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Editor,—Sympathetic ophthalmia with deafness has been reported rarely.12 We describe one such case and explore a hypothesis whereby genetic susceptibility may be associated with cross reactivity of antigens derived from common neural crest tissue.
A 72 year old woman who had previously undergone a left trabeculectomy had a fall in which she sustained a Colles fracture and a left total hyphaema. By 14 days the blood had cleared sufficiently to reveal that she had expelled the entire left iris into the trabeculectomy bleb, with extensive dispersion of uveal pigment into the subconjunctival space. She was also found to have dislocated the lens, and had sustained a choroidal detachment (confirmed by ultrasonography). A non-granulomatous anterior uveitis was noted in the left eye at this time. The initial visual acuity was light perception in the left eye and 6/12 in the right eye.
On the 25th day after the original injury, she experienced pain and blurring of vision in her right eye, with the simultaneous onset of bilateral deafness (with an initial high frequency hearing loss of 60 dB). She was found to have a brisk anterior uveitis, with a dense vitritis in this eye, through which rugose choroidal thickening could just be discerned. At this stage, the right visual acuity had declined to 6/24, and the left eye achieved hand movements.
A diagnosis of sympathetic ophthalmia was made. She received two infusions of intravenous methylprednisolone (1 g each) and oral prednisolone (20 mg daily) was started. Cyclosporin A was commenced, and the dose adjusted to achieve a trough level of 200 μg/l (despite a history of breast cancer in remission). In view of the severity of the injury to the left eye, a left pars plana lensectomy and vitrectomy were performed to assess the visual potential of this eye. The retina was found to be flat, and the macula healthy; therefore, enucleation was not performed. By 3 months she had regained a visual acuity of 6/6 in the sympathising eye, and 6/12 in the exciting eye (with a contact lens incorporating a pupil and an aphakic correction).
However, at 4 months post-injury, reduction of the prednisolone dose to 12.5 mg, and reduction of cyclosporin A to give a trough level of 70 μg/l, was followed by a flare of anterior uveitis in both the exciting and sympathising eyes. This responded to increased prednisolone (15 mg) and an increase in the dose of cyclosporin A to achieve a trough level of 140 μg/l. At this time the exciting eye began to display white choroidal lesions consistent with the appearance of Dalen Fuchs nodules (Fig 1). Prednisolone was gradually reduced to 12.5 mg without further complications and she ultimately achieved a visual acuity of 6/9 in both eyes. Despite treatment, her hearing loss gradually progressed to 90 dB; this has not recovered.
Sympathetic ophthalmia with features of Vogt-Koyanagi-Harada disease (VKH), was initially reported in the 19th century.1 More recently, Nirankari et al have reported one case of sympathetic ophthalmia with profound high frequency deafness which did not recover.2 Rao and Marak3 have performed a clinicopathological survey of 100 pathological specimens of eyes enucleated because of sympathetic ophthalmia. Four of these had VKH overlap features, of which two had hearing loss. The association of sympathetic ophthalmia and deafness is clearly rare, which raises the question of what such overlap cases can teach us about the pathogenesis of VKH. Woods4 attempted to explain why deafness could occur in VKH, hypothesising that pigment present in the auditory labyrinth and the eye could be common targets of autoimmunity. The auditory labyrinth and the uvea are known to have a common embryological origin in the neural crest. Could a genetic predisposition facilitate the recognition of such shared antigens? Sugita et al5 have recently reported that cytotoxic T cells from three patients with VKH and one with sympathetic ophthalmia reacted against the MART 1 melanoma antigen (an antigen carried by skin and eye melanocytes), when presented in association with HLA-A2. Interestingly, two of their three VKH patients carried HLA-A2, HLA-B51, HLA-DR4, and a further VKH patient carried the HLA-A2, and HLA-DR4 antigens. Their sympathetic ophthalmia patient was also A2 positive, but was not positive for either HLA-B51 or HLA-DR4. Our patient was HLA typed and found to carry HLA-A2, HLA-B51, HLA-DR4.
HLA-A2 and HLA-DR4 are common and linked antigens, occurring together in approximately 33% of the population, but HLA-B51 is less common. From 537 random transplant organ donors HLA typed over 3 years, we calculated the frequency of HLA-A2, HLA-B51, HLA-DR4 in the regional population. These specificities were present together in only seven donors, giving a frequency of 1.3%. We propose that patients carrying HLA-A2, HLA-B51, and HLA-DR4 are at increased risk of damage arising in melanocytes of diverse tissues when one tissue is injured, whether in VKH or sympathetic ophthalmia.