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   Table of Contents      
BRIEF REPORT
Year : 2000  |  Volume : 48  |  Issue : 4  |  Page : 313-5

Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors


Medical Research Foundation, Chennai, India

Correspondence Address:
J Biswas
Medical Research Foundation, Chennai
India
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Source of Support: None, Conflict of Interest: None


PMID: 11340892

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Keywords: AIDS-Related Opportunistic Infections, diagnosis, drug therapy, Adult, Cytomegalovirus Retinitis, diagnosis, drug therapy, HIV, immunology, HIV Antibodies, analysis, Humans,


How to cite this article:
Biswas J, Choudhry S, Kumarasamy, Solomon S. Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors. Indian J Ophthalmol 2000;48:313

How to cite this URL:
Biswas J, Choudhry S, Kumarasamy, Solomon S. Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors. Indian J Ophthalmol [serial online] 2000 [cited 2020 Feb 24];48:313. Available from: http://www.ijo.in/text.asp?2000/48/4/313/14836

Immune reconstitution in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART) with cytomegalovirus (CMV) retinitis manifested as posterior segment intraocular inflammation has been reported. We report an adult HIV-positive Indian male with clinically inactive CMV retinitis who developed panuveitis with hypopyon. This was related to immune recovery mediated by combination anti-retroviral treatment, including protease inhibitors.

Indian J Ophthalmol 2000;48:313-15

CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) typically manifests as progressive necrotizing retinitis with little or no intraocular inflammation.[1] Vitritis, when present is mild and minimally symptomatic due to the severe immunodeficiency always associated with AIDS.[1] With the advent of combination antiviral therapy, including human immunodeficiency virus (HIV) specific protease inhibitors, many patients with AIDS may experience immune reconstitution manifesting as a posterior segment inflammatory response in the eye. This has emerged as a new syndrome called Immune Recovery Vitritis[2] (IRV) and is a cause of visual morbidity in patients with AIDS.

We report herein a case of IRV in a 38-year-old HIV-positive male with inactive CMV retinitis. When highly active anti-retroviral therapy (HAART) was initiated, he developed signs of severe intraocular inflammation manifested as panuveitis with hypopyon. This could not be attributed to concomitant ocular treatment, any other ocular pathogen, or reactivation of CMV retinitis. The patient responded to corticosteroid therapy without reactivation of retinitis.


  Case report Top


A 38-year-old male with AIDS first presented to us for a routine ophthalmic examination in August 1998. Twenty-four months before presentation he was diagnosed to have HIV infection following an episode of prolonged fever. At that time, further examination at an AIDS Care Centre revealed pulmonary tuberculosis for which he was treated with a four-drug anti-tubercular regimen (daily dose of oral isoniazid 300mg, oral rifampicin 600mg, oral pyrazinamide 1500mg) and oral ethambutol 1500mg) for four months. This was followed by a two-drug therapy (oral isoniazid 300mg and oral pyrazinamide 1500mg daily) for another two months. Prior to the diagnosis of HIV, he had received treatment for Pneumocystis carinii pneumonia and oral candidiasis, the details of which were not available.

When we first examined him, the eyes and adnexae were normal. He was on regular ophthalmic follow up thereafter and in March 1999 presented with complaints of blurring of vision and photophobia of 15 days' duration in the left eye. He was not on any topical or systemic medication. On examination, his best-corrected visual acuity was 6/5;N6 and 6/6;N8 in the right and left eye respectively. Slitlamp examination showed a quiet eye with no anterior segment abnormalities. Applantation intraocular pressure (IOP) was 16 mm Hg in both eyes. Dilated fundus examination of the left eye showed scattered, granular, yellow-white areas of retinal necrosis in the inferior periphery with patchy haemorrhages, typical of CMV retinitis. There was no evidence of vitritis [Figure - 1]. The fundus of the right eye was unremarkable. Systemic examination did not show evidence of CMV infection elsewhere in the body. The patient received systemic ganciclovir 5mg/kg-body weight intravenously every 12 hours for 14 days. Subsequently, as the patient could not afford maintenance therapy, intravitreal injection of ganciclovir 400 mg was given twice a week for the next three weeks in the left eye. His CD4+ T-lymphocyte count following ganciclovir therapy was 41 x 106 / L and the blood viral load was 2,07,289 copies. At this time, HAART was initiated with zidovudine (AZT), lamivudine (3TC) and crixivan (Indinavir). The patient was reviewed at regular intervals over the next month and CMV retinitis clinically regressed with disappearance of the retinal necrosis and resolution of phlebitis with minimal residual gliosis [Figure - 2]. The CD4+ T-lymphocyte count one month after commencement of HAART increased to 137 x 106 / L.

The patient reported back in July 1999 with sudden diminution of vision and photophobia in the left eye of 3 days duration. He was continuing HAART. On examination, his best-corrected visual acuity in the left eye was 6/60;N36. Slitlamp examination of the left eye showed circumcorneal ciliary congestion, multiple fine keratic precipitates, aqueous flare (3+), aqueous cells (3+), 2mm hypopyon, posterior synechiae and vitreous cells (2+) [Figure - 3]. Slitlamp examination of the right eye was unremarkable. Left fundus examination showed moderate vitritis obscuring retinal details. The right eye fundus was normal. CD4+ T-lymphocyte count at this stage was 172 x 106 / L and the blood viral load was 1,14,716 copies. An anterior chamber tap of the left eye for direct smear and culture for bacteria, fungus and acid-fast bacillus was negative. Immunofluorescence stain for the herpes group of viruses was positive for CMV. The patient was treated with topical prednisolone acetate every hour, topical homatropine twice a day in the left eye and oral prednisolone 40mg per day for one week. The topical and oral steroids were subsequently tapered weekly over a period of six weeks. As the vitritis persisted, posterior subtenon injection with triamcinolone acetate 40mg was given in the left eye. On his last visit in September 1999, the anterior segment inflammation and vitritis subsided and vision improved to 6/24;N18 in the left eye. An epiretinal membrane at the macula was noted on ophthalmoscopy and this could be responsible for the impaired vision.


  Discussion Top


The HAART, a combination of zidovudine (AZT), laimvudine (3TC) and crixivan (Indinavir), containing two classes of drugs against HIV-one a reverse transcriptase inhibitor and the other a protease inhibitor-to prevent viral replication and/or viral protein expression. The addition of specific protease inhibitors has resulted in a significant improvement in immune status in many patients, as indicated by decreased levels of plasma HIV messenger RNA and increased levels of CD4+ T lymphocytes.[3] They competitively inhibit the protease-mediated cleavage of viral poly-proteins, preventing maturation of the infectious virus.[4]

The acceptance of HAART among patients and healthcare providers has had a dramatic impact on the epidemiology and clinical characteristics of many opportunistic infections associated with HIV. This is due to the fact that HAART leads to a rise in the count of CD4+ T-lymphocytes, the body's prime immunoregulatory cells. Although such immune recovery can be partial, it often modulates the presentations of opportunistic infections in AIDS patients.

Immune reconstitution syndrome can cause posterior segment inflammation in CMV retinitis and can lead to visual morbidity in patients with AIDS. This newly recognized condition associated with systemic immune recovery mediated by combination anti-retroviral treatment is aptly called IRV.[2] The documented posterior segment inflammatory entities include moderate to severe vitritis,[2] cystoid macular oedema, [5,6] epiretinal membrane formation[7] and papillitis,[7] tractional retinal detachment with vitreous haemorrhage and proliferative vitreoretinopathy.[8] Vitreomacular traction syndrome[1] and progression of CMV retinitis[3] are reported in patients responding to HAART.

The onset of active CMV retinitis in patients with AIDS is linked with profound immunodeficiency and the CD4+ T lymphocyte count below 100 x 106 / L (100 cells / mm3; usually<50 x l06 / L). It is characterized by necrotising retinitis with little or no intraocular inflammatory response, even in presence of extensive retinal involvement. Panuveitis indicates severe intraocular inflammation, and its presence in immunocompromised diseased state, as seen in our case, represents immune reconstitution due to combined retroviral treatment. This is evidenced by increased levels of CD4+ T lymphocytes (from 41 x 106 / L to 172 x 106 / L over two months). In such a setting hypopyon uveitis is rare and has not yet reported in literature, to the best of our knowledge.

There are a few other causes by which similar intraocular inflammation could occur: (a) due to concomitant treatment with intravitreal injection of ganciclovir, the use of cidofovir[9]or rifabutin;[10] and (b) due to an ocular pathogen other than CMV. Intraocular inflammation in patients with AIDS has been described in both leutic and tuberculous uveitis settings. In our patient there was an interval of one month between the administration of the last dose of intravitreal ganciclovir and the appearance of vitritis; he had not taken cidofovir, rifabutin or any other drug during the course of his illness that could be responsible for the intraocular inflammation; also there was no active retinitis or choroiditis.

Thus it may be reasonably concluded that the hypopyon and posterior segment inflammatory response observed in our case could only be attributed to increased immune function as a result of HAART, and not as a response to concomitant medication, other ocular mechanisms or pathogens other than CMV.

Steroids are the treatment of choice of IRV. Our patient responded well to topical and oral prednisolone and the residual vitritis resolved with periocular triamcinolone acetate. Following treatment, the visual acuity improved to 6/24; N18 without reactivation or progression of CMV retinitis or development of any other pathology. An epiretinal membrane observed over the macula was probably responsible for the reduced vision.

IRV has emerged as a new syndrome and a cause of visual morbidity in patients with AIDS. As IRV can present as panuveitis, we feel it is preferable to call this 'Immune Recovery Uveitis' as it can involve other parts of the uveal tract. However, reports of more cases or a larger study are needed to validate this statement. The condition is associated with improving immune status because of HAART and is reversible with corticosteroid treatment without reactivation of CMV retinitis.



 
  References Top

1.
Canzano JC, Reed JB, Morse LS. Vitreomacular traction syndrome following highly active aniretroviral therapy in AIDS patients with cytomegalovirus. Retina 1998;18:443-47.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.
Karavellas MP, Lowder CY, Macdonald C, Avila UP, Freeman WR. Immune recovery vitritis with inactive cytomegalovirus retinitis: A new syndrome. Arch Ophthalmol 1998;116:169-75.  Back to cited text no. 2
    
3.
Frame RD, Hutchins RK, Skahan KJ, Daria D, Feinberg J. Progression of cytomegaloviral retinitis in a patient responding to highly active antiretroviral therapy. Invest Ophthalmol Vis Sci (abstract) 1999;40:S873.  Back to cited text no. 3
    
4.
Kupperman BD, Petty JG, Richman DD, Mathew WJ, Fullerton SC, Rickman LS, et al. Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus related noninfectious retinal vasculopathy in patients with acquired immune deficiency syndrome. Am J Ophthalmol 1993;115:575-82.  Back to cited text no. 4
    
5.
Gangan PA, Bensen G, Munguia D, Freeman WR. Macular serous exudation in patients with acquired immune deficiency syndrome and cytomegalovirus retinitis. Am J Ophthalmol 1994;118:212-19.  Back to cited text no. 5
    
6.
Weinberg DV, Moorthy RS. Cystoid macular oedema due to cytomegalovirus retinitis in a patient with acquired immune deficiency syndrome. Retina 1996;16:343-44.  Back to cited text no. 6
    
7.
Maguire AM, Nichols CW, Crooks GW. Visual loss in cytomegalovirus retinitis caused by cystoid macular oedema in patients without the acquired immune deficiency syndrome. Ophthalmology 1996:103:601-5.  Back to cited text no. 7
    
8.
Song MK, Karavellas MP, Macdonald JC, Freeman WR. Posterior and anterior segment complications of AIDS patients with immune recovery vitritis. Invest Ophthalmol Vis Sci (abstract), 1999;40:S874.  Back to cited text no. 8
    
9.
Karavellas MP, Plummer DJ, Macdonald JC, Torrlani FJ, Shufelt CJ, Azen SP, Freeman WR. Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful HAART. J Infectious Diseases 1999;179:697-700.  Back to cited text no. 9
    
10.
Arevalo JF, Russack V, Freeman WR. New ophthalmic manifestations of presumed rifabutin-related uveitis. Ophthalmic Surg Lasers 1997;28:321-24.  Back to cited text no. 10
    


    Figures

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


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