Viral causes of the acute retinal necrosis syndrome

PURPOSE: The primary goal of this study was to determine the viral cause of the acute retinal necrosis syndrome in 28 patients (30 eyes). A secondary goal was to investigate possible associations between viral cause and patient age, and viral cause and central nervous system disease. METHODS: A retrospective case series in which we reviewed the laboratory results and clinical histories of 28 patients (30 eyes) diagnosed with acute retinal necrosis syndrome, from whom vitreous or aqueous specimens were received, for diagnostic evaluation using previously described polymerase chain reaction-based assays. RESULTS: Varicella-zoster virus, herpes simplex virus, and cytomegalovirus (CMV) DNA were detected in aqueous and/or vitreous specimens from 27 of 28 patients (29 of 30 eyes with a clinical history of acute retinal necrosis syndrome). No sample was positive for DNA from more than one virus. Varicella-zoster virus DNA was detected in 13 patients (15 eyes). Median age was 57 years. Herpes simplex virus type 1 DNA was detected in seven patients (seven eyes). Median age was 47 years. Six of these patients had a history of herpes simplex virus encephalitis. Herpes simplex virus type 2 DNA was detected in six patients (six eyes). Median age was 20 years. Three of these patients had a likely history of meningitis. Cytomegalovirus DNA was detected in one patient who was immunosuppressed iatrogenically. No viral DNA was detected in one patient from whom a sample was taken after 6 weeks of acyclovir therapy. CONCLUSIONS: The data suggest that varicella-zoster virus or herpes simplex virus type 1 cause acute retinal necrosis syndrome in patients older than 25 years, whereas herpes simplex virus type 2 causes acute retinal necrosis in patients younger than 25 years. A history of central nervous system infection in a patient with acute retinal necrosis syndrome suggests that herpes simplex virus is likely to be the viral cause.     

Demonstration of herpes group virus in acute retinal necrosis syndrome

Tissue for pathologic examination was obtained from three cases of acute retinal necrosis syndrome. Virus particles belonging to the herpesvirus family were demonstrated in retinal biopsies from two patients, one of whom was immunosuppressed. Despite removal of large biopsy specimens, the retina has remained attached for 20 months postoperatively in one case and for three months in the other. In a third patient with acquired immune deficiency syndrome, the clinical course and postmortem immunopathology were suggestive of a herpes simplex virus infection, initially affecting the retina and subsequently the optic nerves, chiasm, tracts, and central nervous system. These cases illustrate that the virus associated with the acute retinal necrosis syndrome is easily demonstrable using vitrectomy and endoretinal biopsy in the acute phase of the disease, but may be difficult to demonstrate in chronically detached atrophic retinas.     

Optic neuropathy and central retinal artery occlusion in a case of herpes zoster ophthalmicus

In this case report the authors present a patient in whom loss of vision developed in the left eye in the early stage of herpes zoster ophthalmicus. He suffered from optic neuropathy followed by central retinal artery occlusion. Ophthalmologists should be aware of this rare and early complication of herpes zoster.     

Detecting herpesvirus DNA in uveitis using the polymerase chain reaction.

BACKGROUND: Herpesviruses are involved in the pathogenesis of many ocular diseases including keratitis, iridocyclitis, and acute retinal necrosis syndrome. The rapid and accurate diagnosis of herpetic infections has become increasingly important with the rising incidence of immunosuppressive diseases. The purpose of this study was to evaluate the use of the polymerase chain reaction (PCR) to detect herpesvirus DNA in uveitis patients. METHODS: Aqueous samples were aspirated from 11 patients with active uveitis of suspected viral origin. Using PCR, masked samples were assayed for herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) to assist in supporting the clinical diagnosis of viral aetiology. Masked controls included 10 aqueous humour specimens from normal patients undergoing cataract surgery and specimens from seven patients diagnosed with active non-viral uveitis--Behçet's disease, sarcoidosis, Fuchs' heterochromic iridocyclitis, or Harada's disease. RESULTS: Ten of 11 cases clinically diagnosed as being of possible viral aetiology yielded aqueous PCR positive for a herpesvirus. Eight patients were PCR positive for amplified HSV DNA, of whom two had acute retinal necrosis, one had corneal endotheliitis, and five had recurrent iridocyclitis. VZV DNA was detected in one case of iridocyclitis, and CMV DNA in one case of chorioretinitis. Successful therapy was based on the PCR results. Ten normal aqueous specimens and the seven uveitis samples from cases not suspected of a viral aetiology were PCR negative for HSV, VZV, and CMV. CONCLUSION: These results demonstrate that detecting herpesvirus DNA in the aqueous humour is useful to support a clinical diagnosis of viral uveitis.     

Penetrating keratoplasty for corneal scarring due to herpes zoster ophthalmicus.

We retrospectively studied the postoperative results in nine patients with corneal scarring due to herpes zoster ophthalmicus who underwent penetrating keratoplasty. This was a highly selected group that satisfied all of the following criteria: (a) absence of active disease of the ocular surface and eyelids, (b) intraocular pressure under control, and (c) absence of active keratouveitis. Penetrating keratoplasty after herpes zoster ophthalmicus may do well in patients with long preoperative quiescent periods in whom these restrictive preoperative criteria are observed.     

Acquired ocular toxoplasmosis and immunosuppression of tumoral thymic origin

A rare case of acute bilateral unifocal chorioretinitis in a 24 years old man is described. The patient had been followed for more than 3 years for a benign thymoma, detected by systematic radiography, that was initially operated on with success. Later, after recurrence of clinical signs a second operation was performed that revealed local invasion of the tumor which was histologically identified as a benign, lymphoid thymoma. Serological data permitted us to attribute the lesions to a sub-acute ganglionary toxoplasmosis, contracted five months before any ocular localization. A treatment including local corticotherapy and oral pyrimethamine and sulfonamide was undertaken. Healing of the retinal lesions occurred slowly. A complete study of the patient's immunity revealed an important deficiency of cell-mediated functions. The problem of diagnosis of opportunistic chorioretinitis is discussed. In patients with impairment of cellular-type immunity, the following are commonly observed: herpes group viral diseases (including cytomegalic inclusion disease), fungus diseases (candida, aspergillus, mucormycosis, cryptococcus), and, rarely, toxoplasmosis. The presence of specific serum antibodies is the most important element in making a diagnosis, considering that the ophthalmoscopic appearance and clinical course may vary.     

Herpes simplex virus isolations from the aqueous humor of patients suffering from focal iritis, endotheliitis, and prolonged disciform keratitis with glaucoma (author's transl)

Aqueous humor from 33 herpes patients, 4 zoster patients, and 14 patients with etiologically unclear anterior uveitis was cultured for the presence of herpes viruses. Nine taps from 8 herpes patients with corneal endothelial disease and/or anterior uveitis yielded herpes simplex virus. In the case of one patient two taps were positive at 14 days' interval. Control cultures from the surface of conjunctiva and cornea were consistently virus-negative. Analysis of the virus-positive cases displayed three remarkable features: 1. Secondary glaucoma was uniformly present. This in itself is an indication for culturable herpes simplex virus in the aqueous. 2. Three clinical pictures could be differentiated biomicroscopically: focal iritis, peripheral endotheliitis, and prolonged disciform keratitis. 3. In a proportion of cases, tissue damage resulting from associated immune reactions seems to be more important for the functional outcome than tissue damage by viral cytolysis itself. After having tried several antiviral substances (trifluorothymidine topically, adeninearabinoside-monophosphate intravenously, human leukocyte interferon intramuscularly and intracamerally) we presently favour a topical combination therapy consisting of trifluorothymidine and steroids. This must be complemented by cycloplegics and--in cases of high intraocular pressure--by acetazolamide.     

Adenine arabinoside in idoxuridine unresponsive and intolerant herpetic keratitis.

Twenty-two patients with active herpes simplex dendritic keratitis, in whom topical idoxuridine was unsuccessful in controlling their disease, were treated with topical adenine arabinoside (ara-A), a purine analogue effective against many DNA viruses. This drug was an effective antiviral agent in these patients. No signs of ocular or adnexal toxicity were noted.     

Oculogenital transmission of type 2 herpes simplex virus in adults

Type 2 (genital) herpes simplex virus (HSV-2) was isolated from three patients (two adults and an 11-year-old girl) with acute ocular infections. Two of these patients had acute blepharoconjunctivitis and one had acute keratoconjunctivitis. Genital herpes infections had preceded the eye infections in the two adults. This was not the case in the 11-year-old, but she had been in close contact with her sister who had apparently had the genital disease. The study strongly suggests transmission of HSV-2 from the genital site to the eye.     

Prophylactic perioperative antiviral therapy for LASIK in patients with inactive herpetic keratitis

PURPOSE: To report the outcome of LASIK in patients with inactive herpetic keratitis in which perioperative antiviral prophylaxis was used to prevent the recurrence of ocular herpes. METHODS: We report an uncontrolled series of five patients with inactive herpetic keratitis for at least 1 year before surgery in whom LASIK was successfully performed. All patients showed normal topography, pachymetry, and corneal sensitivity with no central corneal scarring. Perioperative prophylaxis was used in each case with oral valacyclovir and topical acyclovir ointment. RESULTS: None of the eyes developed reactivation of herpetic keratitis during follow-up. CONCLUSIONS: This study suggests that perioperative antiviral prophylaxis may protect the cornea from herpes simplex virus reactivation after LASIK.     

Congenital diffuse necrotizing herpetic retinitis

NeonatalHerpes simplex infections are usually contracted from the birth canal, and the systemic lesions develop several days to weeks after delivery. We present the clinicopathologic findings in a newborn with a prenatal diagnosis of hydrocephalus who died at 1 day of age. Severe liquefaction necrosis and foci of calcification were present in the brain, adrenal glands, and retina. Cowdry type A intranuclear inclusions were present in the adrenal glands and retina. There was no clinical evidence of genital herpes in either parent. This is the first documented case of in utero transmission ofHerpes simplex infection, confirmed by the polymerase chain reaction, and causing fulminant necrotizing retinitis and encephalitis.     

Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis

Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno‐compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis.     

Clinical pattern of recurrent herpes simplex keratitis

PURPOSE: To document the clinical pattern in recurrent herpes simplex disease. METHODS: Eyes with clinically documented pattern of corneal manifestation on more than one occasion were analysed. For each eye recruited, the clinical pattern of the disease at each recurrence of herpes simplex corneal disease, age, disease-free intervals, triggering factors, laterality and steroid abuse were noted and evaluated. RESULTS: For an average follow up of 6.9 years, a recurrence rate of 0.6 episodes per year was observed. Disease-free intervals of 75.7 months for epithelial herpes simplex disease was considerably longer than the 21.3 months observed for stromal disease. Clinical pattern of recurrence was of the same type following first episode of disciform keratitis, epithelial keratitis and endothelitis in 84%, 72.7%, and 75% of the eyes respectively. CONCLUSION: Herpes simplex disease often recurs in the same manifest clinical pattern as the first episode. This clinical evidence provides additional support for the potential role of herpes simplex biotypes in determining manifestation of clinical disease pattern.     

Akute retinale Nekrose aus Virologensicht

Acute retinal necrosis occurs in approximately one per million persons per year and is caused in approximately 70% of the cases by the varicella zoster virus or in about 30% of the cases by herpes simplex virus. The early diagnosis is primarily based on virus-specific polymerase chain reaction in fluid from the anterior chamber or vitreous humor and can be supported by the determination of specific antibody titers from fluid and serum. Virus detection provides the basis for early causative therapy which limits disease progression and risk of complications. Retinal infections by varicella zoster virus or herpes simplex virus are treated with aciclovir, ganciclovir, or famciclovir. Ganciclovir and valganciclovir are used for the therapy of retinal cytomegalovirus infections. In the case of resistance development, foscarnet or cidofovir are available as second line antiviral drugs. The early use of specific antiviral agents is a crucial prerequisite for optimized therapy of acute retinal necrosis.     

Herpes simplex virus epidemiology and ocular importance

PURPOSE: To review the changing epidemiology of herpes simplex disease and correlate it with the epidemiology of ocular herpes simplex disease. METHOD: A review of pertinent reports in the world literature about the epidemiology of herpes simplex and specifically about ocular herpes simplex. RESULTS: In developed countries, many individuals are reaching adolescence and adulthood without prior herpesvirus infection. Herpes simplex genital infection is increasing at a rapid rate in sexually active adolescents and adults, with about one in six adults now infected in the United States. Similar statistics are confirmatory worldwide in developed countries. Active herpes simplex infection is a risk factor for acquisition of human immunodeficiency virus. The Herpetic Eye Disease Study, as well as prior studies from Moorfields Eye Hospital and the Mayo Clinic in Rochester, Minnesota, provides us with the epidemiology of ocular herpes simplex. Recent studies suggest an older age of onset and perhaps overall more severe ocular disease as compared with the older literature. CONCLUSIONS: Herpes simplex is a significant health concern at present with genital infections increasing in epidemic proportions. This is also reflected in a rise in the incidence of neonatal herpes. Herpes simplex virus type 1 (HSV-1) infection is being acquired for the first time in an older age group. A significant and increasing proportion of genital herpes is caused by HSV-1. Serologic studies are no longer as useful in distinguishing orofacial herpes from genital herpes. More acute retinal necrosis syndrome cases are associated with HSV-2. Speculation about the future of ocular herpes is made based on this changing epidemiology.     

A posterior dislocation of the lens in herpes zoster (author's transl)]

The authors report a case of posterior dislocation of the lens during the natural history of a clinical case of herpes zoster. An echographic B-scan study was carried out to reveal the position and the size and the shape of dislocated lens, together with its structure and that of ocular media. After a discussion on the possible aetiology of the lens dislocation it was considered due to herpes zoster disease, and are reported the possible mechanism of zonula alteration.     

Secondary bacterial keratitis in herpes zoster ophthalmicus

We report a case of an unusual complication of herpes zoster ophthalmicus, secondary bacterial keratitis. Compared with previously reported cases, ours is unique in its early occurrence in the course of zoster and the lack of predisposing factors such as steroid use, contact lens use, or prior corneal disease or surgery. The opportunistic pathogen Branhamella cattarhalis responded well to medical therapy. We feel that bacterial superinfection must always be a concern in patients with herpes zoster keratitis, even early in their often prolonged chronic disease.     

Ocular involvement in an outbreak of herpes gladiatorum.

An epidemic of herpes simplex virus type 1 occurred in 60 of 175 wrestlers (34%) attending a four-week intensive training camp. Five of these 60 patients (8%) developed ocular involvement that included follicular conjunctivitis, blepharitis, and phlyctenular disease. Cultures of the conjunctiva and eyelid vesicles were positive for herpes simplex virus type 1 in four of the five patients with ocular disease. The viral isolates were compared by restriction-endonuclease analysis, which disclosed that three of the four isolates were the same strain. None of the patients had corneal involvement and there has been no evidence of viral recurrence to date. Herpes simplex virus type 1 is a health risk for wrestlers, and ocular infections are part of the clinical spectrum. Prompt diagnosis and appropriate management of the outbreak may reduce the severity of the outbreak transmission.     

Association of varicella zoster dermatitis with acute retinal necrosis syndrome

The authors report seven patients in whom the acute retinal necrosis (ARN) syndrome developed shortly after cutaneous varicella zoster infection. The length of time between the skin infection and ARN varied from 5 days to 3 months. Both eyes were affected in one of seven cases. The ophthalmic branch of cranial nerve V ipsilateral to an affected eye was involved by the zoster dermatitis in only two of the seven cases. The association lends further support to the proposal that herpes zoster virus is a major cause of ARN. A history of recent zoster dermatitis should be sought in patients with ARN.