Chorioretinal Inflammation

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 intra-ocular pressure and the pigment absorbs excess light so avoiding reflection.

This refers to an inflammatory and exudative condition of the choroid and the retina.^2,3 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:

• Congenital toxoplasmosis (CTP): the most common culprit in the immunocompetent child, estimated to occur in about 1-4 cases per 1000 births.
• Congenital cytomegalovirus (CMV): the next most common pathogen in the immunocompetent child.
• Other viral infections: Epstein-Barr virus, varicella-zoster and West Nile virus.
• Bacterial infections: syphilis, tuberculosis, brucellosis, Lyme disease.
• Fungal infections: Candida spp., Aspergillus spp., Fusarium spp., Cryptococcus spp. and dimorphic fungi.
• Occasionally: non infectious causes such as auto-immune conditions, malignancy and sarcoidosis.

It is worth noting that acquired ocular toxoplasmosis is actually more common than the congenital form but congenital cases tend to present with more severe disease.⁴

The exact prevalence is not known but it is thought that there is a large proportion of asymptomatic women of child-bearing age (in the region of 50-80%²) who are seropositive for previous toxoplasmosis infection; thus many cases of toxoplasma chorioretinitis are thought to be reactivation of prenatal infestation.³ This usually occurs between the ages of 10 and 35 and may occur apparently spontaneously. 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 little epidemiological data available.

• 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 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 - 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 maybe 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 was 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).

• 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.

These patients will be further investigated once under the care of the ophthalmologists. The will involve a basic full blood count, renal and liver function tests, inflammatory markers and an auto-immune screen (bloods and chest x-ray) as well 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.

• Systemic infection - congenital disseminated infections can cause a range of problems including intrauterine growth retardation, microcephaly, microphthalmia, cataract, uveitis, 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 - systemic manifestations of the other (rare) causes of chorioretinitis such as auto-immune conditions, malignancy and sarcoidosis.

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.

• 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 depends on individual circumstances but antivirals (e.g. ganciclovir), antibiotics (e.g. for Lyme disease and syphilis), antifungals (e.g. 5-fluorocytosine), antihelmintics (e.g. diethylcarbamazine) and antituberculous drugs may all be used.
  • Systemic disease should be actively ruled out (or treated).
• Treatment of ocular toxoplasmosis⁵
  • This is a self-limiting infection in an immunocompetent patient with mild, peripheral disease.⁶ Treatment for toxoplasma retinochoroiditis 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.⁷
  • 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), adjunct systemic corticosteroids in the immunocompetent patients and topical cycloplegic agents if there is concurrent anterior chamber inflammation.
  • Surgery involving cryotherapy, photocoagulation or a vitrectomy may very occasionally be considered.
  • Prophylactic therapy may be given to immunocompromised patients or cataract surgery patients peri-operatively.

The inflammatory response can spill forward into the vitreous and the anterior chamber so giving rise to an acute anterior uveitis.

Disease associated with congenital viral infection tends to improve in infancy but asymptomatic CTP may progress for years and only become clinically significant many years later.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 clearly centrally placed lesions or large lesions will leave the patient with a residual visual defect and if they are particularly badly placed (over the macula), sight may be lost altogether.