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Year : 2002  |  Volume : 50  |  Issue : 4  |  Page : 319-321

Detection of cytomegalovirus from vitreous humor in a patient with progressive outer retinal necrosis

Medical and Vision Research Foundations, Chennai, India

Correspondence Address:
J Biswas
Medical and Vision Research Foundations, Chennai
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Source of Support: None, Conflict of Interest: None

PMID: 12532499

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A case of progressive outer retinal necrosis (PORN) caused by Cytomegalovirus (CMV), and diagnosed by polymerase chain reaction (PCR) is reported.

Keywords: Progressive outer retinal necrosis, acquired immunodeficiency syndrome, acute retinal necrosis, Cytomegalovirus retinitis, vitreous humor

How to cite this article:
Biswas J, Choudhry S, Priya K, Gopal L. Detection of cytomegalovirus from vitreous humor in a patient with progressive outer retinal necrosis. Indian J Ophthalmol 2002;50:319-21

How to cite this URL:
Biswas J, Choudhry S, Priya K, Gopal L. Detection of cytomegalovirus from vitreous humor in a patient with progressive outer retinal necrosis. Indian J Ophthalmol [serial online] 2002 [cited 2020 Aug 15];50:319-21. Available from: http://www.ijo.in/text.asp?2002/50/4/319/14758

Progressive Outer Retinal Necrosis (PORN) is a morphological variant of necrotising herpetic retinopathy first described by Forster and co-workers in immunocompromised individuals.[1] It is associated with minimal intraocular inflammation and has a rapidly progressive course. Initially multifocal in origin, such lesions rapidly become confluent and primarily involve the outer retina. These lesions typically spare the perivascular retina and ultimately grow to full thickness.[1],[2] Often, rhegmatogenous retinal detachment develops with complete loss of vision in the affected eye despite antiviral therapy.[1][2][3]

We herein report a case of PORN, the first to be described from the Indian subcontinent, in an Asian male patient with acquired immunodeficiency syndrome (AIDS). Cytomegalovirus (CMV) DNA was detected by the polymerase chain reaction (PCR) of the vitreous fluid (VF) specimen in one eye that underwent vitreous surgery, indicating its possible causative role in PORN.

  Case report Top

A 37-year-old heterosexual male with AIDS and a past history of pulmonary tuberculosis and oropharyngeal candidiasis was referred from an AIDS care research center, Chennai in August 1999. He had a 20-day-old history of profound loss of vision in both eyes. He was found to be HIV-positive one year before appearance of the ocular symptoms. His past medical history included thoracic shingles in 1998 and a recurrence of the same in July 1999. Previous investigations showed a CD4+ T-lymphocyte count at 17 cells per cubic millimeter and blood viral load of 248,786 copies, ten days before this visit. On examination, his best-corrected visual acuity was 6/9;N6 in each eye. The anterior segments were quiet in both eyes. The intraocular pressure (IOP) was 14 mm Hg in either eye. Indirect ophthalmoscopic examination of the posterior segment showed bilateral swollen optic discs with numerous multifocal, deep, yellow retinal lesions spread throughout the peripheral fundus, and extending posteriorly ([Figures:1a and b]). There was sparing of the perivascular retina. The vitreous was clear with no inflammatory cells. Fundus fluorescein angiography (FFA) of both eyes demonstrated early blockage and late staining of the retinal lesions. There was no evidence of retinal vascular involvement. Based on the characteristic picture of bilateral, deep, multifocal chorioretinitis with sparing of the perivascular retina, a clinical diagnosis of PORN was made in both eyes. Systemic examination revealed multiple vesicles in a unilateral dermatomal distribution on the upper thorax, typical of cutaneous Herpes zoster infection. The patient was treated with a two-week course of intravenous acyclovir (1500 mg/m3 per day).

Enzyme-linked-immunosorbent-assay (ELISA) for antibodies to CMV, Herpes simplex virus (HSV), Varicella zoster virus (VZV) performed during initial examination showed a high positive titre in serum for Anti-CMV IgM (219 EU), Anti-HSV IgG (147 EU), Anti-HSV IgM (172 EU) and Anti-VZV IgG in 1:80 dilution respectively.

Despite antiviral treatment, the lesions continued to progress rapidly in both eyes to involve the posterior pole. Within four days, the entire retina was involved in both eyes. The visual acuity reduced to hand movements and counting fingers at one metre in the right and left eyes respectively. Anterior chamber (AC) tap was done in the right eye and the aqueous humor (AH) was subjected to virological investigations. Antigens of HSV, VZV and CMV were not detected by the fluorescent antibody technique (FAT). HSV was not isolated in culture. Intravitreal ganciclovir (400mg) was given in the left eye. On follow-up after a week, total rhegmatogenous retinal detachment was seen in the right eye with multiple inferior retinal breaks. The retina was thin and atrophic, rendering it inoperable. The left eye also presented a similar picture, although the posterior pole remained attached. Barrage argon laser photocoagulation to the posterior pole within the vascular arcades was performed in an attempt to contain the detachment in the left eye too. When reviewed 15 days later, total retinal detachment was seen in the left eye. Pars-plana vitrectomy was attempted in this eye, but the procedure was abandoned because the retina was thin, atrophic and contracted.

Postoperatively the patient was given a 4-week course of oral acycloir, 800mg, five times a day. During vitrectomy, vitreous fluid collected from the left eye was subjected to virological studies. Antigens of VZV, HSV or CMV were not detected by FAT and HSV was not isolated in culture. PCR detected the presence of CMV genome ([Figure:2]), while HSV and VZV genomes were not detected. The aqueous humor collected from the right eye earlier was subjected to PCR retrospectively and same three viral genomes were not detected. A convalescent serum sample collected two months after the first one, showed the presence of anti-CMV IgG antibodies in high titre while anti-CMV IgM. Anti-HSV antibodies were not detected either. Anti-VZV IgG was detected at 1:160 dilution and anti-VZV IgM was detected at 1:80 dilution, showing a two-fold rise in titre.

On his last follow-up, two months after the surgery, he had lost perception of light in both eyes.

  Discussion Top

PORN is a recently recognised variant of necrotising herpetic retinopathy representing a distinct form of ARN, developing in patients with AIDS or other conditions causing immune compromise.[1],[2] It is characterised by early macular retinitis in one-third of the patients, with appearance of a cherry-red spot with little or no intraocular inflammation.[1],[2] There is rapid progression with the development of lesions in the mid and peripheral retina with no consistent direction of disease spread, unlike that seen in cases of ARN. Unlike ARN and typical CMV retinitis, which involve full thickness of the retina, this condition early in its course is characterised by deep retinal opacification without granular borders, giving the impression of an "outer retinitis". With progression the areas around retinal vessels became clearer - the "cracked mud" appearance develops.[2] Forster and associates interpreted these findings as regions of perivascular retinal sparing.[1] As the disease progresses, full thickness of the retina is involved forming necrotic, large retinal breaks leading to rhegmatogenous retinal detachment in the majority of the affected eyes. This contributes to the overall poor prognosis. Diagnosis of PORN is always clinical, based on its characteristic appearance. It closely mimics ARN and CMV retinitis.

The clinical expression of viral retinal antigen depends upon the immune status of the host. It varies from mild or classical ARN at one end of the spectrum in patients with undetectable or slight immune dysfunction, to PORN in immunodeficient patients at the other end, with intermediary forms between these two extremes. Our patient had very low levels of CD4+ T-lymphocyte count, indicative of a very poor immune status.

Previous studies indicate that VZV is the only cause of PORN.[1][2][3] In a recent publication Kashiwase et al detected Herpes simplex virus type 1 (HSV 1) - specific antigen from the retinal tissue following enucleation in a patient with PORN, suggesting that HSV 1 is a possible aetiological agent of PORN.[4] Our case was unique in that CMV-DNA was detected in the vitreous fluid by the PCR. ELISA results of CMV showing anti-CMV IgM in the acute sample and anti-CMV IgG in the convalescent sample with the disappearance of the anti-CMV IgM was suggestive of a primary CMV infection. Our findings suggest that PORN, which is a clinical entity, and diagnosed by the morphological features, may also be caused by CMV. The presence of anti-HSV IgG and anti-HSV IgM in the acute sample, which disappeared in the convalescent sample, and the two-fold increase in the anti-VZV IgG and the appearance of anti-VZV IgM in the convalescent sample indicated an increased activity of HSV and VZV respectively, probably elsewhere in the body. It may be recalled that patient had lesions resembling shingles in 1998 and one month before presentation at our hospital; this probably is the reason for the immunological responses to VZV. Activation of more than one of the Herpes group of viruses in immunosuppressed individuals has been described.[5]

Treatment of PORN remains challenging. Visual prognosis is poor with the current therapies. In the study by Engstrom and coworkers,[6] 67% of the patient lost perception of light within 4 weeks of diagnosis, despite treatment. Retinal detachment occurred in 70% of the eyes. A combination of antiviral therapies (both intravitreal and parenteral) including acyclovir, ganciclovir and foscarnet, has been used with partial success to arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye.[7]

In summary, PORN is possibly a morphological syndrome similar to ARN, but could be caused by herpes viral aetiologies including CMV. PCR studies of ocular fluids may aid in diagnosis.

  References Top

Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA. Rapidly Progressive Outer Retinal Necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1990;100:341-48.  Back to cited text no. 1
Margolis TP, Lowder CY, Holland GN, Spaide RF, Logan AG, Weissman SS, et al. Varicella-zoster virus retinitis in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1991;112:119-31.  Back to cited text no. 2
Poavesio CE, Mitchell SM, Barton K, Schwartz SD, Towler HMA, Lightman S. Progressive Outer Retinal Necrosis (PORN) in AIDS patients: A different appearance of varicella-zoster retinitis. Eye 1995;9:271-76.  Back to cited text no. 3
Kashiwase M, Sata T, Yamuachi Y, Minoda H, Usui N, Iwasaki T, et al. Progressive Outer Retinal necrosis caused by herpes simplex virus type in 1 in a patient with acquired immunodeficiency syndrome. Ophthalmology 2000;107:790-94.  Back to cited text no. 4
Sever JL, Rakusan TA, Ellaurie M, Frenkel N, Wyatt LS, Campos JM, et al. Coinfection with herpes virus in young children of HIV-infected women. Paeditr AIDS HIV Infect 1995;6:75-82.  Back to cited text no. 5
Engstrom RE, Holland GN, Margolis TP, Muccioli C, Lidley JI, Belfort R Jr, et al. Progressive outer retinal necrosis syndrome- A variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 1994;101:1488-1502.  Back to cited text no. 6
Ciulla TA, Rutledge BK, Morley MG, Duker JS. The progressive outer retinal necrosis syndrome: Successful treatment with combination antiviral therapy. Ophthalmic Surg Lasers 1998;29:198-206.  Back to cited text no. 7


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