Inflammatory retinal diseases

Intraocular inflammatory disorders encompass a broad spectrum of diseases that are a major cause of severe visual impairment. They may be:

• Specific to the eye (eg, punctate inner choroidopathy).

• Part of a systemic problem (eg, acute retinal necrosis (ARN) due to herpes simplex infection).

• Combination of both (eg, cytomegalovirus (CMV) retinitis in AIDS).

Related articles

• Many retinal inflammatory conditions occur in association with choroidal inflammation - chorioretinitis. See the separate article on Chorioretinal Inflammation for more detail about these conditions.

• Other choroidal disorders are discussed in the separate article Choroidal Disorders. This further describes the group of inflammatory conditions collectively known as the idiopathic multifocal white dot syndromes. There is also a separate article on Birdshot Retinochoroidopathy.

• You will also find that a number of conditions overlap with those of posterior uveitis.

This article outlines the variety of other conditions which cause retinal inflammation.

Retinal vasculitis

This is the generic term to describe the inflammation of retinal vasculature. This may be due to primary ocular disease such as birdshot retinochoroidopathy or sympathetic ophthalmia. It can also be secondary either to infection or systemic disease, a few of which are described below.¹

Although patients can be asymptomatic, many present with a decreased visual acuity, floaters and scotoma. The exact nature of the presentation varies a little with the underlying problem and is described in more detail below.

The underlying disease needs to be identified and treated where appropriate. This may be with antimicrobials in infective cases but most cases need immunosuppression at some point in the course of their treatment.

Retinal vasculitis may be complicated by an arteritis, central retinal vein occlusion or central retinal artery occlusion, vitreous haemorrhage and tractional retinal detachment. The prognosis is dependent on the underlying cause, the severity of the vasculitis and the presence/severity of any complications.

Parasitic infections

Ocular toxoplasmosis²

Infection with the intracellular protozoan Toxoplasma gondii is the most frequent cause of infectious retinitis in immunocompetent individuals. Presentation is usually following reactivation of a prenatal infestation but the infection can also be acquired postnatally.

It can cause a variety of types of retinitis, the end point of which is scarring. Depending on where in the fundus the scarring is, vision may or may not be significantly impaired. Active disease is usually associated with anterior uveitis.

Symptoms

This is often between 10 and 35 years of age with differences of symptoms at different ages:

• Children: reduced visual acuity, strabismus, nystagmus and leukocoria.

• Young people and adults: decreased vision, floaters, photophobia, pain and hyperemia.

AIDS patients often experience pain with marked anterior segment involvement.

Treatment

• Treatment with antibiotics probably reduces the risk of recurrent toxoplasma retinochoroiditis, but there is currently no good evidence that this leads to better visual outcomes.³

• Patients considered for treatment include immunocompromised patients, pregnant women and patients who have lesions that are deemed to be in key positions on the retina or have reached a certain size.

• Treatment will include topical steroid drops (not an injection), antitoxoplasmic agents (sulfadiazine, clindamycin, pyrimethamine, atovaquone, azithromycin),⁴ adjunct systemic corticosteroids in the immunocompetent patients and topical cycloplegic agents if there is concurrent anterior chamber inflammation.

Outcome
This is a self-limiting infection in an immunocompetent patient with mild, peripheral disease. Outcome ultimately depends on the location of the scars.

Ocular toxocariasis⁵

Accidental ingestion of dog roundworm (Toxocara canis) or the cat roundworm (Toxocara cati) gives rise to toxocariasis which can affect the liver, lungs, muscles, eyes and brain.

The eye tends to be affected in older children and in young adults where the larvae migrate to the posterior segment of the eye. When the larvae die, they disintegrate and cause an inflammatory reaction followed by granulation, which is when the patient presents. There are three clinical pictures:

• Diffuse, chronic endophthalmitis (usually presenting between 2 and 9 years of age).

• Posterior pole granuloma (patients aged between 6 and 14 years).

• Peripheral granuloma (adolescence to adulthood).

Uveitis, retinal fibrosis, retinoblastoma and retinal detachment can complicate the picture.

Symptoms

• This is in an otherwise healthy child who may have a history of ingesting dirt (sandpits, poor hand hygiene prior to eating) or owning a puppy.

• There is unilateral presentation with one of decreased vision, red eye or leukocoria ± strabismus.

• Systemic features usually occur in children under the age of 4 and include fever, pneumonitis with bronchospasm, hepatosplenomegaly, fits, myocarditis and (rarely) death.

Treatment

• Antihelmintics, steroids and occasionally surgery to clear the vitreous of debris or to repair any associated retinal detachments.

• Surgery for the other two forms should complications arise (eg, retinal detachment).

• Early vitrectomy may be of value both diagnostically and therapeutically.⁶

Outcome
Generally this is good. However, there is a risk of unilateral blindness in severe cases.

Diffuse unilateral subacute neuroretinitis (DUSN)⁷

Diffuse unilateral subacute neuroretinitis (DUSN) is an ocular infectious disease that can lead to severe visual impairment and blindness. It usually occurs in healthy young individuals and depending on the stage of the disease, it may present as vitritis, multifocal grey-white lesions in the outer retina, derangement of the retinal pigment epithelium, narrowing of the retinal vessels, and optic atrophy.

This is a progressive disease of the retina, which is thought to come about as a result of an inflammatory reaction to the excretory products of larvae (the exact pathogens are not always known). Despite its name, it is not always unilateral.

Symptoms

• Men are more commonly affected than women, presenting in their 20s and 30s with visual loss (mild initially, then becoming severe), scotoma, floaters and an uncomfortable red eye.

• In addition to optic disc swelling, a vasculitis and a vitritis, nematodes can be seen on careful examination. It is occasionally asymptomatic.

Treatment
Laser photocoagulation of the nematodes and antihelmintic treatment. Surgery is occasionally required.

Outcome
DUSN is a sight-threatening disease and the preservation of vision relies on early diagnosis and treatment.⁸

Viral infections

Acute retinal necrosis (ARN)⁹

Common viruses such as herpes simplex and varicella zoster may occasionally give rise to retinitis, as can CMV. However, this often occurs in the context of immunocompromised patients (eg, AIDS patients) and is dealt with separately under 'Cytomegalovirus retinitis', below.

The exception is the rare condition of ARN. Congenital rubella also affects the retina in the form of a visually insignificant pigmentary disturbance (visual problems in these cases occur due to anterior segment abnormalities).

Symptoms

• ARN occurs due to herpes simplex 2, under the age of 15 and to herpes simplex 1 or varicella-zoster virus later on in life.

• The presentation may be insidious (painless decrease in visual impairment) or acute (painful, rapid decrease in vision) in otherwise healthy patients (male:female = 2:1).

• It can be rapidly progressive, and therefore requires prompt and accurate diagnosis to guide initial therapy.¹⁰

• Sequential bilateral involvement occurs in up to a third of cases (usually within three months but it may be up to several years).

Treatment
Antivirals (intravenous in the first instance) followed by systemic steroids and aspirin. Laser treatment and surgery may also be necessary.

Outcome

• The acute phase resolves within about 12 weeks but leaves scars behind - depending on where these are on the retina, vision is affected to a greater or lesser degree.

• Without treatment, the second eye becomes involved in 65% of patients and the overall visual prognosis is guarded.

• Many complications may occur, particularly retinal detachment and, to a lesser extent, ischaemic optic neuropathy.

Cytomegalovirus retinitis¹¹

This tends to occur in the context of severe immunocompromise, most commonly AIDS (see 'Retinal disease in HIV-infected patients', below) but also other causes of immunodeficiency - eg, malignant disease and its treatment. See also the separate article on Cytomegalovirus.

Symptoms

• It may be asymptomatic or present with visual loss/scotomas.

• There will be a 'brush fire' appearance of the fundus with full thickness retinal necrosis (white patches) and associated haemorrhages radiating out towards the periphery.

Treatment

• This is jointly with the physicians and involves virustatic drugs to induce remission, followed by maintenance therapy.

• Antivirals may be oral, via injection into the eye or implant.

Outcome
Reactivation may occur, as well as second eye involvement.¹²

Fungal infections¹³

Histoplasma capsulatum may cause visual problems relating to an exudative maculopathy (see the separate article on Macular Oedema). Note that there is a related disease entity called presumed ocular histoplasmosis syndrome (POHS) in which there is a clinical picture similar to histoplasmosis but with no evidence of H. capsulatum.

Candida albicans infections tend to occur in immunocompromised patients, intravenous drug addicts and in patients with long-term indwelling catheters.

This pathogen gives rise to multifocal retinitis in addition to choroiditis and cotton-ball lesions floating in the vitreous. Cryptococcus neoformans rarely affects the eyes, tending to occur in the central nervous system of AIDS patients.

Symptoms

• Histoplasmosis - asymptomatic unless the macula is involved.

• Candidiasis - progressive unilateral blurring of vision.

• Cryptococcal infection - progressive decrease in visual acuity if lesions threaten macula.

Treatment

• Histoplasmosis is treated only if there is macular neovascularisation (laser photocoagulation). Antifungals (± surgical intervention - eg, vitrectomy) are used in the other fungal infections.

Outcome

• This depends on speed of diagnosis and site of lesion.

• Macular or optic nerve head involvement carries a poor prognosis. Complications such as retinal detachment and retinal necrosis also carry a poor prognosis.

Mycobacterial infections¹³

Tuberculosis

Uveitis and retinitis secondary to tuberculosis are rare in developed countries and usually a suspected diagnosis based on history and after unsuccessful treatment of a prolonged uveitis. Diagnosis is ultimately serological and treatment is with antituberculous drugs.

Leprosy

Leprosy tends to affect the anterior segments of the eye preferentially, causing iritis, trichiasis, keratitis and scleritis.

Spirochaetal infections

Syphilis¹⁴

• Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis. However, necrotising retinitis is a rare manifestation of ocular syphilis and mimics acute retinal necrosis.

• Neuroretinitis results in disc oedema, haemorrhages and, eventually, optic atrophy.

• Neurosyphilis needs to be ruled out (by lumbar puncture) and it is treated with high-dose penicillins (or tetracycline in penicillin-allergic patients).

Lyme disease¹⁵

Neuroretinitis is one of the many ophthalmological pictures that can arise in Lyme disease. Treatment is with doxycycline.

Retinal disease in HIV-infected patients¹⁶

CMV retinitis is the most common ocular infection in AIDS (34% prevalence) and rarely may be the first manifestation of this disease. See 'Cytomegalovirus retinitis', above, for more details about the condition.

The second most common opportunistic infection is caused by an aggressive variant of the varicella-zoster virus, which causes progressive outer retinal necrosis (PORN) - a devastating, rapidly spreading necrotising retinitis associated with a very poor prognosis.

Other pathogens commonly found in this patient group are T. gondii, Pneumocystis jirovecii and Treponema pallidum (causing syphilis). Non-infectious retinal microvasculopathy ('HIV retinopathy') also affects 50-70% of these patients.

Symptoms

This depends on the condition: asymptomatic (HIV retinopathy) to a rapidly progressive bilateral visual loss - PORN. The infective retinitis patients present with a similar, but often more severe, picture than non-AIDS patients:

• CMV retinitis - scotoma/decreased vision in one/both eyes, and floaters.

• PORN - rapid, progressive, painless visual loss.

• Toxoplasmosis - see above, although the presentation tends to be more severe in these patients.

• P. jirovecii - mild decrease in visual acuity (may be asymptomatic).

• Syphilis - may mimic CMV retinitis in appearance and presentation.

Treatment

Treatment of AIDS and of the infecting pathogen. Patients treated for syphilis will also typically nead treatment for chlamydial infections.

Outcome

This is variable depending on the degree of immunosuppression, the infecting pathogen and the severity of the eye problem.

Other inflammatory disorders

Sympathetic ophthalmia

See the separate article on Sympathetic Ophthalmia.

Vogt-Koyanagi-Harada (VKH) syndrome¹⁷

This is an idiopathic multisystem disease most often occurring in Hispanic, Asian and Middle Eastern populations (especially Japanese people) and darkly pigmented individuals.

Skin changes and anterior uveitis predominate in one subgroup of patients, whereas neurological features, retinal inflammation and detachment predominate in another. It is associated with, among others, HLA-DR4, HLA-DR53 and HLA-DQ4.

Symptoms

• There is a very wide spectrum of disease and 'typical' cases are uncommon. Symptoms may include red eyes, decreased vision, photophobia and pain associated with a headache, stiff neck, nausea and vomiting, fever and malaise.

• There may also be hearing loss, dysacousia and tinnitus. The ocular symptoms are bilateral and may follow the non-ocular symptoms once the latter have fully resolved.
  

  • Incomplete VKH is said to have occurred where there are ocular symptoms associated with acoustic or neurological symptoms

  • Probable VKH is described where there are ocular symptoms alone.

Treatment
The key to successful management is early and aggressive steroid treatment (systemic in severe disease) ± immunosuppressing agents.

Outcome

• This tends to be poor, frequently due to the associated retinal detachments, cataracts and glaucoma.

• Full-blown recurrences are rare after the acute stage of VKH disease is over but ocular inflammation may persist after the acute phase.¹⁸

Sarcoidosis-related retinitis¹⁹

See the separate article on Sarcoidosis for more detail on the systemic disease.

This is a multisystem, idiopathic, granulomatous disease which can cause anterior, intermediate or posterior uveitis. Retinal granulomas in the absence of other ocular involvement are possible but uncommon. It results in an anterior, intermediate or posterior uveitis.

Symptoms

• Ocular symptoms from uveitis include blurred vision, photophobia, floaters, redness, scotomata and pain.

• Periocular lesions may produce dry eye symptoms, as well as disfiguring lid, periocular and adnexal lesions.

• Orbital involvement by a mass lesion may cause proptosis and diplopia. It may be asymptomatic.

Treatment

• Management of ocular sarcoid is essentially treatment of the symptoms, ie steroids (topical or injected around the globe) ± non-steroidal anti-inflammatory drugs (NSAIDs).

• Cycloplegia is indicated with acute intense inflammation to relieve ciliary spasm and to prevent formation of posterior synechiae.

• Oral corticosteroids may be indicated where there is orbital involvement.

Outcome

• The ocular outcome is as variable as that of systemic disease. The visual outcome remains favourable but severe complications, including glaucoma, cystoid macular oedema and choroidal neovascularisation, may require prompt and aggressive management.²⁰

• Poor prognostic indicators include a chronic uveitis, glaucoma, cystoid macular oedema and fundus lesions (the latter being associated with an increased incidence of associated neurosarcoidosis).

• Cataracts can also occur.

• Long-term follow-up is needed and relapses are common.

Behçet's-related retinitis²¹

See the separate article on Behçet's disease for more detail on the systemic disease.

This is an idiopathic, recurrent, chronic multisystem disease characterised by recurrent episodes of acute inflammation.

Symptoms
Ophthalmic features include uveitis of the anterior/posterior segments which can be complicated by glaucoma and cataracts.

Treatment
Systemic corticosteroids under the joint care of ophthalmologists and physicians.

Outcome
Variable depending on the severity of the inflammation.

Acute retinal pigment epitheliitis (ARPE)

ARPE is an acute, transient, foveal disturbance of unknown cause which affects young adults.²² It tends to be unilateral. There is no treatment but the prognosis is excellent.