The choroid is the pigmented, highly vascular layer of the globe of the eye, lying between the sclera (on the outside) and the retina (on the inside). It is one of the three components of the uveal tract and is shaped like the body of a rounded wine glass. The optic nerve emerges at its base. The choroid is made up of three layers: the external vessel layer, the capillary layer and the internal Bruch's membrane.
The main function of the choroid is to nourish the outer layers of the retina. It also regulates retinal heat, assists in the control of intraocular pressure and absorbs excess light, thus avoiding internal reflection. The choroid also assists in focusing the eye through changes in choroidal thickness which move the retina forward and back, bringing the photoreceptors into the plane of focus when the focal plane is moved by the wearing of lenses. Secretion of growth factors by the choroid is likely to play an important role in emmetropisation (the adjustment of eye shape during growth to correct myopia or hyperopia.)
This is an inflammatory and exudative condition of the choroid and the retina. When the choroid alone is involved it is called choroiditis. It may be congenital or acquired at any age - particularly in the immunocompromised where it may be the ocular manifestation of severe systemic disease.
Chorioretinitis is usually a response to viral, bacterial, fungal or protozoal infection. It may be limited to the eye but infection may also involve other organs or be generalised. There may be vitreous involvement. Most cases are thought to occur congenitally and they are commonly asymptomatic.
Permanent damage to an area of the choroid will impair the blood supply to the underlying retina, thus leading to loss of vision in the corresponding area of the visual field. The effect on functional vision depends on the location and size of the lesion.
Chorioretinitis in neonates
Congenital toxoplasma and cytomegalovirus (CMV) are the most common causes of congenital chorioretinitis and they are often asymptomatic at birth.
- CMV and other viral chorioretinitis which is asymptomatic at birth tends to remain stable or improve in infancy.
- Chorioretinitis associated with congenital toxoplasmosis (CTP) can progress for years after birth and threaten vision. CTP is frequently bilateral; with healing of lesions, white or dark-pigmented retinal scars result.
Chorioretinitis beyond the neonatal period
Beyond the neonatal period, chorioretinitis can be newly acquired disease or reactivation.
- Acquired toxoplasmosis in immunocompetent older children and adults rarely progresses to chorioretinitis; it is generally unilateral. However chorioretinitis can also result from a dissemination of parasitic infections like Toxocara.
- In severely immunodeficient patients, including those with acquired immunodeficiency syndrome (AIDS), chorioretinitis may be associated with Epstein-Barr virus (EBV), CMV, varicella-zoster virus (VZV), fungal infection, syphilis and toxoplasma.
Other causes of chorioretinitis include:
- Bacterial infections:
- Lyme disease.
- Cat scratch disease (Bartonella henselae).
- Yersinia enterocolitica.
- Very rarely, Whipple's disease.
- Fungal infections:
- Candida spp.
- Aspergillus spp., Fusarium spp.
- Cryptococcus spp.
- Histoplasmosis and dimorphic fungi.
- Intravenous drug use
- IV drug use is known to be associated with a variety of ophthalmological consequences, including fungal chorioretinitis. Typically this involves formation of choroidal and retinal nodules, infection and inflammation. Painful visual loss ensues and endophthalmitis has been described.
- Non-infectious causes:
- Autoimmune conditions
- Malignancy (including choroidal melanoma)
- Sarcoidosis. Peripheral multifocal chorioretinitis (PMC) is characterised by chronic bilateral vitritis and punched-out lesions in the peripheral retina which occur in elderly white women in association with sarcoidosis. The visual outcome tends to be poor.
The prevalence is not known accurately. A large proportion of asymptomatic women of child-bearing age are seropositive for previous toxoplasmosis infection. Many studies have been done to look at the rate of seroconversion of pregnant women and have shown wide-ranging results. One Swedish study showed the incidence of primary infection of 40,000 women during pregnancy was 5.1/10,000 of susceptible pregnant women. The seroprevalence in the southern part of Sweden was 25.7% and in the Stockholm area 14.0%. Older figures suggest that in England and Wales disease due to toxoplasmosis is reported relatively rarely. Studies have estimated that between 7-34% of people in the UK are seropositive.
Many cases of toxoplasma chorioretinitis are thought to be reactivation of prenatal infection. This usually occurs between the ages of 10 and 35 and may occur apparently spontaneously. In some countries, up to 50% of all cases of posterior uveitis are attributable to toxoplasmosis.
The incidence of CMV infection is less well documented in the immunocompetent but CMV chorioretinitis is the most common ocular infection in patients with AIDS. Other infective causes are rare, particularly in the immunocompetent of the Western world. Non-infective causes are also infrequent with few epidemiological data available.
Presentation varies according to the cause and to patient age.
- Older patients more commonly present with reduced visual acuity and with floaters. The degree of one or the other of these symptoms depends on where the inflammatory lesions lie. A child may 'squint' or favour the good eye. There may be reports of inability in seeing objects or apparent clumsiness.
- Occasionally there may be complaints of redness, pupil distortion and photophobia. Symptoms are usually unilateral and tend to develop over several days.
- Congenital infections may present insidiously, with little history and few symptoms. It is difficult to elicit a history of maternal toxoplasmosis infection as it may not have caused symptoms. Contact with cat litter trays and a predilection for eating raw meat are suggestive.
- Congenital infection present due to effects of congenital infection on other organs (see below).
- Other infective causes are diagnosed by process of probability and exclusion. A history of immunodeficiency is significant.
Dilated fundus examination during active choroiditis will reveal pale lesions with reasonably well demarcated borders. They may be single or multiple and look rather as if a small light were being shone from deep behind the retina.
Inactive choroiditis is characterised by atrophic patches which are white, well defined and have areas of mottled pigmentation within them.
Other features of infection may be present, depending on the underlying pathology - eg, central nervous system involvement in toxoplasmosis or syphilis.
A UK survey of ocular toxoplasmosis found that it tended to present under the age of 4 years or over the age of 9 years. Children with congenital infection were usually detected through abnormal vision screening or ocular appearance; children with acquired infections usually presented with acute ocular symptoms.
- Posterior vitreous detachment.
- Retinal detachment.
- Macular disease.
- Intraocular foreign body.
- Choroidal dystrophy.
- Fundal tumour - eg, melanoma, retinoblastoma.
- Presumed ocular histoplasmosis syndrome. This is characterised by peripheral atrophic chorioretinal scars and scarring adjacent to the optic disc and macula. It is associated with smoking and is now thought not to involve histoplasma.
Patients require review in secondary care. Initial tests should include a basic FBC, renal tests and LFTs, inflammatory markers and an autoimmune screen (bloods and CXR); plus, serological and microbiological tests to rule out infection. It is rare that more is needed but a biopsy of the lesion is possible if the diagnosis is uncertain and the symptoms progress or don't respond. Immunocompromised patients will need a thorough work-up to exclude systemic infection.
Ancillary techniques which may aid diagnosis by imaging the posterior pole of the eye include:
- Systemic infection - congenital disseminated infections can cause a range of problems, including intrauterine growth restriction, microcephaly, hearing defects, osteomyelitis, enlarged liver and spleen, lymphadenopathy, dermal erythropoiesis, carditis and congenital heart disease. Acquired systemic infections with the above pathogens also cause a range of problems. Infection in immunocompromised patients can be severe and life-threatening.
- Other ocular problems - microphthalmia, cataract and uveitis (due to congenital infections).
- Other - systemic manifestations of the other (rare) causes of chorioretinitis, such as autoimmune conditions, malignancy and sarcoidosis.
The inflammatory lesions will be assessed in terms of number, size and location, particularly proximity to the macula and the disc and whether or not they lie within the arterial arcade.
Patients presenting with floaters and/or reduced visual acuity should have a thorough fundal examination. If this cannot be performed in the primary care setting or by an ophthalmic optician, or if the fundus looks in any way abnormal, referral should be made. The degree of urgency depends a little on the duration of symptoms but it is good practice for the patient to be seen within 24 hours.
- Treatment of chorioretinitis is carried out by an ophthalmologist and subsequent monitoring is within an eye unit.
- Treatment of infectious chorioretinitis may involve observation or antimicrobials ± topical steroid treatment: this depends on the causative pathogen and a number of other criteria.
- Antimicrobials used depend on individual circumstances but antivirals (eg, ganciclovir), antibiotics (eg, for Lyme disease and syphilis), antifungals (eg, 5-fluorocytosine), anthelmintics (eg, diethylcarbamazine) and antituberculous drugs may all be used.
- Systemic disease should be actively ruled out (or treated).
Treatment of ocular toxoplasmosis
- This is a usually a self-limiting infection which does not require treatment in an immunocompetent patient with mild disease of the peripheral retina. However, cases of severe acute disseminated toxoplasmosis (including chorioretinitis) in immunocompetent patients, requiring treatment, have been reported due to new, virulent strains of Toxoplasma gondii.
- Treatment aims to reduce the risk of permanent visual impairment (by reducing the size of the retinochoroidal scar), the risk of recurrence and the severity and duration of acute symptoms. However, there is a lack of evidence about the efficacy of antibiotics.Traditional short-term treatment of active toxoplasmic retinochoroiditis lesions does not prevent subsequent recurrences.
- Decisions about treatment should be made by an ophthalmologist familiar with the disease.
- 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.
- In pregnancy, spiramycin treatment reduces vertical transmission and should be started immediately on diagnosis of recently acquired maternal infection.
- Treatment will include topical steroid drops, antibiotics, adjunct systemic corticosteroids in the immunocompetent patients and topical cycloplegic agents if there is concurrent anterior chamber inflammation.
- Antibiotic therapy usually involves a combination of drugs over several weeks. Examples are pyrimethamine with sulfadiazine, or trimethoprim-sulfamethoxazole (Bactrim®) with or without adjunctive clindamycin, or pyrimethamine and azithromycin. Other drugs used include atovaquone or intravitreal injection of clindamycin. Folinic acid helps to reduce bone marrow toxicity with pyrimethamine.
- Surgery involving cryotherapy, photocoagulation or a vitrectomy may very occasionally be considered.
- Recurrences can be reduced with long-term, intermittent trimethoprim-sulfamethoxazole.
- Immunosuppressed patients may need maintenance treatment.
- Prophylactic therapy may be given to immunocompromised patients or cataract surgery patients perioperatively.
- The inflammatory response can spill forward into the vitreous and the anterior chamber so giving rise to an acute anterior uveitis.
- Macular oedema and choroidal neovascularisation are possible complications; there may be a role for treating these using anti-vascular endothelial growth factors.
- Poor vision in one eye during childhood may cause amblyopia.
Disease associated with congenital viral infection tends to improve in infancy but asymptomatic toxoplasmosis may progress. The retina scars once a lesion has occurred. Therefore, the prognosis largely depends on the size of the residual lesion and its location. Small peripheral lesions are completely asymptomatic (it is not uncommon to find these incidentally when examining the patient for another problem). However, centrally placed or large lesions will leave the patient with a residual visual defect.
Nevertheless, a UK survey of children with toxoplasmic retinochoroiditis found that, overall, the visual prognosis was good.
Further reading and references
Clinical Ophthalmology, A Systematic Approach
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Battaglia Parodi M, Iacono P, Verbraak FD, et al; Antivascular endothelial growth factors for inflammatory chorioretinal disorders. Dev Ophthalmol. 201046:84-95. Epub 2010 Aug 10.