Cytomegalovirus Anterior Uveitis

Fig. 10.1
(a) Slit lamp photograph of an eye with acute recurrent Cytomegalovirus anterior uveitis showing a few fine to large keratic precipitates with diffuse iris atrophy. (b) Fundal photograph of the same eye showing advanced cupping form repeated episodes of recurrences


Fig. 10.2
Slit lamp photograph of another eye with acute recurrent Cytomegalovirus anterior uveitis showing nodular endothelial lesions

  1. (b)

    Chronic anterior uveitis


Similarly, there is only minimal injection and AC activity. The KPs may be pigmented and are more numerous and diffusely distributed ranging in size from fine stellate to mutton fat (Fig. 10.3). Nodular endothelial lesions may be present in about 60% of the eyes. The AC activity in these eyes is again mild, but diffuse iris atrophy is more common. The IOP is often elevated, but the mean of the highest IOP (33 to 39 mmHg) is generally lower than in the acute form. Nonetheless 36 % of the eyes eventually developed GON [61, 64].


Fig. 10.3
Slit lamp photograph of an eye with chronic persistent Cytomegalovirus anterior uveitis showing diffuse fine- to medium-sized keratic precipitates

10.4.2 Complications of CMV Anterior Uveitis

The main causes of visual loss are GON, cataract, and corneal endothelial damage. However, there are few systematic analyses of their prevalence, and the wide variations in the definition of outcomes and patients may have had previous glaucoma or cataract surgery. Hence, it is difficult to derive their true prevalence.

Glaucoma as defined by the presence of GON or need for glaucoma surgery is estimated to vary from 12 to 60 % [62, 7173, 7882, 87, 133] and the prevalence of cataract at 14 to 60 % [71, 7880].

Some patients with CMV anterior segment infection present as a corneal endotheliitis with areas of stromal edema ranging from small localized lesions to diffuse edema (Fig. 10.4). Some of these patients were diagnosed during investigation for graft failure post-corneal transplant surgery, but some also had a history of previous hypertensive anterior uveitis. While small focal lesions may resolve with therapy, up to 63 % of eyes developed persistent diffuse edema causing visual loss despite medical therapy [75, 79, 87, 134142]. Endothelial cell loss has been shown to occur in eyes with CMV anterior uveitis and is correlated with the viral load [81, 133]. Hence, the endothelial damage may be a consequence of repeated episodes of inflammation or related to the use of corticosteroids in some of these eyes [122, 123].


Fig. 10.4
Slit lamp photograph of an eye with chronic Cytomegalovirus anterior uveitis showing fine to large keratic precipitates with a small area of mild stromal edema

10.4.3 Posterior Uveitis

Although CMV predominantly affects the anterior segment in immunocompetent patients, there have been isolated case reports of retinitis. Although these patients were not HIV-positive nor transplant recipients, a significant number had received corticosteroids including periocular or intravitreal injections or corticosteroid implants or had associated systemic conditions which may impair the immune response such as diabetes mellitus. In contrast to HIV-infected patients with CMV retinitis, anterior chamber inflammation, vitritis, and vascular occlusion were common associated findings in the immunocompetent patients [114, 118121].

Even more of an enigma was the development of an autoimmune retinopathy in a patient with recurrent CMV anterior uveitis. This otherwise healthy man had multiple relapses with oral valganciclovir and eventually required intravitreal ganciclovir implants for control. Although the anterior segment was quiet, he developed progressive retinal atrophy in the affected eye with constriction of visual fields and ablation of electroretinogram responses. Since the fellow eye was entirely normal, despite the presence of anti-retinal autoantibodies in his serum, a retinal dystrophy or paraneoplastic retinopathy was felt to be unlikely cause of the changes [143].

A small case series suggest that posterior segment changes in eyes with CMV anterior uveitis may be more common than what was previously thought. Although none of the 11 patients in this series had retinitis, nine (82 %) had some form of retinal abnormalities including prolonged arm retinal time (mean of 25 seconds) on fundus fluorescein angiography (FFA) in all nine (100 %), disc swelling in three patients of which two were only evident on FFA, and macula edema in four eyes. Only one of the 11 patients, who had macula edema, had atherosclerotic risk factors including diabetes mellitus, hypertension, and hyperlipidemia. Therefore, these changes may be secondary to a subclinical CMV vasculitis [144].

10.5 Diagnosis

There are no clinical features that are pathognomic of CMV anterior uveitis, and the only diagnostic test available today that can distinguish it from an idiopathic hypertensive uveitis or that caused by other viruses is aqueous analysis using polymerase chain reaction (PCR) techniques for viral nucleic acid and/or intraocular antibody production as these patients are usually negative for sera CMV antigen and CMV IgM. Conventional stains or cytologic techniques require much larger volumes of fluid than what can be obtained via an aqueous tap, and the sensitivity of viral cultures is highly vulnerable to the condition of the specimen and contamination. Unfortunately even with PCR or intraocular antibody production techniques, a significant proportion of cases may be missed due to various reasons. Firstly, even with PCR, which enables the amplification of miniscule amounts of viral nucleic acid, the viral load in the limited volume of aqueous available may be below the detection limits of the test. Secondly, due to short-lived nature of the inflammation in eyes with acute recurrent disease, the detection of actively replicating virus may be subject to the timing of the tap. In addition, there is also data showing that there are differences in the load of viral antigen and viral antibody production between immunocompetent and immunocompromised patients [145148]. Hence, these two tests complement each other and both should be done if available. In the series by Kongyai et al., the combination of antigen detection by PCR with the detection of a rise in the ratio of intraocular IgG to serum IgG of more than three (Goldmann-Witmer coefficient ) resulted in a higher sensitivity than if only either had been done alone. Only 60 % of the cases would have detected using PCR alone, and using GWC alone would have detected only 70 % of the cases [65].

Although an aqueous tap is a relatively safe procedure with only rare reports of introduction of air into the anterior chamber, transient hyphema, wound leak, and localized lens damage, these tests are costly and not readily accessible [59, 149, 150]. Therefore, other diagnostic techniques such as confocal microscopy have been assessed as for their potential in aiding diagnosis as it has been able to demonstrate the presence of an “owl’s eye sign,” which represents CMV inclusion bodies, in eyes with corneal endotheliitis [151]. It has not been proven though to be sufficiently sensitive nor specific in its ability to differentiate between infectious and noninfectious cases of anterior uveitis [152156].

10.6 Differential Diagnosis

10.6.1 Systemic Disease

The infectious mononucleosis-like syndrome characteristically results from infection by the Epstein-Barr virus where a lymphadenopathy is more common and the heterophile antibody is usually positive. However, a number of other viruses such as the human herpes virus 6, HIV, hepatitis virus, and rubella as well as other microbes including Toxoplasma gondii have also been implicated as causative organisms [157].

10.6.2 Ocular Disease

Hypertensive anterior uveitis may be idiopathic in origin as in the Posner-Schlossman syndrome and Fuchs’ uveitis syndrome or be caused by other viruses including herpes simplex virus (HSV), varicella zoster virus (VZV), and rubella. Unless there are accompanying dermatological or corneal manifestations of HSV/VZV such as a vesicular rash or a disciform stromal keratitis or dendritic epitheliopathy, it remains difficult to distinguish between the various viruses as well as an idiopathic cause based on clinical features alone as there is considerable overlap of features with none that is pathognomic [64, 73, 158] (Table 10.1). For example, sector iris atrophy that was initially attributed solely to VZV was subsequently seen also in CMV and HSV infections [76, 113, 159]. Moreover skin lesions are absent in zoster sine herpete [160], and there is also a possibility of concomitant infection by two viruses [161].

Table 10.1
Comparison of clinical features of viral anterior uveitis

Clinical features





Mean age at presentation (SD/range) years

35 (12)

43 (15) to 50 (range 15–83)

53 (23) to 61 (32–80

Acute – 37 (12)

Chronic – 54 (17–79) to 65 (9)

Clinical course

Chronic 52/54 (96 %)

Acute 23/38 (61 %)

Acute 6/10 (60 %)

Acute recurrent 35/50 (70 %)

Keratic precipitates
Nodular endothelial lesions

Acute recurrent – 9/35 (26 %)

Chronic − 9/15 (60 %)

>2+ AC cells

8/56 (14 %)

21/39 (54 %)

2/10 (20 %)

Fibrin formation

1/8 (13 %)

1/20 (5 %)


Iris changes

 Segmental/focal atrophy

3/54 (5.5 %)

1/8 (13 %) to 18/37 (48.6 %)

1/10 (10 %) to 8/20 (40 %)



8/54 (14.8 %)

3/37 (8.1 %) to 1/8 (13 %)

0 to 1/20 (5 %)

Acute 15/35( 43 %)

Chronic 6/18 (33 %) to 9/15 (60 %)

4/20 (20 %)


45/55 (88 %)

10/23 (43 %)

5/6 (83 %)


Posterior synechiae

4/55 (7.3 %)

2/8 (25 %) to 14/37 (38 %)

6/20 (30 %) to 4/10 (40 %)

None to 1/18 (5 %)

Mean of maximum IOP (range)





Acute recurrent, 50 (28–80)

Chronic, 35 (18–64) to 41(14–70)

IOP > 30 mmHg

13/53 (25 %)

18/39 (46 %)

5/10 (50 %)

Acute 34/35 (97 %)

Chronic 8/14 (57 %)

Corneal changes


2/56 (3.6 %)

Nil to 12/36 (33 %)

1/20 (5 %) to 2/10 (25 %)


 Coin-shaped lesions
Chronic 2/18 (11 %)

2/8 (25 %)

4/20 (20 %)

1/18 (6 %)

Data from references [64, 73, 158]

10.7 Management

10.7.1 Antiviral Therapy

Ganciclovir, a guanosine analogue, was the main antiviral drug used in the management of systemic as well as CMV anterior uveitis. It is administered as an initial induction dose of 5 mg/kg/body weight twice daily for 2–3 weeks followed by oral ganciclovir maintenance. It may be given prophylactically or preemptively in transplant patients (Table 10.2). Valganciclovir, its prodrug, does not require an intravenous induction dose due to its significantly better bioavailability that has largely replaced systemic ganciclovir. It is given orally commencing with an induction dose of 900 mg twice daily for 2–4 weeks followed by maintenance dose 450 mg twice daily for 6 or more weeks according to the immune status of the patient and may be discontinued when this normalizes. In addition, in HIV-infected patients with CMV retinitis, it may also be administered as intravitreal injections of 2 mg/0.1 ml weekly or as an intravitreal implant containing 4.5 mg of the drug released over 5 to 8 months. Other antiviral options in the management of systemic CMV as well as CMV retinitis are foscarnet and cidofovir.

Table 10.2
Ganciclovir/valganciclovir regimes for treatment of viral anterior uveitis

Antiviral agents




Intravenous 5 mg/kg/body weight twice daily for 2–3 weeks

Intravitreal injections

2 mg/0.1 ml weekly for 12 weeks

Intravitreal implant

4.5 mg slow release over 5 to 8 months (Vitrasert™ – not available )

Topical ganciclovir gel

4 to 5 times daily for 12 weeks

Valganciclovir oral

900 mg twice daily for 2–3 weeks


Topical ganciclovir gel4–5 times daily tapered after 12 weeks to 3 times daily if quiescent



450 mg twice daily for 6 weeks

Systemic and intravitreal ganciclovir and oral valganciclovir have been used in a similar fashion to treat CMV anterior uveitis. Ganciclovir is also commercially available as a topical 0.15 % ophthalmic gel. However, the optimal therapeutic regime is uncertain as there are considerable variations in the baseline characteristics of patients, treatment duration, as well as endpoints of treatment. Generally, 75 % of treated patients respond to therapy with resolution of the inflammation within a month, but the relapse rate is also as high. Hence, most studies advocate long-term treatment. This however poses issues of costs as well as potential for severe adverse effects such as hematological abnormalities (neutropenia, thrombocytopenia, anemia), neurological (confusion, hallucinations), and gastrointestinal symptoms (abdominal pain, vomiting, diarrhea), among others. Topical ganciclovir gel, while it had a lower response rate of 67 %, has minimal adverse effects, is fairly well tolerated, and is less costly. A 2 % solution may be prepared from lyophilized ganciclovir and all treated eyes responded, with resolution of the AC inflammation and control of the IOP, and were negative for CMV on repeat taps. Relapse however similarly occurred upon stopping treatment [71, 72, 7687, 133, 162].

10.7.2 Anti-inflammatory Agents

Most authors advocate adjunctive anti-inflammatory agents such as topical corticosteroids and/or nonsteroidal anti-inflammatory drugs in reducing the inflammation in eyes with anterior uveitis. However, corticosteroids should be used judiciously as there is concern that they may possibly potentiate the infection resulting in permanent endothelial damage as discussed above.

10.7.3 Glaucoma Management

Glaucomatous optic neuropathy is a major cause of visual loss in CMV anterior uveitis. Hence, IOP management is a vital component in their management. While there have been sporadic reports suggesting that the prostaglandin analogues may induce or potentiate a viral anterior uveitis, they are effective options if the IOP remains uncontrolled, with careful monitoring for any exacerbation of the inflammation. Pilocarpine on the other hand is contraindicated as it increases the blood-ocular permeability. Glaucoma surgery may be required in refractory cases or where there is progressive optic nerve damage.

10.8 Prognosis

The visual outcome of CMV anterior uveitis is not well studied as most authors examine mainly recurrences with few reports of visual acuity. The prevalence of the main causes of visual loss is also not well documented with considerable variations in the definition of glaucoma as well as the population analyzed. However, the inflammation in acute recurrent anterior uveitis is short-lived, and the attacks may be few and far between. Although the IOP is more refractory in chronic uveitis, it is less elevated than in the acute form, and hence central vision may be preserved in these eyes. In most studies, at least 80 % of eyes have 20/40 or better vision at the last visit. In a series by Hwang et al., 13 of 20 eyes had a final vision worse than 20/40, four of which were possibly due to GON [71, 76, 78, 79, 82, 87, 133, 162].


CMV anterior uveitis presents predominantly as a hypertensive uveitis and may be acute recurrent or chronic in its course. There are considerable similarities with other viral as well as idiopathic causes, and it can only be diagnosed by aqueous analysis for viral nucleic acid by PCR and/or intraocular antibody synthesis. While it responds to all formulations of ganciclovir/valganciclovir, the relapse rate is also high and long-term treatment may be required. Most patients achieve a good visual outcome unless they develop severe GON or corneal endothelial damage.

Core Message

Ocular CMV classically presents as a retinitis in immunocompromised individuals with rare instances of anterior segment involvement. On the other hand, in immunocompetent persons, CMV anterior uveitis is increasingly recognized as a cause of hypertensive uveitis especially in Asia. Hence, it is important to avoid the use of corticosteroids alone unless aqueous analysis can be performed to exclude a viral etiology.



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Sep 25, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Cytomegalovirus Anterior Uveitis
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