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Publication Details Feroze KB, Gulick PG.

Human Immunodeficiency Virus (HIV) is a retrovirus which causes a multisystemic disease called Acquired Immune Deficiency Syndrome (AIDS). Ocular manifestations are commonly seen in HIV patients, and the first description of the same was by Maclean more than 20 years ago. HIV retinopathy is fairly common in HIV positive patients and is the most common cause of loss of vision in these patients.


HIV is a retrovirus which replicates in CD 4 T lymphocytes transmitted by exposure to blood and other body fluids. The natural history of an untreated HIV infected person can be divided into three stages namely, stages of primary infection, clinical latency and finally the stage of opportunistic infections, called AIDS. CDC defines AIDS as being present when there is an AIDS-defining disease or a CD4 T cell count less than 200/microliters. Retinopathy in HIV/AIDS may be due to microvasculopathy or opportunistic infections or malignancies. HIV microvasculopathy is considered to be the commonest posterior segment HIV manifestation and is seen in 40% to 60% of HIV-positive patients. Image result for cytomegalovirus (CMV) retinitis is thought to be one of the commonest vision-threatening posterior segment manifestation of HIV, but its incidence is declining in the highly-active antiretroviral therapy (HAART) era.


As of December 2006, the WHO estimates that, globally, there are about 39.5 million people infected with HIV. Studies suggest that between 5% to 25% of all HIV patients in developing countries may become blind in their lifetime. Diseases of the retina and choroid are extremely common in HIV patients and may cause visual loss. It is suggested that greater lifespans of patients with HIV result in increasing numbers of patients with opportunistic infections of the retina. There is also a difference in the infection patterns seen in developed and developing countries. CMV retinitis is less common in developing countries compared to developed countries and the HIV infected in the developing countries are more prone to infections by toxoplasma, tuberculosis (TB), and herpes zoster virus (HZV). This difference reflects more exposure to these causative agents, differences in HIV subtypes and higher death rates early in the course of the disease in the developing world.


Ocular involvement in HIV occurs most commonly due to opportunistic infections and neoplasms. Opportunistic infections like CMV retinitis occur with a significantly reduced CD4 T-cell count. Unlike other diseases, ocular infection in these immunosuppressed patients is associated with minimal inflammatory signs. HIV microvasculopathy, which is also sometimes called HIV retinopathy, is thought to be due to either immune complex deposition, increased plasma viscosity or invasion of vascular endothelium by HIV. Its prevalence is inversely proportional to the CD4 count.

Opportunistic infections in the posterior segment are manifestations of disseminated disease in AIDS and can manifest as retinitis or choroiditis. Retinitis is more commonly seen compared to choroiditis. Retinitis in quiet eyes occurs with lower CD4 counts and is most commonly due to CMV or progressive outer retinal necrosis (PORN) whereas retinitis in an inflamed eye is associated with higher CD4 counts and may be due to acute retinal necrosis (ARN), toxoplasmosis, syphilis, or late stages of cryptococcosis.

Unusual malignancies have also been reported in the posterior segment of patients suffering from HIV.

The institution of HAART has caused a dramatic improvement in the immune status of HIV infected individuals and a change in the clinical presentation and course of opportunistic infections. However improvement in immunity may be associated with an inflammatory response called Immune recovery uveitis.

History and Physical

Microvasculopathy, the most common ocular manifestation of HIV, is seen in 40% to 60% of HIV positive patients and is associated with low CD4 counts. Most patients are asymptomatic. Clinical findings include cotton wool spots at the posterior pole. It may be associated with intraretinal hemorrhages and microvascular changes like microaneurysms and telangiectasia. It can be differentiated from CMV retinitis by the presence of fewer hemorrhages and the absence of subtle iritis or vitritis.

Large vessel occlusions like central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and branch retinal artery occlusion (BRAO) are infrequently seen and may be associated with a viral retinitis.

CMV retinitis is the commonest ocular opportunistic infection in AIDS patients. Before the introduction of HAART, it was a very common cause of blindness in HIV/AIDS  and remains so in developing countries. There are three clinical forms of CMV retinitis. The classical form also called the pizza or cottage cheese with ketchup retinopathy is characterized by confluent areas of retinal necrosis with hemorrhages seen in the posterior pole. These lesions enlarge and may coalesce and ultimately lead to full thickness retinal necrosis, gliosis, and pigment epithelial atrophy. Patients may present with loss of visual field or acuity. The second form, the indolent variety, is characterized by granular peripheral retinal lesions with little or no hemorrhages. The third form is called frosted branch angiitis, which is characterized by marked vascular sheathing. Loss of vision in CMV retinitis can occur due to the direct involvement of macula or optic nerve, RD and also due to immune recovery uveitis. Widespread use HAART has caused a change in the natural history of CMV retinitis, leading to marked reduction in the incidence of this condition and clinical findings not seen in classical CMV retinitis like AC and vitreous inflammation.

Retinal whitening and hemorrhages characterize necrotizing viral retinitis, but the lesions are usually multifocal, progress rapidly and may be associated with skin lesions. There are two clinical forms: ARN and PORN. ARN is characterized by peripheral retinal necrosis, associated with marked anterior uveitis and vitritis. Pain is usually seen, associated with blurred vision and floaters. Multifocal, deep retinal infiltrates, with minimal vitritis characterize PORN.

Toxoplasma retinochoroiditis in HIV patients is usually bilateral and multifocal and may be associated with central nervous system (CNS) involvement. The retinal lesions may resemble CMV retinitis, but have fewer hemorrhages and marked intraocular inflammation.

Ocular syphilis is seen in 2% of patients and may present as anterior segment inflammation or diffuse intraocular involvement. Pneumocystis carinii choroiditis is another opportunistic infection, characterized by bilateral, multifocal, yellowish, choroidal lesions, associated with a clear vitreous. Cryptococcal choriditis may also be seen. Mycobacterium tuberculosis may cause the development of multifocal choroidal tubercles, mainly at the posterior pole.

Patients with CMV retinitis on HAART may suffer from a condition called immune recovery uveitis which causes dimunition of vision and is characterized by cataract, vitritis, macular edema, optic disc edema, epiretinal membrane and proliferative vitreoretinopathy. It is the leading cause of new visual loss in persons with AIDS and is seen in about 16% to 63% of HAART responders. The severity of inflammation is dependant on the immunity, severity of CMV retinitis, CMV antigen load and previous treatment.


A thorough history, disease progression by monitoring CD 4 counts, slit lamp examination and dilated fundoscopy is useful. The CD4 T-cell count and now more recently viral load can be taken as a predictor of ocular involvement in HIV patients. Visual acuity, visual field testing, testing of ocular movements, pupillary examination and fundus examination are important in detecting the various infections and other conditions associated with HIV. Posterior segment involvement in HIV patients can be diagnosed by dilated fundus examination with a direct or indirect ophthalmoscope, and investigations may be done, for example, VDRL test, FTA-ABS test, and tests for TB.

Treatment / Management

HIV microvasculopathy is usually asymptomatic and does not require any treatment.

CMV retinitis is treated with drugs such as valganciclovir, oral or intravenous ganciclovir, ganciclovir implant, fomivirsen, foscarnet, and cidofovir.

Necrotising herpetic retinitis requires aggressive treatment with antivirals. ARN is managed with systemic acyclovir, followed by barrage laser photocoagulation after resolution of retinitis to prevent retinal detachment.

Treat retinal choroiditis with pyrimethamine and sulfonamides; steroids are not indicated.

Pneumocystis choroiditis can be treated with systemic pentamidine, trimethoprim, and sulfamethoxazole or dapsone.

Fluconazole maintenance therapy is recommended for prophylaxis against cryptococcosis for all HIV  patients.

Anti-TB drugs are used for ocular tuberculosis and penicillin for ocular syphilis.

Pearls and Other Issues

With the widespread implementation of HAART and advent of better medications, the lifespan of HIV patients is increasing. They are also more prone to develop the ocular manifestations and at risk for visual loss. Comprehensive eye examination in HIV infected individuals should be conducted. Health education regarding the ocular manifestations and complications will increase awareness and reduce morbidity.


To access free multiple choice questions on this topic, click here.


1.Luo J, Jing D, Kozak I, Huiming Z, Siying C, Yezhen Y, Xin Q, Luosheng T, Adelman RA, Forster SH. Prevalence of ocular manifestations of HIV/AIDS in the highly active antiretroviral therapy (HAART) era: a different spectrum in Central South China. Ophthalmic Epidemiol. 2013 Jun;20(3):170-5. [PubMed]2.Chiotan C, Radu L, Serban R, Cornăcel C, Cioboată M, Anghelie A. Posterior segment ocular manifestations of HIV/AIDS patients. J Med Life. 2014 Sep 15;7(3):399-402. [PMC free article] [PubMed]3.Banker AS. Posterior segment manifestations of human immunodeficiency virus/acquired immune deficiency syndrome. Indian J Ophthalmol. 2008 Sep-Oct;56(5):377-83.[PMC free article] [PubMed]4.Moraes HV. Ocular manifestations of HIV/AIDS. Curr Opin Ophthalmol. 2002 Dec;13(6):397-403. [PubMed]5.Robinson MR, Ross ML, Whitcup SM. Ocular manifestations of HIV infection. Curr Opin Ophthalmol. 1999 Dec;10(6):431-7.[PubMed]6.Cunningham ET, Margolis TP. Ocular manifestations of HIV infection. N. Engl. J. Med. 1998 Jul 23;339(4):236-44. [PubMed]

Publication Details

Author Information


Kaberi B. Feroze1; Peter G. Gulick2.


1 King Faisal University2 Michigan State University

Publication History

Last Update: October 27, 2018.


Copyright © 2018, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license, and any changes made are indicated.


StatPearls Publishing, Treasure Island (FL)

NLM Citation

Feroze KB, Gulick PG. HIV, Retinopathy. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-.



Colour vision in AIDS patients without HIV retinopathy

Author links open overlay panelJoergSommerhalderaEdoardoBaglivoabChristineBarbeyaBernardHirschelbAndreRothaMarcoPelizzoneaShow morehttps://doi.org/10.1016/S0042-6989(98)00011-XGet rights and contentUnder an Elsevier user licenseopen archive


Patients suffering from AIDS develop ocular complications, the most frequent being HIV retinopathy. It is however not clear, if functional visual impairments can be observed as early indicators of ocular complications, before clinical diagnosis of HIV retinopathy is made at fundus examination. To address this issue, we measured colour vision in a group of 49 AIDS subjects with normal clinical fundi using the `two equation method'. This method, combining red-green Rayleigh and the blue-green Moreland metameric matches, enables more complete and quantitative assessments of colour vision than those based on pigmentary tests. Data were collected on our computer controlled colorimeter and compared to those of normal subjects. While most AIDS subjects without HIV retinopathy demonstrated normal colour vision, a significant portion of them had wider matches than normal subjects (11% for the Rayleigh equation and 16% for the Moreland equation). Furthermore, matching ranges of the Moreland equation were significantly correlated with CD4 lymphocyte counts. Patients with low CD4 values tended to produce larger matching ranges than the patients with high CD4 values. A within subject study on 17 patients confirmed this trend and showed that the patients who increased/decreased their CD4 blood counts generally improved/impaired their colour discrimination in the Moreland match. No such correlation was found between the matching ranges of the Rayleigh equation and the CD4 counts. These results show that colour discrimination is slightly reduced in some AIDS subjects, although there are no detectable ocular complications. They also suggest two different types of colour vision impairments in AIDS patients without retinopathy: one reversible process affecting colour discrimination in the blue-green range; and another irreversible process affecting colour discrimination in the red-green range.


AIDSColour discriminationColour matchingColour vision testing

1. Introduction

Since 1982, it has become obvious that 90% of the patients suffering from Acquired Immunodeficiency Syndrome (AIDS) develop ocular complications [1]. Among ocular manifestations, HIV retinopathy represents the most common manifestation observed in these patients and is clinically detected in approximately two thirds of them [2]. Some studies have demonstrated that these anomalies are present in all patients when tested by fluorescein angiography or at post-mortem examination 3, 4. It remains unclear, however, if HIV retinopathy is the consequence of an infection of the vascular endothelium by HIV, the consequence of vascular damage resulting from circulating immune complexes, the consequence of an abnormal retinal blood flow, or a mixture of these.

Recently various authors have reported deficits in colour vision in AIDS patients. Quiceno et al. [5]found significantly higher error scores for the Farnsworth 100-Hue test in AIDS patients than in patients with AIDS related complex, HIV-positive patients or normal controls. They did not identify a specific axis for these colour vision impairments but correlated them with HIV retinopathy. Geier et al. [6]confirmed this observation when they found a clear correlation between colour contrast sensitivity in all three axis and the severity of HIV retinopathy (number of cotton wool spots). They also found (weaker) correlations between Walter Reed staging and colour contrast sensitivity, or between CD4 lymphocyte counts and colour contrast sensitivity. Finally, Kozak and Bullimore [7]found that even HIV-positive patients without HIV retinopathy can have S-cone/tritanopic abnormalities. Possible explanations for the mechanisms leading to such colour vision impairment were largely discussed in these papers but no certain etiologic factor has been determined up to now. However, colour vision impairments in patients with normal clinical fundi may be early indicators for upcoming ocular involvement in AIDS disease.

The aim of this study was to find out whether measurable modifications of colour vision in AIDS patients without clinical HIV retinopathy could be observed using the `two equation method'. This method, which combines the red-green Rayleigh equation and the blue-green Moreland equation, is based on metameric colour matches 8, 9. It was demonstrated 10, 11, 12, 13that metameric matches enable more powerful quantitative assessments of normal and defective colour vision than pseudo-isochromatic or arrangement tests (e.g. Farnsworth 100-Hue, Ishihara plates or tests on computer graphics systems).

2. Methods

2.1. Subjects

49 Patients (13 females and 36 males, 94 eyes) with AIDS attending the HIV/AIDS Clinic of the Geneva University Hospital participated in this study. Age ranged from 29 to 49 years (mean and median age 37 years). CD4 lymphocyte counts ranged from 4 cells/ml to 600 cells/ml (median 70 cells/ml). All patients were Caucasians except two of Afro-Caribbean origin.

The patients were selected on the basis of two complete ocular examinations (visual acuity, slit-lamp biomicroscopy, tonometry, and direct and indirect ophthalmoscopy) performed by one of us (EB). The first examination enabled us to preselect patients showing no ocular complication. The second examination, performed one month later, served as a control and only patients showing no ocular complication at both examinations were included in the study. At the time of participation in this study, none of them had an acute opportunistic infection anywhere and all of them had normal clinical fundi. Inclusion criteria were: (1) age of 18 years or more; (2) visual acuity of 0.8 or better; and (3) normal clinical fundi. Exclusion criteria were: (1) a history of congenital or acquired eye disease; (2) diabetes; (3) drug abuse; (4) myopia demanding a correction of more than −3D; and (5) other diseases influencing colour vision (e.g. vascular eye diseases related to arterial hypertension or sudden hearing loss). Informed consent was obtained for each patient and a good motivation for the test was demanded. When tested all patients were on customized individual anti-retroviral therapy such as Bactrim® (trimethoprim-sulfamethoxazole), Retrovir® (AZT) (Geier et al. [14]reported in a case report on two patients a temporary alteration of tritan colour contrast sensitivity at the beginning of Zidovudine (AZT) treatment; none of our patients was at the beginning of an AZT treatment), 3TC® (Lamivudine), Zerit® (Stavudine) or Hivid® (Zalcitabine) and some of them received protease inhibitors such as Invirase® (Saquinavir), Norvir® (Ritonavir) or Crixivan® (Indinavir).

All patients had one full colour vision examination. Furthermore, we asked the patients to come back for a second test to investigate possible individual changes in their colour vision. Only 17 patients (34 eyes) out of 49 actually came back for a second examination. The time between the first and second test varied from 2 to 20 months.

2.2. Colour vision assessment and statistical analysis

All colour vision tests were conducted by the same person (JS) on our laboratory computer-controlled anomaloscope (a commercial version of this instrument is now available from Interzeag AG (Schlieren, Switzerland) but the 7° observation field size is however not yet implemented in this miniaturised instrument) with four independent light channels [15]. The Rayleigh equation (670+545≡589 nm) on a 2° circular observation field was always tested first. Afterwards the Moreland equation (490+436≡desaturated 480 nm) was tested on a 7° observation field. After each colour vision test the optical density of the crystalline lens was measured with the Lens Opacitometer 701™ (the Lens Opacitometer 701™ is available from Interzeag, Switzerland; for more technical details see [16]) to exclude colour vision impairment due to abnormal optical lens density.

The colour vision testing procedure was exactly identical to the one used for a previous normal population study [17](a more detailed description of the testing procedure itself and the statistical analysis of the subject's responses can be found in 18, 19). The result of the colour vision test are two values expressed on a 0–100 scale: the match-mid-point (MMP), assessing the perceptual relationship between the colours defined by the mixture field primaries (used to equalize the reference primary), and the matching range (MR) assessing colour discrimination around the reference primary.

The data of the previous normal population study (100 subjects, mean age 29 years) were used to establish reference distributions and limits for normal subjects. Student's t-test was used to assess the statistical significance of differences between group means, while the F-test was used to compare variances of group distributions. The significance of correlations between CD4 blood counts and colour vision results was tested using correlation coefficient testing [20].

3. Results

The results of our colour vision measurements on the AIDS subjects are summarized in Fig. 1 (the MMP values of our reference normal population were slightly shifted towards the lower wavelength primary, primarily to compensate for the mean age difference of 8 years between the AIDS patients and the normal subjects; for the influence of age on colour vision results see 21, 22, 23). While most AIDS patients without retinopathy had normal colour vision, 10 (11%) out of 92 eyes exceeded the normal limits in the Rayleigh equation and 15 (16%) out of 92 eyes exceed the normal limits in the Moreland equation. Surprisingly, only 3 eyes showed abnormal results in both equations. Since the normal limits were computed to be exceeded in only 5% (by definition) of the cases in a normal population, abnormal results appear to be slightly more frequent in our AIDS patient data. More detailed statistical analysis were done to see if this trend was significant.

Fig. 1. Colour vision in 49 AIDS patients. MR vs. MMP. The triangle indicates the region of possible results. The rectangle at the bottom indicates the region of normal results. Results lying outside the rectangle are considered as abnormal colour vision results.

3.1. MMP

Histograms of all the MMP values measured on the AIDS subjects are presented in Fig. 218, 19. These data were fitted to a normal-distribution and compared to those obtained (by exactly the same procedure) on normal subjects. There is no statistically significant difference between the MMP distributions, either for the Rayleigh equation (unpaired t-test P=0.36) or for the Moreland equation (unpaired t-test P=0.69).

Fig. 2. Histograms for the MMP of 49 AIDS patients. A normal distribution is fitted to the data and compared with the distribution for normal subjects.

3.2. MR

Histograms of the MR values measured on the AIDS subjects are presented in Fig. 3. These data were fitted to a log-normal distribution (for more details concerning our data analysis using log-normal distributions see [17]). Comparisons with the distributions obtained (with exactly the same procedure) on normal subjects reveal that the AIDS patients had significantly larger MRs on both equations (unpaired t-test P=0.028 for the Rayleigh equation; P=0.002 for the Moreland equation). A close look at the fitted curves shows that the log MR distribution for the Moreland equation is simply shifted towards higher values, while the log MR distribution of the Rayleigh equation is not only slightly shifted towards higher values but also significantly larger than the log MR distribution for the normal subjects (F-test P=0.006).

Fig. 3. Histograms for the log MR of 49 AIDS patients (the finite size of the smallest steps in the iterative algorithm determining the MR results in artefactual clustering of data for extremely small matching ranges, therefore we ignored these data before fitting log MR with a normal distribution which explains the empty lower parts under the fitted normal distributions). A normal distribution is fitted to the data and compared with the corresponding distribution for normal subjects.

3.3. Correlation with the CD4 blood count

The only parameter which was found to be significantly correlated with the CD4 lymphocyte counts is the MR of the Moreland equation (Fig. 4a, P<0.05) (we could not find any significant correlation between colour vision results and other parameters, such as best corrected visual acuity or lens opacity). Patients with low CD4 values have a tendency to produce larger MRs than patients with high CD4 values. Moreover, for the 17 patients tested twice, we found a significant correlation between the ΔMR of the Moreland equation and ΔCD4 counts (Fig. 4b, P=0.01), confirming the correlation between the MR of the Moreland equation and the CD4 blood counts. CD4 count improvement results generally in MR improvement. It is interesting to note that in the case of these 17 patients, we have a within subject study where individual variability of colour vision does not smear out the results.

Fig. 4. (a) Log MR for the Moreland equation vs. CD4 lymphocyte counts (artificially low MR values were uniformly fixed at a MR value of 0.4 units; there is no change in significance if we ignore these data when computing the regression). CD4 values are indicated on a logarithmic scale. (b) Log MR change in the Moreland equation vs. CD4 count change for 17 AIDS patients. Positive values indicate higher values at the second examination (positive ΔCD4 values≡improvement of the CD4 lymphocyte counts; negative Δ log MR values≡improvement of colour discrimination).

4. Discussion

This study shows a slight impairment of colour vision in some AIDS patients with normal clinical fundi. In these cases, the effect of the HIV disease is essentially reflected by a reduced colour discrimination in the Moreland and/or the Rayleigh equations. Our results for the Moreland equation confirm earlier results by Kozak and Bullimore [7]who found reduced S-cone contrast sensitivity for HIV patients without clinical signs and a very recent study of Muller et al. [24]who have reported an elevated error scores for the Farnsworth–Munshell 100-Hue test in HIV patients without HIV retinopathy.

We found significant correlations between the CD4 blood count values and colour discrimination in the Moreland equation: (1) in all tested patients, higher CD4 blood counts were significantly correlated with better colour discrimination; and, (2) in the 17 patients tested twice, improvements/impairments in CD4 blood counts were significantly correlated to improvements/impairments of colour discrimination. Geier et al. [6]had found a significant correlation between CD4 blood counts and tritan/protan colour contrast sensitivity in a group of subjects including patients with HIV retinopathy, while Mueller et al. [24]did not find any significant correlation between Farnsworth 100-Hue error scores and CD4 blood counts in their subjects without HIV retinopathy. The discrepancy of our results with the latter study is probably due to the lesser sensitivity and specificity of the Farnsworth 100-Hue test.

The observed colour vision impairment in AIDS patients without HIV retinopathy and the correlation between their MR results for the Moreland equation and CD4 lymphocyte counts can not indicate the exact mechanisms leading to HIV retinopathy. Some medicaments are known to affect colour vision [25]. Although the medication might cause the observed impairments in colour discrimination, this is very unlikely, because increases in CD4 blood counts were correlated with improved colour discrimination. Furthermore, these improvements suggest that the pathological processes affecting colour vision could be (at least partially) reversible.

While colour vision was impaired in a similar number of patients in the Rayleigh and in the Moreland equation, it is interesting to note that only 3 cases had abnormal colour vision results in both equations. Moreover, in contrast to the Moreland equation, colour discrimination in the Rayleigh equation was not significantly correlated with the CD4 counts. As a consequence, one may postulate two types of colour vision impairment in AIDS patients without HIV retinopathy: one process, affecting colour discrimination in the Moreland equation, which is reversible; and a second process, affecting colour discrimination in the Rayleigh equation, which is apparently irreversible (a learning process would not only affect the Moreland equation but also the Rayleigh equation and it would not be correlated to CD4 counts, thus, a learn effect can therefore be excluded). This hypothesis needs to be confirmed by more measurements and the long term follow up of AIDS patients.

Impairment of colour vision can be an indicator for subsequent ocular complications. Early detection of such ocular complications is becoming more and more important since successful research in AIDS treatment leads to longer life expectation for these patients.


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