HHV6, HHV7, and HHV8

Fig. 16.1
Slit-lamp photograph of HHV6 DNA-positive keratitis

Patients with HHV7-related ocular diseases have active inflammation of the anterior segment of the eye; that is, there are anterior chamber cells, keratic precipitates, ocular hypertension, and/or corneal edema that initiates from corneal periphery and gradually progresses to total corneal area [9].

HHV8-related ocular neoplastic diseases such as Kaposi’s sarcoma of the ocular adnexa or conjunctival Kaposi’s sarcoma include a vascular-like lesion composed of spindle-shaped cells [21]. In AIDS patients with Kaposi’s sarcoma, many more patients might have some form of ocular involvement. A case with bilateral Kaposi’s sarcoma was reported for a HIV-positive homosexual male with histological, DNA and serological evidence of HHV8 [11]. Patients with HHV8-related ocular inflammatory disease similar to those with HHV7 disease have active inflammation of the anterior segment of the eye and/or corneal edema [12]. We have summarized the systemic and ocular diseases associated with HHV6, HHV7, and HHV8 infection (Table 16.1).

Table 16.1
Summary of systemic and ocular diseases with HHV6-, HHV7-, HHV8-associated infection


Systemic disease

Ocular disease


Exanthema subitum

AIDS-associated retinitis

Iritis (uveitis)
Infections of CNS

Corneal inflammation (keratitis)
Optic neuropathy


Exanthema subitum

Iritis (uveitis)
Corneal endotheliitis


Kaposi’s sarcoma

Iritis (uveitis)
Multicentric Castleman disease

Corneal endotheliitis
Primary effusion lymphoma

Conjunctival Kaposi’s sarcoma
Kaposi’s sarcoma of the ocular adnexa

CNS central nervous system

16.5 Diagnosis

The diagnosis of HHV6 can be challenging due to the high prevalence of infection and viral persistence. Detection of the viral genome indicates active or latent infections in the ocular samples. PCR tests have been established in order to detect active HHV6 infections [4, 22, 23]. Using these PCR techniques, HHV6 genomic DNA was found in ocular inflammatory diseases. For example, high copy numbers of HHV6 DNA can be detected in ocular samples using quantitative PCR examination (Fig. 16.2). For such diagnosis, ocular samples (aqueous humor, vitreous fluids, cornea tissues, and other ocular samples) need to be collected.


Fig. 16.2
Detection of HHV6 DNA using quantitative real-time PCR

HHV7 or HHV8 genomic DNA has also been detected by PCR in ocular samples. For the diagnosis of corneal endotheliitis, an aqueous humor sample is prepared for examination. A case of HHV7-related corneal endotheliitis after Descemet’s stripping endothelial keratoplasty is shown in Fig. 16.3.


Fig. 16.3
Slit-lamp photograph(left) and fluorescein stain (right) of HHV7-positive corneal endotheliitis. Localized corneal edema in the inferior peripheral area is shown by the white arrowheads in a slit-lamp photograph (left), and epithelial edema is stained by fluorescein staining (right) with keratic precipitates and mild anterior chamber inflammation

16.6 Differential Diagnosis

Differential diagnosis of viral involvement in ocular disease is not yet possible because the involvement of HHV6, HHV7, or HHV8 in ocular infections has not yet been clearly demonstrated. In particular, it is necessary to differentiate HHV7- or HHV8-related corneal endotheliitis from other viral causes including herpes simplex, varicella zoster virus, and cytomegalovirus. In cases after corneal transplantation, specific viral involvement in allograft rejection needs to be differentiated.

16.7 Management

It is still controversial whether antiviral medication should be used or not for the treatment of HHV6-related ocular diseases. However, in our experience, the intraocular viral DNA level and intraocular inflammation decreased in response to an antiviral agent plus systemic steroids [20]. Antiviral agents such as valaciclovir or valganciclovir should be used for such treatment. These results suggest that HHV6 has some role in the pathological physiology of ocular inflammation.

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Sep 25, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on HHV6, HHV7, and HHV8

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