Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis.

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83).

Cytomegalovirus Uveitis: Taiwan expert consensus.

Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan.

First-line management of necrotizing herpetic retinitis by prioritizing the investigation of immune status and prognostic factors for poor visual outcomes.

PURPOSE: To review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR. METHODS: Retrospective evaluation of a series of patients with NHR at our tertiary center between 2012 and 2021 using demographic, clinical, ophthalmologic, virological, therapeutic, and prognostic characteristics was performed. Patients were classified by NHR type: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis. RESULTS: Forty-one patients with NHR were included: 59% with ARN, 7% with PORN, and 34% with CMV retinitis. All patients with CMV retinitis and PORN were immunocompromised versus 21% of patients with ARN. CMV infection was found in 14 (34%) patients, varicella zoster virus infection in 14 (34%) patients, herpes simplex virus type 2 infection in 8 (20%) and type 1 infection in 5 (12%) patients. Intravenous antiviral therapy was received by 98% of patients and intravitreal antiviral injections by 90% of patients. The overall complication rate during follow-up was 83% of eyes. Most frequent complications were retinal detachment (33% eyes) and retinal break (29% eyes). Prognostic factors for poor visual outcomes were pre-existing monocular vision loss in contralateral eye among 17% of patients, bilateral NHR in 17% of patients, posterior pole involvement in 46% of eyes, and involvement > 2 retinal quadrants in 46% of eyes. CONCLUSIONS: The visual prognosis of patients with NHR remains poor. Prompt investigation of immune status and presence of factors justifying intravitreal antiviral injections must be prioritized to initiate and adapt management while awaiting causative virus confirmation.

Correlation of Adenoviral Titers with Severity of Adenoviral Conjunctivitis and Time to Viral Clearance for 21 Days.

SIGNIFICANCE: This investigation reports the correlation of conjunctival viral titers in adenoviral conjunctivitis with patient-reported symptoms and clinician-graded signs for 21 days of follow-up. PURPOSE: Adenoviral conjunctivitis is a highly contagious viral eye infection with significant morbidity and economic impact. This study investigates whether severity of signs and symptoms and time to viral clearance are correlated with conjunctival viral titers at baseline and during 21 days of follow-up. METHODS: The Reducing Adenoviral Patient Infected Days study was a pilot study of the efficacy of a single in-office administration of ophthalmic 5% povidone-iodine. This article outlines longitudinal analyses after the primary outcome report. Of 212 participants screened, 28 participants with quantitative polymerase chain reaction-confirmed adenoviral conjunctivitis were randomized and had follow-up visits on days 1, 2, 4, 7, 14, and 21. At each visit, clinician-graded signs, participant-reported symptoms, and a conjunctival swab for quantitative polymerase chain reaction analysis were obtained. The correlation of viral titers with symptoms and signs was calculated: (1) cross-sectionally at each visit and (2) longitudinally for 21 days using a repeated-measures mixed-effects model. RESULTS: Twenty-five of 28 participants had sufficient data for this report. Higher viral titers for 21 days were correlated with greater severity of symptoms (tearing, matting, and redness, r ≥ 0.70; P < .02) and greater severity of clinical signs (bulbar redness and serous discharge, r ≥ 0.60; P < .01). Eyes with highest baseline viral titers required longer time to viral clearance ( r = 0.59, P = .008). Signs and symptoms persisted in approximately half of the eyes even after viral clearance. CONCLUSIONS: Higher conjunctival viral titers across 21 days were strongly correlated with more severe signs and symptoms and longer time to viral clearance. Our results also indicate that symptoms and signs can persist after viral clearance.

Cytomegalovirus Anterior Uveitis: Clinical Manifestations, Diagnosis, Treatment, and Immunological Mechanisms.

Little is known regarding anterior uveitis (AU), the most common ocular disease associated with cytomegalovirus (CMV) infection in immunocompetent populations. CMV AU is highly prevalent in Asia, with a higher incidence in men. Clinically, it manifests mainly as anterior chamber inflammation and elevated intraocular pressure (IOP). Acute CMV AU may resemble Posner-Schlossman syndrome with its recurrent hypertensive iritis, while chronic CMV AU may resemble Fuchs uveitis because of its elevated IOP. Without prompt treatment, it may progress to glaucoma; therefore, early diagnosis is critical to prognosis. Knowledge regarding clinical features and aqueous humor analyses can facilitate accurate diagnoses; so, we compared and summarized these aspects. Early antiviral treatment reduces the risk of a glaucoma surgery requirement, and therapeutic effects vary based on drug delivery. Both oral valganciclovir and topical ganciclovir can produce positive clinical outcomes, and higher concentration and frequency are beneficial in chronic CMV retinitis. An extended antiviral course could prevent relapses, but should be limited to 6 months to prevent drug resistance and side effects. In this review, we have systematically summarized the pathogenesis, clinical features, diagnostic and therapeutic aspects, and immunological mechanisms of CMV AU with the goal of providing a theoretical foundation for early clinical diagnosis and treatment.

[Chinese expert consensus on diagnosis and treatment of viral corneal endotheliitis (2023)].

Viral corneal endotheliitis, a blinding corneal disease, is often misdiagnosed due to the diverse clinical manifestations, complex conditions, unclear diagnostic criteria, and limited methods of ocular virus detection. In addition, there is still a lack of unified and standardized treatment for viral corneal endotheliitis. The consensus, basing upon the latest research progress and expert recommendations regarding the clinical care of patients with viral corneal endotheliitis, targets to offer best practice advice for the clinical management of viral corneal endotheliitis and has been fully discussed by the experts of the Ocular Infection Group of Chinese Ophthalmologist Association.

A case of recurrent viral retinitis treated with intravitreal antiviral agents in a silicone oil filled eye.

PURPOSE: To report a case of recurrent acute retinal necrosis (ARN) in an eye filled with silicone oil previously complicated by rhegmatogenous retinal detachment (RRD). OBSERVATIONS: A 68-year-old gentlemen with successfully treated herpes simplex virus type 1 (HSV1) ARN complicated by RRD requiring pars plana vitrectomy (PPV) with silicone oil tamponade, presented with a relapse of ARN with silicone oil in situ. Remission of recurrent retinitis was achieved using combined systemic oral and intravitreal antiviral therapy. CONCLUSIONS AND IMPORTANCE: RRD is a significant complication of ARN which may require surgery with silicone oil tamponade. Recurrence of ARN retinitis can be effectively treated with intravitreal Ganciclovir and Foscarnet injections in a silicone oil filled eye with concurrent oral antiviral therapy. Aqueous humour sampling proved useful in the monitoring of disease activity.

Cytomegalovirus as a cause of recurrent corneal endotheliitis in the Canadian population.

OBJECTIVE: To report the clinical manifestations, response to antiviral treatment, and long-term visual outcomes of cytomegalovirus endotheliitis in a Canadian population. DESIGN: Retrospective case series. PARTICIPANTS: A total of 9 eyes of 7 patients referred to a cornea subspecialty clinic in a major Canadian centre with corneal endotheliitis. METHODS: A retrospective review of all patients presenting with corneal endotheliitis to 1 corneal surgeon was completed. Patients underwent anterior chamber biopsy with positive cytomegalovirus polymerase chain reaction. All patients received systemic valganciclovir for a minimum of 3 months. Primary outcomes included visual acuity, intraocular pressure control, medication dependence, and corneal status. RESULTS: The average follow-up was 76.4 ± 11.8 months. Two patients had bilateral disease. Corneal manifestations included linear, disciform, and circinate patterns of endotheliitis. Best-corrected visual acuity improved from a mean of 0.48 ± 0.19 logMAR at presentation to 0.24 ± 0.11 logMAR at last follow-up. Intraocular pressure decreased from a peak of 35 ± 3.1 mm Hg to 14.2 ± 4.3 mm Hg. Antiglaucoma medications were reduced from 2.6 ± 0.45 to 0.89 ± 0.29 agents. Two eyes required endothelial transplantation. Valganciclovir therapy was well tolerated by all patients; at the time of last follow-up, all patients were stable on low-dose valganciclovir at an average dose of 1395 mg per week. CONCLUSIONS: Cytomegalovirus is an uncommon but clinically significant cause of corneal endotheliitis that must be considered in the differential diagnosis of corneal endotheliitis, even in the immunocompetent population. Our results support prior findings that this entity responds robustly to oral valganciclovir and demonstrate for the first time the efficacy of chronic low-dose antiviral maintenance therapy.

Ripasudil Eyedrops Ameliorated Bullous Keratopathy Complicated with Cytomegalovirus Corneal Endotheliitis: A Case Report.

PURPOSE: We describe a case of bullous keratopathy complicated with cytomegalovirus (CMV) corneal endotheliitis that was successfully treated with ripasudil eye drops. METHODS: A retrospective case report. RESULTS: A 65-year-old female patient diagnosed with CMV-associated anterior uveitis in the right eye was referred to us when anterior uveitis recurred with bullous keratopathy. Initial best-corrected visual acuity (BCVA) was 0.4 (decimal visual acuity). Her condition did not improve with anti-CMV treatment, and BCVA decreased to 0.07. At this point, intraocular pressure (IOP) was 20 mmHg, and ripasudil eye drops were started for IOP control. After 1 month, not only had IOP decreased to 14 mm Hg but the condition of the corneal edema had also improved. The central corneal thickness decreased to a normal level, and the BCVA recovered to 0.8. CONCLUSION: Ripasudil eye drops not only lower IOP in patients with CMV corneal endotheliitis but may also have the potential to treat bullous keratopathy.

Acute retinal necrosis: clinical features, management and outcomes.

PURPOSE: To evaluate the clinical features, treatment, and visual outcome of patients with acute retinal necrosis (ARN). METHODS: The data of patients were retrospectively reviewed. Factors associated with visual loss and factors affecting the risk for retinal detachment (RD) development were evaluated. RESULTS: Twenty-four eyes of 24 patients (7 female/17 male, mean age 43.7 years, mean follow-up period 31.0 months) were included. In ocular fluid samples of 15 (83%) out of 18 eyes, polymerase chain reaction (PCR) tests were positive for herpes simplex virus (seven eyes; 39%), varicella zoster virus (six eyes; 33%), cytomegalovirus (one eye; 6%), and adenovirus (one eye; 6%). Central retinal occlusive vasculitis was observed in three (13%) eyes. Systemic antiviral therapy was given to all patients, and additional intravitreal ganciclovir was administered in seven eyes (29%). The most common complication was RD (46%). There was no statistically significant difference in the frequency of RD between herpes simplex virus- and varicella zoster virus-positive patients (p = .617). The rate of RD was similar in eyes undergoing prophylactic laser photocoagulation (LPC), eyes undergoing vitrectomy + LPC, and eyes not undergoing LPC (p = .237). The number of eyes with final visual acuity below 20/200 was significantly higher in eyes with RD than without RD (p = .047). CONCLUSION: Prophylactic LPC and vitrectomy did not show clear benefits in terms of preventing RD development. RD was the most common complication and a major factor for a poor visual prognosis.

The Relationship between Clinical Findings and Viral Load in Adenoviral Keratoconjunctivitis.

The aim of this study was to evaluate the relationship between clinical findings and viral load in adenoviral keratoconjunctivitis (Ad-Kc). In this cross-sectional study, 30 eyes of 30 patients with Ad-Kc were assessed. Real-time polymerase chain reaction was performed to detect and quantify adenovirus in all samples. Patients were divided into three subgroups according to baseline viral load (<107, 107-108, >108 human adenovirus [HAdV] copies/mL). The duration of follow-up, HAdV DNA copy number, treatment regimen, and detailed clinical findings, including uncorrected visual acuity, eyelid edema, conjunctival hyperemia, chemosis, follicular reaction, corneal involvement, conjunctival pseudomembrane, and subepithelial infiltrates (SEIs) were recorded. This study showed that a high initial viral load was associated with the development of SEIs and pseudomembrane formation (P < 0.05). The clinical findings and ocular complications of Ad-Kc were similar in the treatment groups at the final examination (P > 0.05). Our results show that a high initial viral load in Ad-Kc may be predictive of inflammatory sequelae. Determining the initial viral load in Ad-Kc may help understand the clinical course of the disease better and prevent complications.

Preliminary clinical report of alternate episodes of Posner-Schlossman syndrome and viral keratitis.

Posner-Schlossman syndrome (PSS) and viral keratitis have a shared pathogen and are common diseases in China, but there are few case reports on whether these two diseases occur concurrently or alternately. After long-term clinical observations, six patients with alternating episodes of PSS and viral keratitis were confirmed at our hospital in the past 10 years. Of the six patients, three were female and three were male. Four patients had monocular PSS with ipsilateral monocular viral keratitis, one had monocular PSS with bilateral viral keratitis, and one had bilateral PSS with bilateral viral keratitis. Of the six cases, three had epithelial viral keratitis and three had endothelial viral keratitis. In four cases, the interval between the onset of the two diseases ranged from 8 days to 3 years, and two cases showed overlapping manifestations of the two diseases in 3 to 6 days, both with incomplete absorption of keratic precipitates. The six cases had intermittent episodes of both diseases and significant loss of corneal sensation during the onset of viral keratitis, and were effectively treated with antiviral therapy. PSS and viral keratitis may alternate episodically, and clinical attention should be paid to these conditions. The mechanism of the alternate episodes might be associated with viral infection and the use of glucocorticoids.

Host Immune Response and Associated Clinical Features in a Primary Cytomegalovirus Eye Infection Model Using Anterior Chamber Inoculation.

Purpose: To investigate the pathogenesis of cytomegalovirus (CMV)-associated anterior segment infection in immunocompetent hosts and evaluate the effects of ganciclovir and glucocorticoid treatment in management of the disease. Methods: We used an inoculation model to reproduce CMV anterior segment infection in immunocompetent rats. Flow cytometry, cytokine analysis, histopathological sections, and quantitative polymerase chain reaction were performed to investigate the immune response after CMV infection. The effects of ganciclovir and glucocorticoid treatment were also assessed. Results: Anterior chamber inoculation of CMV in rats provoked characteristic pathological features of human CMV anterior segment infection. The innate and adaptive immunity sequentially developed in an anterior segment after inoculation, and the elevation of intraocular pressure (IOP) was highly associated with ocular infiltration and inflammation. Early ocular immune response reduced virus DNA in the anterior segment and alleviated viral lymphadenopathy. Early intervention with ganciclovir enhanced the release of cytokines associated with T response and facilitated recruitment of NKT and T cells in drainage lymph nodes. Glucocorticoid treatment, alone or combined with ganciclovir, decreased elevation of IOP but also impeded DNA clearance. Conclusions: The inoculation model reproduced characteristic pathological features of human CMV anterior segment infection. The use of glucocorticoid in current practice may hinder viral clearance, and ganciclovir therapy can assist cytokine expression to combat the virus.

Herpes Simplex Virus 1 Anterior Uveitis following Coronavirus Disease 2019 (COVID-19) Vaccination in an Asian Indian Female.

PURPOSE: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female. METHODS: Retrospective case report. RESULT: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELDTM (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks. CONCLUSION: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.

Clinical characteristics of virus-related uveitic secondary glaucoma: focus on cytomegalovirus and varicella zoster virus.

BACKGROUND: We aimed to analyze the clinical characteristics of secondary glaucoma related to cytomegalovirus (CMV)- and varicella zoster virus (VZV)-positive uveitis. METHODS: In this retrospective study, we enrolled patients with anterior uveitic secondary glaucoma. All the patients underwent aqueous and serum analyses for viral antibody through enzyme-linked immunosorbent assay. Among the 60 included patients, 22 had CMV-negative Posner-Schlossman syndrome (CMV-negative PSS), 25 had CMV-positive PSS, and 13 had VZV-positive anterior uveitis secondary glaucoma (VZV-AUSG). We evaluated the following main indicators: age, disease duration, intraocular pressure (IOP), cup-to-disc ratio, best corrected visual acuity (BCVA), corneal endothelial cell (CEC) count, ocular morphological changes, and medical treatments. RESULTS: We found that 53.2% (25/47) patients with PSS were CMV-positive. Patients with CMV-positive PSS had a larger cup-to-disc ratio (p = .043), lower CEC density (p = .017), more severe CEC loss (p < .001), and more iris depigmentation (p = .006) than CMV-negative PSS patients. Compared with patients with CMV-positive PSS, those with VZV-AUSG were older (p = .003), presented a higher IOP (p = .015), and had poorer BCVA (p < .001). Patients with CMV-positive PSS and VZV-AUSG all accepted ganciclovir treatment, and those with CMV-positive PSS used fewer antiglaucoma agents simultaneously compared with CMV-negative PSS (p = .005) and VZV-AUSG (p < .001). All three groups had a comparable proportion of patients requiring antiglaucoma surgery. CONCLUSIONS: We observed some distinctive clinical features in CMV-positive PSS compared with CMV-negative PSS. Further, we found that patients with VZV-AUSG presented with a higher IOP and worse visual acuity, and required more antiglaucoma medication than those with CMV-positive PSS.

Viral Anterior Uveitis. / Virale anteriore Uveitis.

Differential diagnosis of viral anterior uveitis (AU) based on the typical clinical findings (anterior chamber inflammation, morphology of the keratic precipitates, severity of IOP increase in relapse) is often straightforward. When differential diagnosis is difficult clinically, analysis of aqueous humour by PCR and/or antibody testing (Goldmann-Witmer coefficient) may be helpful. While both modalities are highly specific, they lack absolute sensitivity. Patients with HSV, VZV and CMV associated uveitis require both antiviral as well as antiinflammatory medication and often additional antiglaucomatous therapy, depending on IOP. In contrast, specific antiviral treatment is not possible in rubella associated AU and steroids should be administered with extreme caution due to their adverse effects. With all subtypes of virus associated AU, recurrent episodes put the patients at risk of developing secondary glaucoma, which often requires surgical treatment.

Risk Factors for Retinal Detachment in Acute Retinal Necrosis.

PURPOSE: Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN. DESIGN: Retrospective cohort study. SUBJECTS: Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020. METHODS: A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN. MAIN OUTCOME MEASURES: Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications). RESULTS: Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN. CONCLUSIONS: Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Anterior uveitis and vasculitis in primary infection with VZV in a diabetic patient.

We present a case of ocular involvement in the context of a varicella zoster virus primary infection, in a 30-year-old man with type 1 diabetes. The ophthalmological examination revealed unilateral anterior uveitis resistant to topical treatment, which was complicated by association of vitritis and onset of retinal vasculitis diagnosed by angiography fluorescein. Herpetic eye involvement was confirmed by anterior chamber PCR for varicella- zoster virus. In addition, we started the treatment with oral valacyclovir 1 gram every 8 hours and 15 mg oral corticosteroid with very satisfactory results, without observing any side effects. Very few cases have been published on this topic, given the low prevalence of this ocular complication.