Ocular surface and adnexa of the eye (eyebrow, conjunctiva, eyelids, and lacrimal apparatus)
Anterior segment of the eye (cornea, anterior chamber and iris)
Before ART, up to 70% of PLWH developed some form of ocular involvement as a result of OIs, HIV-associated tumours, or direct infection by HIV. Ocular manifestations 
in frequency as the CD4 count 
. Patients with CD4 count <200 cells/µL should be closely examined for signs of ocular disease which may be asymptomatic in the early stages. Close cooperation with ophthalmology is essential to ensure timely therapeutic interventions to risk of visual impairment and blindness. ART the incidence of ocular complications by 26-50% and altered the natural history of many OIs.
Ophthalmic manifestations of HIV infection can be classified as:
• Ocular surface and adnexa of the eye:
• conjunctival microvasculopathy
• Anterior segment of the eye:
• superficial candidal keratitis
• Posterior segment of the eye:
• progressive outer retinal necrosis
• toxoplasmosis retinochoroiditis
• Neuro-ophthalmic manifestation.
Dry eye is frequent among PLWH. Results from HIV-mediated inflammation and damage to the lacrimal glands. Patients complain of burning uncomfortable red eyes.
Treatment is with artificial tears and lubricating ointments.
Occurs in 70–80% of PLWH. Exact aetiology not known, but may be related to viscosity and immune complex deposits. Conjunctival changes are found near the limbus and can only be detected by slit-lamp examination. Features include segmental vascular dilation and narrowing, micro-aneurysms and appearance of comma-shaped vascular fragments.
Results from reactivation of a latent infection by VZV in the dorsal root of the trigeminal root ganglion. It is recognized by characteristic vesicular eruptions, which is often preceded by pain. Usually involves the upper lid, does not cross the midline, and may be associated with blepharitis, conjunctivitis, keratitis, uveitis, and necrotizing retinitis, which may occur at same time or soon afterwards. Complications and post-herpetic neuralgia in the immunosuppressed.
Early retinal lesions similar to CMV, but rapidly progressive, deep, and multifocal with risk of retinal detachment, which may lead to blindness in days without prompt treatment.
Characteristic rash and its distribution are usually sufficient to establish the diagnosis. Serological tests and PCR rarely needed.
IV aciclovir is the treatment of choice along with aciclovir eye drops if corneal involvement. Valaciclovir can be used after initial improvement or mild disease with good CD4 count. Other problems, such as anterior uveitis are treated with topical steroids and mydriatics.
KS is a vascular neoplasm, which is almost exclusively seen in patients with AIDS. Up to 20% of patients with skin KS have eyelid and conjunctival lesions. Lesions appear as violaceous non-tender nodules on the eyelid or conjunctiva, although conjunctival lesions may resemble traumatic haemorrhages.
Options include surgical removal, cryotherapy, α-interferon and intralesional chemotherapy. Systemic chemotherapy may be needed if extensive disease (see Chapter 54, ‘Kaposi’s sarcoma,’ pp. 611–613). Radiation is effective, but may be complicated by loss of eyelashes and conjunctivitis.
Discrete, rounded, pearly white umbilicated lesions of the eyelids can be a presenting ocular feature of HIV disease. The eyelid is involved in 5% of HIV. Lesions can be extensive and disfiguring with severe immune deficiency.
Options include incision and curettage, cryotherapy, and trichloroacetic acid. However, spontaneous regression may occur with ART.
May be due to an interaction between HIV, sunlight, and HPV infection. Tumour appears as a pink, gelatinous growth, usually in the interpalpebral area and may extend onto the cornea. An engorged blood vessel feeding the tumour is seen.
Options are local excision, and local excision and cryotherapy.
• Viral: HSV and VZV are the most common infections, may recur and may be resistant to treatment. VZV keratitis is associated with herpes zoster ophthalmicus.
• Bacterial: rare in HIV, but severe.
• Fungal: Candida albicans and Candida parapsilosis are the commonest fungal infections in HIV, albeit rare, and normally seen in advanced HIV. Symptoms include eye pain, photophobia, and discharge and foreign-body sensation. Slit-lamp examination reveals corneal stromal infiltrate with a feathery border. Associated small focal lesions around the 1° corneal infiltrate are often present, along with conjunctival injection, anterior chamber reaction, and hypopyon. Diagnosis can be established by identifying fungal elements in corneal scrapings and fungal culture. Responds well to topical antifungals.
Causes:
• severe with ocular toxoplasmosis, tuberculosis, syphilis, bacterial, and fungal retinitis.
• Retinitis and retinochoroiditis sequelae.
• Part of generalized autoimmune and endogenous uveitis (e.g. Reiter syndrome).
Can be a direct manifestation of HIV infection, autoimmune or drug-induced (rifabutin), secondary to direct toxic effect upon the non-pigmented epithelium of the ciliary body and infections e.g. VZV, HSV, CMV, Toxoplasma gondii, and Toxoplasma syphilis.
A syndrome where PLWH with prior CMV retinitis experience an increase in intra-ocular inflammation following ART. Mainly involves anterior uveal tract and vitreous, and is commonly associated with a marked disturbance of visual function due to macular oedema and epi-retinal membrane formation. The marked cellular infiltration of the vitreous (in the absence of an active retinal or chorioretinal lesion) is the hallmark of this phenomenon. Responds well to systemic steroids.
Asymptomatic and occurs in >50% of PLWH. Seen as transient cotton wool spots (light-coloured retinal deposits 2° to infarcts of the nerve fibre layer), intra-retinal haemorrhages and micro-aneurysms. Often occurs simultaneously in the conjunctiva. Aetiology not known, but thought 2° to HIV infection of retinal vascular cells.
Treatment is based on delaying the progression of the disease associated with HIV
CMV retinitis results from reactivation of infection acquired in childhood or early adult life. The most common eye OI in the pre ART era occurring in 30–40% of patients with CD4 count <50 cells/µL. Bilateral in 30–50% and optic nerve papillitis in 5%. Serious visual complications can be avoided by detecting early features with regular dilated fundal examination for at risk patients (CD4 <100 cells/µL).
Symptoms depend on site and extent of retinal involvement. Peripheral retinal lesions are asymptomatic. Earliest and most common symptoms are floaters (representing foci of inflammatory cells in the vitreous, attempting to contain the infection). Other symptoms include flashing lights, blurring/loss of central vision and scotomata. Initial focus of retinal inflammation expands peripherally, inducing retinal necrosis.
Early active lesions appear as multiple granular white dots with occasional haemorrhages. With further progress, areas of retinitis enlarge by following the vascular arcades, resulting in an arcuate or triangular zone of infection. Areas of active infection may also be linear, following the retinal vessels or nerve-fibre layer into the periphery. Early CMV lesions may be confused with cotton-wool spots (due to HIV vasculopathy), which may co-exist. Serial drawings or retinal photographs are helpful in differentiation. Continuing activity of the necrotic process results in atrophic features with thinning of the retina resulting in visualization of the underlying choroid. Other features of CMV retinitis include vascular attenuation, vessel occlusion, vitritis, and anterior uveitis (Plate 31). May be complicated by retinal detachment and cataract.
Plate 31 CMV retinitis (44).
Occasionally, it may be difficult to establish the cause of retinitis.
Usually clinical, all patients presenting with CD4 <100 cells/µL should have slit lamp examination. Confirmed by obtaining a vitreous sample for CMV PCR. A rising CMV VL, detected by PCR, is associated with eye and other organ disease.
ART improves response to treatment, prognosis, and relapse rates.
IV ganciclovir, given as an induction course for 2–3 weeks (5 mg/kg body weight 12-hourly) followed by maintenance therapy (5 mg/kg body weight 7 days a week or 6 mg/kg body weight 5 days a week). Side-effects include rigors and neutropenia that may require discontinuation of treatment or the use of granulocyte colony stimulating factor. Oral valganciclovir 900 mg bd for 3 weeks followed by 900 mg od produces blood levels comparable with IV ganciclovir. Main side-effects are bone marrow suppression and GI upset.
Intravitreal ganciclovir implants are very effective, but need to be replaced after 6–9 months; does not give protection to the other eye or protect against systemic disease.
IV foscarnet, given as an induction course for 2–3 weeks (60 mg/kg body weight 8-hourly) followed by maintenance therapy (90–120 mg/kg body weight od). Given when ganciclovir is not tolerated due to its toxicity. Side-effects include nephrotoxicity, convulsions, meatal ulceration, and electrolyte disturbance. Has infusion time and requires an infusion pump.
IV cidofovir plus oral probenecid is effective in ganciclovir-resistant CMV, but is highly nephrotoxic and myelosuppressive.
Response to therapy achieved in 80–90%. Without immune reconstitution, the median time to relapse is 50–120 days using standard anti-CMV treatment. Maintenance therapy can be stopped once immune reconstitution is achieved.
ARN is usually due to VZV infection, and less commonly HSV or CMV. Can occur at any stage of HIV infection. Presents with eye pain associated with scotomata progressing rapidly to visual loss. The other eye is involved in one-third. Fundal examination shows prominent anterior chamber reaction, marked vitritis, occlusive retinal and choroidal vasculitis, and full-thickness retinal necrosis. It can lead to retinal detachment in 75% of cases and blindness in 64% of cases within 2–3 months. May be complicated by proliferative retinopathy and retinal detachment. The diagnosis is mainly clinical and is confirmed by PCR assays on vitreous samples.
IV aciclovir or oral valaciclovir or famciclovir combined with laser treatment to prevent retinal detachment.
PORN is severe viral retinitis without vitritis or retinal vasculitis. The main cause is VZV. HSV, CMV and Epstein–Barr virus are also implicated. It is usually seen in patients with severe immune deficiency, an average CD4 count of 20 cells/uL. Typical features are multifocal retinal opacities starting at the peripheral retina, involving the posterior pole in 30% of cases, rapidly coalescent and progressing to complete retinal necrosis. The main symptom is rapid loss of vision. The retina typically shows a white lesion with no haemorrhages or exudates. Diagnosis with vitreal biopsy and viral PCR.
IV aciclovir can be associated with progression. IV ganciclovir can be associated with significant toxicity. Intra-vitreal ganciclovir and foscarnet may be superior.
Very poor and retinal detachment is common. Resolution may leave a white plaque with the appearance of ‘cracked mud’.
Accounts for only 1–2% of retinitis in PLWH, 30–50% of them have concurrent CNS involvement. Unlike the immunocompetent patients, PLWH often have bilateral and multifocal disease associated with anterior uveitis, and later on vitritis, and no pigmented scars adjacent to the areas of retinal necrosis. Toxoplasmosis in immunocompromised patients is not self-limiting.
Fundal examination reveals characteristic extensive fluffy areas of retinal whitening with accompanying vitritis, but unlike CMV infection retinal haemorrhaging is less likely. Toxoplasma serological tests are unreliable to make a diagnosis, but the absence of toxoplasma IgG antibodies makes it less likely.
Pyrimethamine plus sulfadiazine or clindamycin plus folinic acid. Equally good response may be obtained with atovaquone. Long-term maintenance treatment with clindamycin and pyrimethamine usually required.
Posterior segment infection is seen in advanced HIV disease. More common in PWID and may be associated with infected lines in the seriously sick. In the initial stages, floaters are the main symptom. With progression, whitish ‘puff-balls’ and vitreous strands develop. Later, similar infiltrates appear in the choroid and retina, and may extend into the overlying vitreous. Majority of patients have systemic candidiasis.
Blood cultures, and vitreous aspiration and diagnostic vitrectomy for fungal culture and histological examination.
Depends on severity of ocular involvement and presence of systemic disease. Original foci should be looked for and removed (e.g. central line). Systemic antifungals, e.g. liposomal amphotericin, voriconazole, and fluconazole.
Occur in 10%. Most common features include papilloedema, cranial nerve palsies, ophthalmoplegia, and visual field defects. Caused by lymphoma and any CNS infection, most frequently cryptococcal meningitis, neurosyphilis, and toxoplasmosis. HIV encephalopathy and progressive multi-focal leukoencephalopathy may have similar complications.
Investigate by magnetic resonance imaging, lumbar puncture (CSF-cell count, cytology, culture, and serology).