Systemic Antiviral Therapy Research Articles

Atypical associations of viral anterior uveitis with glaucoma-a series of challenging scenarios with review of literature

ABSTRACT Purpose To report unusual associations, atypical clinical presentations, and outcomes of tailored treatment of viral uveitis and glaucoma Methods Patients diagnosed with viral uveitis with associated glaucoma, seen at a tertiary eye care center between 2013 and 2020, were screened. Twenty-four patients with unclassified or atypical clinical presentations of viral uveitis, atypical clinical course, or with diagnostic challenges and associated glaucoma, were included. Patients with classical features of viral anterior or posterior uveitis, other forms of autoimmune/infectious/traumatic uveitis, were excluded. Results Viral re-activation causing recurrent choroidals after glaucoma filtering surgery responsive to systemic antiviral therapy, massive pigment dusting/plume as a presenting feature, multiple progressive focal anterior synechiae similar to iridocorneoendothelial (ICE) syndrome, were seen in this cohort of unusual viral uveitis in glaucoma. A high index of suspicion helped diagnose a viral etiology in cases with high intraocular pressure (IOP) after uneventful Ahmed glaucoma valve surgery (AGV) or post-YAG capsulotomy laser, presumed Posner-Schlossman syndrome with multiple recurrences or presumed steroid glaucoma. All patients responded well with anti-viral and tailored concomitant steroids, anti-glaucoma therapy with loss of visual acuity seen in one eye developing optic atrophy. Conclusions Uncommon clinical presentations or associations of viral uveitis in glaucoma should be kept in mind. A high index of suspicion and tailored prompt treatment may ensure good outcomes preventing further visual morbidity in glaucoma.

Congenital Cytomegalovirus Infection Initially Managed as Congenital Rubella Syndrome

Congenital cytomegalovirus (CMV) infection (cCMV) is challenging to differentiate from congenital rubella syndrome (CRS) clinically. Virus detection and serological tests are needed. However, they are often not readily available or are expensive. This is a case of a five-month-old male with bilateral cataracts. He was jaundiced at birth and started having seizure episodes at one month of age. He was also diagnosed with right inguinal hernia and had abnormal bilateral hearing tests. Both eyes were noted to have leukocoria at two months of age. There was dazzle on both eyes and sclerae were anicteric. Examination revealed dense cataracts on both eyes, but their ocular ultrasound results were essentially normal. Due to the bilateral hearing loss and bilateral cataracts, CRS was initially considered despite the absence of heart abnormality since there were reported CRS cases without the complete triad. However, possible coinfection or another disease was considered due to the presence of jaundice, seizures, and hernia, which were never seen in our previous CRS patients nor were reported in the literature. The patient underwent cataract extraction on both eyes without intraocular lens implantation (IOL) as recommended for CRS cataracts to prevent severe inflammation. TORCH (TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex) test was negative for rubella but positive for CMV. As such, the patient would have benefitted from early IOL implantation. The patient was then referred to a national medical center for possible treatment. However, since the patient already tested negative for CMV polymerase chain reaction (PCR) there, systemic antiviral therapy was no longer initiated. This case presented the challenge of clinically differentiating cCMV and CRS.

Herpes simplex virus stromal keratitis and endotheliitis after femtosecond laser–assisted cataract surgery and astigmatic keratotomy

Two weeks after uneventful femtosecond laser–assisted cataract surgery (FLACS) with laser astigmatic keratotomy (AK) in the right eye, a 72-year-old woman developed a corneal ulcer and infiltrate in the superonasal AK incision, with severe anterior chamber reaction. She was initially treated for bacterial followed by fungal keratitis, without resolution. She was referred to our university corneal service for consultation. Based on clinical presentation and slitlamp examination, the patient was diagnosed with herpes simplex virus keratitis (HSK). The patient was administered topical steroid eyedrops and systemic antiviral therapy, with full resolution of the keratitis. To the authors’ knowledge, this is the first reported case of herpes simplex virus stromal keratitis and endotheliitis after FLACS combined with AK. This report postulates about possible etiologic factors for activation of HSK after femtosecond laser treatment and proposes preventative actions.

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy.

Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR. A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively. CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR. Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.

RETINAL DETACHMENT AFTER ACUTE RETINAL NECROSIS AND THE EFFICACIES OF DIFFERENT INTERVENTIONS: A Systematic Review and Metaanalysis.

To estimate the rate of retinal detachment (RD) after acute retinal necrosis (ARN) and evaluate the efficacies of different interventions. The databases Medline and EMBASE from inception to March 2020 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated using generalized linear mixed models. Sixty-seven studies involving 1,811 patients were finally included. The pooling results suggested the general RD rate of ARN was 47%. The RD rate increased with the extent of retinitis and was slightly lower when involved Zone III. The RD rate was 37% for herpes simplex virus ARN and 46% for varicella-zoster virus ARN; 52% for immunocompetent patients and 39% for immunocompromised patients. Retinal detachment presented in 2% of eyes at the first visit. Systemic antiviral therapy could lower the RD rate significantly from 67% to 43%, and prophylactic vitrectomy could lower the RD rate significantly from 45% to 22%. Systemic antiviral therapy plus vitrectomy achieved the lowest RD rate to 18%. Although the efficacy of prophylactic laser or intravitreal antiviral therapy was still limited. Prophylactic vitrectomy might significantly increase the incidence of proliferative vitreoretinopathy from 7% to 32%. About half of the eyes might develop RD during the entire course of ARN. Systemic antiviral therapy and prophylactic vitrectomy are effective interventions to prevent RD, whereas the roles of prophylactic laser or adjunctive intravitreal antiviral therapy are still unclear. Varicella-zoster virus ARN and cases with extensive retinitis might need intensified interventions.

Outcomes of Combination Systemic and Intravitreal Antiviral Therapy for Acute Retinal Necrosis

Determine the efficacy of combination intravitreal and systemic antiviral therapy for the treatment of acute retinal necrosis (ARN) and risk factors impacting visual acuity (VA) and retinal detachment (RD) outcomes. Single-center retrospective case series. Patients with an ARN diagnosis based on clinical features and polymerase chain reaction confirmation who were treated at a tertiary referral, university-based academic practice. Patient records were reviewed for demographic information including age and gender. Snellen VA, disease findings including RD outcomes, optic nerve involvement, and treatments were recorded. Incidence rates of major VA and RD outcomes were calculated based on the number of events and exposure times. Cox proportional hazards regression modeling and survival analyses were used to identify factors related to VA and RD outcomes over time. Logarithm of the minimal angle of resolution VA, 2-line or more VA gain, severe vision loss (SVL) of 20/200 or worse, RD development, and fellow eye involvement. Twenty-three eyes of 21 patients (11 male, 10 female) were reviewed. Thirteen patients (62%) had herpes simplex virus and 8 patients (38%) had varicella zoster virus. The event rate for 2-line or more VA gain was 0.49 events/eye-year (95% confidence interval [CI], 0.26-0.86 events/eye-year), whereas the rate of SVL was 0.61 events/eye-year (95% CI, 0.34-1.02 events/eye-year). Retinal detachment development was observed at a rate of 0.59 events/eye-year (95% CI, 0.33-1.00 events/eye-year). Thirteen of 23 eyes (57%) demonstrated RD with a mean time of 120 days after ARN diagnosis. With each additional quadrant of retina involved, a greater risk of RD development over time was observed (hazard ratio, 2.21; 95% CI, 1.12-4.35). Nine percent of eyes progressed with additional quadrantic involvement, despite combination systemic and intravitreal antiviral therapy; however, none of the 19 patients demonstrating unilateral ARN showed fellow-eye involvement after initiation of therapy. Combination intravitreal and systemic antiviral therapy for ARN can be effective in improving VA and limiting retinitis progression. Each additional quadrant of retina involved was associated with a 2.2-fold greater risk of RD, which may impact monitoring, timing of intervention, and patient counseling.

АНАЛИЗ КЛИНИЧЕСКОГО СЛУЧАЯ ПАЦИЕНТА С КРАСНЫМ ПЛОСКИМ ЛИШАЕМ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА, АССОЦИИРОВАННЫМ С ВИРУСОМ ЭПШТЕЙНА―БАРР

Subject. Lichen planus is a chronic inflammatory disease of the skin and mucous membranes, less commonly affecting nails and hair, the typical elements of which are papules. In the structure of diseases localized on the oral mucosa, chronic lichen planus is up to 35―40 %. A number of authors indicate the nature of the development of lichen planus in the oral cavity caused by herpes, in particular type 4 herpes virus (Epstein―Barr).
 The goal is to increase the efficiency of diagnosis and treatment of patients with lichen planus associated with the Epstein―Barr virus.
 Methodology. This article illustrates the experience of managing a patient with exudative-hyperemic form of lichen planus associated with Epstein―Barr virus and the inclusion of antiviral drugs in the treatment regimen. The paper used clinical and laboratory methods for diagnosing the conditions under study.
 Results. In the course of the observation, a positive clinical and laboratory dynamics of the conditions under study was revealed when applying the modernized treatment plan for lichen planus. The appointment of systemic and local antiviral therapy can reduce the treatment time for lichen planus on the mucous membrane of the oral cavity and not resort to the appointment of local hormone therapy.
 Conclusions. In order to increase the effectiveness of the therapy for lichen planus, it is necessary to conduct a study to identify specific DNA not only for Epstein―Barr virus, but also for all herpes viruses due to immunotropy and persistence mainly in the cells of the oral mucosa. The use of a systemic antiviral component reduces the treatment time for dental manifestations of lichen planus and eliminates the need for corticosteroid therapy, which improves the quality of life of patients.

Bilateral cytomegalovirus retinitis comorbid with diabetic macular edema

Cytomegalovirus (CMV) retinitis comorbid with diabetic retinopathy is uncommon. We report a case of bilateral CMV retinitis and diabetic retinopathy in a patient who underwent pancreas transplantation and share the experience of the treatment outcome. An 18-year-old male diagnosed with type-1 diabetes mellitus received pancreas transplantation and immunosuppressive therapy suffered from progressively blurred vision in both eyes for several days. His visual acuity was 20/100 in the right eye and 20/50 in the left eye. Ophthalmic examination revealed bilateral diabetic macular edema (DME) without intraocular inflammatory signs in either eye. The DME subsided after 2 monthly intravitreal injections of aflibercept. However, bilateral panuveitis with CMV retinitis was observed after antivascular endothelial growth factor therapy. The retinitis subsided gradually but completely after systemic and intravitreal antiviral therapy. However, bilateral DME recurred and persisted despite repeated injections of aflibercept during the resting follow-up period. Our case suggests that CMV retinitis can coexist with other retinal diseases, including diabetic retinopathy. Treatment is difficult in such cases.

An International Epidemiology Study to Determine the Prevalence of Preexisting Cell-Mediated Immunity to Adeno-Associated Virus (AAV) in Adults with Severe Hemophilia

Introduction: Adeno-associated virus (AAV) is a versatile gene therapy vector utilized widely in clinical gene transfer studies. AAV serotype 8 (AAV8) has been used successfully as a vector in liver-directed gene transfer in hemophilia clinical trials, and a recombinant AAV8 vector is used currently in Shire's BAX 888 clinical study (NCT03370172) for the treatment of patients with severe hemophilia A. However, 1 recognized limitation of intravenous administration of recombinant AAV is the barrier posed by preexisting immunity against AAV and the cross-reactivity of anti-AAV antibodies between various serotypes that results from natural exposure to the wild-type viruses. Neutralizing antibodies (NAbs) resulting from humoral immune responses can compromise vector transduction, and reactivation of memory T cells from cell-mediated immune responses can abrogate transgene expression and eliminate transduced cells. Understanding the prevalence of cell-mediated immune responses in the hemophilia population and the association between cell-mediated and humoral immunity is important in developing effective gene therapies.Objectives: To determine the prevalence of preexisting immunity towards AAV8 and AAV2 in the adult population of patients with hemophilia A and B, and to characterize the association between cell-mediated immunity and humoral immunity.Methods: In this ongoing study, peripheral blood samples were collected at outpatient visits from adult males (age 18-75 years) with severe hemophilia A (plasma factor VIII [FVIII] activity <1%) or hemophilia B (plasma factor IX [FIX] activity ≤2%) for determination of immunity towards AAV8 and AAV2. Patients could elect to participate in a single baseline visit or in the longitudinal study arm for up to 3 annual visits. Patients with inhibitors or a history of inhibitors to FVIII or FIX, an underlying lymphocyte disorder, or currently receiving cytotoxic chemotherapy, monoclonal antibodies, immunoglobulins, immunosuppression, or systemic antiviral therapy were excluded. The cell-mediated immune response against AAV8 peptide antigens was quantified using an interferon-γ enzyme-linked ImmunoSpot (ELISPOT) assay to determine the number of T cells responsive to 3 different pools of AAV8 capsid-specific protein fragments. Each AAV8 antigen pool consisted of 50-60 nonoverlapping peptides composed of 15 amino acid residues. Results were considered positive if the signal was >3 times above the background and >60 cells/million. Serum was collected for assessment of humoral immunity (AAV8 NAbs or AAV2 NAbs) using a cell-based transduction inhibition assay (titer cutoff: ≥1:5).Results: A total of 41 patients have enrolled in the study to date (mean ± SD age: 33.8 ± 11.1 years) and ELISPOT data are available for 37 patients. Of those with available data, 9/37 patients (24.3%) had a positive ELISPOT to ≥1 of the 3 AAV8 peptide pools tested. One patient tested positive for peptide pool 1, 3 for peptide pool 2, and 7 for peptide pool 3 (2 patients [5.6%] tested positive for both pools 2 and 3). Of the 9 patients with positive AAV8-specific ELISPOT results, 6 (66.7%) also had a positive result for AAV8 NAbs, while of 27 patients with negative ELISPOT results, 11 (40.7%) had a positive result for AAV8 NAbs.Conclusions: The results from this ongoing international epidemiology study demonstrate that the prevalence of preexisting cell-mediated immunity to AAV8 resulting from natural exposure to wild-type AAV is approximately 1 in 4 adult males with severe hemophilia A or B. Furthermore, there appears to be a correlation between cell-mediated and humoral immune responses, as two thirds of patients with positive AAV8-specific ELISPOT results also tested positive for AAV8 NAbs. Understanding the relationship between cell-mediated and humoral immunity and how it may affect an individual's response to AAV-based gene therapy will be key to successfully developing this novel therapy. DisclosuresRajavel:Shire: Employment, Equity Ownership. Chapin:Shire: Employment, Equity Ownership. Tang:Shire: Employment.

Requirement of longer term antiviral therapy in patients with cytomegalovirus anterior uveitis with corneal endothelial cell damage.

BackgroundThe aim of the study was to investigate the efficacy of therapy in patients with cytomegalovirus (CMV) anterior uveitis.Patients and methodsWe reviewed the records of patients with CMV anterior uveitis who attended our institution between October 2010 and December 2015 and who were confirmed to have CMV DNA in the aqueous humor by polymerase chain reaction analysis.ResultsFourteen immunocompetent patients (10 men and 4 women, total of 17 eyes) were enrolled. The mean ± SD age at the onset of antiviral therapy was 63.1 ± 11.3 years (range, 44–87 years). CMV DNA was not detected in the aqueous humor of 3 patients on initial testing, but it was detected on subsequent analysis. All patients underwent systemic antiviral therapy. Among the patients who were followed up for more than 6 months after starting systemic antiviral therapy, systemic antiviral therapy was successfully terminated in all 4 patients without corneal endothelial loss but had to be continued because of disease recurrence on its termination in 5 of 8 patients (62.5%) with corneal endothelial damage (P = 0.038).ConclusionsPatients with corneal endothelial cell loss are likely to require longer term antiviral therapy than those without endothelial damage. In addition, whereas definitive diagnosis of CMV anterior uveitis requires the detection of CMV DNA in aqueous humor by polymerase chain reaction, one-fifth of patients in the present study tested negative on initial examination.

Herpes Zoster Optic Neuropathy.

Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON. A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes. Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5-4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6-30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.

Research progress on the diagnosis and treatment of acute retinal necrosis

Acute retinal necrosis is an uncommon but devastating and potentially blinding ophthalmopathy featured with unfavorable prognosis as the lesions tend to develop rapidly in a circumferential way in few days. Therefore timely diagnosis and early treatment are of great significance. The polymerase chain reaction test on intraocular fluid can improve specificity and sensitivity of the etiological detection for acute retinal necrosis. Etiology results included in the diagnostic criteria is favorable for etiological diagnosis. Current treatment for acute retinal necrosis is generally based on systemic antiviral therapy, and supported by hormone and antithrombotic drugs, while surgical treatment should be considered when the disease progresses. This article reviews the research progress on the diagnosis and treatment of acute retinal necrosis in an effort to improve the diagnosis and treatment performance of acute retinal necrosis. (Chin J Ophthalmol, 2018, 54: 306-311).

Orbital Apex Syndrome Secondary to Herpes Zoster Ophthalmicus.

Orbital apex syndrome is a rare complication of herpes zoster ophthalmicus. A patient being followed in our clinic for herpes zoster ophthalmicus developed orbital apex syndrome in the second week of treatment. Clinical diagnosis was supported by magnetic resonance imaging. Treatment with systemic steroid and antiviral therapy resulted in total regression of ophthalmoplegia at 2 months. However, optic neuropathy-induced vision loss was permanent. This case report examines orbital apex syndrome secondary to herpes zoster ophthalmicus, which has rarely been documented in the ophthalmic literature.

High ocular CMV copies and mismatched receipts may predict poor visual prognosis in CMV retinitis patients following allogeneic haematopoietic stem cell transplantation

BackgroundTo summarize the clinical characteristics and potential factors affecting the visual outcomes in patients with cytomegalovirus retinitis following allogeneic haematopoietic stem cell transplantation (HSCT).MethodsThis retrospective study enrolled 12 patients (19 eyes) with cytomegalovirus retinitis after HSCT at Guangzhou First People’s Hospital in China between January 2013 and December 2014. Demographic and clinical characteristics, ocular manifestations and visual outcomes were evaluated by reviewing medical records at the Departments of Hematology and Ophthalmology. All patients were followed up at least 6 months after stopping antiviral therapy. The visual outcome was defined as improvement, stabilization and deterioration.ResultsThe subjects were composed of 7 human leucocyte antigen-matched and 5 mismatched receipts. All patients received combined systemic and intravitreous antiviral therapy. Eleven eyes gained improved or stabilized visual acuity, while 8 eyes suffered deterioration. Eyes with cytomegalovirus load less than 1 × 104 copies/ml in vitreous accounted for higher rate in eyes with good visual prognosis than those with cytomegalovirus copies above 1 × 104 copies/ml (52.63% vs 5.26%, P < 0.001). Human leucocyte antigen-matched receipts gained better visual prognosis than those mismatched ones (47.37% vs10.53%, P < 0.05). The virus types, cytomegalovirus peak in the blood, involved retinal zone and size had no influence on the visual outcomes (all P > 0.05).ConclusionsHigh ocular cytomegalovirus copies and mismatched receipts may be potential adverse factors affecting visual outcomes in cytomegalovirus retinitis patients following allogeneic HSCT.

Surgical management of Acute Retinal Necrosis (ARN): timing and outcomes

PurposeTo evaluate the demographics, etiology, clinical and surgical management, and functional outcomes of an Acute Retinal Necrosis (ARN) series from a referral Italian Centre. Both clinical characteristics and treatment strategies of ARN are valid and debated issues. Several dedicated articles appear every year in highly impacted medical journals.MethodsObservational series of biopsy‐proven ARN cases between January 2010 and March 2017. All the considered patients had the last visit in 2017. Soon after diagnosis patients had received systemic antiviral therapy according to the specific guidelines. No intravitreal injections or “early” (i.e. in the absence of retinal detachment, RD) pars plana vitrectomy (PPV) were adopted.ResultsSeven patients (5 men) were included with a mean age of 52 ± 18 years (range 31–78 years). HZV was detected in 4 cases, HSV in 2 cases, CMV in 1 case (the sole with positive serology for HIV). PPV was performed in 6/7 subjects, with a mean delay of 43±33 days since diagnosis. Only in 1 case silicone tamponade removal was successfully reached. A second PPV was required in 4/6 patients, because of RD recurrence or posterior bleeding. In one HSV case a complete healing was achieved with medical treatment. Visual acuity (VA) averagely improved in the whole cohort either between diagnosis (0.91 ± 0.25 logMAR) and the end of follow up (0.77±0.51 logMAR); or between preoperatively (1.15 ± 0.03 logMAR) and the end of follow up. In both cases, however, statistic was not significant (p &gt; 0.05).ConclusionsThe efficacy of prophylactic laser in our series, as in the literature, remains unclear. VA improvement was achieved even without early PPV. This evidence, along with the possible adjuvant effect of intravitreal antivirals, warrant comparative discussion with literature data.

Intravitreal Administration of Antiviral Agents in Silicone Oil–Filled Human Eyes

To report our experience with intra-silicone oil (SO) injection of antiviral agents for treatment of viral retinitis and to review the relevant literature. Two case reports and a literature review. Two patients with viral retinitis and SO tamponade. Two patients with viral retinitis were treated with intravitreal injections of low-dose ganciclovir (2mg/0.05 ml), foscarnet (1.2 mg/0.05 ml), or both after retinal detachment repair with SO tamponade, in addition to systemic antiviral therapy from 2014 through 2015. The literature on the use of intraocular antiviral agents in the setting of SO vitreous substitute was reviewed. Clinical outcomes after administration of intra-SO antiviral therapy. A patient with progressive outer retinal necrosis received 5 intra-SO injections of low-dose ganciclovir and foscarnet after surgery over 6 weeks. Another patient with acute retinal necrosis received weekly low-dose foscarnet injections into his SO-filled eye for 8 weeks after surgery. Significant retinitis regression with long-term retinitis control was achieved in both patients throughout follow-up. No articles reporting the administration of soluble antiviral agents into an SO-filled human eye were identified. Our preliminary findings indicate that administration of low-dose ganciclovir and foscarnet into an SO-filled eye may be used as adjunctive treatment for viral retinitis. Further studies are needed to confirm these results.

Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology

To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN). Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective. Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear. Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis ofARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.

СLINICAL FEATURES, DIAGNOSIS AND TREATMENT OF PATIENTS WITH RETINAL DETACHMENT DUE TO ACUTE RETINAL NECROSIS

This article deals with the PCR diagnostic results of the vitreous and retina biopsy material in patients suffering from panuveitis with retinal detachment. Rhegmatogenous retinal detachment with partial hemophthalmia was diagnosed as a result of primary diagnosis. The pair eyes were intact. Ultrasound B-scan, electrophysiological studies, ocular fundus photoregistration and standard ophthalmological examination was conducted for all patients. As a special method of investigation, PCR diagnostics of a biopsy material from a primary vitrectomy was used as a special method. In ten patients with panoveitis, acute retinal necrosis and retinal detachment, vitrectomy with endolaser coagulation of the retina and a silicone tamponade was performed. Vitrectomy with endolaser retinal photocoagulation and silicone oil tamponade was performed in ten cases of panuveitis with acute retinal necrosis and retinal detachment; postoperatively systemic antiviral therapy was administered for 6–12 weeks. In the postoperative period, all patients underwent a course of systemic antiviral therapy with valaciclovir 500 mg twice a day for 6-12 weeks. In the absence of effect, valganciclovir 900 mg twice daily for 21 days was additionally used. As a result of PCR-diagnostics mixed infection (in the biopsy of the retina — viral DNA, in the biopsy of the vitreous body — DNA of the mycobacterium tuberculosis) was detected in 2 patients with the most severe retinal necrosis and panoveitis with funnel-shaped retinal detachment, Viral DNA was found in the retina biopsy specimen in one patient, and in the vitreous biopsy specimen DNA of the pathogen was not detected. Early primary vitrectomy promotes the most functional results: best corrected visual acuity after removal of the silicone oil reached 0,3–0,6 in the Golovin-Sivtsev table. The obtained data had shown, PCR is the most informative method for determining the etiology of the process is PCR diagnostics of the retina biopsy that with panoveitis with acute retinal necrosis. A potential cause of this nosological form is a mixed infection, namely, the combination of the viral nature of the disease with tuberculosis, although it is not always possible to identify all etiological agents.

Mixed infections and inflammatory ophthalmic diseases: clinical and laboratory observations

Over the period 2013-2016, 34 patients (14 men and 20 women) with different inflammatory processes in the eye who appeared DNA-positive for mycoplasmas (Mycoplasma hominis, Ureaplasma urealyticum) and/or chlamydiae (Chlamydia trachomatis) (PCR testing of tear fluid and/or urine) were followed up. All patients were examined for intensive production of herpesvirus, adenovirus, and enterovirus DNA in biological fluids. After being consulted by related specialists, all the patients started local and systemic (antibacterial and antiviral) therapy. In the end of the latter, laboratory tests were repeated. Among all the clinical forms, anterior segment inflammation (i.e. of conjunctiva, cornea, and the anterior vascular tract) prevailed - 76%. In most patients, mycoplasmas and/or chlamydiae formed associations with herpesviruses (n=19; 56%). Bacterial DNA alone (mycoplasma and/or chlamydia) was detected in 12 cases (35%). In 4 cases, mycoplasma and/or chlamydia DNA was detected in tear fluid, in 19 patients - in urine, and in 10 patients - in both secreta. Local and systemic causal treatment enabled resolution of the complaints and symptoms and yielded negative results of follow-up laboratory tests. More than a half of the patients demonstrated concomitant viral-bacterial infection (22 cases). The presence of bacterial/viral DNA in biological secreta, as revealed by PCR, reflects the systemic nature of the infection process and, thus, necessitates engagement of related specialists (dermatologists, urologists, gynecologists).

Clinical Study: Lotion Containing Propolis Special Extract GH 2002 0.5% vs. Placebo as On-Top Treatment of Herpes Zoster

Background: The aim of the clinical trial was to establish the contribution of propolis special extract GH 2002 as constituent of a lotion for the supportive treatment of Herpes zoster. Methods: 60 patients with diagnosed Herpes zoster were either treated with a propolis containing (n = 33) or an identical, but propolis-free lotion (n = 27) for 28 days, as an add-on therapy to oral antiviral treatment with aciclovir. Study parameters were the assessment of pain on a visual analogue scale, the assessment of the formation of new vesicles, and the safety of application of the preparation. Results: Improvement of pain was significantly better and quicker in the propolis lotion group (p < 0.001 at all visits). On day 3/4, the reduction of pain versus baseline was 54% versus 20% reduction in favour of propolis lotion. On day 14 the results were 80% versus 42% pain reduction. Healing of lesions was significantly quicker with the propolis-containing lotion: at visit 3 on day 7, 21% versus none of the patients showed a closed skin with or without crusting. After 14 days, the comparison showed 57.6% versus 25.9%. At least 50% of propolis-treated patients were lesion-free on day 14, versus day 28 in the control group (p = 0.013). The formation of new vesicles was also significantly suppressed. On day 3/4 the number of newly formed vesicles was 15 versus 25, on day seven the number of new vesicles was 4 versus 14 (p < 0.001). The advantage of propolis lotion was confirmed through the global assessment of efficacy by the physician, with 75.8 versus 33.3% “good” to “excellent” ratings already on day 3/4, 90.9 vs. 44.4% on day 7, and 100 vs. 74.1% on day 28 (p < 0.001). Skin tolerability was excellent, no allergic reactions, skin irritations or other adverse events were observed. Conclusion: The observations clinically confirm antiviral and anti-inflammatory effects of propolis special extract GH 2002 and at the same time demonstrate the benefits of the topical add-on to the systemic antiviral therapy of Herpes zoster.