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Clinicopathologic Reports, Case Reports, and Small Case Series
April 2002

Cytomegalovirus Retinitis in Patients With Good Syndrome

Arch Ophthalmol. 2002;120(4):510-512. doi:

Hypogammaglobulinemia and secondary systemic opportunistic infections are recognized associations in patients with thymoma,1 and the simultaneous occurrence of thymoma and hypogammaglobulinemia is referred to as Good syndrome.2

We report herein the presentation, clinical course, and outcome of 2 consecutive patients with vitreous biopsy–proved cytomegalovirus (CMV) retinitis associated with thymoma and immunodeficiency but with no evidence of other systemic CMV infection.

Report of Cases
Case 1

A 45-year-old woman was referred to Moorfields Eye Hospital, London, England, in November 1998 with a 2-month history of bilateral posterior uveitis that was not responding to topical treatment. The patient had no history of ocular disease, and her medical history included a thymoma treated by excision and postoperative radiotherapy in 1996, myasthenia gravis (positive acetylcholine receptor antibody), vasculitis (p–anti-neutrophil cytoplasmic antibody positive) with mild renal impairment, and recurrent chest infections. She also had had a recent episode of chicken pox before the onset of ocular symptoms. The patient was being treated with prednisolone, 10 mg/d, and azathioprine, 100 mg/d.

On examination, her visual acuities were 20/20 OD and 20/40 OS. Bilateral mild anterior uveitis was present, with normal intraocular pressures. Funduscopic examination showed a bilateral mild vitritis associated with bilateral superotemporal active retinitis (Figure 1). There was also an associated superotemporal macula-on rhegmatogenous detachment of the retina in the right eye. A clinical diagnosis of bilateral acute retinal necrosis was made, and the patient was treated with intravenous valacyclovir hydrochloride (10 mg/kg 3 times daily), oral prednisolone (45 mg/d), and topical 1% prednisolone acetate and 1% cyclopentolate hydrochloride. The patient subsequently underwent a right vitrectomy with injection of silicone oil for treatment of her detached retina and bilateral argon laser to demarcate the areas of active retinitis. Polymerase chain reaction examination of a vitreous sample taken during vitrectomy was positive for CMV DNA and negative for herpes simplex virus 1 and herpes zoster virus DNA. Analysis of blood samples disclosed a marked selective CD4 T-cell lymphocytopenia, with a reduced CD4/CD8 ratio of 0.25 (reference range, 0.66-3.52) but a normal B cell count. The patient had no serum antibodies for human immunodeficiency viruses 1 and 2 and had markedly low IgA levels (44 mg/dL), with mildly elevated IgM (199 mg/dL) and IgG (2020 mg/dL) levels. Polymerase chain reaction examination of peripheral blood was negative for CMV DNA. The patient's CD4 cell count did not return to normal, and her immune status remained unchanged despite cessation of azathioprine therapy. A chest x-ray film was clear, with no evidence of opportunistic infection. Because her retinitis was improving after a week of systemic treatment, the patient was discharged from the hospital on a regimen of oral acyclovir (because the patient preferred not to receive ganciclovir) and a tapering course of oral prednisolone. Six weeks later, the retinitis relapsed in the left eye and treatment was changed to intravenous ganciclovir followed by insertion of a slow-release intravitreal implant. The retinitis in her left eye resolved after 1 week, and the ganciclovir implant has been subsequently exchanged on a regular basis to control the patient's disease because her CD4 cell count has remained low.

Figure 1.
 Funduscopic photograph of the
left eye of patient 1 showing mild vitritis with peripheral cytomegalovirus
retinitis.

Funduscopic photograph of the left eye of patient 1 showing mild vitritis with peripheral cytomegalovirus retinitis.

Case 2

A 65-year-old woman was referred to Moorfields Eye Hospital in April 2000 with a 1-week history of floaters and progressive reduction in visual acuity of the right eye after a flulike illness that lasted a few days. The patient had no history of ocular disease, but her medical history was remarkable for a malignant thymoma that had been excised in 1998 and recurrent chest infections associated with bronchiectasis. On examination, her visual acuities were hand movements and 20/20 OS, with a right-sided relative afferent pupillary defect. Slitlamp examination showed a mild right anterior uveitis with normal intraocular pressures. Funduscopic examination showed a moderate vitritis and a swollen, hyperemic optic disc associated with retinitis along the right inferotemporal vascular arcade and affecting the macula (Figure 2). Polymerase chain reaction examination of a vitreous tap confirmed the presence of CMV DNA and was negative for herpes simplex viruses 1 and 2, herpes zoster virus, and Epstein-Barr virus DNA. The patient was treated with topical corticosteroids and repeated intravitreal injections of foscarnet sodium (2.4 mg each) and oral gancyclovir (1 g 3 times daily). Despite control of the retinitis, the patient's vision failed to improve because of optic atrophy. Polymerase chain reaction examination of peripheral blood was negative for CMV DNA. A chest x-ray film was not suggestive of any acute opportunistic infections, and analysis of blood samples showed a raised CD8 cell count of 976 cells/µL (reference range, 200-900 cells/µL), with a reduced CD4/CD8 ratio of 0.6 (reference range, 0.66-3.52) and a low B lymphocyte count of 1 (reference range, 100-500). The patient had no serum antibodies for human immunodeficiency viruses 1 and 2, low IgA (56 mg/dL) and IgM (43 mg/dL) levels, and a normal IgG level (640 mg/dL).

Figure 2.
 Funduscopic photograph of the
right eye of patient 2 showing cytomegalovirus retinitis along the inferotemporal
vascular arcade with involvement of the macula and optic nerve head.

Funduscopic photograph of the right eye of patient 2 showing cytomegalovirus retinitis along the inferotemporal vascular arcade with involvement of the macula and optic nerve head.

Comment

About a third of thymomas are associated with more than 20 different paraneoplastic syndromes, the 3 most commmon being myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia (6% of cases).1 The simultaneous occurrence of thymoma and hypogammaglobulinemia was first described in 19542 and was referred to as Good syndrome. Other systemic associations reported with thymomas include myasthenia gravis, IgG gammopathy, disorders of cell-mediated immunity, polyarthropathy, lichen planus, and hemolytic anemia.3 To the best of our knowledge, the 2 patients described herein are the first reported cases of CMV retinitis associated with the syndrome of thymoma and immunodeficiency.

Recurrent bronchopulmonary disease often leading to bronchiectasis is the most common clinical presentation of Good syndrome, and both our patients had had recurrent chest infections. Conversely, CMV is the opportunistic pathogen most frequently reported in the literature and has caused bronchopneumonia, watery diarrhea, disseminated infection, and fatal encephalitis.4,5

No retinal lesions have been previously reported in patients with Good syndrome and systemic CMV infections. The ocular manifestations of this syndrome described in the literature are limited to 2 cases of toxoplasma retinitis6,7 and 1 case of bilateral, nonsimultaneous recurrent herpetic keratitis.8

Although CMV disease occurs most often in patients with depressed cell-mediated immunity, there is evidence that humoral immunity plays a protective role against the virus.9 Before the acquired immunodeficiency syndrome epidemic, fewer than 50 cases of CMV retinitis in patients with noncongenital CMV disease were reported in the literature. These cases developed in severely immunocompromised patients with organ transplants or a variety of malignancies associated with the use of immunosuppressive chemotherapy.9

Therefore, our cases illustrate a widening clinical spectrum of CMV disease in patients with immunodeficiency associated with thymoma. Clinicians should be aware of this association, as early recognition and treatment can improve prognosis.

Corresponding author and reprints: Susan Lightman, PhD, FRCP, FRCOphth, FMedSci, Moorfields Eye Hospital, City Road, London EC1V 2PD, England (e-mail: s.lightman@ucl.ac.uk).

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Holland  GNTufail  AJordan  MC Cytomegalovirus diseases. Pepose  JSHolland  GNWilhelmus  KReds.Ocular Infection and Immunity. St Louis, Mo Mosby–Year Book Inc1996;1088- 1128
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