Herpetic Retinitis Research Articles

Demographic Features, Diagnoses and Real-World Clinical Management of Uveitis in Japan

ABSTRACT Purpose This study aimed to investigate demographic features, diagnoses of uveitis (intraocular inflammation), and real-world clinical practice in the use of local and systemic therapies for patients with uveitis in Tokyo, Japan. Methods Clinical records of 1,174 consecutive new patients (480 males, 694 females) referred to the Kyorin Eye Center, Kyorin University Hospital between January 2011 and December 2018 were retrospectively reviewed. Results Mean age at presentation was 52.6 years (range 4–94 years). By anatomic location, 439 patients (37.4%) had anterior uveitis, 18 (1.5%) had intermediate uveitis, 214 (18.2%) had posterior uveitis and 503 (42.8%) had panuveitis. The 3 most common diagnoses were sarcoidosis (9.1%), Vogt-Koyanagi-Harada (VKH) disease (8.3%), and acute anterior uveitis (5.7%). Compared to our previous study, rates of herpetic anterior uveitis and cytomegalovirus (CMV) retinitis increased while tuberculosis-related uveitis decreased. Unclassified uveitis remained the most common diagnosis (44.9%). Systemic corticosteroids and/or immunomodulatory agents were used in only 18.3% of patients. Immunomodulatory drugs including biologic agents were utilized in 4.9% of patients. Conclusions The most common uveitis anatomic type was panuveitis due mainly to high rates of sarcoidosis and VKH disease. Diagnoses of herpetic anterior uveitis and CMV retinitis increased, while tuberculosis-related uveitis decreased. Less than one-fifth of uveitis patients required systemic treatment.

A Better Understanding of the Clinical and Pathological Changes in Viral Retinitis: Steps to Improve Visual Outcomes.

Infectious retinitis, though rare, poses a significant threat to vision, often leading to severe and irreversible damage. Various pathogens, including viruses, bacteria, tick-borne agents, parasites, and fungi, can cause this condition. Among these, necrotizing herpetic retinitis represents a critical spectrum of retinal infections primarily caused by herpes viruses such as varicella-zoster virus (VZV), herpes simplex virus (HSV), and cytomegalovirus (CMV). This review underscores the retina's susceptibility to viral infections, focusing on the molecular mechanisms through which herpetic viruses invade and damage retinal tissue, supported by clinical and preclinical evidence. We also identify existing knowledge gaps and propose future research directions to deepen our understanding and improve therapeutic outcomes.

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

PurposeTo review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR.MethodsRetrospective 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.ResultsForty-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.ConclusionsThe 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.

Advances in the microbiological diagnosis of herpetic retinitis.

Viral retinitis associated with herpesvirus is one of the most severe forms of uveitis and is a potentially sight-threatening ophthalmologic disease. The prognosis is poor and a rapid and aggressive management is necessary to improve the visual and sometimes vital prognosis of these patients. The treatments used are not without side effects, while many differential diagnoses exist, such as toxoplasmic retinochoroiditis, syphilitic retinitis, endogenous endophthalmitis and intraocular lymphoma. Causatives viruses are herpes simplex virus, varicella-zoster virus, and cytomegalovirus, which require rapid detection in ocular fluid, mainly aqueous humor. However, only a small amount of intraocular fluid is available for analysis. Advances in microbiological diagnostic techniques therefore were key factors in improving the management of these diseases. Historically, the diagnosis was based on immunological tests but more recently advances in molecular biology, in particular polymerase chain reaction, have played a crucial role to obtain a reliable and rapid diagnosis of viral retinitis associated with herpesvirus, as discussed in this review.

Changing Trends in Uveitis in the United Kingdom: 5000 Consecutive Referrals to a Tertiary Referral Centre

ABSTRACT Purpose To demonstrate changes in the demography and diagnosis of uveitis in a specialist clinic in the United Kingdom. Methods Retrieval of data including all new referrals to Manchester Uveitis Clinic from 1991 to 2020. The incidence and proportions of diagnoses between 4 quartiles was compared. Results 5000 patients with uveitis were seen. Referral rates trebled over time. Highly significant increases in referrals were seen for multiple evanescent white dot syndrome-spectrum disorders, syphilis and tuberculosis; increases were also seen for herpetic retinitis, vitreoretinal lymphoma and sarcoidosis. Highly significant decreases were seen for Fuchs’ uveitis, Behçet’s uveitis and ocular toxoplasmosis. Conclusions Subspecialisation and de-skilling has changed referral patterns to specialist clinics; changes cannot be entirely attributed to disease incidences, which also vary between countries. International data are non-comparable. There are clear changes in referral patterns and disease incidence in this population, influenced by evolving diagnosis. Local data should steer care planning.

Retinitis due to Rickettsia infection

A 67-year-old woman with type 2 diabetes presented to our hospital with decreased left vision for 7 days. On examination, right visual acuity was 20/30, and left visual acuity was 20/50. Intraocular pressures were both normal. Anterior chambers were deep and uninflamed, with bilateral nuclear sclerotic cataracts. There was mild left vitritis, but none in the right eye. Right fundoscopy was normal. Left fundoscopy showed one-disc diameter of unifocal retinitis along the superior vascular arcade (figure A). Left fluorescein angiography revealed late staining in the area of retinitis. The patient was treated presumptively with anti-toxoplasmosis and anti-herpes therapy (oral pyrimethamine [100 mg for the first day then 50 mg daily] and oral sulfadiazine [1 g three times daily] for toxoplasmosis, and intravenous aciclovir [800 mg three times daily] for herpetic retinitis), while awaiting laboratory results. PCR testing of anterior chamber taps were negative for Herpes simplex virus and toxoplasmosis. Negative Treponema pallidum hemagglutination and venereal disease research laboratory test excluded syphilis. Negative QuantiFERON-TB Gold test and tuberculin skin test were negative, and eliminated tuberculosis as a possible cause. Serum angiotensin converting enzyme and lysozyme were normal, which made sarcoidosis an unlikely explanation for the clinical findings. The patient's vision worsened to 20/200 in the left eye. Fundoscopy showed ongoing retinitis with a new retinal haemorrhage and serous macular detachment. She subsequently disclosed having episodes of malaise, headache, myalgia, skin rash (figure B), and fever (maximum 39·5°C; unresponsive to amoxicillin 500 mg three times a day), following travel to rural Algeria. Serology for Rickettsia conorii showed an elevated IgG titer of 1024 g/L, but was negative for IgM. Anterior tap PCR and cutaneous biopsy were negative for Rickettsia. Fundoscopy improved markedly after 7 days of treatment with doxycycline (200 mg daily). After 2 months, visual acuity was 20/20 and the retinitis resolved fully. This case illustrates the importance of careful history taking, and maintaining an index of suspicion for Rickettsia in patients who have travelled to an endemic area and present with fever, skin rash, and retinitis.

TCL-361: Bendamustine as Front-Line Therapy in T-Cell Prolymphocytic Leukemia: A Monocentric Experience

Introduction T-cell prolymphocytic leukemia (T-PLL) is a rare T-cell-neoplasm that is characterized by uncontrolled proliferation of mature T-cell lymphocytes with a very poor prognosis. Nowadays, alemtuzumab as a single agent is the best available option for both treatment-naive and relapsed/refractory patients; however, its efficacy is hampered by various adverse events (AEs) such as infusion-associated reactions, autoimmune AEs, and opportunistic infections. Objective We conducted a monocentric, retrospective study to evaluate the safety and efficacy of bendamustine, which is a bifunctional mechlorethamine derivative with alkylating and antimetabolite activities, as first-line therapy in patients unfit for alemtuzumab. Patients and Methods We collected clinical and biological data of 7 T-PLL patients treated with bendamustine between 2014 and 2020 in our institution. Four out of seven (57%) were males, the median age at diagnosis was 73 years (65–83 years). The median time from diagnosis to treatment was 15 months. Bendamustine was administered intravenously (90 mg/m2 on days one and two, every four weeks) for up to six cycles. Results Overall response rate was 57%, 3 patients achieved complete response (43%), and one partial response (14%). One patient experienced stable disease, and two patients progressed during treatment. Five patients (71%) experienced a relapse. Median overall survival (OS) was 63.7 months (19–108); median OS for responding patients was 187 months versus 24 months for non-responding patients (p=0.093). Median progression-free survival (PFS) was 12 months (11–13). Three patients received second-line therapy: one patient was treated with gemcitabine; the others received a second bendamustine course. Two patients received a third-line therapy with combination chemotherapy: COMP (prednisone, cyclophosphamide, vincristine, myocettm) and CVP (cyclophosphamide, vincristine, prednisone). Two patients experienced infusion-associated reactions. Four patients experienced hematological toxicities: one thrombocytopenia G3, 3 neutropenia G3 requiring G-CSF administration. Four patients received co-trimoxazole prophylaxis, one received acyclovir prophylaxis. One patient experienced herpetic retinitis. Premature termination ( Conclusions Our data are consistent with scientific literature. This treatment is feasible and safe, with an acceptable toxicity profile. Although alemtuzumab remains the standard of care of this rare disease, bendamustine might be a valid option either for unfit patients or for undeferrable disease.

Herpetic retinits… Who is the guilty one?

AbstractThe presentation will cover the approach for the diagnosis and treatment of herpetic retinitis. It will provide with a practical approach on when and what to suspect and how to handle a potential visual threatening such as herpetic retinitis.

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review.

Necrotising retinitis is a rare ocular infection that historically led to high rates of visual morbidity. While acute retinal necrosis occurs in immunocompetent patients, the majority of cases are associated with immunocompromise such as in cytomegalovirus retinitis and progressive outer retinal necrosis. This review summarises the clinical and diagnostic features, management, and outcomes of herpetic retinitis. Iatrogenic immunosuppression is increasingly being utilised for a wide range of indications, and biologic agents especially so due to their targeted nature. While the intended actions are well-studied, the flow-on effects and complex interaction with host immunity are not well understood. Furthermore, biologics are frequently used concomitantly with other immunosuppressive agents, potentiating the immunodepression. This article reviews the literature on biologic immunosuppression and viral retinitis, and presents an approach to the vulnerable or affected patient. Early identification, prompt and aggressive treatment, and a multidisciplinary approach to managing immunodeficiency are the cornerstones of management.

Chronic Herpetic Retinitis: Clinical Features and Long-Term Outcomes

ABSTRACTIntroduction: Chronic uveitis treated with immunosuppressive agents may have unfavorable outcomes due to delays in diagnosis. The aim of this study was to review initial data from clinical and ocular assessments and patient outcomes following specific treatments for atypical herpes virus ocular infections.Methods: The records of four consecutive patients with recurrent uveitis for at least five years treated in our department between 2001 and 2016 were retrospectively reviewed. They had atrophic retinal lesions resulting in an unfavorable outcome with lesion progression and vision loss under immunosuppressive treatment. Varicella zoster virus (1 case) and herpes simplex virus type 2 (3 cases) were detected in ocular samples.Results: Uveitis was granulomatous and bilateral (3 cases) or unilateral (1 case). Immunosuppressive treatments worsened the clinical situation whereas antiherpetic treatments improved the control of intraocular inflammation.Conclusion: This description should be added to the broad repertoire of clinical polymorphisms associated with herpes virus infections. Recognizing these cases should be useful due to their sensitivity to antiherpetic treatments.

Intraocular T-cell Prolymphocytic Leukemia Masquerading as Necrotizing Herpetic Retinitis

An elderly lady with a history of T-cell pro-lymphocytic leukemia apparently successfully treated with alemtuzumab presented with unilateral intraocular inflammation masquerading as viral retinitis...

In-bag dislocation of intraocular lens in patients with uveitis: a case series.

BackgroundImprovement in surgical devices and intraocular lenses has made modern cataract surgery a safe procedure with decreasing complication rates. Intraocular lens dislocation is a serious complication after cataract surgery. Although most dislocations occur during the first week postoperative period, late intraocular lens dislocation occurring 3 months or later post-surgery has been reported with increasing frequency in recent years as a result of progressive zonular dehiscence. We report the clinical features, management and outcomes of five cases of late in-bag dislocation of intraocular lens in patients with underlying uveitis. This is a retrospective case series and literature review.ResultsWe identified five eyes in five patients with uveitis and late in-bag intraocular lens dislocation. Two patients had multifocal choroiditis, two herpetic uveitis and retinitis and two Fuchs’ heterochromic iridocyclitis in five patients. Mean age at the time of cataract surgery was 50. Best vision ranged from counting fingers to 6/18 preoperatively and ranged from 6/36 to 6/6 postoperatively. All had right eye dislocation with mean time from initial cataract surgery to intraocular lens dislocation of 81 months. Explantation of dislocated intraocular lens and vitrectomy were performed in four cases; three had anterior chamber intraocular lens placement. One case was managed conservatively. Best vision ranged from light perception to 6/7.5 at time of dislocation and ranged from 6/36 to 6/6−2 at follow-up.ConclusionsLate in-bag dislocation intraocular lens can complicate cataract surgery in patients with underlying uveitis. This case series identified that the mean time to in-bag intraocular lens dislocation in five uveitis patients was 81 months after uncomplicated cataract surgery, comparable with the time reported in the available literature of patients with pseudoexfoliation syndrome. This series also found that lens explantation and replacement with anterior chamber intraocular lens achieved good outcomes. Further investigation is warranted to ascertain the strategies to identify patients at risk and to prevent and better manage intraocular lens dislocation in patients with uveitis.

Long-term follow-up of herpetic non-necrotizing retinopathy with occlusive retinal vasculitis and neovascularization.

BackgroundHerpetic necrotizing retinitis is a well-recognized entity. A few cases of herpetic non-necrotizing retinitis were previously reported.FindingsWe retrospectively report two cases of herpetic non-necrotizing retinopathy with a long follow-up. A 19-year-old woman presented with a bilateral diffuse occlusive retinal vasculitis, peripheral neovascularization, and no signs of retinal necrosis. Long-lasting immunosuppressive treatment failed to control the vasculitis until herpes simplex virus type 1 (HSV1) was demonstrated by polymerase chain reaction (PCR) in the aqueous. Acyclovir was then added and immunosuppressive tapered and eventually stopped resulting in a resolution of vasculitis. Only two relapses occurred during the next 6 years and responded rapidly to oral acyclovir.An 11-year-old boy presented with unilateral scar of stromal keratitis, severe vitritis, and optic disc neovascularization, followed 6 weeks later by peripheral occlusive retinal vasculitis. Therapeutic and diagnostic vitrectomy was performed, and PCR was found to be positive for varicella zoster virus (VZV) in a vitreous specimen. The inflammation responded to oral acyclovir therapy. Recurrence of anterior uveitis with iris depigmentation occurred 4 months after treatment was arrested. After 4 years, he presented again with a recurrence of anterior inflammation and cystoid macular edema (CME). No sign of inflammation was seen for the next 10 years.ConclusionsThese rare cases support the possible role of herpes viruses (HSV or VZV) in occlusive vasculitis without retinal necrosis. PCR was useful to raise the diagnosis and to adapt the treatment. A good response was obtained on oral antiviral therapy.

Learning about herpes infections by using animal models

AbstractOcular infections caused by members of the herpesvirus family may have serious and sometimes, sight‐threatening, consequences. As has been for so many disease processes, animal models have been used to better understand the pathogenesis of herpetic keratitis and retinitis in human patients. While no animal model has absolute fidelity to its human counterpart, careful interpretation and extrapolation of results from animal studies may provide valuable information/insight about the pathogenesis of human disease. This presentation will provide an overview of animal models of keratitis and retinitis, summarize the strengths and weaknesses of the models, and discuss how what has been learned from these models has advanced our knowledge of the mechanisms of human ocular disease and/or has led to new therapeutic approaches to these diseases.

Progressive Outer Retinal Necrosis Secondary to Herpes Simplex Virus Type 2.

Progressive outer retinal necrosis is an aggressive form of necrotizing herpetic retinitis that presents in immunocompromised patients. It is usually secondary to varicella zoster virus or, rarely, herpes simplex virus type 1. The authors report a case of progressive outer retinal necrosis associated with herpes simplex virus type 2 in a patient with a history of congenital herpes. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:xxx-xxx.].

HERPETIC VIRAL RETINITIS

Human Herpes Virus (HHV) is a DNA virus and is the most important viral pathogen causing intraocular inflammation. HHV is classified into types 1-8. Among these types, HHV-1, HHV-2, HHV-3 Varicella Zoster Virus (VZV) and HHV-5 Cytomegalovirus (CMV) are known to cause herpetic viral retinitis, including acute retinal necrosis and CMV retinitis. Herpes viral retinitis can be diagnosed from characteristic ocular findings and viral identification by PCR of the aqueous humor. Recently, therapy has become more effective than in the past. Herpes viral retinitis gradually progresses if appropriate treatment is not provided with regard to the patient’s immune status. Further advances in diagnostic methods and treatment are required in the future.

Non-cytomegalovirus Ocular Opportunistic Infections in Patients With Acquired Immunodeficiency Syndrome

To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in the era of highly active antiretroviral therapy. Multicenter, prospective, observational study of patients with AIDS. Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3months for outcomes. At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis, 0.014/ 100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates= 21.7 deaths/100 PY [P= .02] and 12.8 deaths/100 PY [P= .04]), respectively, than those for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P= .47). Eyes with newly diagnosed herpetic retinitis appeared to have a poor visual prognosis, with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively). Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality.

A therapeutic challenge in AIDS-associated viral retinitis

Sir, Progressive outer retinal necrosis (PORN) is a herpetic retinitis characterized by multifocal deep retinal lesions progressing to confluent necrosis and a high likelihood of retinal detachment. The visual prognosis in patients with PORN is extremely poor, with final visual acuity of no light perception reported in up to 67% in some series.1, 2 We report a therapeutic challenge of AIDS-associated viral retinitis in which the ganciclovir implant contributed to the eradication of PORN recalcitrant to systemic and intravitreal antivirals.

Animal models of herpetic retinitis

AbstractThe Herpes simplex virus (HSV) is characterized its ability to replicate in the nervous system, before inducing a latent infection with potential reactivation. Most frequent ocular complications of recurrent HSV infection are keratitis and conjunctivitis. Less frequently, the iris and the ciliary body may also be involved (anterior uveitis). The most severe HSV ocular infection is retinitis, a rare but potentially blinding disease, due to frequent bilateral involvement. Studies on human post‐mortem tissues showed that HSV is widely distributed in the population, with a preferential location within the trigeminal ganglions (innervating the cornea), but also in the superior cervical ganglions (innervating the iris) or in brain/medullar tissues (innervating the retina). Animal models have been developed to understand the pathogenic processes that lead to this rare but devastating retinal disease. Since human is the only natural host of HSV, it is difficult to obtain a perfect animal model that perfectly mimics the disease. Several animal models, based on different inoculation procedures, are thus necessary to circumscribe the anatomical, cellular and molecular aspects that lead to retinal infection. Finally, HSV retinitis appears as a clinical condition that is highly constrained by the relationships between the strain of the virus and the immune response of the host.

HIV/AIDS in the Developing World

This article reviews information available from developing countries including those in Africa Asia Eastern Europe Latin American and the Caribbean regarding the current state of the HIV/AIDS epidemic. It also discusses the common ocular manifestations associated with HIV/AIDS including: HIV microvasculopathy cytomegalovirus (CMV) retinitis ocular toxoplasmosis non-CMV herpetic retinitis neuro-ophthalmic complications herpes zoster ophthalmicus and ocular neoplasia.