place. All patients with VZV-induced skin disease alone (control group) displayed intense DH when tested with VZV antigen. In contrast, subsets of patients with ARN or ZO-AU displayed loss of VZV-specific DH. Patients with the most severe ARN or ZO-AU had the lowest DH responses to VZV antigens. Serum anti-VZV antibody titers were higher in ARN patients than in normal controls, and the anti-viral titer correlated inversely with the intensity of anti-VZV DH responses. VZV-specific DH responses were restored in patients who recovered from ARN. Patients with ZSH-AU also failed to display VZV-specific DH. The absence of DH reactivity to VZV antigens (i.e. immune deviation) appears to be a concomitant feature of VZV uveitis of high intensity, implying that virus-specific DH may interfere with the emergence of VZV-induced ARN or anterior uveitis.