HTLV-1 in Ophthalmology

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus described as a causative agent for human disease. In the field of ophthalmology, a close relationship between HTLV-1 infection and uveitis was identified through a series of clinical and laboratory studies in the late 1980s-1990s. Since then, HTLV-1-related ocular manifestations such as keratoconjunctivitis sicca, interstitial keratitis, optic neuritis and adult T-cell leukemia/lymphoma (ATL)-related ocular manifestations have continuously been reported. During the three decades since the association between HTLV-1 and ocular pathologies was discovered, ophthalmic practice and research have advanced with the incorporation of new technologies into the field of ophthalmology. Accordingly, new findings from recent research have provided many insights into HTLV-1-associated ocular diseases. Advanced molecular technologies such as multiplex polymerase chain reaction (PCR)/broad-range PCR using ocular samples have enabled rapid and accurate diagnosis. Advanced ophthalmic technologies such as widefield fundus camera and optical coherence tomography (OCT) have clarified various features of HTLV-1-associated ocular manifestations, and identified characteristics such as the "knob-like ATL cell multiple ocular infiltration" (KAMOI) sign. Advanced drug delivery methods such as intravitreal injection and sub-Tenon injection have led to progress in preventing disease progression. This article describes global topics and the latest research findings for HTLV-1-associated ocular diseases, with reference to a large-scale nationwide survey of ophthalmologists. Current approaches and unmet needs for HTLV-1 infection in ophthalmology are also discussed.

Keywords: ATL-related ocular diseases; HTLV-1 uveitis; human T-cell leukemia virus type 1; ocular infiltration; ocular inflammation; uveitis.

FIGURE 1

(A) Advances in imaging technology. Cytomegalovirus (CMV) retinitis in a patient infected by HTLV-1. Widefield fundus cameras can reveal the lesion (CMV retinitis, white arrow) at the peripheral retina and can track the lesion during follow-up. (B) Advances in imaging technology. Optical coherence tomography clearly captures cystoid macular edema accompanied by HTLV-1 uveitis.

FIGURE 2

(A) HTLV-1 uveitis (HU). Vitreous opacity is seen in the right eye. Vitreous opacity disturbs light penetration, preventing clear and detailed visualization of the retina. (B) Ocular complications secondary to HU. Posterior subcapsular cataract secondary to HU is clearly evident. A phaco dislocation technique is used to perform cataract surgery with a low level of aggression and high degree of safety.

FIGURE 3

Keratoconjunctivitis sicca (KCS) in an HTLV-1-infected patient. Reduction of the tear meniscus is seen (white arrow). Tear breakup time in this patient was 2 s. Rose bengal staining shows damage to the ocular surface (reproduced with permission from Ide et al., 2016).

FIGURE 4

Knob-like ATL cell multiple ocular infiltration (KAMOI) sign. KAMOI sign (A,B; white arrows) can be seen at the bulbar conjunctiva around the corneal limbus and at the palpebral conjunctiva around the lacrimal punctum (A) (reproduced with permission from Kamoi et al., 2016) and retina (B). Infiltrated ATL cells in the vitreous tend to form multiple clusters (C).

FIGURE 5

Cytomegalovirus retinitis. Cytomegalic cell infiltration and accompanying retinal necrosis are captured by widefield fundus camera and OCT in a patient with ATL.

FIGURE 6

ATL-related scleritis. Conjunctival and scleral injections are evident.