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Neuro-ophthalmological disorders in HIV infected

subjects with neurological manifestations
J-C Mwanza, L K Nyamabo, T Tylleskär and G T Plant

Br. J. Ophthalmol. 2004;88;1455-1459

doi:10.1136/bjo.2004.044289

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1455

EXTENDED REPORT

Neuro-ophthalmological disorders in HIV infected subjects

with neurological manifestations
J-C Mwanza, L K Nyamabo, T Tylleskär, G T Plant
...............................................................................................................................
Br J Ophthalmol 2004;88:1455–1459. doi: 10.1136/bjo.2004.044289

Aims: To determine the frequency and features of neuro-ophthalmological manifestations in neurologically

symptomatic HIV infected patients and to assess whether or not the visual evoked potential (VEP) features
in these patients differ from those of neurologically asymptomatic HIV infected patients.
Methods: Neuro-ophthalmological evaluation was performed in 166 neurologically symptomatic
confirmed HIV positive patients, of whom 75 with normal ophthalmological examination were further
studied by means of VEPs. The VEPs values were compared to those obtained from 53 other confirmed HIV
positive subjects with neither ophthalmological nor neurological manifestations, who served as a
See end of article for comparison group and to the references values of our laboratory.
authors’ affiliations Results: An abnormal neuro-ophthalmological examination was noted in 99/166 patients (60%). Eye
....................... movement disorders were present in 99 patients (51%). Visual field defects were detected in 39% of the
Correspondence to: patients. Optic neuropathy was noted in 31%, papilloedema in 27% and ocular motor nerve palsies in
Jean-Claude Mwanza, 26% of the patients. Toxoplasmosis and cryptococcosis were the most frequent associated pathologies,
University of Bergen, though in some patients the HIV itself was the presumed cause. VEPs were abnormal in 57% and 42% of
Centre for International patients with and without neurological manifestations, respectively. Compared to asymptomatic patients,
Health, Armauer Hansen
Building, N-5021 Bergen, symptomatic patients had a significantly increased mean latency; however, both groups had significant
Norway; jcmwanza@ increase in mean latency compared to reference values.
hotmail.com Conclusion: Neuro-ophthalmological manifestations are common in neurologically symptomatic HIV
Accepted for publication infected patients. Subclinical dysfunction in the visual pathways is a common phenomenon in both HIV
6 April 2004 infected patients with and without neurological symptoms, but neurologically symptomatic patients seem to
....................... have more damage in their visual pathways.

T
he human immunodeficiency virus (HIV) infection visual evoked potential (VEP) features in HIV infected
remains a major health problem in many developing patients with neurological symptoms differ from those of
countries. More than 40 million people are currently HIV infected patients without neurological symptoms.
living with the HIV.1 Infection by HIV leads to a wide range of
clinical pictures as it may involve almost all systems,
SUBJECTS AND METHODS
including the nervous system and the eye. The nervous
Subjects
system is involved in up to 50% of the HIV infected subjects,
The participants were all recruited from the Department of
resulting in different patterns of neurological involvement at
Neurology and the Unit of Infectious Diseases of the
some point during the infection.2–4 Additionally, histological
Kinshasa University Hospital in Kinshasa, from August to
studies have shown that 75–90% of AIDS patients incur
damage to the brain, including the optic nerve.5 Furthermore, December 2001 and from July to December 2002. They
numerous reports have described HIV associated eye consisted of 166 confirmed HIV infected patients (91 males
abnormalities, which affect 70–80% of all patients early or and 75 females, mean age 39.5 (SD 8.7) years, age range 20–
late during the course of their illness.6 61 years) with neurological manifestations (group I) and 53
Neuro-ophthalmological disturbances have been widely other confirmed HIV infected subjects (28 males and 25
described in both asymptomatic HIV positive subjects and in females, mean age 39.9 (6.2) years, age range 27–53 years)
those with full blown AIDS. In patients with AIDS there is a without any neurological manifestations (group II) or
3%–8% incidence of neuro-ophthalmological disorders.7–10 In ophthalmological complaints at the time of the study.
addition, it has been shown that asymptomatic HIV infected Neuro-ophthalmological examination was performed in all
subjects, even in early stages of the infection, exhibit ocular patients with neurological manifestations. In addition, VEPs
electrophysiological and psychophysical abnormalities. In were recorded in 75 patients of those with neurological
recent years, there have been extensive studies on the ocular manifestations (symptomatic patients) and in all 53 patients
manifestations of AIDS, but only few of them have reported without neurological manifestations (asymptomatic patients)
on systematic evaluation of the HIV/AIDS related neuro- who served as a comparison group, with the understanding
ophthalmological manifestations,7 9 and only a few reviews that they all had visual acuity of 0.8 or better, no
have been published on this specific topic.11–13 Moreover, ophthalmoscopic detectable abnormalities, and no visual
there are, to the best of our knowledge, no published reports field defects. Another group of healthy controls previously
specifically focusing on the prevalence and clinical features of investigated served as the laboratory reference material.14
the neuro-ophthalmological manifestations in neurologically
symptomatic HIV infected patients. Thus, we wished (1) to
determine the prevalence and features of neuro-ophthalmo- Abbreviations: ADC, AIDS related dementia complex; CRY,
logical manifestations in neurologically symptomatic HIV cryptococcosis; HIV, human immunodeficiency virus; LPH, lymphoma;
infected patients, and (2) to determine whether or not the TBC, tuberculosis; TXP, toxoplasmosis; VEP, visual evoked potential

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1456 Mwanza, Nyamabo, Tylleskä r, et al

Methods RESULTS
Ophthalmological examination The clinical examination included 166 HIV infected patients
A routine neuro-ophthalmological examination was per- with various neurological manifestations. Their repartition
formed in all symptomatic patients. Visual acuity was according to the cause of neurological disturbances was as
measured with a Snellen chart and objective refraction was follows: cerebral toxoplasmosis 77 (46%), cryptococcal
assessed using retinoscopy and Javal keratometry. The pupils meningitis 46 (28%), tuberculous meningitis 23 (14%),
were checked for size, reactivity to light, and near targets. AIDS related dementia complex (ADC) 14 (8%), cerebral
Eyelids were examined to search for possible ptosis and lymphoma four (2%), and herpes zoster two (1%).
retraction. Ocular motility (ductions and versions) was tested The neuro-ophthalmological manifestations are outlined in
in each of the cardinal positions of gaze. Saccades were table 1. Overall, an abnormal examination was found in 99
qualitatively assessed using a home made device consisting of patients (60%). Among these patients, we found ocular
two alternating light spots horizontally separated 50 cm apart movement abnormalities in 85 patients, visual field defects in
in front of the subject. Pursuit eye movements were checked 60 patients, optic neuropathy in 52 patients, papilloedema in
by asking the patient to maintain the fixation on a light spot 45 patients, and ocular nerve palsies including conjugate gaze
moving slowly and horizontally from right to left and vice and palsy convergence deficiency in 43 patients. Less
versa in front of him. Colour vision performance was assessed common findings included upper eyelid retraction secondary
with Ishihara plates, and ocular fundus was examined by to palsy of the seventh cranial nerve and cortical blindness.
direct ophthalmoscopy through dilated pupils (tropicamide Of the 85 patients with eye movement disturbances,
eye drops 1%) with special attention drawn on the sharpness abnormal saccades and abnormal eye pursuits were observed
of the margin and the colour of the optic disc. A Goldmann in 71 and 65 patients or 43% and 39% of the study
perimeter was used to assess the visual fields. population, respectively. Most of these 85 patients (53
patients or 62%) had both abnormal saccades and abnormal
VEP recording procedure pursuit eye movements while 18 and 12 patients had only
VEP recordings were obtained monocularly using the abnormal saccades and abnormal pursuits, respectively.
following settings: stimulus number = 128, analysis period Saccades were slow in all patients and delayed in initiation
= 300 ms, band pass = 1–70 Hz on a Cadwell 5200A, USA in most of them. Only two patients presented with opposite
device. The visual stimulus was a pattern reversal checker- way saccades. Abnormal pursuit eye movements consisted of
board displayed on a 14 inch black and white monitor saccadic movements.
(Philips, Italy), placed at 1 m from the patient. Checks were Visual field defects were present in 39% of the 153 subjects
oblong and each check measured 1.71 degrees of visual angle in whom the test was performed. Both visual field deficits
horizontally and 0.85 degrees vertically. The checkerboard consistent with retinal pathology, damage of the anterior and
had a 90% contrast with a luminance of 2 cd/m2 and 90 cd/ posterior visual pathways, were observed.
m2 for the black and white checks, respectively. Room Fifty two patients had optic neuropathy that presented
lighting was kept constant during the examination (5 cd/ clinically as neuroretinitis, anterior or retrobulbar optic
m2). Cortical responses were recorded using silver chloride neuropathy. Most of these patients (n = 30) had unilateral
electrodes placed over the occipital cortex 2 cm above the involvement.
inion for the active, in the midline 2 cm anteriorly for the Ocular motor nerve palsies involving the abducens (17%)
reference. The mid-frontal electrode was used as ground. and the oculomotor (9%) were the most frequent. Unilateral
Responses to 100 reversals were averaged. The P100 involvement and isolated form were predominant.
component of the cortical response and the peak to peak Table 1 also shows the causes of the different neuro-
N75-P100 amplitude were considered for measurement. P100 ophthalmological manifestations in this series of patients.
latency values of the 75 patients in group I were compared to Toxoplasmosis was the predominant cause associated with
those in group II using the Student’s t test. The values optic neuropathy (40%). Most cases of third cranial nerve
obtained from these groups were further compared to the palsy (47%), sixth cranial nerve palsy (39%), and visual field
reference values of our laboratory. defect (35%) were seen in patients with cryptococcosis while

Table 1 Frequency and aetiology of neuro-ophthalmological manifestations in 166 HIV positive patients with neurological
manifestations
Manifestations Total (%) TXP (n = 77) CRY (n = 47) TBC (n = 23) LPH (n = 4) HZV (n = 2) HIV only (n = 14)

Any manifestation 99 (60) 35 32 15 3 2 12

Optic neuropathy 52 (31)
Neuroretinitis 25 (15) 17 – 2 – 1 5
Anterior optic neuropathy 16 (10) 3 3 5 – – 5
Retrobulbar optic neuropathy 11 (7) 1 6 1 – 1 2
Eye movement disorders 85 (51)
Abnormal saccades 71 (43) 27 18 12 2 2 10
Abnormal pursuits 65 (39) 24 17 10 2 1 11
Nystagmus 2 (1) 1 – – 1 – –
Ocular motor palsy 43 (26)
IIIrd cranial nerve 15 (9) 4 7 1 1 1 1
IVth cranial nerve 2 (1) – 1 – – – 1
VIth cranial nerve 28 (17) 7 13 4 2 – 2
Convergence insufficiency 1 (1) – 1 – – – –
Supranuclear gaze palsy 2 (1) 2 – – – – –
Visual field defects 60 (39) 19 21 10 3 – 7
Papilloedema 45 (27) 10 11 10 3 1 10
Optic atrophy 8 (5) 1 4 – 2 1 –
Cortical blindness 1 (1) 1 – – – – –

TXP, toxoplasmosis; CRY, cryptococcosis; TBC, tuberculosis; LPH, lymphoma.

*Total number of patients examined = 153.

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Neuro-ophthalmology of neuro-AIDS 1457

Table 2 VEP features in HIV infected patients with neurological manifestations

(symptomatic patients), without neurological manifestations (asymptomatic patients), and
laboratory reference values
Symptomatic patients Asymptomatic patients
(n = 75) (n = 53) References

Abnormal VEPs, n (%) 43 (57%)` 22 (42%)

Mean latency (SD) (ms) 115 (14)*,
109 (9)* 100 (5)
Mean amplitudes (SD) (mV) 8 (3)*,
9 (5)* 15 (5)

*Significantly different from reference values,
significantly different from asymptomatic patients, `not significantly
different from asymptomatic patients.

most cases of abnormal saccades (71%) and pursuits (78%) neuro-ophthalmological complications in sub-Saharan Africa
were observed in patients in whom the HIV itself was the is largely not known, the results of the present study may be
presumed aetiology of neurological symptoms. Half of considered as a starting point for more studies in the future.
patients with optic atrophy had cryptococcosis. Cortical The relation between HIV infection and the occurrence of
blindness was observed in a single patient with cerebral neuro-ophthalmological complications has been established
toxoplasmosis. for some years. Indeed, several studies have shown that
The results of the VEP recordings are summarised in patients with full blown AIDS or symptomatic HIV infection
table 2. Altogether, VEPs were abnormal in 57% of HIV frequently exhibit neuro-ophthalmological manifestations,
positive patients with neurological symptoms and in 42% of which result from central nervous system (CNS) opportunis-
those without neurological symptoms. Although there was a tic infections and neoplasms as well as the direct effect of the
trend that symptomatic patients are more likely to have virus itself acting alone or in combination with other
abnormal VEPs, this trend was not statistically significant cofactors yet to be determined.7 9 11 However, only very few
(x2 = 3.11, p = 0.07). In the symptomatic patients VEPs were large studies have specifically assessed the relative prevalence
abnormal in 8/11 patients (73%) with HIV itself as the of the different neuro-ophthalmological disorders, which has
presumed cause of neurological manifestations, in 11/18 been reported to range between 3% and 8%.7 9 Surprisingly,
patients (61%) with cryptococcosis, in 7/13 patients (54%) there has not been a single report of such disorders in the
with tuberculosis, and in 17/33 patients (52%) with subgroup of neurologically symptomatic AIDS patients. The
toxoplasmosis. Logistic regression analysis revealed that difference in the homogeneity of the study population
none of the aetiologies significantly influenced the VEP. explains the huge difference in the prevalence of the neuro-
Only 2/75 (3%) of symptomatic patients and 1/43 (2%) of the ophthalmological manifestations. The high prevalence found
asymptomatic patients had unilateral alteration of VEP. Both in the present study indicates that HIV patients with
groups showed a significant increase of the mean P100 neurological symptoms are at higher risk for neuro-ophthal-
latency compared to the reference values obtained in our mological complications.
laboratory. Symptomatic patients had a significantly pro- Optic neuropathies have been described in HIV patients.
longed mean P100 latency compared to the asymptomatic They may be caused by a variety of pathologies including
patients (p = 0.01). There was no significant difference in the infectious, compressive and inflammatory processes. Of
mean amplitude of the two groups of HIV patients (p = 0.17), interest is the optic neuropathy related to the HIV itself.17 18
though both showed a significant decrease compared to the In this series HIV was assumed to induce primary optic
reference values (p,0.05). In both groups of HIV patients no neuropathy in seven patients, representing 4% of the study
correlation (symptomatic patients: r = 20.029, asymptomatic population and 7% of patients with neuro-ophthalmological
patients: r = 20.020) could be found between the P100 manifestations. The diagnosis was made by exclusion, in the
latency and the amplitude. absence of both any ophthalmoscopically observable retino-
pathy and any other cause of optic neuropathy. There is
DISCUSSION currently enough evidence that the optic nerves of HIV
This study has generated two types of results. Firstly, it was infected patients can undergo chronic degeneration resulting
found that 60% of HIV patients with neurological symptoms in axonal loss.10 19 Despite the enormous amount of research
have neuro-ophthalmological manifestations on clinical devoted to neurodegeneration in HIV infection, there remain
examination, which means that neurologically symptomatic a number of unclarified questions in relation to the
HIV infected patients commonly exhibit neuro-ophthalmo- mechanism by which HIV induces primary optic neuropathy.
logical manifestations. Secondly, VEPs were abnormal in 57% The current widely accepted theory emphasises the key role
of HIV positive patients with neurological manifestations and of tumour necrosis factor alpha (TNF-a) in the genesis of
in 42% of those without neurological manifestations. primary HIV optic neuropathy.20 21 In HIV dementia, which is
There are some limitations that need to be considered, a good example of axonal death in HIV patients and where
especially regarding the distribution of aetiologies in the the pathogenesis of neuronal damage has been widely
present series of patients. In contrast with the developed investigated, the damage has been ascribed at least partly
world where the incidence of neurological complications to the combined effect of neurotoxic agents including viral
decreases following the introduction of highly active anti- proteins and neurotoxic factors released from activated
retroviral therapy,15 16 the incidence of CNS related HIV microglia and macrophages.5 22 Thus, our opinion is that
pathologies are increasing in sub-Saharan Africa because primary optic neuropathy may result from the combination of
these drugs are not available. It is therefore likely that the both mechanisms, with the understanding that the mechan-
prevalence of HIV related neuro-ophthalmological manifes- ism having the key role may vary depending on factors yet to
tations found in this study is high in comparison to that be determined by further studies.
reported in Western countries. Some other factors such as the In this study, eye movement disorders (abnormal saccades
lack of both prophylaxis against opportunistic infections and and pursuits) were the most frequent manifestations
appropriate complementary tests may have a role in the regardless of the aetiology. They were present in half of
observed prevalence. Since the magnitude of HIV associated the study population and in 86% of patients with

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1458 Mwanza, Nyamabo, Tylleskä r, et al

neuro-ophthalmological complications. This finding is con- In conclusion, neuro-ophthalmological manifestations are

sistent with the result of previous clinical and electrophysio- various and common in neurologically symptomatic HIV
logical studies, which have shown that abnormal saccades infected patients in sub-Saharan Africa. They are mainly
and smooth pursuits are present in HIV infected subjects caused by opportunistic infections, among which toxoplas-
including those without any other clinical manifestation of mosis and cryptococcosis are the most common. The VEP
HIV infection.23–27 These ocular movement disturbances are results indicate that subclinical dysfunction in the visual
believed to be more frequent in subjects with HIV dementia. pathways is a common phenomenon in both HIV infected
Some investigators have postulated that in asymptomatic patients with and without neurological symptoms, but
HIV subjects they represent early manifestations of HIV neurologically symptomatic patients seem to have more
dementia.28 In our series 12/14 patients with HIV dementia damage to their visual pathways.
had abnormal saccades and pursuits. Besides, many others
without dementia but with other HIV related CNS diseases ACKNOWLEDGEMENTS
exhibited the same manifestations. Whether or not all cases The Norwegian Educational Loan Fund and the University of Bergen,
of ocular movements disorders are exclusively caused by HIV Norway, supported this study. We wish to thank Dr José Nkoy at the
itself is therefore questionable, as concurrent opportunistic Unit for Infectious Diseases, Department of Internal Medicine,
Kinshasa University Hospital, for assistance in tracing the patients.
infections and other factors yet to be elucidated may have a
role in the genesis of such abnormalities. Most patients with .....................
eye movement disturbances had both abnormal saccades and Authors’ affiliations
pursuits. This, together with the high prevalence of eye J-C Mwanza, Department of Ophthalmology, Kinshasa University
movement disturbances, suggests that the anatomical struc- Hospital, Kinshasa, Democratic Republic of Congo
tures involved in the control of saccades and smooth pursuits L K Nyamabo, Department of Neurology, Kinshasa University Hospital,
are frequently involved in HIV infected subjects. Kinshasa, Democratic Republic of Congo
The prevalence of ocular nerve palsy found in the present J-C Mwanza, T Tylleskär, Centre for International Health, University of
study is 25%. In the series reported by Helweg-Larsen et al,29 Bergen, Bergen, Norway
G T Plant, Department of Neuro-ophthalmology, The National Hospital
only 17 of 589 patients with neurological manifestations (3%)
for Neurology and Neurosurgery and Moorfields Eye Hospital, London,
had ocular nerve palsy. The prevalence of such disorders in UK
patients with AIDS, regardless of the presence of neurological
symptoms, has been reported to range between 3% and
8%.9 30 31 Similarly to previous reports,7 9 32 palsies involving REFERENCES
the sixth and third cranial nerves were the most frequent in 1 UNAIDS. Annual report, December 2003.
2 Gongora-Rivera F, Santos-Zambrano J, Moreno-Andrade T, et al. The clinical
the present study, and toxoplasmosis and cryptococcosis were spectrum of neurological manifestations in AIDS patients in Mexico. Arch Med
the two most common causes. The sixth cranial nerve has a Res 2000;31:393–8.
long course, which makes it more vulnerable, especially to 3 Perriens JH, Mussa M, Luabeya MK, et al. Neurological complications of HIV-
1-seropositive internal medicine inpatients in Kinshasa, Zaire. J Acquir
high intracranial pressure. The trochlear nerve, though the Immune Defic Syndr 1992;5:333–40.
longest of the ocular motor nerves, seems to be rarely 4 Levy RM, Bredesen DE, Rosenblum ML. Neurologic complications of HIV
affected. It is however worth stressing that in a number of infection. Am Fam Physician 1990;41:517–36.
cases the exact cause of cranial nerve palsy is complicated by 5 Gray F, Adle-Biassette H, Chretien F, et al. Neuropathology and
neurodegeneration in human immunodeficiency virus infection. Pathogenesis
the presence of concurrent multiple potential underlying of HIV-induced lesions of the brain, correlations with HIV-associated disorders
aetiologies. and modifications according to treatments. Clin Neuropathol
VEPs were abnormal in 57% and 42% of patients with and 2001;20:146–55.
6 Jabs D, Quinn T. Acquired immunodeficiency syndrome. In: Pepose J,
without neurological symptoms, respectively. In HIV infected Holland G, Wilhelmus K, eds. Ocular infection and immunity. St Louis: Mosby-
subjects subclinical abnormal VEPs have been reported to Year Book, 1996:289–310.
range from 3% to 49%,33–36 though completely normal VEPs in 7 Keane JR. Neuro-ophthalmologic signs of AIDS: 50 patients. Neurology
1991;41:841–5.
both neurologically symptomatic and asymptomatic HIV 8 Jabs DA, Green WR, Fox R, et al. Ocular manifestations of acquired immune
infected subjects have also been found.37 Interestingly, the deficiency syndrome. Ophthalmology 1989;96:1092–9.
number of subjects with abnormal VEPs did not differ 9 Mansour AM. Neuro-ophthalmic findings in acquired immunodeficiency
syndrome. J Clin Neuroophthalmol 1990;10:167–74.
significantly in the two groups. These findings may indicate
10 Sadun AA, Pepose JS, Madigan MC, et al. AIDS-related optic neuropathy: a
that HIV positive patients with neurological symptoms are histological, virological and ultrastructural study. Graefes Arch Clin Exp
not at higher risk for optic nerve damage than those without Ophthalmol 1995;233:387–98.
neurological manifestations. They further support both the 11 Currie J. AIDS and neuro-ophthalmology. Curr Opin Ophthalmol
1995;6:34–40.
hypothesis according to which axonal loss of the optic nerve 12 Friedman DI. Neuro-ophthalmic manifestations of human immunodeficiency
is a common process occurring in all HIV infected subjects38 39 virus infection. Neurol Clin 1991;9:55–72.
and the results of previous histological studies.10 19 The 13 Woods AD, Caputo MK. Neuro-ophthalmic manifestations of AIDS. Optom
Clin 1996;5:113–52.
significant difference observed between the mean latencies 14 Mwanza JC, Lysebo D, Kayembe DL, et al. Visual evoked potentials in konzo,
of subjects with and those without neurological symptoms a spastic paraparesis of acute onset in Africa. Ophthalmologica
may suggest that the earlier have more damage in the visual 2003;217:381–6.
pathways compared to the latter. There is currently consider- 15 Maschke M, Kastrup O, Esser S, et al. Incidence and prevalence of
neurological disorders associated with HIV since the introduction of highly
able evidence suggesting that, despite normal visual acuity, active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry
HIV infected subjects may have subclinical dysfunction of the 2000;69:376–80.
optic nerves/retrochiasmal visual pathways that can be 16 Sacktor N, Lyles RH, Skolasky R, et al. HIV-associated neurologic disease
incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology
detected using electrophysiological methods.33 35 Whether 2001;56:257–60.
alteration of electrophysiology found in this study originates 17 Goldsmith P, Jones RE, Ozuzu GE, et al. Optic neuropathy as the presenting
only from the optic nerve dysfunction remains unclear, since feature of HIV infection: recovery of vision with highly active antiretroviral
therapy. Br J Ophthalmol 2000;84:551–3.
a loss of cortical neurons has been found in asymptomatic 18 Larsen M, Toft PB, Bernhard P, et al. Bilateral optic neuritis in acute human
HIV positive subjects in early stages of the infection.40 These immunodeficiency virus infection. Acta Ophthalmol Scand 1998;76:737–8.
lesions as well as others affecting the retrogeniculate part of 19 Tenhula WN, Xu SZ, Madigan MC, et al. Morphometric comparisons of optic
the visual pathways, especially the primary visual cortex, may nerve axon loss in acquired immunodeficiency syndrome. Am J Ophthalmol
1992;113:14–20.
result in delay in both cortical processing and signal 20 Madigan MC, Sadun AA, Rao NS, et al. Tumor necrosis factor-alpha (TNF-
generation and thus in VEP abnormalities. alpha)-induced optic neuropathy in rabbits. Neurol Res 1996;18:176–84.

www.bjophthalmol.com
 Downloaded from bjo.bmjjournals.com on 26 August 2006
Neuro-ophthalmology of neuro-AIDS 1459

21 Lin XH, Kashima Y, Khan M, et al. An immunohistochemical study of TNF- 32 Engstrom JW, Lewis E, McGuire D. Cranial neuropathy and and the acquired
alpha in optic nerves from AIDS patients. Curr Eye Res 1997;16:1064–8. immunodeficiency syndrome. Neurology 1991;41:374.
22 Kolson DL, Lavi E, Gonzalez-Scarano F. The effects of human immuno- 33 Malessa R, Agelink MW, Diener HC. Dysfunction of visual pathways in HIV-1
deficiency virus in the central nervous system. Adv Virus Res 1998;50:1–47. infection. J Neurol Sci 1995;130:82–7.
23 Johnston JL, Miller JD, Nath A. Ocular motor dysfunction in HIV-1-infected 34 Pierelli F, Soldati G, Zambardi P, et al. Electrophysiological study (VEP, BAEP)
subjects: a quantitative oculographic analysis. Neurology 1996;46:451–7. in HIV-1 seropositive patients with and without AIDS. Acta Neurol Belg
24 Friedman DI, Feldon SE. Eye movement abnormalities in the AIDS dementia 1993;93:78–87.
syndrome. Neurology 1989;39:355. 35 Iragui VJ, Kalmijn J, Plummer DJ, et al. Pattern electroretinograms and visual
25 Merrill PT, Paige GD, Abrams RA, et al. Ocular motor abnormalities in human evoked potentials in HIV infection: evidence of asymptomatic retinal and
immunodeficiency virus infection. Ann Neurol 1991;30:130–8. postretinal impairment in the absence of infectious retinopathy. Neurology
26 Castello E, Baroni N, Pallestrini E. Neurotological auditory brain stem 1996;47:1452–6.
response findings in human immunodeficiency virus-positive patients without 36 Farnarier G, Somma-Mauvais H. Multimodal evoked potentials in HIV infected
neurologic manifestations. Ann Otol Rhinol Laryngol 1998;107:1054–60. patients. Electroencephalogr Clin Neurophysiol 1990;41:355–69.
27 Sweeney JA, Brew BJ, Keilp JG, et al. Pursuit eye movement dysfunction in 37 Smith T, Jakobsen J, Gaub J, et al. Clinical and electrophysiological studies of
HIV-1 seropositive individuals. J Psychiatry Neurosci 1991;16:247–52. human immunodeficiency virus-seropositive men without AIDS. Ann Neurol
28 Currie J, Benson E, Ramsden B, et al. Eye movement abnormalities as a 1988;23:295–7.
predictor of the acquired immunodeficiency syndrome dementia complex. 38 Sample PA, Plummer DJ, Mueller AJ, et al. Pattern of early visual field loss in
Arch Neurol 1988;45:949–53. HIV-infected patients. Arch Ophthalmol 1999;117:755–60.
29 Helweg-Larsen S, Jakobsen J, Boesen F, et al. Neurological complications and 39 Plummer DJ, Bartsch DU, Azen SP, et al. Retinal nerve fiber layer evaluation in
concomitants of AIDS. Acta Neurol Scand 1986;74:467–74. human immunodeficiency virus-positive patients. Am J Ophthalmol
30 Freeman WR, Lerner CW, Mines JA, et al. A prospective study of the 2001;131:216–22.
ophthalmologic findings in the acquired immune deficiency syndrome. 40 Tran Dinh YR, Mamo H, Cervoni J, et al. Disturbances in the cerebral
Am J Ophthalmol 1984;97:133–42. perfusion of human immune deficiency virus-1 seropositive asymptomatic
31 Palestine AG, Rodrigues MM, Macher AM, et al. Ophthalmic involvement in subjects: a quantitative tomography study of 18 cases. J Nucl Med
acquired immunodeficiency syndrome. Ophthalmology 1984;91:1092–9. 1990;31:1601–7.

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