The choroid: what is it?

This is the pigmented, highly vascular layer of the globe, lying between the sclera (on the outside) and the retina (on the inside).^[1] It is one of the three components of the uveal tract and is shaped a little like the body of a rounded wine glass. The optic nerve emerges at its base and the other two components of the uveal tract sit anteriorly: the ciliary body lies around the rim and the iris stretches over the opening. It is made up of three layers, each of which can be affected by disease processes. There is the external vessel layer, the capillary layer and the internal sheet-like Bruch's membrane. The main function of the choroid is to nourish the outer layers of the retina but it is also thought to regulate retinal heat, to assist in the control of intraocular pressure, and the pigment absorbs excess light so avoiding reflection.

Chorioretinitis

This refers to an inflammatory and exudative condition of the choroid and the retina.^[2] It is most often a response to an infection which may be generalised and involve several organs or it may be limited to the eye. There may be vitreous involvement (so giving rise to posterior uveitis). It may be congenital or acquired at any age - particularly in the immunocompromised where it may be the ocular manifestation of severe systemic disease. Causes include:^[2]

• Congenital toxoplasmosis: the most common culprit in the immunocompetent child.
• Congenital cytomegalovirus (CMV): the next most common pathogen in the immunocompetent child.
• Other parasites: Toxocara spp., Baylisascaris spp. (the raccoon roundworm) and onchocerciasis (filariasis).
• Other viral infections: varicella-zoster virus,^[3] herpes simplex virus, rubella, Epstein-Barr virus, lymphocytic choriomeningitis virus^[4] and West Nile virus.^[5]
• Bacterial infections: tuberculosis,^[6] syphilis,^[7] brucellosis, Lyme disease, cat scratch disease (Bartonella henselae), Yersinia enterocolitica and (very rarely) Whipple's disease.^[8]
• Fungal infections: Candida spp., Aspergillus spp., Fusarium spp., Cryptococcus spp., histoplasmosis and dimorphic fungi.
• Occasionally: non-infectious causes such as autoimmune conditions, malignancy and sarcoidosis.
• Causes found in immunocompromised patients include syphilis,^[7] toxoplasmosis, fungi, Epstein-Barr virus, CMV, varicella-zoster.

Epidemiology

The exact prevalence is not known but it is thought that there is a large proportion of asymptomatic women of child-bearing age who are seropositive for previous toxoplasmosis infection; thus, 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.^[9]

The incidence of CMV infection is less well documented in the immunocompetent but this 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.

It is worth noting that acquired ocular toxoplasmosis may be equally, or more, common than the congenital form,^[10] but congenital cases tend to present with more severe disease.^[11]

Presentation^[2]

• Symptoms - presentation varies according to the specific underlying factor but the key thing is that, unlike anterior uveitis, pain tends to be a minor complaint in many individuals. 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. Occasionally, there may be complaints of redness, pupil distortion and photophobia. Usually, symptoms are unilateral and tend to develop over several days.
• Further clues in history - congenital infections may present insidiously, with little in the way of history or symptoms. It is very difficult to elicit a history of maternal toxoplasmosis infection as this parasite may remain dormant for many decades and initial infection may not necessarily have caused symptoms. Contact with cat litter trays and a predilection for eating raw meat are suggestive. Other infective causes are diagnosed by process of probability and exclusion. A history of immunodeficiency is significant. The child may 'squint' or favour the good eye. There may be reports of inability in seeing objects or apparent clumsiness.
• Signs - dilated fundus examination of the patient with active choroiditis will reveal pale lesions with reasonably well demarcated borders. They may be single or multiple and look rather like a small light were being shone at you 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 (they look more like a cigarette burn on a piece of cloth). See the various references under 'Document references and Internet and further reading' for retinal photographs.
• Systemic features - 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 at the extremes of childhood (under 4 years or over 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.^[10]

Differential diagnosis

• Posterior vitreous detachment.
• Retinal detachment.
• Macular disease.
• Intraocular foreign body.
• Inactive choroiditis lesions may look a little like some of the choroidal dystrophies. Any of the other choroidal disorders listed below will also be ruled out by the ophthalmologist on examining the eye.

Investigations

These patients will be further investigated once under the care of the ophthalmologists. The will involve a basic FBC, renal and liver function tests, 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 completely unknown and the symptoms progress or don't respond. Immunocompromised patients will need a more thorough work-up to exclude systemic infection.

Ancillary techniques used to image the posterior pole of the eye include optical coherence tomography^[12] and fundus autofluorescence imaging.^[13]

Associated diseases

• 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 the immunocompromised patient can be severe and life-threatening.
• Other ocular problems - microphthalmia, cataract, uveitis (due to congenital infections).
• Other - systemic manifestations of the other (rare) causes of chorioretinitis, such as autoimmune conditions, malignancy and sarcoidosis.

Staging

The inflammatory lesions will be assessed in terms of number, size (usually measured in disc diameters) and their location, with a particular note of the proximity to the macula, the disc and whether or not they lie within the arterial arcade.

Management

• Referral: 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 principles:
  • Treatment of chorioretinitis is carried out by an ophthalmologist and subsequent monitoring is within an eye unit. There will be liaising with the physicians where systemic disease is involved.
  • Treatment of infectious chorioretinitis may involve simple observation or antimicrobials ± topical steroid treatment: this depends on the causative pathogen and a number of other criteria (see the case of ocular toxoplasmosis below).
  • Antimicrobials used depend on individual circumstances but antivirals (eg ganciclovir), antibiotics (eg for Lyme disease and syphilis), antifungals (eg 5-fluorocytosine), antihelminthics (eg diethylcarbamazine) and antituberculous drugs may all be used.
  • Systemic disease should be actively ruled out (or treated).
• Treatment of ocular toxoplasmosis:^[14][15]
  • 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 from rural French Guiana.These were thought to be due to new, virulent strains of Toxoplasma gondii.)^[16]
  • Decisions about treatment should be made by an ophthalmologist familiar with the disease. 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,^[17] and traditional short-term treatment of active toxoplasmic retinochoroiditis lesions does not prevent subsequent recurrences.^[9]
  • 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 for toxoplasmosis 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^[2] or intravitreal injection of clindamycin.^[9] Folinic acid helps to reduce bone marrow toxicity with pyrimethamine.^[2]
  • 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.

Complications

• 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 a role for treating these using anti-vascular endothelial growth factors.^[18]
• Poor vision in one eye during childhood may cause amblyopia (squint).

Prognosis

Disease associated with congenital viral infection tends to improve in infancy, but asymptomatic toxoplasmosis may progress.^[2] 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 (the patient may never present with these in the first place; it is not uncommon to find these incidentally when examining the patient for another problem), but centrally placed lesions or large lesions will leave the patient with a residual visual defect, particularly if located over the macula. However, a UK survey of children with toxoplasmic retinochoroiditis found that, overall, the visual prognosis was good.^[10]