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1. OCULAR
MANIFESTATION
OF
HIV
GROUP 4

2. INTRODUCTION
The human immunodeficiency virus (HIV) is a virus that lowers the ability of your
immune system to fight against common infections and diseases. AIDS is a
condition in humans in which life-threatening infections can happen when your
immune system has been badly damaged by the HIV virus.1 HIV infection spreads
through sexual contact, the passing from mother to child through breast milk, or
the use of contaminated needles, blood products, or transfusions. It can be found
in these bodily fluids as both free virus particles and as a virus inside infected
immune cells. It infects vital cells such as helper cells or CD4+ cells (T cells) found
in the white blood cells of the human immune system, and its infection results in
variety of symptoms that can differ, depending on how long an individual has
been infected.2

3. HIV is treated with antiretroviral drugs (Known as ARVs), which help to prevent
the virus from multiplying within the body system, enabling it to heal, and
preventing any further damage. In essence, they are useful in prolonging and
improving a quality of life.3

4. HOW HIV SYSTEMATICALLY AFFECTS A
HUMAN BEING
Those who contract HIV for the first time may or may not become ill since they are
asymptomatic and hence in the second stage of the disease. When the virus
continues to spread throughout the body, the immune system gradually
deteriorates. HIV-positive people who are symptomatic experience flu-like
symptoms as fever, sore throat, swollen glands, or skin rashes. Moreover, they
might also develop diarrhoea, shortness of breath, or other generalized systemic
symptoms like fever and weight loss.
To fight infections, the immune system has a variety of white blood cells. HIV
targets the CD4 cells, a kind of white blood cell, specifically (T-cells). The immune
system depends on CD4 cells because they defend people against illnesses and
infections.

5. • HIV enters CD4 cells and replicates, or rather generates copies of, itself there. Following
the death of the CD4 cells, the new HIV copies seek out more CD4 cells to enter and re-
start the cycle. Nonetheless, the immune system produces more CD4 cells in an effort to
suppress HIV. However, the quantity of virus in the body increases and lowers the
number of CD4 cells when the body cannot produce CD4 cells quickly enough. A person
becomes ill at this point because the immune system can no longer regulate HIV.
• An individual's immune system is seriously damaged by HIV. There is a high chance of
developing serious illnesses and infections like AIDS (acquired immunodeficiency
syndrome) when the immune system is compromised.

6. Fig.1 From: The role of CD38 in HIV infection

7. HIV affects the following organ systems:
• Respiratory and cardiovascular system
– - HIV makes it difficult to combat
respiratory illnesses like the flu and the
common cold. In addition, it raises risks
for lung cancer and tuberculosis since
CD4 counts are low.
• Also, it raises the chance of developing
pulmonary arterial hypertension (PAH),
a condition marked by elevated blood
pressure in the arteries that carry blood
to the lungs. With time, PAH's stress on
the heart might lead to heart failure.
: Fig.2. Illustration by Maya Chastain

8. • Digestive system – HIV has an impact on the digestive system, which causes a
decrease in appetite and makes it challenging to eat appropriately, which leads to
weight loss. HIV can also cause oral thrush, a fungal infection that produces
inflammation and white spots on the tongue and inside the mouth, as well as
oesophageal inflammation that makes it difficult to swallow and eat
• Central nervous system (CNS)- Advanced HIV can damage the nerves, a condition
known as neuropathy, which can result in pain and numbness in the hands and feet.
It may also result in anxiety and sadness
• Integumentary system- HIV has a systemic impact on the integumentary system
because it causes rashes and eczema and makes a person more susceptible to
herpes viruses, such as herpes Zoster.

9. Although HIV affects a number of different systems in the body, 70–80% of people
experience ocular manifestations at some point in their lifespan. It may affect the
eye directly or indirectly through multiple opportunistic illnesses. HIV related ocular
manifestations can affect any part of eye from the anterior to posterior segments,
including the optic nerve and the optic tract. 6
ANTERIOR SEGMENT MANIFESTATIONS
The anterior segment of the eye is predisposed to disorders that involve the
conjunctiva, cornea and the iris in HIV infection. The most common complications
include infectious keratitis, dry eye, corneal dry toxicity, and uveitis, all of which
carry a high risk for vision loss, especially if they go unnoticed or are misdiagnosed.

10. INFECTIOUS KERATITIS
In HIV patients, it may be caused by viral, bacterial, fungal or protozoan infections.
Viral Keratitis: Varicella Zoster Virus(VZV) Keratitis is most common in HIV positive
patients, presenting with mild anterior uveitis, intraocular pressure, and iris
shrinkage.7 It does not usually involve dermatome( areas of your skin that are mainly
supplied by spinal nerves). Treatment involves Acyclovir but when Postherpetic
neuralgia is present, it is usually reduced with oral antidepressant or anaesthetic
cream.
Herpes simplex virus keratitis, which is less frequent than VZV keratitis and affects the
limbus, has larger dendrites and a higher recurrence rate when compared to patients
who have normal immune response. Sometimes it occurs without any dendrite
patterns. Treatment includes Acyclovir, and some of the topical options like
Vidarabine and Idoxuridine.

11. CORNEAL DRUG TOXICITY
Vortex keratopathy is the pattern associated with drug toxicity brought on mostly by
acyclovir, and clears up when the medication is stopped. Keratopathy is brought on by
substances with lipophilic characteristics, such as amiodarone and chloroquine.8
Fig. 3. Amiodarone-induced vortex keratopathy.
(Image courtesy of Francis S. Mah, MD.)

12. DRY EYE
20% of patients show a decreasingly changed breakup time test. This symptom may
be caused by a variety of factors, but the main one appears to be HIV-mediated
inflammation that destroys the major and accessory lacrimal glands.
ANTERIOR UVEITIS
More than 50% of individuals will experience anterior uveitis, making it a fairly
frequent symptom. VZV and HSV frequently cause mild iridocyclitis, whereas severe
inflammation is caused by toxoplasmosis retinochoroiditis and syphilis
chorioretinitis. 9 Treatment of these conditions is directed to the agents. Another
type of anterior uveitis is brought on by some medications, such as rifabutin, which
in one-third of patients results in iridocyclitis hypopyon, and also by cidofovir, which
in almost half of patients results in a moderate to severe inflammation of the
anterior chamber.7

13. POSTERIOR SEGMENT MANIFESTATIONS
HIV infection predisposes the posterior segment of the eye to conditions that affect
the retina, choroid, and optic nerve. These conditions are essentially divided into two
groups: those with infectious causes and those with non-infectious causes. HIV-
associated retinopathy and changes in the optic disc are two disorders with non-
infectious causes. Cytomegalovirus retinitis (CMVR), toxoplasmosis, and other
opportunistic infections are among the diseases having infectious cause.
MANIFESTATIONS DUE TO NON-INFECTIOUS INFECTIONS

14. HIV RETINOPATHY
It is a non-infectious microvascular condition which is best characterized by cotton
wool spots, retinal haemorrhages, Telangiectatic vascular changes and areas of
capillary non-perfusion.10
Cotton wool spots
Cotton-wool spots (CWS) are the most prevalent ocular micro-angiopathic signs and
symptoms of HIV, but they are non-specific and can occur in a wide range of illnesses,
including diabetes, hypertension, and anaemia.11 They are caused by a
circulatory destruction within tiny areas of the retina. The presence of CWS shows a
microvascular change in HIV/AIDS that is probably connected to the condition's high
levels of circulating immune complexes.

15. Fig.4. Cotton wool spots (Photo courtesy of Dr Linda
Visser)

16. Retinal haemorrhages
Retinal haemorrhages show up as flame-shaped spots when they affect the nerve
fibre layer and as dot-and-blot patterns when they affect the deeper layers of the
retina.14,15 They are less common than CWS and are thought to affect 30% of people
with advanced HIV. The retinal vessels resemble those of diabetic retinopathy,
which is characterized by thicker basement membranes, swelling of endothelial
cells, and pericyte necrosis. It is suggested that vascular damage includes the build-
up of immunoglobulins, direct HIV infection of endothelial cells, and hyper-viscosity
brought on by increased red blood cell aggregation.15
Telangiectatic vascular changes
Retinal telangiectasias are a rare group of idiopathic abnormalities of the retinal
vasculature that are characterized by irregular dilation, microaneurysms, and
vascular failure. They can occur in people with HIV.16

17. MANIFESTATIONS DUE TO OPPORTUNISTIC INFECTIONS
Individuals with advanced HIV may be affected by several opportunistic infections
of the retina and choroid. Cytomegalovirus retinitis is the most common one in
individuals with HIV.
CYTOMEGALOVIRUS RETINITIS
Patients who are immunosuppressed are more likely to develop the serious, vision-
threatening condition known as cytomegalovirus retinitis (CMVR). The frequency of
CMVR in HIV patients has significantly decreased with antiretroviral therapy,
besides the fact it is still the most prevalent ocular opportunistic infection and the
main cause of blindness in this population. It may also result from other
immunosuppressive conditions, such as iatrogenic immunosuppression,
hematologic malignancies, and organ transplantation

18. Although CMV infection can occur in healthy people, it is unusual to have
symptomatic infections in people who are not immunologically compromised. In 75–
85% of cases, CMV presents as an opportunistic infection. CMV retinitis (CMVR) is
among the most harmful signs of CMV infection in the eye. Its symptoms include
inflammation, bleeding, and necrosis of the complete thickness of the retina, which
appears as a whitish opacification of the retina with exudates and haemorrhages.18
Potential consequences of CMVR include retinal detachment and long-term visual
loss.17,19
Ocular signs of CMVR are considered an AIDS defining disease and, in the absence of
established immunological suppression, should raise suspicion for HIV infection.
Additional symptoms connected to CMVR that can also be noticed include solid
organ transplants, hematologic cancer, and medications brought on by
immunosuppression. Despite the high incidence of CMV antibodies in HIV infection,
it has been discovered that the clinical symptoms of CMV disease typically do not
appear until the CD4+ count falls below 100 CD4+ cells/mm3.

19. As a result, CMV retinitis has been divided into sight-threatening and non-sight-
threatening categories.20 Sight-threatening lesions originate in the posterior pole
and are more oedematous and fluffy in form, while non-sight-threatening lesions
are often granular in appearance, start in the periphery, and frequently lead to
symptoms of flashes or floaters.20 Sometimes CWS and cytomegalovirus necrosis are
mistaken for each other, although CMV lesions have a tendency to become larger
and combine over time to form expansive, wedge-shaped areas of involvement.
Infected patients make complaints of hazy vision, scotomas, light flashes, or floaters,
but 15% of them are frequently asymptomatic despite having severe or eyesight-
threatening CMV retinitis. As a result, it is advised15 that those with CD4+ cell counts
of less than 50 cells/mm3 undergo routine dilated fundus examinations every three
months. When patients have vision loss, it may be severe and irreversible and may
be caused by one of three causes, including immune healing, direct injury to the
macula and optic nerve, retinal detachment, which can still happen even after CMV
retinitis has cleared up.

20. Figure 1. Example of CMV Retinitis
https://doi.org/10.1371/journal.pmed.0040334.g001
Treatment for CMV focuses on curing the infection as well as restoring
immunological function lost to HIV. While antiretrovirals (ARVs) are continued
permanently, CMV-specific medicine is only given until the immune system has
recovered to a CD4+ cell count of at least 100 cells/mm3, which is reached after a
certain amount of time has passed.22

21. TOXOPLASMA RETINOCHOROIDITIS
This disorder is caused by a parasitic protozoan called toxoplasma gondii which is
found to affect close to 11% of people who are affected by HIV/AIDS. The protozoan
may exist in three forms namely, sporozoites which result from the parasite’s sexual
cycle, bradyzoites which are gradually procreating organisms that embodied in
tissue cysts and are restricted to muscles and brain, and tachyzoites which are
quickly separating organisms found in host tissues during the infection’s acute
phase. 10 It can be characterized by “fluffy” spots on the retinal whitening. The
appearance of this condition in individuals with immune deficiency is dissimilar as
its manifestation is often bilateral, multifocal and not affiliated with scars occurring
on the choroid and retina.

22. FUNGAL RETINITIS
Fungal retinitis is mostly caused by a fungal organism called Candida. Candida
retinitis is most common in HIV patients and can be seen by a fluffy white “sort of
heap” of infiltrates of the retina which further amplify to affect vitreous.15
BACTERIAL RETINITIS
Bacterial retinitis occurs frequently in patients who are on an advanced stage of HIV
and posterior portion infection that is unable to respond to the causes of other
microorganisms (protozoan, fungi , virus) Ocular syphilis is the most common
intraocular bacterial infection. It’s total retinitis is found in 1.5% of HIV-infected
patients.14 The infections progress as the damaged retina is permeated with many
histiocytes containing intracytoplasmic, enclosed bacterial forms.

23. CONCLUSION
In conclusion, HIV has been found to have a negative effect on the body,
badly compromising on individual’s immune system. Furthermore, the
Human Immunodeficiency Virus can severely affect the ocular structure of an
individual. Ocular manifestations are common in patients with AIDS.
Cytomegalovirus retinitis which is one of the ocular manifestations of
HIV/AIDS presented a major vision-threatening problem in patients and can
possibly lead to blindness.

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