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Year : 1995  |  Volume : 43  |  Issue : 2  |  Page : 63-68

Clinical features and virologic studies in viral retinitis

From Vision and Medical Research Foundations, Sankara Nethralaya, Madras, India

Correspondence Address:
Jyotirmay Biswas
Vision and Medical Research Foundations, Sankara Nethralaya, 18 College Road, Madras 600 006
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Source of Support: None, Conflict of Interest: None

PMID: 8818312

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Viral retinitis is an important infectious disease of the retina which can occur in both healthy and immunocompromized or immunodef icient individuals. The clinical picture and the role of laboratory studies in diagnosis of viral retinitis are still not well-defined. We correlated the clinical picture and virologic study in the serum and vitreous specimens by Enzyme-linked Immunosorbent Assay (ELIS A), rapid immunofluorescence technique and culture in five clinically suspected patients of viral retinitis. None of the patients had any evidence of systemic viral infections. In four patients, the virus was detected by immunofluorescence, ELISA or culture from the vitreous sample. Paired serum samples showed elevation of antiviral IgG titre in two cases and high antiviral IgM titre in all cases. Our study evaluated the role of virological investigations of vitreous aspirate and rising antibody titre in the paired serum samples in the diagnosis of active viral retinitis.

Keywords: Viral retinitis - Acute retinal necrosis Multifocal choroiditis - Herpes simplex virus - Cytomegalovirus - Epstein Barr virus - ELISA - Rapid immunofluorescence test -Viral culture.

How to cite this article:
Biswas J, Madhavan H N, Gopal L, Badrinath S S. Clinical features and virologic studies in viral retinitis. Indian J Ophthalmol 1995;43:63-8

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Biswas J, Madhavan H N, Gopal L, Badrinath S S. Clinical features and virologic studies in viral retinitis. Indian J Ophthalmol [serial online] 1995 [cited 2024 Feb 26];43:63-8. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1995/43/2/63/25259

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Viral retinitis is an important vision-threatening infectious disease of the retina which can occur in both immunocompetent and immunocompromized or immunodeficient (acquired immunodeficiency syndrome - AIDS[1]) individuals. In immunocompetent patients, acute retinal necrosis (ARN) has been recognised as a vision-threatening inflammation caused primarily by herpes group of viruses.[2],[3] Epstein Barr virus has been described in various ocular inflammatory diseases including multifocal choroiditis in healthy patients.[4],[5] In immunocompromized or immunodeficient patients, various opportunistic viral infections can occur; the most common being cytomegalovirus(CMV) infection. Other less common viruses causing retinal infections include herpes simplex virus (HSV) and varicella zoster virus (VZV).[5] Although viral retinitis can usually be identified by the fundus picture and circumstantial evidence of immunosuppression (use of immunosuppressive drugs or a diagnosis of AIDS), the precise diagnosis and identification of the virus can be done best only with the help of rapid and sensitive virological studies. In case of diagnostic dilemma of a suspected viral retinitis, vitreous and retinal specimens are of greater diagnostic value[6-8] than serologic studies.[9]Although medical treatment is the mainstay of management of such patients, many develop retinal detachment necessitating vitreoretinal surgery. This provides an opportunity to obtain aqueous and vitreous samples which can be subjected for virological study such as assay of anti-viral IgG and IgM antibodies, detection of viral antigen by immunofluorescence (IF) and isolation of the virus in cell cultures. In this paper, we have attempted to correlate antibody titre of viruses in the serum and vitreous of five cases of viral retinitis and evaluated the role of such tests in the diagnosis and management. We also have evaluated the role of relapsing titre in the serum of these cases.

  Materials and methods Top

Between January 1991 and December 1992, five cases of suspected viral retinitis had virological studies of both serum and vitreous samples. None of these patients had evidence of systemic viral infection at the time of presentation. The diagnosis was made from the history and the characteristic fundus picture. The clinical summaries of these five cases are given in [Table - 1] [Figure - 1]-[Figure:6]. Paired serum samples from four patients and a single serum sample from one patient were assayed for IgG and IgM antibodies against herpes simplex virus, cytomegalovirus and Epstein Barr virus (EBV) by Enzyme-linked Immunosorbent Assay (ELISA) method. Solid phase enzyme immune assay for measurement of anti-Herpes simplex virus antibody was done using antigen prepared from HSV type 1 (strain No.$753166; National Institute of Virology, Pune). The virus was grown in Vero cell line (NFATCC, Pune) and the antigen was prepared as described by Fortier et al.[10] ELISA tests for measurement of anti-CMV (Diamedix) and anti-EBV (Virotech) antibodies were carried out using commercial kits. Both IgG and IgM antibodies against the viruses were assayed. Paired serum samples were tested together at the same time against each viral antigen though in one patient the second sample was obtained 14 months after and therefore could not be considered as a convalescent sample. Vitreous aspirates from four patients were assayed for anti- HSV and CMV antibodies (both IgG and IgM) by ELISA at 1:5 to 1:40 in doubling dilutions to detect the local production of antibodies. Vitreous aspirate cytospin smears were stained by immunofluorescence to detect HSV and CMV antigens using fluorescein labelled monoclonal antisera (DAKO Corporation, CA, USA). Virus isolations (HSV and CMV) were done from vitreous aspirates in Vero cell line (NFATCC, Pune) and human fibroblasts from tenon's capsule of the eye (maintained in this laboratory). One HSV isolate from a patient was typed by microneutralisation test using type specific antisera (DAKO Corporation, CA, USA). The sera of all the five patients were tested for HIV-1 and HIV-2 by ELISA.

  Results Top

Clinical diagnosis of the five cases include two cases of acute retinal necrosis and one case each of CMV retinitis, HSV retinitis and EBV retinochoroiditis. Results of the virological studies of the serum and vitreous samples are given in [Table - 2]. HIV-1 and HIV-2 from serum samples were found to be negative in all five patients.

  Discussion Top

Viral retinitis is increasingly being recognized as the cause of vision-threatening posterior segment inflammation. Typical clinical features in these cases can suggest specific viral aetiology as was seen in two cases of ARN (cases 1, 2) and in one case of CMV retinitis (case 3) in our series. In the remaining two cases (cases 4, 5) although suspicion of viral infection was made, specific viral aetiology could be established only from the study of vitreous and serum samples.

Infected retina in viral retinitis is likely to shed viable virus in the vitreous cavity. Demonstration of the virus from vitreous fluid depends on the stage of the disease, the severity of the infection and sampling techniques. Isolation of the virus by tissue culture is often time-consuming and can even be negative. Hence, obtaining vitreous sample in the initial stage of the disease for rapid virological tests can be of great diagnostic value. Rademakers et al,[11] have found intraocular antibody production against one or more viruses of the herpes class in 6 out of 22 patients of idiopathic uveitis who required pars plana vitrectomy. Pepose et al[12] also highlighted the importance of analysing paired intraocular and serum antibody titres for herpes group of viruses in acute retinal necrosis syndrome and other viral retinitis.

In all the five cases in our series, virological studies of serum and/or vitreous samples either provided the diagnosis or confirmed the same. In the first case of ARN, serum sample showed positive titres for HSV, CMV and EBV. However, rising titre was seen only for CMV. The vitreous aspirate on immunofluorescent study revealed cytomegalovirus. Viral inclusions were seen in histopathological study of the inflammatory membranes removed from the surface of the retina during vitrectomy [Figure:7]. This also supported the diagnosis of viral retinitis. In the second case of acute retinal necrosis, there was rising titre against herpes simplex virus. Vitreous sample provided further evidence of the same virus [Figure:8].

Since the sensitivity and specificity of serologic tests have not been established in this viral retinitis, the diagnosis of ARN is usually made on clinical basis. However, in case of atypical presentation, or where the diagnosis is notcertain, diagnostic vitrectomy with or without retinal biopsy can direct the diagnosis.[2] In both the cases there was initial resolution of inflammation with intravenous and oral acyclovir therapy but subsequently the patient developed dense vitritis and rhegmatogenous retinal detachment with advanced proliferative vitreoretinopathy. Such complications are known to occur in ARN resulting in poor visual outcome.[13]

In our third case, anti-CMV IgG antibody was found in the serum. However, this finding is not of much diagnostic value as most adults have positive CMV antibody titres and a negative result does not necessarily rule out CMV infection.[9] A four-fold or more rise in antibody titre in the convalescent serum strongly indicated active CMV infection. Since the patient developed rhegmatogenous retinal detachment with proliferative vitreoretinopathy in one eye, vitrectomy and scleral buckling was done which provided us the opportunity to study the vitreous specimen. The vitreous specimen on immunofluorescence study revealed CMV. As diagnosis can often be made fairly well clinically, the role of obtaining aqueous or vitreous sample in the diagnosis of CMV retinitis is restricted to atypical cases or as confirmation if the patient undergoes vitrectomy for any reason. Intravenous ganciclovir (DHPG, cytovene) and foscarnet (foscavir) are found to be beneficial in the management of CMV retinitis.[9] Our patient showed excellent response to intravenous ganciclovir substantiating the diagnosis.

In our fourth case, the serum sample showed very high titre of anti-HSV antibody and the vitreous fluid obtained by diagnostic vitrectomy showed HSV by immunofluorescence study of direct smear. This result confirmed our clinical diagnosis and helped us to institute specific therapy with intravenous acyclovir. The patient showed complete resolution of viral retinitis. However, vision in one eye remained poor due to optic atrophy despite complete regression of retinal inflammation. Herpes simplex viral retinitis due to HSV-1 has been described in both healthy and immunosuppressed adults. Retinal inflammation described include bilateral chorioretinitis,[14] panuveitis with choroidal haemorrhages, retinal exudates and retinal oedema,[15] rapidly progressive acute retinal necrosis involving the posterior pole with exudative retinal detachment.[16] In all these cases diagnosis of HSV-1 was confirmed by demonstration of the virus from ocular fluid or tissue specimen. Serologic assays for HSV 1 or HSV-2 infection is of value only when a four-fold or greater rise in anti-HSV antibodies can be demonstrated from acute and convalescent serum. Demonstration of the virus can be done in tissue culture by characteristic cytopathic effects between 48 to 96 hours. Immunofluorescent assay, restriction endonuclease analysis of viral DNA from the serum and ocular fluid can identify the presence of HSV-1.[17]Chorioretinal biopsy has been found to be useful in demonstration of the virus in the retinal tissue.[14]

In our fifth case, the serologic evidence of IgM and IgG antibody to viral capsid antigen of EBV virus indicated the possible role of this virus as an aetiological agent. The association of this virus has been reported in isolated cases[4] and in a series of patients of multifocal choroiditis.[5] None of the ten patients reported by Tiedeman[5] had systemic features of infectious mononucleosis as our patient. In a recent study, Spaide et al[18] have not found association of EBV with multifocal choroiditis and panuveitis in their series of patients. Serological test for EBV - specific antibodies, especially IgM antibodies to viral capsid antigen (VCA) are diagnostic of a primary EBV infection. IgG antibodies to VCA persist lifelong and indicate a past exposure. Antibodies to Epstein Barr nuclear antigens are seen consistently in all patients with infectious mononucleosis due to EBV.

So far, all reported cases of EBV choroiditis were either self-limiting or responded well to corticosteroid therapy. There is no study to demonstrate EBV from retinochoroidal tissue or vitreous fluid in such cases. Our patient responded to a course of systemic steroid.

These five cases illustrate the role of serologic and vitreous fluid study in this rare form of vision-threatening retinal or retinochoroidal inflammation. While the serologic study, especially the presence of IgM antibodies indicate a recent viral infection, demonstration of a four-fold or more rise of titre in the convalescent serum can establish such aetiological association. Demonstration of anti-viral antibody from the vitreous sample by immunological tests in a progressive vision-threatening inflammation guides the clinician in establishing the diagnosis and instituting specific treatment. As viral retinitis, especially CMV, can occur in patients with AIDS, it is important to screen all such cases for HIV infection[1] by ELISA test. If the patients are found to be HIV positive, additional treatment against HIV infection is mandatory. As there is likelihood of increase of infective retinitis cases, awareness of clinical features and supportive, rapid virological studies are necessary for early diagnosis and proper management. It is therefore necessary for the clinician to understand the significance of such virological studies in order to correlate with the clinical picture.

  References Top

Biswas, Rao NA. Diagnosis and management of ocular lesions in acquired immunodeficiency syndrome. Indian J Ophthalmol 36:151-155,1988.  Back to cited text no. 1
Freeman WR, Thomas EL, Rao NA, et al. Demonstration of herpes group virus in acute retinal necrosis syndrome. Am J Ophthalmol 102:701-709,1986.  Back to cited text no. 2
Culbertson WW, Blumenkranz MS, Pepose JS, et al. Varicella zoster virus is a cause of the acute retinal necrosis syndrome. Ophthalmology 93:559-569,1986.  Back to cited text no. 3
Raymond LA, Wilson CA, Linnemann CC Jr, et al. Punctate outer retinitis in acute Epstein Barr virus infection. Am J Ophthalmol 104:424-426, 1987.  Back to cited text no. 4
Tiedeman JS. Epstein Barr viral antibodies in multifocal choroiditis and panuveitis. Am J Ophthalmol 103:659-663, 1987.  Back to cited text no. 5
Pepose JS. Infectious retinitis. Diagnostic modalities. Ophthalmology 93:570-573, 1983.  Back to cited text no. 6
Peyman GA, Goldberg MF, Uninsky E, et al. Vitrectomy and intravitreal antiviral drug therapy in acute retinal necrosis syndrome: Report of two cases. Arch Ophthalmol 102:1618-1621, 1984.  Back to cited text no. 7
Freeman WR, Wiley CA, Gross JG, et al. Endoretinal biopsy in immunosuppressed and healthy patients with retinitis: Indications, utility and techniques. Ophthalmology 96:1559-1565, 1989.  Back to cited text no. 8
Yoser SL, Forster DJ, Rao NA. Systemic viral infections and their retinal and choroidal manifestations. Surv Ophthalmol 37:313-352, 1993.  Back to cited text no. 9
Fortier B, Chabrolle AD, Huranx JM. Comparison of an ELISA technique with quantal microneutralisation test for seroryping HSV-1 and HSV-2 infected patients. J Virol Meeth 11:11-20, 1982.  Back to cited text no. 10
11. Rademakers AJJM, Luyendijk L, Maas S, Kijlstro A. Intraocular antibody production against viruses. In: Depnouchamps JP, Veroughstraetc C, Caspers-Veil, Tassignon MJ (eds), Recent Advances in Uveitis. Amsterdam, Kugler publication, pp. 273-276, 1993.  Back to cited text no. 11
Pepose J, Flowers B, Stewart JA, et al. Herpes virus antibody levels in the etiologic diagnosis of the acute retinal necrosis syndrome. Am J Ophthalmol 113:248-256, 1992.  Back to cited text no. 12
Duker JS, Blumenkranz MS. Diagnosis and management of the acute retinal necrosis (ARN) syndrome. Surv Ophthalmol 35:327-343, 1991.  Back to cited text no. 13
Grutzmacher RD, Henderson D, McDonald PJ, et al. Herpes simplex chorioretinitis in a healthy adult. Am J Ophthalmol 96:788-796, 1983.  Back to cited text no. 14
Pavan-Langston D, Brockhurst RJ. Herpes simplex panuveitis: A clinical report. Arch Ophthalmol 81:783-787, 1969.  Back to cited text no. 15
Duker JS,NielsonJC, Eagle RC Jr, etal. Rapidly progressive acute retinal necrosis secondary to Herpes simplex virus Type 1. Ophthalmology 97:1638-1643, 1990.  Back to cited text no. 16
Pepose JS, Kreiger AE, Tomiyasu U, et al. Immunocytologic localization of herpes simplex type 1 viral antigens in herpetic retinitis and encephalitis in an adult. Ophthalmology 92:160-166, 1985.  Back to cited text no. 17
Spaide RF, Sugin S, Yannuzzi LA, et al. Epstein-Barr virus antibodies in multifocal choroiditis and panuveitis. Am J Ophthalmol 112:410-413, 1991.  Back to cited text no. 18


  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]

  [Table - 1], [Table - 2]

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