Journal of Medical Academics
Volume 6 | Issue 2 | Year 2023

Ocular and Neuro-ophthalmic Conditions Causing Visual Impairment in Human Immunodeficiency Virus: A Case Series

Sumit Arora1, Sharmila Dudani2, Charu Mohan3, Mamadur MR Shankar4, Piyush Chaturvedi5, Athul Hema Kumar6

1,3,6Department of Medicine, Army College of Medical Sciences, Delhi, India

2Department of Pathology, Army College of Medical Sciences, Delhi, India

4Department of Surgery, Army College of Medical Sciences, Delhi, India

5Department of Ophthalmology, Base Hospital Delhi Cantonment, Delhi, India

Corresponding Author: Charu Mohan, Department of Medicine, Army College of Medical Sciences, Delhi, India, Phone: +91 9810946939, e-mail:

Received: 08 November 2023; Accepted: 08 December 2023; Published on: 30 December 2023


Introduction: Human immunodeficiency virus (HIV) is a retrovirus that causes a multisystem disease namely acquired immunodeficiency syndrome (AIDS). Visual impairment related to HIV could be caused by opportunistic infections in the eye or neuro-ophthalmic axis, vascular abnormalities, neoplasms, and adverse medication effects.

Materials and methods: We carried out a retrospective analysis of the clinical, radiological, laboratory, immunovirological, therapeutic, and survival data of 1,480 HIV-positive patients from 2016 to 2022 to look for cases presenting with significant visual loss in one or both eyes attributable to HIV infection at our center. We have presented descriptive details of six such patients in tabular form.

Results: Out of the 1,480 people living with HIV/AIDS (PLHA) screened 14 presented with a significant visual loss out of which 10 had cytomegalovirus (CMV) retinitis, two patients had cortical blindness secondary to progressive multifocal leukoencephalopathy (PMLE) one patient each had cryptococcal meningitis, and ocular syphilis.

Conclusion: Cytomegalovirus (CMV) retinitis remains the commonest cause of visual loss in PLHA in the combination antiretroviral therapy (cART) era. Neuro-ophthalmic diseases are an important cause of visual loss in HIV infection. Early diagnosis through routine ophthalmologic screening, serological screening for syphilis, and cryptococcal infection of patients with low clusters of differentiation 4 (CD4) is essential to prevent visual loss in these subsets of patients.

How to cite this article: Arora S, Dudani S, Mohan C, et al. Ocular and Neuro-ophthalmic Conditions Causing Visual Impairment in Human Immunodeficiency Virus: A Case Series. J Med Acad 2023;6(2):61–65.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Cryptococcal meningitis, Human immunodeficiency virus, Neuro-ophthalmic, Progressive multifocal leukoencephalopathy, Syphilis, Visual loss


Human immunodeficiency virus (HIV) is a retrovirus that causes a multisystem disease namely acquired immunodeficiency syndrome (AIDS). It replicates in clusters of differentiation 4 (CD4) T lymphocytes and transmission occurs through sexual intercourse, blood, and blood products, infected needles, through the transplacental route, and mother’s milk.1 Studies suggest that approx 5–25% of all HIV patients become blind in their lifetime in developing countries.2

Visual impairment related to HIV could be caused by opportunistic infections in the eye or neuro-ophthalmic axis, vascular abnormalities, neoplasms, and adverse medication effects.2 Introduction of highly active antiretroviral therapy (HAART) has changed the prevalence and pattern of HIV-related ocular manifestations.2

Ocular structures affected by HIV include the adnexa, anterior segment, posterior segment, and orbit along with neuro-opthalmological manifestations.

Adnexal involvement in HIV-infected persons may include herpes zoster opthalmicus (HZO), Kaposi’s sarcoma, molluscum contagiosum, and conjunctival microvasculopathy. HZO is seen in 5–15% of HIV patients and may be associated with the simultaneous occurrence of keratitis, scleritis, uveitis, retinitis, or encephalitis.

Anterior segment involvement in HIV includes keratoconjunctivitis sicca, keratitis, and iridocyclitis. Keratoconjunctivitis sicca or dry eyes is seen in 20% of HIV patients. Keratitis is rare, occurring in <5% of cases but can lead to loss of vision. Iridocyclitis is common in HIV and may be seen in association with toxoplasmosis, syphilis, tuberculosis, bacterial or fungal infections as well as following medications like rifabutin and cidofovir.

Posterior segment involvement in HIV is a common cause of visual loss. These include retinal microangiopathy, cytomegalovirus (CMV) retinitis, varicella zoster virus (VZV) retinitis, toxoplasma chorioretinitis, and bacterial and fungal retinitis.3 CMV retinitis is seen in 30–40% of HIV-infected individuals with CD4 counts <100/mm.4 Ocular syphilis is seen in 2% of patients and may present with anterior segment inflammation or diffuse intraocular involvement.

Neuro-ophthalmic manifestations are seen in 10–15% of patients and may be caused by cryptococcal meningitis, neurosyphilis, central nervous system (CNS) lymphoma toxoplasmosis, and progressive multifocal leukoencephalopathy (PMLE). Orbital involvement is rare in HIV and may be due to orbital lymphoma, and Aspergillus orbital cellulitis.

Human immunodeficiency virus (HIV) has been isolated from tears, cornea, vitreous, and chorioretinal tissue in affected persons. A >90% of HIV-infected individuals live in developing countries. India and the African continent have seen an exponential increase in the number of people infected with HIV, contributing to more than two-thirds of the world’s population of HIV-infected individuals.5

Though isolated reports regarding neuro-ophthalmic manifestations in HIV from India are available,6,7 this case series is a representative analysis of the clinicopathological spectrum, CD4 counts, HIV RNA levels, and outcomes of ocular and neuro-ophthalmic manifestations in HIV patients presenting with significant visual loss in at least one eye.


Approval from the Institutional Ethics Committee was obtained and an observational, retrospective single-center study in accordance with the tenets of the Declaration of Helsinki was undertaken. Only proven incident cases of HIV patients who reported significant visual loss attributed directly or indirectly to HIV infection were included. We analyzed the ophthalmological, radiological, laboratory, immune-virological, therapeutic, and survival data of 1,480 HIV-positive patients from 2016 to 2022. Of these 14 patients presented with severe visual loss in one or both eyes attributable directly or indirectly to HIV infection from which we selected a series of six patients who represented a spectrum of lesions in the eye and neuro-ophthalmic axis for descriptive analysis. Archived material (clinical data, records of ophthalmic examination) of these patients were also reviewed.

Eye examination findings were documented from records of visual acuity tests, intraocular pressure measurement, fundus examination, and pupillary examination. Adnexa as well as cranial nerves had also been checked for any abnormality. Snellen visual acuity charts, Schiotz tonometer, indirect ophthalmoscope, and slit lamp biomicroscope were the tools that had been utilized for ophthalmic examination. CD4 counts were determined by using BD FACS Canto II flow cytometry (BD Biosciences, United States of America) and HIV viral load [real-time polymerase chain reaction (RT-PCR)] by GeneXpert system, CBNAAT by Cepheid India Pvt Ltd.

Magnetic resonance imaging (MRI), computed tomography (CT) scan, visual evoked potential (VEP), cerebrospinal fluid (CSF), PCR for viral DNA, sputum examination, mycobacterium tuberculosis (MTB) GeneXpert, electroencephalogram (EEG), and serologic studies were done wherever indicated.


Among the 1,480 HIV patients whose data was reviewed, 14 HIV patients reported significant visual loss attributable to HIV-related illness, and six patients were selected for descriptive analysis in the study.

Clinical presentation of sudden or slowly developing loss of vision in one or both eyes was seen in all patients. We had 10 cases of CMV retinitis (of which two have been included in the tabular analysis as representative) and two cases of PMLE, with the PMLE patients presenting with cortical blindness due to occipital lobe involvement, one case each of ocular syphilis and cryptococcal meningitis with retrobulbar neuritis. The fundus images of the patients with CMV retinitis and ocular syphilis are attached as Figures 1 and 2. The MRI of orbits taken in patients with cryptococcal meningitis and the MRI brain of PMLE patients are attached as Figures 3 and 4, respectively.

Fig. 1: Fundus image of patient with cytomegalovirus retinitis, showing large areas of retinal necrosis with interspersed intraretinal hemorrhage. The area beyond necrosis shows peri-phlebitis and frosted branch angiitis

Fig. 2A and B: (A) Fundus image of patient with ocular syphilis showing vitritis with optic disc edema and peripapillary hemorrhages suggestive of active optic neuritis; (B) Fundus image of other eye of same patient with ocular syphilis, also showing a similar picture of active vitritis with additional features of vasculitis, retinitis, and intraretinal hemorrhage

Fig. 3: The MRI of orbit showing optic nerve edema (red arrow) in a patient of cryptococcal meningitis with retrobulbar neuritis

Fig. 4: The MRI brain T2 weighted MRI image showing hyperintensities in the left occipital lobe neuritis

The clinical case summary of all six patients is outlined in Table 1. In the described patients, visual loss was the presenting symptom of HIV in five out of six patients, and HIV status was detected on further evaluation. One patient presented with CMV retinitis-related visual loss while on a failing antiretroviral therapy (ART) regime. The median age of patients was 38.5 years [interquartile range (IQR) 16–58]. Five out of six patients were male. The median CD4 count was 67/mm3 (IQR 52–231). Median HIV RNA at presentation was 1 × 105 (IQR 66 × 103–10 × 105). None of the patients reported complete visual recovery in both eyes and four out of six patients reported variable visual recovery. Mortality was seen in two patients with PMLE due to comorbidities unrelated to the disease of the neuro-ophthalmic axis.

Table 1: The clinical case summary of all six patients is outlined
S. No. Age/sex Outcome Clinical presentation Treatment given CD4 HIV RNA Cause Modality of diagnosis
1 16/Female 30% recovery of vision Fever, cough, and weight loss in 3 months
Headache, vomiting, and sudden bilateral loss of vision
l-amphotericin, fluconazole and flucytosine 67 4 × 105 Retrobulbar neuritis due to cryptococcal meningitis CSF/MRI
2 29/Male 30% recovery in one eye Acute onset visual loss LE, followed by RE over 1 week Intravitreal ganciclovir and oral valganciclovir 58 8.6 × 103 CMV retinitis Clinical and fundus
3 39/Male LE full recovery/RE poor recovery Acute loss of vision RE followed by LE Intravitreal ganciclovir, oral valganciclovir 108 6.6 × 104 CMV retinitis Clinical and fundus
4 58/Male Expired Fever, cough since 2 weeks. Abnormal behavior and diminished/loss of vision. Associated TB lung ART 67 1 × 107 PMLE MRI brain/CSF JC virus
5 38/Male Expired—cancer anal canal Abnormal behavior, visual loss, and Anton syndrome ART 52 1.28 × 105 PMLE MRI brain/CSF JC virus
6 48/Male LE—complete vision loss RE—full recovery Subacute loss of vision in both eyes over 2– 3 months Benzylpenicillin 231 7.3 × 104 Ocular syphilis Clinical and treponema pallidum
hemagglutination assay

CMV, cytomegalovirus; HIV-RNA expressed as copies/mL; PMLE, progressive multifocal leukoencephalopathy, JC virus, John Cunningham virus


Visual symptoms in HIV patients may afflict the anterior segment, posterior segment, ocular adnexa, or neuro-ophthalmic tract. They may be generated both by the HIV virus itself (microangiopathy, retinitis, and neuroretinal disorder), by opportunistic infections of the eye (CMV retinitis, toxoplasma, TB, and syphilis), or brain (cryptococcosis, TB, and PMLE) and tumors (lymphoma, Kaposi’s sarcoma, and squamous cell carcinoma).

Some studies have shown that ocular manifestations accompanied approximately 70–80% of HIV-positive patients before the introduction of ART.1 Interestingly, some workers have shown the prevalence of ocular manifestations to be higher in patients on ART therapy (32.6%) than those patients not on ART (17.9%).8

However, patients presenting with significant visual loss attributable to HIV-related illness are much less common. In our study, 0.95% of all patients screened at our center in the study period were detected to have significant visual loss due to HIV-related illness.

The median CD4 T-cell count in our study was 67 cells/mm3 and was much lower than the average CD4 T-cell count of 126 cells/mm in HIV patients who presented without visual manifestations indicating a poor immune status.1 A statistically significant negative correlation has been seen between ocular manifestations and CD4 T-cell count.7,9

Before the advent of ART, CMV retinitis was the commonest ocular manifestation in developed countries affecting 30–40% of HIV infected individuals. Though its incidence has declined significantly after the advent of successful treatment it still remains the commonest cause of visual impairment in HIV patients.4 Heiden and coworkers have reported CMV retinitis as a significant cause of HIV-related blindness accounting for almost 90% of cases.10 Our data suggests approximately 57% of patients having visual loss were due to CMV retinitis. CMV retinitis was a common manifestation in HIV patients from other centers in India as well in the pre-HAART and early post-HAART era with prevalence ranging from 17 to 19%,11,12 which has dropped to <2%13 and 0.54% of all patients at our center in the post-HAART era.

The CMV reaches the retina hematogenous and due to impaired CD4 function may proliferate in the retina. Visual loss can occur due to direct damage to the macula or optic nerve or retinal detachment. Twenty percent of patients with CMV retinitis may develop immune recovery uveitis (IRU) after ART initiation. It is observed that CMV retinitis, keratoconjunctivitis sicca, and retinal microvasculopathy occur commonly when the CD4 count falls below 100 cells/mm3. We have included two cases of CMV retinitis in descriptive analysis whose CD4 counts were 58 and 108 cells/mm, respectively which is in concordance with the observations of Sharma et al. who reported a significant inverse association of CMV retinitis and CD4 T-cell counts.7

In Africa, CMV retinitis is less common with prevalence rates ranging from 0 to 8.5%.8,10 Ocular findings in the case of visual acuity loss were the destruction of retinal tissue in the posterior pole ranging from 54 to 84% of cases and retinal detachment ranging from 26 to 63% of cases.14 Blindness from CMV is permanent and may occur even before the full destruction of the retina.10 However, in our study one patient with CMV retinitis recovered 30% vision in one eye with permanent loss of visual loss in the other eye, whereas the other patient had full recovery of vision in his left eye with permanent loss of visual loss in the other eye.

Though many of our patients present with HIV retinopathy none of them developed visual impairment and hence were not included in the study.

Progressive multifocal leukoencephalopathy (PMLE) is a progressive fatal demyelinating disorder associated with human polyomavirus JC and may occur as a complication of immunodeficiency states.15 In HIV patients, the risk factor for the development of PMLE is CD4 counts are <200 cells/mm3.

Our patients with PMLE had much lower CD4 counts of 67 and 52 cells/mm3, respectively, and HIV RNA viral load of 1.02 × 106 and 1.28 × 105, respectively. Visual loss was due to damage to the visual cortex in the occipital lobes.

Retrobulbar neuritis due to cryptococcal meningitis is a well-known cause of neuro-ophthalmic disorders in HIV patients, which may also present with papilledema as well as ocular motor nerve palsies.16 It is a common central nervous system fungal infection in patients with HIV and a major etiologic agent of chronic meningitis in this population.17 Our patient presented with cryptococcal meningitis with acute onset bilateral visual loss. Her ophthalmologic examination was normal except for left-sided lateral rectus palsy and MRI showed bilateral optic nerve swelling and edema. Loss of visual acuity is common in undeveloped areas and may be seen in up to 10% of patients with HIV and cryptococcus infections.18 This is in concordance with our findings as our patient also had only 30% recovery of vision. In contrast, loss of visual acuity is less often seen in developed countries.19

There is a reemergence of ocular syphilis in patients coinfected with HIV, which is seen in both developed and developing nations.20 Our patient presented with syphilitic posterior uveitis with progressive subacute visual loss in both eyes. Panuveitis seems to be the most common manifestation of ocular syphilis as shown in a study by Sudarshan et al.12 Other manifestations include vitritis, anterior uveitis, posterior uveitis, and diffuse retinitis. Vitritis and diffuse retinitis were seen with low CD4 counts (<100/mm3) whereas the not-so-common finding of classical placoid chorioretinitis was seen with higher CD4 counts (>400/mm). Though a good response to ART and systemic penicillin therapy is seen, recurrences and IRU may occur.12 Our patient had complete recovery of vision in one and partial recovery in the other eye.

We did not report any bacterial, mycobacterial, protozoal, or helminthic disease. Adnexal lesions, neoplasms, conjunctival microvasculopathy, as well as posttreatment manifestations were not seen.

Some workers have reported that viral infections like HZO, herpes simplex, and molluscum contagiosum are more common in India.5 We reported two cases of HZO but not lead to any permanent visual impairment.

Neoplasms were uncommon in the Indian setting. Kaposi’s sarcoma may be seen in up to 30% of patients in the United States.5 Kaposi’s sarcoma was not seen in the present study and is relatively uncommon in other studies from India. Squamous cell carcinomas of the conjunctiva, though uncommon in the developed world, maybe the first presenting sign in up to 50% of African patients.21 No such case has been reported in our study.


Ocular and neuro-ophthalmic manifestations are diverse and frequent in patients with HIV infection and as they are vision-threatening, tend to affect the quality of life. They are an indicator of the immune status of the patient as most are seen with low CD4 T-counts. CMV retinitis remains the commonest cause of visual loss in HIV though overall incidence of the disease may be declining. As the clinical presentations may be atypical, awareness and regular ophthalmic examination should be a part of the standard of care for HIV patients to prevent visual loss. Further prospective studies should be done to find out why some ocular findings are more common in our setting.


The study is limited by the small number of cases and the retrospective nature of data.


All authors contributed equally.


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