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Editor,—We describe a rare case of bilateral optic neuropathy caused by HIV which responded to highly active antiretroviral therapy (HAART).
In March 1996, a 52 year old man presented with a 6 month history of slowly deteriorating vision in both eyes. By the time he sought medical help he had difficulty reading the newspaper and watching television. He was otherwise well except for a chronic productive cough.
He had worked for many years as a teacher in Botswana. He was heterosexual. His only risk factor for HIV transmission was a single encounter with an African woman in the mid 1980s. In 1988 he had dengue fever and malaria. The latter was treated in the UK with quinine and fansidar. In 1995 he was treated in Botswana for a pneumonic illness. He was known to be hypertensive and was taking nifedipine, bendrofluazide, and atenolol. There was nothing else of relevance in his history.
On examination he was clubbed and had bilateral coarse crepitations. General examination was otherwise normal. Higher mental function was normal. Visual acuities were 6/18 on the right and 6/9 on the left. He had marked colour desaturation being able to read 2/17 Ishihara plates with the right eye and 3/17 with the left. Both visual fields showed a marked concentric constriction (Fig 1A). Funduscopy revealed bilateral optic disc pallor (Fig 2). Intraocular pressures were normal. Eye movements were normal. His visual evoked response was virtually extinguished on the right and was delayed and of small amplitude on the left. No pattern evoked responses were seen on the ERG. The remainder of the neurological examination was normal.
Full blood count, electrolytes, glucose, B12, folate and folate levels were all normal. Autoantibody screen and syphilis serology were negative. Haemophilus influenzae was grown from his sputum but neither acid fast bacilli nor Pneumocystis carinii were detected. Toxoplasma serology showed no significant titres. Other viral serology including cytomegalovirus (CMV) antibody, hepatitis B surface antigen, and hepatitis C antibody were negative.
A chest radiograph showed bilateral basal shadowing. A high resolution computed tomograph scan confirmed bronchiectasis. A magnetic resonance imaging scan of head and orbits was normal. His CSF contained 28 white cells all of which were lymphocytes. The CSF protein was 0.73 g/l (normal <0.4 g/l) and glucose of 2.5 mmol/l (plasma 5.5 mmol/l). No organisms were detected. CSF cryptococcal antigen test (latex agglutination) was negative.
The lymphocyte subsets showed a T helper cell count (CD4) of 100 cells ×106/l (normal 700–1100) and T suppressor cell count of 2232 cells ×106/l (normal 500–900). In view of his history he was counselled and consented to HIV testing. HIV-1 antibody test was positive.
He was commenced on triple therapy zidovudine 200 mg three times daily, lamivudine 150 mg twice daily, indinavir 800 mg three times daily (HAART or highly active antiretroviral therapy) with co-trimoxazole prophylaxis for Pneumocystis carinii. He responded well clinically and on review at 6 months his vision had improved to 6/9 and 6/6 in his right and left eyes respectively with a concomitant improvement in his visual fields at 24 months (Fig 1B). His CD4 count rose to 170 cells ×106/l and HIV viral load (Roche Amplicor) was below 400 copies/ml 6 months after initiating HAART. Unfortunately, the HIV viral load at presentation was not available.
Visual deterioration in HIV is a common problem. Ocular manifestations of HIV include retinal microangiopathy, opportunistic retinal infections, Kaposi's sarcoma of the conjunctiva and eyelids, and herpes zoster ophthalmicus. Retinal disease occurs frequently, sometimes in association with optic nerve disease. Occasionally the optic nerve is selectively involved. The commonest aetiology is opportunistic infection. Most case reports have focused on the role of opportunistic infections such as syphilitic optic perineuritis, CMV papillitis, varicella zoster optic neuritis, or cryptococcal retrobulbar neuritis.1 Other causes include toxoplasmosis and tuberculosis. Indeed, a search for these aetiological agents is the priority when faced with an HIV positive patient with an optic neuropathy. However, sometimes no opportunistic infection is found and the HIV virus itself is assumed to be causing the optic neuropathy.
In our case funduscopy excluded CMV and toxoplasma retinopathy. The other infective aetiologies were excluded by serological testing. Magnetic resonance imaging excluded a compressive lesion. It is possible that our patient had idiopathic bilateral optic neuropathy with spontaneous improvement. However, it is exceedingly rare for simultaneous, rather than stepwise, bilateral visual deterioration to occur with progressive deterioration for months and then a slow delayed recovery. One of the best series of bilateral optic neuropathy remains that by Hierons and Lyle in 1959.2 They reported 47 cases of bilateral optic neuritis, seven of which developed simultaneous bilateral visual disturbance. Two of these seven patients regained their vision over 6–12 months. Therefore, given the rarity of such an idiopathic presentation and the temporal relation of the improvement to HAART it is very likely that our patient had a primary HIV related optic neuropathy.
Primary HIV infection is well known to cause neurological disease. However, there has only been one case report of bilateral retrobulbar optic neuropathy in whom the presumed aetiology was the HIV virus itself.3 Newman and Lessell reported two patients who were already known to be HIV positive. The first patient was a 39 year old man who awoke with bilateral blurred vision and slight retrobulbar pain. His vision continued to deteriorate to 5/200 right eye and hand movement perception in the left eye. Funduscopy was normal. Four weeks into his illness he was commenced on AZT. Within 10 days his vision was beginning to improve. Eight months later his acuity was 20/70 right eye and 20/40 left eye. He was left with bilateral optic atrophy. The second patient did not improve with AZT but did show improvement with prednisolone. The only other case of optic neuropathy due to primary HIV infection was of a man with sudden monocular blindness.4 This was clinically due to an anterior ischaemic optic neuropathy, presumed to be secondary to an optic nerve microangiopathy.
What is the mechanism of the optic neuropathy? There is a significant loss of cortical neurons and optic nerve axons in patients with AIDS.5 6 Also far fewer AIDS patients have ocular signs than have ocular lesions discovered on post mortem. Therefore, it is not surprising that changes were noted in the optic nerves of eight AIDS patients who did not have visual signs or symptoms before death as well as those who did. Patchy axonal degeneration, oligodendrocyte, and myelin degeneration were noted in association with mononuclear cell infiltration, suggesting that optic nerve degeneration may be mediated by HIV infected macrophages.7 The HIV virus infects mononuclear phagocytic cells rather than neurons or oligodendrocytes so the neuronal losses must occur through a secondary mechanism. A more recent study has shown that optic nerve astrocytes in four patients with primary HIV related optic neuropathy stain strongly for tumour necrosis factor α (TNFα). No comparable staining was seen in control optic nerves.8 TNFα, an immunomodulatory agent, thus appears to be a major player in HIV induced neuronal apoptosis.
In conclusion, HIV may directly cause an optic neuropathy. The improvement of our patient's vision with HAART is suggestive that much of the optic nerve failure is due to a reversible dysfunction of the optic neurons rather than their death.